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Background: Large-scale HIV genotype drug resistance study has not been conducted in Chongqing. Methods: A retrospective study was conducted on people living with HIV(PLWH) who received HIV-1 genotype resistance testing at Chongqing Public Health Medical Center from May 2016 to June 2023. The HIV-1pol gene was amplified through RT-PCR and analyzed in terms of genotypic drug resistance. Results: Of the 3015 PLWH tested for HIV-1 drug resistance, 1405 (46.6%) were resistant to at least one antiviral drug. Among non-nucleoside reverse transcriptase inhibitors (NNRTIs), 43.8% were resistant, compared to 29.5% for nucleoside reverse transcriptase inhibitors (NRTIs) and 3.4% for protease inhibitors (PIs). V179D/E and K103N/S were identified as the common mutation sites in the NNRTIs class of drugs, M184V/I and K65R/N were reported as the most common mutation sites in NRTIs, while thymidine analogue mutation (TAM) group was identified in 373 samples. L10FIV was the most common mutation in PIs. The dominant HIV-1 subtype was CRF07_BC. Conclusions: The high prevalence of HIV-1 drug resistance in Chongqing underscores the imperative for rigorous surveillance of the local HIV epidemic. Furthermore, TAMs are associated with HIV-1 multidrug resistance, and timely detection of drug resistance is helpful to reduce the emergence and spread of such drug-resistant strains. [ABSTRACT FROM AUTHOR]

Background: The significance of CXCL5 in pancreatic cancer is unclear, although it has been implicated in the malignant process of many different types of cancer. Research on the impact of CXCL5 on immune cell infiltration and the malignant phenotype of pancreatic cancer is needed. This study aimed to examine the connection between CXCL5 expression and immune cell infiltration and the malignant phenotype of pancreatic cancer. Methods: Tissue samples and clinical information were collected from 90 patients with pancreatic cancer. Tumour tissues and adjacent tissues were made into a tissue microarray and stained for immunohistochemistry analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were performed to measure the expression level of CXCL5. CXCL5-overexpressing/CXCL5-knockdown cell lines were constructed via transfection for cytological experiments. CCK-8, cell apoptosis, cell cycle, cell invasion, and cell colony formation assays were used to detect the effect of CXCL5 on the malignant phenotype of pancreatic cancer cells. Finally, a mouse model of pancreatic cancer was constructed for in vivo verification. Results: Compared with control cells, pancreatic cancer cells overexpressing CXCL5 exhibited increased proliferation, migration, and invasion but decreased apoptosis. Conversely, knockdown of CXCL5 did not enhance the malignant phenotype of pancreatic cancer cells. Spearman correlation analysis indicated that there was a significant negative correlation between CXCL5 levels and the CD8 IRS. However, there was a significant positive correlation between FOXP3 IRS and CXCL5 levels. Conclusions: CXCL5 is highly expressed in pancreatic cancer and promotes the malignant phenotype of pancreatic cancer cells. CXCL5 is associated with immunosuppressive FOXP3 + T-cell infiltration, which facilitates the formation of an immunosuppressive microenvironment (with low CD8 + T-cell infiltration). [ABSTRACT FROM AUTHOR]

Background: Gestational Diabetes Mellitus (GDM) poses significant risks to maternal and fetal health. Current diagnostic methods based on glucose tolerance tests have limitations for early detection. tRNA‐derived small RNAs (tsRNAs) have emerged as potential molecular regulators in various diseases, including metabolic disorders. However, the diagnostic value of tsRNAs in plasma for early GDM or postpartum remains unclear. Methods: This longitudinal study profiled the expression of tsRNAs across different gestational stages and postpartum in women with GDM (n = 40) and healthy control gestational women (HCs, n = 40). High‐throughput small RNA sequencing identified candidate tsRNAs, which were then validated and correlated with clinical biochemical markers such as fasting blood glucose (FBG), HOMA‐IR, and GHbA1c. Results: tRF‐1:32‐Val‐AAC‐1‐M6, tRF‐1:31‐Glu‐CTC‐1‐M2, and tRF‐1:30‐Gly‐CCC‐1‐M4 were consistently upregulated in the GDM group compared to HCs during the second trimester (p < 0.05). Only tRF‐1:31‐Glu‐CTC‐1‐M2 was highly expressed during the first trimester, and tRF‐1:30‐Gly‐CCC‐1‐M4 increased during postpartum. tRF‐1:31‐Glu‐CTC‐1‐M2 showed a significant correlation with FBG levels in the first trimester (R = 0.317, p = 0.047). The expression of tRF‐1:30‐Gly‐CCC‐1‐M4 was significantly correlated with HOMA‐IR (r = 0.65, p < 0.001) and GHBA1c (r = 0.33, p = 0.037) during postpartum. A joint diagnostic model incorporating tsRNAs expression and clinical markers demonstrated enhanced predictive power for GDM (ROC AUC = 0.768). Conclusion: Our results revealed distinct expression patterns of specific tsRNAs in GDM, showcasing their correlation with key metabolic parameters. This underscores their promising role as biomarkers for early prediction and diagnosis of GDM. The integration of tRFs into a composite biomarker panel holds the potential to improve clinical outcomes by enabling personalized risk assessment and targeted interventions. [ABSTRACT FROM AUTHOR]

Background: Lowe syndrome is characterized by the presence of congenital cataracts, psychomotor retardation, and dysfunctional proximal renal tubules. This study presents a case of an atypical phenotype, investigates the genetic characteristics of eight children diagnosed with Lowe syndrome in southern China, and performs functional analysis of the novel variants. Methods: Whole-exome sequencing was conducted on eight individuals diagnosed with Lowe syndrome from three medical institutions in southern China. Retrospective collection and analysis of clinical and genetic data were performed, and functional analysis was conducted on the five novel variants. Results: In our cohort, the clinical symptoms of the eight Lowe syndrome individuals varied. One patient was diagnosed with Lowe syndrome but did not present with congenital cataracts. Common features among all patients included cognitive impairment, short stature, and low molecular weight proteinuria. Eight variations in the OCRL gene were identified, encompassing three previously reported and five novel variations. Among the novel variations, three nonsense mutations were determined to be pathogenic, and two patients harboring novel missense variations of uncertain significance exhibited severe typical phenotypes. Furthermore, all novel variants were associated with altered protein expression levels and impacted primary cilia formation. Conclusion: This study describes the first case of an atypical Lowe syndrome patient without congenital cataracts in China and performs a functional analysis of novel variants in the OCRL gene, thereby expanding the understanding of the clinical manifestations and genetic diversity associated with Lowe syndrome. [ABSTRACT FROM AUTHOR]

Hyperlipidemia is a risk factor for stroke, and worsens neurological outcome after stroke. Endothelial progenitor cells (EPCs), which become dysfunctional in cerebral ischemia, hold capacity to promote revascularization. We investigated the role of dyslipidemia in impairment of EPC-mediated angiogenesis in cerebral ischemic mice. The high fat diet (HFD)-fed mice following by ischemic stroke exhibited increased infarct volumes and neurological severity scores, and poorer angiogenesis. Bone marrow-EPCs treated with palmitic acid (PA) showed impaired functions and inhibited activity of AMP-activated protein kinase (AMPK). Notably, AMPK deficiency aggravated EPC dysfunction, further decreased mitochondrial membrane potential, and increased reactive oxygen species level in EPCs with PA treatment. Furthermore, the expression of fatty acid oxidation (FAO)-related genes was remarkably reduced, and carnitine palmitoyltransferase 1A (CPT1A) protein expression was downregulated in AMPK-deficient EPCs. AMPK deficiency aggravated neurological severity scores and angiogenesis in ischemic brain of HFD-fed mice, accompanied by suppressed protein level of CPT1A. EPC transplantation corrected impaired neurological severity scores and angiogenesis in AMPK-deficient mice. Our findings suggest that AMPK deficiency aggravates poor angiogenesis in ischemic brain by mediating FAO and oxidative stress thereby inducing EPC dysfunction in hyperlipidemic mice. [ABSTRACT FROM AUTHOR]

Objective: Pyrotinib, a new irreversible dual pan-human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase inhibitor blocking EGFR and HER2, has achieved a promising efficacy for advanced HER2-positive (HER2+) breast cancer. This study intended to further investigate the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2+ breast cancer treatment. Methods: Thirty-eight HER2+ breast cancer patients who received neoadjuvant pyrotinib and trastuzumab plus chemotherapy (docetaxel and carboplatin) were retrospectively reviewed. Clinical response by Response Evaluation Criteria in Solid Tumors (RECIST), pathological complete response (pCR), and adverse events data was retrieved. Results: According to the RECIST, the complete response rate was 0.0%, 10.5%, and 15.8% after second-cycle, fourth-cycle, and sixth-cycle therapy, respectively; whereas the objective response rate was 76.3%, 92.1%, and 100.0%, accordingly. The total pCR (tpCR) rate was 52.6%, the pCR rate of the breast was also 52.6%, and the pCR rate of lymph nodes was 86.8%. The tpCR rate was lower in patients with HER2 immunohistochemistry (IHC)++ and amplification by fluorescent in situ hybridization (FISH) than in those with HER2 IHC+++ (14.3% vs. 61.3%, p = 0.024), which was also lower in patients with Ki-67 expression ≥30% than in those with Ki-67 expression <30% (40.0% vs. 76.9%, p = 0.031). The common adverse events included diarrhea (84.2%), anemia (73.7%), nausea and vomiting (63.2%), fatigue (50.0%), hypomagnesemia (44.7%), leukopenia (42.1%), thrombocytopenia (39.5%), elevated transaminase (36.8%), and pruritus (31.6%). Conclusions: Pyrotinib and trastuzumab plus chemotherapy serve as an acceptable neoadjuvant regimen exhibiting good efficacy and tolerance in HER2+ breast cancer patients, while further large-scale validation is warranted. [ABSTRACT FROM AUTHOR]

Background: Salidroside is the major bioactive and pharmacological active substance in Rhodiola rosea L. It has been reported to have neuroprotective effects on cerebral ischemia/reperfusion (I/R). However, whether salidroside can enhance neural regeneration after cerebral I/R is still unknown. This study investigated the effects of salidroside on the endogenous neural regeneration after cerebral I/R and the related mechanism. Methods: Focal cerebral I/R was induced in rats by transient middle cerebral artery occlusion/reperfusion (MCAO/R). The rats were intraperitoneally treated salidroside once daily for 7 consecutive days. Neurobehavioral assessments were performed at 3 days and 7 days after the injury. TTC staining was performed to assess cerebral infarct volume. To evaluate the survival of neurons, immunohistochemical staining of Neuronal Nuclei (NeuN) in the ischemic hemisphere were conducted. Also, immunofluorescence double or triple staining of the biomarkers of proliferating neural progenitor cells in Subventricular Zone (SVZ) and striatum of the ischemia hemisphere were performed to investigate the neurogenesis. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of neurotrophic factors (NTFs) brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Expression of Notch1 and its target molecular Hes1 were also analyzed by western-blotting and RT-PCR. Results: Salidroside treatment ameliorated I/R induced neurobehavioral impairment, and reduced infarct volume. Salidroside also restored NeuN positive cells loss after I/R injury. Cerebral I/R injury significantly increased the expression of 5-Bromo-2'-Deoxyuridine (BrdU) and doublecotin (DCX), elevated the number of BrdU/Nestin/DCX triple-labeled cells in SVZ, and BrdU/Nestin/glial fibrillary acidic protein (GFAP) triple-labeled cells in striatum. Salidroside treatment further promoted the proliferation of BrdU/DCX labeled neuroblasts and BrdU/Nestin/GFAP labeled reactive astrocytes. Furthermore, salidroside elevated the mRNA expression and protein concentration of BDNF and NGF in ischemia periphery area, as well. Mechanistically, salidroside elevated Notch1/Hes1 mRNA expression in SVZ. The protein levels of them were also increased after salidroside administration. Conclusions: Salidroside enhances the endogenous neural regeneration after cerebral I/R. The mechanism of the effect may involve the regulation of BDNF/NGF and Notch signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives: Genetics have been shown to have a substantial impact on amyotrophic lateral sclerosis (ALS). The ALS process involves defects in axonal transport and cytoskeletal dynamics. It has been identified that KIF1A, responsible for encoding a kinesin-3 motor protein that carries synaptic vesicles, is considered a genetic predisposing factor for ALS. Methods: The analysis of whole-exome sequencing data from 1,068 patients was conducted to examine the genetic link between ALS and KIF1A. For patients with KIF1A gene mutations and a family history, we extended the analysis to their families and reanalyzed them using Sanger sequencing for cosegregation analysis. Results: In our cohort, the KIF1A mutation frequency was 1.31% (14/1,068). Thirteen nonsynonymous variants were detected in 14 ALS patients. Consistent with the connection between KIF1A and ALS, the missense mutation p.A1083T (c.3247G>A) was shown to cosegregate with disease. The mutations related to ALS in our study were primarily located in the cargo-binding region at the C-terminal, as opposed to the mutations of motor domain at the N-terminal of KIF1A which were linked to hereditary peripheral neuropathy and spastic paraplegia. We observed high clinical heterogeneity in ALS patients with missense mutations in the KIF1A gene. KIF5A is a more frequent determinant of ALS in the European population, while KIF1A accounts for a similar proportion of ALS in both the European and Chinese populations. Conclusion: Our investigation revealed that mutations in the C-terminus of KIF1A could increase the risk of ALS, support the pathogenic role of KIF1A in ALS and expand the phenotypic and genetic spectrum of KIF1A-related ALS. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have indicated that HOTTIP and MEG3 are associated with the initiation and progression of various types of tumors, including nasopharyngeal carcinoma (NPC). This investigation aimed to elucidate the impact of HOTTIP and MEG3 polymorphisms on the susceptibility and clinicopathologic characteristics of NPC. Methods: This research employed next-generation sequencing and multiplex PCR to assess the polymorphisms of HOTTIP rs1859168 and MEG3 rs7158663 in 200 NPC and 200 healthy individuals respectively. HOTTIP and MEG3 expression were assessed via qRT-PCR assessment. Furthermore, the genotypes and alleles frequency of rs1859168 and rs7158663 were compared between healthy and NPC individuals to elucidate their influence on NPC susceptibility and relation with clinicopathologic characteristics. Results: In comparison with the healthy cohort, the presence of HOTTIP rs1859168 CC genotype and the C allele were markedly linked with increased NPC incidence (p < 0.05). Furthermore, the MEG3 rs7158663 AA genotype and the A allele also indicated an increased risk of NPC (p < 0.05). The subgroup analysis of age, EBV infection, gender, nationality, smoking, and drinking status revealed no marked association between rs1859168 and rs7158663 genotypes and these potential confounding factors. Moreover, it was observed that rs1859168 CC and rs7158663 AA genotypes were related to local tumor invasion and lymph node metastasis. Additionally, HOTTIP indicated a marked elevation, while MEG3 substantially reduced in NPC samples than the normal nasopharyngeal biospecimens. Patients who carried CC or CA genotypes rather than the HOTTIP rs1859168 AA genotype, had substantially higher HOTTIP levels, while patients with rs7158663 AA or GA genotypes indicated notably lower expression of MEG3 than GG genotype carriers. Conclusion: Individuals with genetic variants of HOTTIP rs1859168 and MEG3 rs7158663 might have an increased risk of NPC susceptibility and related clinicopathologic characteristics, potentially by affecting the expression of HOTTIP and MEG3. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common fatal neurodegenerative disease among the elderly worldwide, characterized by memory and cognitive impairment. The identification of biomarkers for AD is crucial and urgent to facilitate the diagnosis and intervention. The aim of this study was to evaluate the diagnostic value of acyl-Coenzyme A thioesterase 7 (ACOT7) as a serum biomarker for the prediction of AD. In our study, we observed a significant increase in ACOT7 expression in patients (n = 366) with AD and animal (n = 8-12) models of AD, compared to the control group. A significant negative correlation was found between ACOT7 levels and Mini-Mental State Examination (MMSE) scores (r = -0.85; p < 0.001). The analysis of the receiver operating characteristic curve (ROC) showed that the area under the curve (AUC) for ACOT7 was 0.83 (95% confidence intervals: 0.80-0.86). The optimal cut-off point of 62.5 pg./mL was selected with the highest sum of sensitivity and specificity. The diagnostic accuracy of serum ACOT7 for AD was 77% (95% confidence intervals: 72-82%), with a sensitivity of 80% (95% confidence intervals: 75-84%) and a specificity of 74% (95% confidence intervals: 69-79%). Moreover, the ROC analysis showed that the AUC of Aβ42/40 ratio is 0.70, and the diagnostic accuracy was 72%, with 69% sensitivity and 76% specificity. Compared with the AD traditional marker Aβ42/40 ratio, ACOT7 shows better superiority as a new serum candidate biomarker of AD. By suppressing the ACOT7 gene, our study provides evidence of the involvement of ACOT7 in the metabolism of amyloid precursor protein (APP), resulting in alterations in the expression levels of Aβ42, BACE1 and βCTF. ACOT7 has the ability to modulate the amyloidogenic pathway of APP metabolism, while it does not have an impact on the non-amyloidogenic pathway. In conclusion, the findings of our study suggest that serum ACOT7 may serve as a promising and non-invasive biomarker for AD. [ABSTRACT FROM AUTHOR]

Female breast cancer is the most common and the fifth deadliest cancer worldwide. It is influenced by a combination of genetic, hormonal, and environmental factors. The excision repair cross‐complementation group 3 gene (ERCC3) has recently been identified as a breast cancer susceptibility gene in various cohorts of different geographical and ethnic origin. To explore the role of ERCC3 mutations in breast cancer development and pathological diagnosis, genetic analysis was conducted in 291 patients and 291 controls from mainland China. Bioinformatic analysis and immunohistochemistry (IHC) were performed. A novel ERCC3 mutation p.Y116X was identified in a breast cancer family, while no frequency bias for the genotype and allele of rs754010782 and rs371627165 was observed (all P > 0.05). Bioinformatic analysis revealed that ERCC3 expression was negatively associated with estrogen receptor (ER), progesterone receptor (PR), nontriple‐negative status, and nodal status of breast cancers. ERCC3 amplifications and deep deletions primarily occurred in breast invasive cancer not otherwise specified (NOS) and metaplastic breast cancer, respectively. The decreased ERCC3 expression in tumor tissues of patient with p.Y116X mutation was found by IHC. The ERCC3 mutation p.Y116X may increase breast cancer risk in the Han‐Chinese population. ERCC3 exhibits potential as a biomarker for the pathological diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

Chrysanthemum (Chrysanthemum morifolium, ground-cover Chrysanthemums), one of the important garden flowers, has a high ornamental and economic value. However, its ornamental value is significantly diminished by the low temperature experienced in northeastern China. Here, metabolomics and transcriptomics were performed on three Chrysanthemum cultivars before and after a low temperature to investigate the dynamic metabolite changes and the molecular regulatory mechanisms. The results showed that 1324 annotated metabolites were detected, among which 327 were identified as flavonoids derived from Chrysanthemum. The accumulation of metabolites and gene expression related to the flavonoid biosynthesis pathway significantly increased in the three cultivars under the low temperature, indicating flavonoid metabolism actively participates in the Chrysanthemum cold response. Specifically, the content of cyanidin and pelargonidin derivatives and the expression of anthocyanin biosynthesis genes significantly increases in XHBF, providing a reasonable explanation for the change in petal color from white to purple under the low temperature. Six candidate UDP-glycosyltransferase genes involved in the glycosylation of flavonoids were identified through correlation networks and phylogenetic analysis. CmNAC1, CmbZIP3, and other transcription factors potentially regulating flavonoid metabolism and responding to low temperatures were discovered by correlation analysis and weighted gene co-expression network analysis (WGCNA). In conclusion, this study elucidated the specific response of flavonoids to low temperatures in Chrysanthemums, providing valuable insights and metabolic data for investigating cold tolerance. [ABSTRACT FROM AUTHOR]

Lung cancer is a malignant tumor with highly heterogeneous characteristics. A classic Chinese medicine, Pinellia ternata (PT), was shown to exert therapeutic effects on lung cancer cells. However, its chemical and pharmacological profiles are not yet understood. In the present study, we aimed to reveal the mechanism of PT in treating lung cancer cells through metabolomics and network pharmacology. Metabolomic analysis of two strains of lung cancer cells treated with Pinellia ternata extracts (PTE) was used to identify differentially abundant metabolites, and the metabolic pathways associated with the DEGs were identified by MetaboAnalyst. Then, network pharmacology was applied to identify potential targets against PTE-induced lung cancer cells. The integrated network of metabolomics and network pharmacology was constructed based on Cytoscape. PTE obviously inhibited the proliferation, migration and invasion of A549 and NCI-H460 cells. The results of the cellular metabolomics analysis showed that 30 metabolites were differentially expressed in the lung cancer cells of the experimental and control groups. Through pathway enrichment analysis, 5 metabolites were found to be involved in purine metabolism, riboflavin metabolism and the pentose phosphate pathway, including D-ribose 5-phosphate, xanthosine, 5-amino-4-imidazolecarboxyamide, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Combined with network pharmacology, 11 bioactive compounds were found in PT, and networks of bioactive compound–target gene–metabolic enzyme–metabolite interactions were constructed. In conclusion, this study revealed the complicated mechanisms of PT against lung cancer. Our work provides a novel paradigm for identifying the potential mechanisms underlying the pharmacological effects of natural compounds. [ABSTRACT FROM AUTHOR]

Introduction: The Vel– phenotype is a rare blood group, and it is challenging for identifying this phenotype due to limited available reagents. Moreover, there are relatively few studies on genomic editing of erythroid antigens and generation of knockout (KO) cell lines at present. Methods: To identify the high-efficiency small-guiding RNA (sgRNA) sequence, candidate sgRNAs were transfected into HEK 293T cells and analyzed using Sanger sequencing. Following this, the high-efficiency sgRNA was transfected into K562 cells using lentivirus transduction to generate KO Vel blood group gene cells. The expression of the Vel protein was detected using Western blot on single-cell clones. Additionally, flow cytometry was used to detect the erythroid markers CD235a and CD71. Hemoglobin quantification and Giemsa staining were also performed to evaluate the erythroid differentiation of KO clones induced by hemin. Results: The high-efficiency sgRNA was successfully obtained and used for CRISPR-Cas9 editing in K562 cells. After limiting dilution and screening, two KO clones had either deleted 2 or 4 bases and showed no expression of the Vel protein. In the hemin-induced KO clone, there was a significant difference in erythroid marker and hemoglobin quantification compared to untreated cells. The morphological changes were also observed for the hemin-induced KO clone. Conclusion: In this study, a highly efficient sgRNA was screened out and used to generate Vel erythroid antigen KO single-cell clones in K562 cells. The edited cells could then be induced to undergo erythroid differentiation with the use of hemin. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to establish a diagnostic model of endometriosis (EM) based on disulfidptosis‐related genes (DRGs). Materials and Methods: The mRNA expression data of EM were downloaded from the gene expression omnibus database and subjected to differential analysis, and co‐expression analysis was performed based on 10 disulfidptosis genes to acquire DRGs. The differentially expressed DRGs were subjected to biofunctional analysis. Lasso analysis and support vector machine‐recursive feature elimination (SVM‐RFE) analysis were employed to extract the intersection of feature genes as biomarkers, and the diagnostic values of biomarkers for EM were evaluated based on receiver operating characteristic curves. The correlations between biomarkers and the immune microenvironment were assessed by Pearson analysis of biomarkers and immune cell infiltration levels. Results: Transforming growth factor β stimulated protein clone 22 domain family member 4 (TSC22D4), and F‐box/SPRY domain‐containing protein 1 (FBXO45) worked as the diagnostic classifiers in EM, with an obvious decrease in FBXO45 expression and an evident increase in TSC22D4 expression. The areas under the curves of FBXO45 and TSC22D4 were 0.752 and 0.706, respectively, and the area of FBXO45 combined with TSC22D4 reached 0.865, suggesting that TSC22D4 and FBXO45 had high predictive values. The diagnostic markers were closely correlated with immune cell infiltration. Conclusion: The diagnostic markers constructed based on disulfidptosis are good predictors for EM, which have close correlations with EM. [ABSTRACT FROM AUTHOR]

Objectives: To assess the role of TNF‐α/TNFR2 axis on promoting angiogenesis in oral squamous cell carcinoma (OSCC) cells and uncover the underlying mechanisms. Materials and Methods: The expression of TNFR2 and CD31 in OSCC tissues was examined; gene expression relationship between TNF‐α/TNFR2 and angiogenic markers or signaling molecules was analyzed; the expression of angiogenic markers, signaling molecules, TNFR1, and TNFR2 in TNF‐α‐stimulated OSCC cells treated with or without TNFR2 neutralizing antibody (TNFR2 Nab) were assessed; the concentration of angiogenic markers in the supernatant of OSCC cells was detected; conditioned mediums of OSCC cells treated with TNF‐α or TNF‐α + TNFR2 Nab were applied to human umbilical vein endothelial cells (HUVECs), followed by tube formation and cell migration assays. Results: Significantly elevated expression of TNFR2 and CD31 in OSCC tissues was observed. A positive gene expression correlation was identified between TNF‐α/TNFR2 and angiogenic markers or signaling molecules. TNFR2 Nab inhibited the effects of TNF‐α on enhancing the expression of angiogenic factors and TNFR2, the phosphorylation of the Akt/mTOR signaling pathway, HUVECs migration, and tube formation. Conclusions: TNFR2 Nab counteracts the effect of TNF‐α on OSCC cells through the TNFR2/Akt/mTOR axis, indicating that blocking TNFR2 might be a promising strategy against cancer. [ABSTRACT FROM AUTHOR]

Schima superba, commonly known as the Chinese guger tree, is highly adaptable and tolerant of poor soil conditions. It is one of the primary species forming the evergreen broad-leaved forests in southern China. Dirigent proteins (DIRs) play crucial roles in the synthesis of plant lignin and lignans, secondary metabolism, and response to adversity stress. However, research on the DIR gene family in S. superba is currently limited. This study identified 24 SsDIR genes, categorizing them into three subfamilies. These genes are unevenly distributed across 13 chromosomes, with 83% being intronless. Collinearity analysis indicated that tandem duplication played a more significant role in the expansion of the gene family compared to segmental duplication. Additionally, we analyzed the expression patterns of SsDIRs in different tissues of S. superba. The SsDIR genes exhibited distinct expression patterns across various tissues, with most being specifically expressed in the roots. Further screening identified SsDIR genes that may regulate drought stress, with many showing differential expression under drought stress conditions. In the promoter regions of SsDIRs, various cis-regulatory elements involved in developmental regulation, hormone response, and stress response were identified, which may be closely related to their diverse regulatory functions. This study will contribute to the further functional identification of SsDIR genes, providing insights into the biosynthetic pathways of lignin and lignans and the mechanisms of plant stress resistance. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the most common malignant tumor. In the present study, we identified a long non‐coding RNA (lncRNA) AC100826.1 (simplify to Lnc1), which was highly expressed in non‐small cell lung cancer (NSCLC) tissues compared with the paracancerous tissues. We also observed the critical role of Lnc1 in regulating the metastasis ability of NSCLC cells. Methods: RNA sequencing was performed to detect differential expression levels of lncRNAs in NSCLC tissues and its paracancerous tissues. Effects of Lnc1 on cell proliferation, invasion, and migration were determined by CCK‐8, transwell and scratch assays. The xenograft experiment confirmed the effect of Lnc1 on NSCLC cells proliferation and migration abilities in vivo. RT‐qPCR and western blots were performed to determine the expression levels of mRNAs and proteins. Results: The expression level of Lnc1 was related to multiple pathological results, knockdown of Lnc1 can inhibit the proliferation and metastasis abilities of NSCLC cells. silencing phospholipase C, β1(PLCB1) can reverse the promoting effects of overexpression Lnc1 on NSCLC cells proliferation and migration abilities. In addition, the Rap1 signaling pathway was implicated in the regulation of Lnc1 in NSCLC metastasis. Conclusion: Our results suggest that Lnc1 regulated the metastatic ability of NSCLC cells through targeting the PLCB1/Rap1 signal pathway. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether galangin (Gal) affects the proliferation, migration, invasion and apoptosis of osteosarcoma MG63 cells by regulating the cGAS/STING signaling pathway. Methods: Human osteosarcoma MG63 cells were cultured in vitro and treated with Gal at concentrations of 0, 5, 15, 25, 50, 100 and 200 μmol/L for 48 hours, and the effect of Gal on cell viability was detected by CCK-8 method. MG63 cells were divided into the control group (untreated cells), the Gal low concentration group (Gal-L group, treated with 50 μmol/L Gal), the Gal high concentration group (Gal-H group, treated with 100 μmol/L Gal), and the Gal-H+STING inhibitor group (Gal-H+H-151 group, treated with 100 μmol/L Gal+8 μmol/L H-151). EdU staining method, scratch healing test, Transwell chamber method and flow cytometry were used to detect cell proliferation, migration, invasion and apoptosis of cells in each group. Western blot was applied to detect the expression levels of cGAS and STING proteins in cells of each group. Results: Compared with the control group, the proliferation activity, migration, and invasion abilities of the cells in the Gal-L and Gal-H groups were significantly decreased (all P<0.05); the apoptosis rate and the expression levels of cGAS and STING proteins were significantly increased (all P<0.05). Compared with the Gal-H group, the proliferation activity, migration, and invasion abilities of the cells in the Gal-H+H-151 group were significantly increased (all P<0.05); the apoptosis rate and the expression levels of cGAS and STING proteins were significantly decreased (all P<0.05). Conclusion: Gal may inhibit the proliferation, migration and invasion and promote the apoptosis of osteosarcoma cells by activating the cGAS/STING signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The Prunus sibirica seeds with rich oils has great utilization, but contain amygdalin that can be hydrolyzed to release toxic HCN. Thus, how to effectively reduce seed amygdalin content of P. sibirica is an interesting question. Mandelonitrile is known as one key intermediate of amygdalin metabolism, but which mandelonitrile lyase (MDL) family member essential for its dissociation destined to low amygdalin accumulation in P. sibirica seeds still remains enigmatic. An integration of our recent 454 RNA-seq data, amygdalin and mandelonitrile content detection, qRT-PCR analysis and function determination is described as a critical attempt to determine key MDL and to highlight its function in governing mandelonitrile catabolism with low amygdalin accumulation in Prunus sibirica seeds for better developing edible oil and biodiesel in China. Results: To identify key MDL and to unravel its function in governing seed mandelonitrile catabolism with low amygdalin accumulation in P. sibirica. Global identification of mandelonitrile catabolism-associated MDLs, integrated with the across-accessions/developing stages association of accumulative amount of amygdalin and mandelonitrile with transcriptional level of MDLs was performed on P. sibirica seeds of 5 accessions to determine crucial MDL2 for seed mandelonitrile catabolism of P. sibirica. MDL2 gene was cloned from the seeds of P. sibirica, and yeast eukaryotic expression revealed an ability of MDL2 to specifically catalyze the dissociation of mandelonitrile with the ideal values of Km (0.22 mM) and Vmax (178.57 U/mg). A combination of overexpression and mutation was conducted in Arabidopsis. Overexpression of PsMDL2 decreased seed mandelonitrile content with an increase of oil accumulation, upregulated transcript of mandelonitrile metabolic enzymes and oil synthesis enzymes (involving FA biosynthesis and TAG assembly), but exhibited an opposite situation in mdl2 mutant, revealing a role of PsMDL2-mediated regulation in seed amygdalin and oil biosynthesis. The PsMDL2 gene has shown as key molecular target for bioengineering high seed oil production with low amygdalin in oilseed plants. Conclusions: This work presents the first integrated assay of genome-wide identification of mandelonitrile catabolism-related MDLs and the comparative association of transcriptional level of MDLs with accumulative amount of amygdalin and mandelonitrile in the seeds across different germplasms and developmental periods of P. sibirica to determine MDL2 for mandelonitrile dissociation, and an effective combination of PsMDL2 expression and mutation, oil and mandelonitrile content detection and qRT-PCR assay was performed to unravel a mechanism of PsMDL2 for controlling amygdalin and oil production in P. sibirica seeds. These findings could offer new bioengineering strategy for high oil production with low amygdalin in oil plants. [ABSTRACT FROM AUTHOR]

Introduction: Aspergillus cristatus is a homothallic fungus that is used in the natural fermentation process of Chinese Fuzhuan tea and has been linked to the production of bioactive components. However, not much is known about the variations present in the fungus. To understand the variation of the dominant microorganism, A. cristatus, within dark tea, the present study investigated the genetic and morphological diversity of 70 A. cristatus collected across six provinces of China. Methods: Expressed sequence tags-simple sequence repeats (EST-SSR) loci for A. cristatus were identified and corresponding primers were developed. Subsequently, 15 specimens were selected for PCR amplification. Results: The phylogenetic tree obtained revealed four distinct clusters with a genetic similarity coefficient of 0.983, corresponding to previously identified morphological groups. Five strains (A1, A11, B1, D1, and JH1805) with considerable differences in EST-SSR results were selected for further physiological variation investigation. Microstructural examinations revealed no apparent differentiation among the representative strains. However, colony morphology under a range of culture media varied substantially between strains, as did the extracellular enzymatic activity (cellulase, pectinase, protease, and polyphenol oxidase); the data indicate that there are differences in physiological metabolic capacity among A. cristatus strains. Discussion: Notably, JH1805, B1, and A11 exhibited higher enzymatic activity, indicating their potential application in the production of genetically improved strains. The findings provide valuable insights into species identification, genetic diversity determination, and marker-assisted breeding strategies for A. cristatus. [ABSTRACT FROM AUTHOR]

Jujubae Fructus, the fruit of Ziziphus jujuba Mill has been used as one of the medicine food homology species for thousands of years in China. Studies have shown that the active ingredients of Jujubae Fructus have a variety of biological effects, but its role in the aging process still lacks knowledge. Here, we investigated the effect of Jujubae Fructus extract (JE) on Caenorhabditis elegans lifespan and its potential mechanism. The lifespan of C. elegans treated with JE was signifificantly increased in a dose-dependent manner. In addition, JE treatment prolonged the reproductive period and increased normal activity during aging in C. elegans. Similarly, JE supplementation also enhanced the resistance to heat and oxidative stress in C. elegans. Furthermore, the mutant worms' lifespan assays demonstrated that JE requires daf-16 to prolong lifespan. DAF-16::GFP analysis of TJ356 showed that JE treatment translocates DAF-16::GFP to nucleus in transgenic worms. By analyzing the downstream of daf-16, we identify that JE may regulate sod3 downstream of daf-16. Mutant worms' lifespan and transgenic reporter gene expression assays revealed that increasing SOD-3 expression was critical for extending longevity in C. elegans with JE therapy. Collectively, these data indicate that JE may have an important role in C. elegans longevity that is dependent on DAF-16 and SOD-3. [ABSTRACT FROM AUTHOR]

Simple Summary: Lead is a major source of heavy metal pollution, which can harm both the environment and people's health. High levels of Pb can slow down the growth and development of insects and may even cause them to die by damaging their cells. The aim of this study was to explore gene expression in the midgut of Bombyx mori when exposed to lead (Pb). This study gives us new insights into how insects protect themselves from Pb challenge and helps us understand the complex ways insects get rid of harmful substances at a deeper level. Lead (Pb) is a major source of heavy metal contamination, and poses a threat to biodiversity and human health. Elevated levels of Pb can hinder insect growth and development, leading to apoptosis via mechanisms like oxidative damage. The midgut of silkworms is the main organ exposed to heavy metals. As an economically important lepidopteran model insect in China, heavy metal-induced stress on silkworms causes considerable losses in sericulture, thereby causing substantial economic damage. This study aimed to investigate Pb-induced detoxification-related genes in the midgut of silkworms using high-throughput sequencing methods to achieve a deeper comprehension of the genes' reactions to lead exposure. This study identified 11,567 unigenes and 14,978 transcripts. A total of 1265 differentially expressed genes (DEGs) were screened, comprising 907 upregulated and 358 downregulated genes. Subsequently, Gene Ontology (GO) classification analysis revealed that the 1265 DEGs were distributed across biological processes, cellular components, and molecular functions. This suggests that the silkworm midgut may affect various organelle functions and biological processes, providing crucial clues for further exploration of DEG function. Additionally, the expression levels of 12 selected detoxification-related DEGs were validated using qRT-PCR, which confirmed the reliability of the RNA-seq results. This study not only provides new insights into the detoxification defense mechanisms of silkworms after Pb exposure, but also establishes a valuable foundation for further investigation into the molecular detoxification mechanisms in silkworms. [ABSTRACT FROM AUTHOR]

The tree peony, a traditional flower in China, has a short and concentrated flowering period, restricting the development of the tree peony industry. To explore the molecular mechanism of tree peony flowering-stage regulation, PoEP1, which regulated the flowering period, was identified and cloned based on the transcriptome and degradome data of the early-flowering mutant Paeonia ostii 'Fengdan' (MU) and Paeonia ostii 'Fengdan' (FD). Through bioinformatics analysis, expression pattern analysis, and transgene function verification, the role of PoEP1 in the regulation of tree peony flowering was explored. The open-reading frame of PoEP1 is 1161 bp, encoding 386 amino acids, containing two conserved domains. PoEP1 was homologous to the EP1 of other species. Subcellular localization results showed that the protein was localized in the cell wall and that PoEP1 expression was highest in the initial decay stage of the tree peony. The overexpression of PoEP1 in transgenic plants advanced and shortened the flowering time, indicating that PoEP1 overexpression promotes flowering and senescence and shorten the flowering time of plants. The results of this study provide a theoretical basis for exploring the role of PoEP1 in the regulation of tree peony flowering. [ABSTRACT FROM AUTHOR]

Pinus yunnanensis is an important component of China's economic development and forest ecosystems. The growth of P. yunnanensis seedlings experienced a slow growth phase, which led to a long seedling cultivation period. However, asexual reproduction can ensure the stable inheritance of the superior traits of the mother tree and also shorten the breeding cycle. The quantity and quality of branching significantly impact the cutting reproduction of P. yunnanensis, and a shaded environment affects lateral branching growth, development, and photosynthesis. Nonetheless, the physiological characteristics and the level of the transcriptome that underlie the growth of lateral branches of P. yunnanensis under shade conditions are still unclear. In our experiment, we subjected annual P. yunnanensis seedlings to varying shade intensities (0%, 25%, 50%, 75%) and studied the effects of shading on growth, physiological and biochemical changes, and gene expression in branching. Results from this study show that shading reduces biomass production by inhibiting the branching ability of P. yunnanensis seedlings. Due to the regulatory and protective roles of osmotically active substances against environmental stress, the contents of soluble sugars, soluble proteins, photosynthetic pigments, and enzyme activities exhibit varying responses to different shading treatments. Under shading treatment, the contents of phytohormones were altered. Additionally, genes associated with phytohormone signaling and photosynthetic pathways exhibited differential expression. This study established a theoretical foundation for shading regulation of P. yunnanensis lateral branch growth and provides scientific evidence for the management of cutting orchards. [ABSTRACT FROM AUTHOR]

Background: Currently, the treatment and prevention of migraine remain highly challenging. Mendelian randomization (MR) has been widely used to explore novel therapeutic targets. Therefore, we performed a systematic druggable genome-wide MR to explore the potential therapeutic targets for migraine. Methods: We obtained data on druggable genes and screened for genes within brain expression quantitative trait locis (eQTLs) and blood eQTLs, which were then subjected to two-sample MR analysis and colocalization analysis with migraine genome-wide association studies data to identify genes highly associated with migraine. In addition, phenome-wide research, enrichment analysis, protein network construction, drug prediction, and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic drugs. Results: We identified 21 druggable genes significantly associated with migraine (BRPF3, CBFB, CDK4, CHD4, DDIT4, EP300, EPHA5, FGFRL1, FXN, HMGCR, HVCN1, KCNK5, MRGPRE, NLGN2, NR1D1, PLXNB1, TGFB1, TGFB3, THRA, TLN1 and TP53), two of which were significant in both blood and brain (HMGCR and TGFB3). The results of phenome-wide research showed that HMGCR was highly correlated with low-density lipoprotein, and TGFB3 was primarily associated with insulin-like growth factor 1 levels. Conclusions: This study utilized MR and colocalization analysis to identify 21 potential drug targets for migraine, two of which were significant in both blood and brain. These findings provide promising leads for more effective migraine treatments, potentially reducing drug development costs. [ABSTRACT FROM AUTHOR]

Background: TMPRSS2, a key molecule for SARS-CoV-2 invading human host cells, has an association with cancer. However, its association with lung cancer remains insufficiently unexplored. Methods: In five bulk transcriptomics datasets, one single‐cell RNA sequencing (scRNA-seq) dataset and one proteomics dataset for lung adenocarcinoma (LUAD), we explored associations between TMPRSS2 expression and immune signatures, tumor progression phenotypes, genomic features, and clinical prognosis in LUAD by the bioinformatics approach. Furthermore, we performed experimental validation of the bioinformatics findings. Results: TMPRSS2 expression levels correlated negatively with the enrichment levels of both immune-stimulatory and immune-inhibitory signatures, while they correlated positively with the ratios of immune-stimulatory/immune-inhibitory signatures. It indicated that TMPRSS2 levels had a stronger negative correlation with immune-inhibitory than with immune-stimulatory signatures. TMPRSS2 downregulation correlated with increased proliferation, stemness, genomic instability, tumor progression, and worse survival in LUAD. We further validated that TMPRSS2 was downregulated with tumor progression in the LUAD cohort we collected from Jiangsu Cancer Hospital, China. In vitro and in vivo experiments verified the association of TMPRSS2 deficiency with increased tumor cell proliferation and invasion and antitumor immunity in LUAD. Moreover, in vivo experiments demonstrated that TMPRSS2-knockdown tumors were more sensitive to BMS-1, an inhibitor of PD-1/PD-L1. Conclusions: TMPRSS2 is a tumor suppressor, while its downregulation is a positive biomarker of immunotherapy in LUAD. Our data provide a potential link between lung cancer and pneumonia caused by SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. Methods: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. Results: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88–0.95, P = 2.92 × 10−7) and Europe (OR = 0.92, 95%CI 0.88–0.95, P = 4.61 × 10−6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL (http://canernaqtl.whu.edu.cn/#/) to serve as an informative resource for advancing this field. Conclusion: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers. [ABSTRACT FROM AUTHOR]

The acetylation of histone lysine residues regulates multiple life processes, including growth, conidiation, and pathogenicity in filamentous pathogenic fungi. However, the specific function of each lysine residue at the N-terminus of histone H3 in phytopathogenic fungi remains unclear. In this study, we mutated the N-terminal lysine residues of histone H3 in Fusarium pseudograminearum, the main causal agent of Fusarium crown rot of wheat in China, which also produces deoxynivalenol (DON) toxins harmful to humans and animals. Our findings reveal that all the FpH3K9R, FpH3K14R, FpH3K18R, and FpH3K23R mutants are vital for vegetative growth and conidiation. Additionally, FpH3K14 regulates the pathogen's sensitivity to various stresses and fungicides. Despite the slowed growth of the FpH3K9R and FpH3K23R mutants, their pathogenicity towards wheat stems and heads remains unchanged. However, the FpH3K9R mutant produces more DON. Furthermore, the FpH3K14R and FpH3K18R mutants exhibit significantly reduced virulence, with the FpH3K18R mutant producing minimal DON. In the FpH3K9R, FpH3K14R, FpH3K18R, and FpH3K23R mutants, there are 1863, 1400, 1688, and 1806 downregulated genes, respectively, compared to the wild type. These downregulated genes include many that are crucial for growth, conidiation, pathogenicity, and DON production, as well as some essential genes. Gene ontology (GO) enrichment analysis indicates that genes downregulated in the FpH3K14R and FpH3K18R mutants are enriched for ribosome biogenesis, rRNA processing, and rRNA metabolic process. This suggests that the translation machinery is abnormal in the FpH3K14R and FpH3K18R mutants. Overall, our findings suggest that H3 N-terminal lysine residues are involved in regulating the expression of genes with important functions and are critical for fungal development and pathogenicity. [ABSTRACT FROM AUTHOR]

Immunotherapy improves the prognosis of patients with advanced lung cancer. The expression level of PD-L1 in lung cancer tissue is the most reliable marker for predicting the efficacy of immunotherapy. However, the relationship between PD-L1 expression level and clinicopathological characteristics in patients with lung adenocarcinoma is unclear. The paper aims to analyze the correlation between PD-L1 expression and clinicopathological features in surgically resected lung adenocarcinoma. Clinicopathological data of 100 patients with surgically resected lung adenocarcinoma admitted to the Department of Thoracic Surgery of our hospital from January 2021 to August 2021 were retrospectively analyzed. Immunohistochemistry showed that 36 patients had positive PD-L1 results in postoperative tumor tissues (incidence rate, 36.0%). The tumor-node-metastasis stage, tumor stage, node stage, degree of differentiation, smoking history, and intravascular cancer embolus were statistically different between the two groups (P < 0.05). Multivariate logistic regression analysis showed that postoperative pathological stages above stage II, T3-4, N1-2, poorly differentiated tumors, and positive intravascular cancer embolus were independent factors for PD-L1 positive in lung adenocarcinoma tissue. Therefore, these patients require more attention in the clinic to increase the efficiency of immunotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Tetranychus truncatus (Acari: Tetranychidae) is the dominant pest on many crops in China. The resistant strain cultivated by pyridaben in our laboratory showed higher adaptability to high temperature than the susceptible strain. Antioxidant enzymes can reduce the damage of reactive oxygen species (ROS) caused by high temperature. Therefore, the antioxidant enzyme genes of T. truncatus were screened, and their biological information was analyzed. The expression patterns of antioxidant enzyme genes in two strains of T. truncatus under high temperature stress were determined by RT-qPCR method, and their functions were verified by RNA interference (RNAi) technology. The experimental results provide a theoretical basis for understanding the occurrence of agricultural mites under the background of climate warming and applying gene regulation technology to control T. truncatus in the future. Tetranychus truncatus (Acari: Tetranychidae) has caused serious economic losses on some crops (soybean, corn, and cotton) in China, and has developed resistance to most acaricides. Our laboratory study found that T. truncatus was resistant to pyridaben and also adapted to high temperature (34–40 °C). High temperature stress may cause arthropods to produce a large amount of reactive oxygen species (ROS), causing oxidative damage. Antioxidant enzymes, as the main antioxidants, can reduce the damage caused by excessive ROS in arthropods. In order to study the adaptation mechanism of the pyridaben-resistant strain of T. truncatus to high temperature and the role of antioxidant enzyme genes under high temperature stress, four antioxidant enzyme genes, TtSOD, TtPOD3, TtPOD4, and TtGSTs2, were screened according to the transcriptome sequencing data of pyridaben-susceptible and -resistant strains in T. truncatus. Firstly, the phylogeny and structure analyses of these four genes were carried out. Then, real-time quantitative PCR (RT-qPCR) technology was used to analyze the gene expression patterns of antioxidant enzymes in two strains of T. truncatus at three different high temperature ranges (34 °C, 38 °C, and 42 °C). The results showed that the expression levels of four antioxidant enzyme genes of two strains of T. truncatus were induced by high temperature stress, and the expression levels of antioxidant enzyme genes were significantly different in each development state. The gene expression of antioxidant enzyme genes in resistant strains at the adult stage was significantly higher than that in susceptible strains. After the TtSOD and TtPOD4 genes of adult mites of the resistant strain were silenced by RNA interference (RNAi) technology, the mortality rate of mites with TtPOD4 gene silencing reached 41.11% after 96 h at 34 °C, which was significantly higher than that of the control and TtSOD gene silencing. It has been confirmed that the TtPOD4 gene plays a key role in the adaptation of pyridaben-resistant strain of T. truncatus to high temperature. It lays a theoretical foundation for revealing the thermal adaptation mechanism of T. truncatus. [ABSTRACT FROM AUTHOR]

Simple Summary: In order to withstand extreme temperatures, organisms can change their behavior, physiology, and biochemistry prior to or in reaction to environmental variations. This allows them to enhance their chances of survival under challenging conditions. However, lizards are ectothermic, relying on environmental temperature for body heat and making them highly susceptible to climate change. Mitochondria play a crucial role in maintaining body temperature, regulating metabolic rates, and preventing cellular oxidative damage. If mitochondrial respiratory chain complexes become damaged or disrupted, this can be fatal. Mitochondrial DNA also serves as a sentinel for cell stress. Here, we focused on the lizard Sphenomorphus incognitus (Squamata:Scincidae) to explore the expression of the 13 mitochondrial protein-coding genes (PCGs) responding to a wide range of temperatures: 4 °C, 8 °C, 25 °C (control group), 34 °C, and 38 °C for 24 h. The aim was to explore the potential cold resistance and heat tolerance mechanisms of lizards by examining the expression of mitochondrial genes under gradient temperature conditions, as a means to assess the adaptability of lizards in the current context of climate change. In the context of global warming, the frequency of severe weather occurrences, such as unexpected cold spells and heat waves, will grow, as well as the intensity of these natural disasters. Lizards, as a large group of reptiles, are ectothermic. Their body temperatures are predominantly regulated by their environment and temperature variations directly impact their behavior and physiological activities. Frequent cold periods and heat waves can affect their biochemistry and physiology, and often their ability to maintain their body temperature. Mitochondria, as the center of energy metabolism, are crucial for maintaining body temperature, regulating metabolic rate, and preventing cellular oxidative damage. Here, we used RT-qPCR technology to investigate the expression patterns and their differences for the 13 mitochondrial PCGs in Sphenomorphus incognitus (Squamata:Scincidae), also known as the brown forest skink, under extreme temperature stress at 4 °C, 8 °C, 34 °C, and 38 °C for 24 h, compared to the control group at 25 °C. In southern China, for lizards, 4 °C is close to lethal, and 8 °C induces hibernation, while 34/38 °C is considered hot and environmentally realistic. Results showed that at a low temperature of 4 °C for 24 h, transcript levels of ATP8, ND1, ND4, COI, and ND4L significantly decreased, to values of 0.52 ± 0.08, 0.65 ± 0.04, 0.68 ± 0.10, 0.28 ± 0.02, and 0.35 ± 0.02, respectively, compared with controls. By contrast, transcript levels of COIII exhibited a significant increase, with a mean value of 1.86 ± 0.21. However, exposure to 8 °C for 24 h did not lead to an increase in transcript levels. Indeed, transcript levels of ATP6, ATP8, ND1, ND3, and ND4 were significantly downregulated, to 0.48 ± 0.11, 0.68 ± 0.07, 0.41 ± 0.08, 0.54 ± 0.10, and 0.52 ± 0.07, respectively, as compared with controls. Exposure to a hot environment of 34 °C for 24 h led to an increase in transcript levels of COI, COII, COIII, ND3, ND5, CYTB, and ATP6, with values that were 3.3 ± 0.24, 2.0 ± 0.2, 2.70 ± 1.06, 1.57 ± 0,08, 1.47 ± 0.13, 1.39 ± 0.56, and 1.86 ± 0.12, respectively, over controls. By contrast, ND4L exhibited a significant decrease (to 0.31 ± 0.01) compared with controls. When exposed to 38 °C, the transcript levels of the 13 PCGs significantly increased, ranging from a 2.04 ± 0.23 increase in ND1 to a 6.30 ± 0.96 rise in ND6. Under two different levels of cold and heat stress, the expression patterns of mitochondrial genes in S. incognitus vary, possibly associated with different strategies employed by this species in response to low and high temperatures, allowing for rapid compensatory adjustments in mitochondrial electron transport chain proteins in response to temperature changes. Furthermore, this underscores once again the significant role of mitochondrial function in determining thermal plasticity in reptiles. [ABSTRACT FROM AUTHOR]

Heat shock proteins (HSPs) are a class of highly conserved proteins that play an important role in biological responses to various environmental stresses. The mariculture of Thamnaconus septentrionalis, a burgeoning aquaculture species in China, frequently encounters stressors such as extreme temperatures, salinity variations, and elevated ammonia levels. However, systematic identification and analysis of the HSP70 and HSP90 gene families in T. septentrionalis remain unexplored. This study conducted the first genome-wide identification of 12 HSP70 and 4 HSP90 genes in T. septentrionalis, followed by a comprehensive analysis including phylogenetics, gene structure, conserved domains, chromosomal localization, and expression profiling. Expression analysis from RNA-seq data across various tissues and developmental stages revealed predominant expression in muscle, spleen, and liver, with the highest expression found during the tailbud stage, followed by the gastrula, neurula, and juvenile stages. Under abiotic stress, most HSP70 and HSP90 genes were upregulated in response to high temperature, high salinity, and low salinity, notably hspa5 during thermal stress, hspa14 in high salinity, and hsp90ab1 under low salinity conditions. Ammonia stress led to a predominance of downregulated HSP genes in the liver, particularly hspa2, while upregulation was observed in the gills, especially for hsp90b1. Quantitative real-time PCR analysis corroborated the expression levels under environmental stresses, validating their involvement in stress responses. This investigation provides insights into the molecular mechanisms of HSP70 and HSP90 in T. septentrionalis under stress, offering valuable information for future functional studies of HSPs in teleost evolution, optimizing aquaculture techniques, and developing stress-resistant strains. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap ‘n’ Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate various stress responses by regulating the transcription of a variety of antioxidant and cytoprotective genes, they play distinct roles in bone metabolism and remodeling. However, the precise roles of both transcription factors in bone loss induced by prolonged Cd exposure remain unclear. OBJECTIVES: We aimed to understand the molecular mechanisms underlying Cd-induced bone loss, focusing mainly on the roles of NRF2 and NRF1 in osteoclastogenesis provoked by Cd. METHODS: Male wild-type (WT), global Nrf2-knockout (Nrf2-/-) and myeloid-specific Nrf2 knockout [Nrf2(M)-KO] mice were administered Cd (50 or 100 ppm) via drinking water for 8 or 16 wk, followed by micro-computed tomography, histological analyses, and plasma biochemical testing. Osteoclastogenesis was evaluated using bone marrow-derived osteoclast progenitor cells (BM-OPCs) and RAW 264.7 cells in the presence of Cd (10 or 20 nM) with a combination of genetic and chemical modulations targeting NRF2 and NRF1. RESULTS: Compared with relevant control mice, global Nrf2-/- or Nrf2(M)-KO mice showed exacerbated bone loss and augmented osteoclast activity following exposure to 100 ppm Cd in drinking water for up to 16 wk. In vitro osteoclastogenic analyses suggested that Nrf2-deficient BM-OPCs and RAW 264.7 cells responded more robustly to low levels of Cd (up to 20 nM) with regard to osteoclast differentiation compared with WT cells. Further mechanistic studies supported a compensatory up-regulation of long isoform of NRF1 (L-NRF1) and subsequent induction of nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 (NFATc1) as the key molecular events in the Nrf2 deficiency-worsened and Cd-provoked osteoclastogenesis. L-Nrf1 silenced (via lentiviral means) Nrf2-knockdown (KD) RAW cells exposed to Cd showed dramatically different NFATc1 and subsequent osteoclastogenesis outcomes compared with the cells of Nrf2-KD alone exposed to Cd, suggesting a mitigating effect of the Nrf1 silencing. In addition, suppression of reactive oxygen species by exogenous antioxidants N-acetyl-L-cysteine (2 mM) and mitoquinone mesylate (MitoQ; 0.2 μM) mitigated the L-NRF1-associated effects on NFATc1-driven osteoclastogenesis outcomes in Cd-exposed Nrf2-KD cells. CONCLUSIONS: This in vivo and in vitro study supported the authors’ hypothesis that Cd exposure caused bone loss, in which NRF2 and L-NRF1 responded to Cd and osteoclastogenic stimuli in a cooperative, but contradictive, manner to coordinate Nfatc1 expression, osteoclastogenesis and thus bone homeostasis. Our study suggests a novel strategy targeting NRF2 and L-NRF1 to prevent and treat the bone toxicity of Cd. [ABSTRACT FROM AUTHOR]

The identification and expression of germ cells are important for studying sex-related mechanisms in fish. The vasa gene, encoding an ATP-dependent RNA helicase, is recognized as a molecular marker of germ cells and plays a crucial role in germ cell development. Silurus asotus, an important freshwater economic fish species in China, shows significant sex dimorphism with the female growing faster than the male. However, the molecular mechanisms underlying these sex differences especially involving in the vasa gene in this fish remain poorly understood. In this work, the vasa gene sequence of S. asotus (named as Savasa) was obtained through RT-PCR and rapid amplification of cDNA end (RACE), and its expression in embryos and tissues was analyzed using qRT-PCR and an in situ hybridization method. Letrozole (LT) treatment on the larvae fish was also conducted to investigate its influence on the gene. The results revealed that the open reading frame (ORF) of Savasa was 1989 bp, encoding 662 amino acids. The SaVasa protein contains 10 conserved domains unique to the DEAD-box protein family, showing the highest sequence identity of 95.92% with that of Silurus meridionalis. In embryos, Savasa is highly expressed from the two-cell stage to the blastula stage in early embryos, with a gradually decreasing trend from the gastrula stage to the heart-beating stage. Furthermore, Savasa was initially detected at the end of the cleavage furrow during the two-cell stage, later condensing into four symmetrical cell clusters with embryonic development. At the gastrula stage, Savasa-positive cells increased and began to migrate towards the dorsal side of the embryo. In tissues, Savasa is predominantly expressed in the ovaries, with almost no or lower expression in other detected tissues. Moreover, Savasa was expressed in phase I–V oocytes in the ovaries, as well as in spermatogonia and spermatocytes in the testis, implying a specific expression pattern of germ cells. In addition, LT significantly upregulated the expression of Savasa in a concentration-dependent manner during the key gonadal differentiation period of the fish. Notably, at 120 dph after LT treatment, Savasa expression was the lowest in the testis and ovary of the high concentration group. Collectively, findings from gene structure, protein sequence, phylogenetic analysis, RNA expression patterns, and response to LT suggest that Savasa is maternally inherited with conserved features, serving as a potential marker gene for germ cells in S.asotus, and might participate in LT-induced early embryonic development and gonadal development processes of the fish. This would provide a basis for further research on the application of germ cell markers and the molecular mechanisms of sex differences in S. asotus. [ABSTRACT FROM AUTHOR]

This research focuses on 72 approved varieties of colored wheat from different provinces in China. Utilizing coefficients of variation, structural equation models, and correlation analyses, six agronomic traits of colored wheat were comprehensively evaluated, followed by further research on different dwarfing genes in colored wheat. Using the entropy method revealed that among the 72 colored wheat varieties, 10 were suitable for cultivation. Variety 70 was the top-performing variety, with a comprehensive index of 87.15%. In the final established structural equation model, each agronomic trait exhibited a positive direct effect on yield. Notably, plant height, spike length, and flag leaf width had significant impacts on yield, with path coefficients of 0.55, 0.40, and 0.27. Transcriptome analysis and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) validation were used to identify three dwarfing genes controlling plant height: Rht1, Rht-D1, and Rht8. Subsequent RT-qPCR validation clustering heatmap results indicated that Rht-D1 gene expression increased with the growth of per-acre yield. Rht8 belongs to the semi-dwarf gene category and has a significant positive effect on grain yield. However, the impact of Rht1, as a dwarfing gene, on agronomic traits varies. These research findings provide crucial references for the breeding of new varieties. [ABSTRACT FROM AUTHOR]

[Display omitted] • Imidacloprid-resistant N. lugens population rapidly adapted to resistant rice IR36. • Insecticide resistance-related genes nAChR - 7 - like and CYP4C61 contributed to the adaptation to resistant rice in N. lugens. • One avirulent/susceptible genotype and two virulent/resistant genotypes could be inferred from the corresponding alleles of genes nAChR - 7 - like and CYP4C61. • The virulent/resistant genotypes of N. lugens already existed in the wild in China with increasing frequencies along with insecticide usage. Preventing crop yield loss caused by pests is critical for global agricultural production. Agricultural pest control has largely relied on chemical pesticides. The interaction between insecticide resistance and the adaptation of herbivorous pests to host plants may represent an emerging threat to future food security. This study aims to unveil genetic evidence for the reduction in the profitability of resistant cultivars derived from insecticide resistance in target pest insects. An experimental evolution system encompassing resistant rice and its major monophagous pest, the brown planthopper Nilaparvata lugens , was constructed. Whole genome resequencing and selective sweep analysis were utilized to identify the candidate gene loci related to the adaptation. RNA interference and induced expression assay were conducted to validate the function of the candidate loci. We found that the imidacloprid-resistant population of N. lugens rapidly adapted to resistant rice IR36. Gene loci related to imidacloprid resistance may contribute to this phenomenon. Multiple alleles in the nicotinic acetylcholine receptor (nAChR)- 7 - like and P450 CYP4C61 were significantly correlated with changes in virulence to IR36 rice and insecticide resistance of N. lugens. One avirulent/susceptible genotype and two virulent/resistant genotypes could be inferred from the corresponding alleles. Importantly, we found that the virulent/resistant genotypes already exist in the wild in China, exhibiting increasing frequencies along with insecticide usage. We validated the relevance of these genotypes and the virulence to three more resistant rice cultivars. Knockdown of the above two genes in N. lugens significantly decreased both the resistance to imidacloprid and the virulence towards resistant rice. Our findings provide direct genetic evidence to the eco-evolutionary consequence of insecticide resistance, and suggest an urgent need for the implementation of predictably sustainable pest management. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) is a nervous system disease leading to motor and sensory dysfunction below the injury level, and can result in paralysis. MicroRNAs (miRNAs) play a key role in SCI treatment, and related research provides insights for SCI diagnosis and treatment. Bibliometrics is an important tool for literature statistics and evaluation, objectively summarizing multidimensional information. This study comprehensively overviews the field through bibliometric analysis of miRNA and SCI research, providing contemporary resources for future collaboration and clinical treatment. Materials and methods: In this study, we searched the Web of Science Core Collection (WOSCC) database. After careful screening and data import, we extracted annual publications, citation counts, countries, institutions, authors, journals, highly cited articles, co-cited articles, keywords, and H-index. Bibliometrics and visualization analyses employed VOSviewer, CiteSpace, the R package "bibliometrix," and online analytic platforms. Using Arrowsmith, 1 we determined miRNA-SCI relationships and discussed potential miRNA mechanisms in SCI. Results: From 2008 to 2024, the number of related papers increased annually, reaching 754. The number of yearly publications remained high and entered a period of rapid development. Researchers from 50 countries/regions, 802 institutions, 278 journals, and 3,867 authors participated in the field. Currently, China has advantages in the number of national papers, citations, institutions, and authors. However, it is necessary to strengthen cooperation among different authors, institutions, and countries to promote the production of important academic achievements. The research in the field currently focuses on nerve injury, apoptosis, and gene expression. Future research directions mainly involve molecular mechanisms, clinical trials, exosomes, and inflammatory reactions. Conclusion: Overall, this study comprehensively analyzes the research status and frontier of miRNAs in SCI. A systematic summary provides a complete and intuitive understanding of the relationship between SCI and miRNAs. The presented findings establish a basis for future research and clinical application in this field. [ABSTRACT FROM AUTHOR]

Amylose content (AC) stands as a pivotal determinant of rice grain quality, primarily governed by the Waxy gene (Wx). The allelic variation within this gene, particularly the presence of the Wxmp allele derived from the ancestral Wxmq allele, significantly influences AC and is prevalent among soft japonica rice varieties in southern China. Although both alleles are associated with lower AC, there remains a paucity of detailed understanding regarding the interplay between specific functional single nucleotide polymorphisms (SNPs) within these alleles and the overarching rice grain quality. To investigate this, we engineered three distinct transgenic rice lines, each harboring the Wxmp, Wxmq, or Wxb−5c alleles in the background of the glutinous rice cultivar Nip(wx). This suite of transgenic rice lines showcased varying degrees of grain transparency inversely correlated to AC, which in turn influenced other physicochemical properties of the rice grains, such as taste value of cooked rice, gel consistency, and starch pasting properties. Additionally, analyses of gene expression and enzyme activity revealed that the functional SNPs, Ex4-53G to A and Ex5-53T to C, lead to a decline in the activity of granule-bound starch synthase I (GBSSI) without altering expression levels. [ABSTRACT FROM AUTHOR]

Objectives: In order to evaluate the effect of methacrylated hyaluronic acid (HAMA) hydrogels containing the recombinant human amelogenin (rhAm) in vitro and in vivo. Background: The ultimate goal in treating periodontal disease is to control inflammation and achieve regeneration of periodontal tissues. In recent years, methacrylated hyaluronic acid (HAMA) containing recombinant human amyloid protein (rhAm) has been widely used as a new type of biomaterial in tissue engineering and regenerative medicine. However, there is a lack of comprehensive research on the periodontal regeneration effects of this hydrogel. This experiment aims to explore the application of photoresponsive recombinant human amelogenin‐loaded hyaluronic acid hydrogel for periodontal tissue regeneration and provide valuable insights into its potential use in this field. Materials and Methods: The effects of rhAm‐HAMA hydrogel on the proliferation of human periodontal ligament cells (hPDLCs) were assessed using the CCK‐8 kit. The osteogenic differentiation of hPDLCs was evaluated through ALP staining and real‐time PCR. Calvarial parietal defects were created in 4‐week‐old Sprague Dawley rats and implanted with deproteinized bovine bone matrix in different treatment groups. The animals were euthanized after 4 and 8 weeks of healing. The bone volume of the defect was observed by micro‐CT and histological analysis. Results: Stimulating hPDLCs with rhAm‐HAMA hydrogel did not significantly affect their proliferation (p >.05). ALP staining and real‐time PCR results demonstrated that the rhAm‐HAMA group exhibited a significant upregulation of osteoclastic gene expression (p <.05). Micro‐CT results revealed a significant increase in mineralized tissue volume fraction (MTV/TV%), trabecular bone number (Tb.N), and mineralized tissue density (MTD) of the bone defect area in the rhAm‐HAMA group compared to the other groups (p <.05). The results of hematoxylin and eosin staining and Masson staining at 8 weeks post‐surgery further supported the results of the micro‐CT. Conclusions: The results of this study indicate that rhAm‐HAMA hydrogel could effectively promote the osteogenic differentiation of hPDLCs and stabilize bone substitutes in the defects that enhance the bone regeneration in vivo. [ABSTRACT FROM AUTHOR]

Numerous members of the WOX gene family play pivotal roles during the processes of growth and development in many plants, as has been demonstrated. Cymbidium goeringii, Cymbidium ensifolium, and Cymbidium sinense are ornamental plants with a fascinating floral morphology that are economically important in China. However, there is limited knowledge about the members of the WOX gene family and their functions in these three Cymbidium species. Hence, the WOX genes in three Cymbidium species were identified on the ground of the genomes data of C. goeringii, C. ensifolium, and C. sinense in this study. These identified WOX genes were further studied for their physicochemical properties, evolutionary relationship, gene structure, protein structure, and cis-acting elements of promoters, as well as the expression pattern of the WOX genes in different tissues of C. goeringii. The findings revealed that eight WOX genes in C. goeringii, twelve WOX genes in C. ensifolium, and nine WOX genes were identified. These WOX genes were further subdivided into WUS, ancient, and intermediate clades. The length of the coding region ranged from 149 to 335 aa, and it was predicted that all WOX genes would be located on the cell nucleus. The promoter cis-acting elements primarily comprised stress response, phytohormone response, plant growth and development, and transcription factor elements. Furthermore, both the transcriptomic data and RT-qPCR analysis showed that most WOX genes may be involved in multiple developmental stages of C. goeringii. To sum up, these results may serve as a theoretical foundation for further study of the function analysis of WOX genes in orchids. [ABSTRACT FROM AUTHOR]

A weedy rye, Secale cereale subsp. segetale found in Xinjiang, China, possess strong stress tolerance, tillering capacity and many useful traits. The study aims to better understand the genetic diversity of segetale rye from China at the molecular level. The genetic diversity of 92 populations (bulked samples) and further 168 plants (individual samples from 14 populations) in the segetale rye were analyzed using 47 polymorphic EST-SSR (expressed sequence tags derived microsatellite) molecular markers. A total of 211 bands were amplified by 47 EST-SSR primers in the 92 populations. Among them, there were 190 polymorphic bands, with an average of 4.04 bands per primer and an average polymorphic ratio of 88.4%. The variation range of PIC (polymorphic information content) was 0.16–0.94 with the average 0.75, indicating abundant genetic diversity of weedy rye populations. The clustering analysis of 92 populations based on Nei's genetic distance showed that their average genetic distance was near 0.35, and 92 populations from different regions of Xinjiang were relatively scattered, generally close genetic distance between populations in the same region. Similar rule was found between individual plants in same population using clustering and principal coordinate analysis (PCoA). To 168 individual plants from 14 populations, analysis found that the average genetic differentiation among populations was 0.143, and the genetic diversity of the segetale rye populations mainly existed within populations (85.7%). Abundant genetic diversity was found within different regions and populations of segetale rye from China. The research provides a theoretical basis on the application of elite genes of segetale rye to the genetic improvement of rye and wheat. [ABSTRACT FROM AUTHOR]

Bacterial blight of rice is a devastating disease caused by the gram-negative bacteria Xanthomonas oryzae pv. oryzae (Xoo). Chinese Xoo strain pathotypes IV, V, and IX are the major virulent Xoo strain types in South China sequentially from the 1990s to the present. Here, we report the isolation of GD0201 and GD0202, which belong to pathotypes IV and IX, respectively, and the complete genome sequence and transcriptomic analysis of GD0201 (IV), GD1358 (V), and GD0202 (IX). We found that resistance genes xa5, Xa23, and Xa27 confer strong resistance to all three Xoo strains, indicating that they are currently good choices for resistance rice breeding. The genome analysis reveals fewer TAL and non-TAL effector coding genes in GD0202 than in the other two strains, potentially contributing to its strong virulence. Transcriptomic analysis of ZH11 inoculated with the three Xoo strains strongly suggests that three Xoo strains for better infection repress the ethylene response factor (ERF) gene family members. Furthermore, weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) analysis revealed 14 hub genes potentially associated with rice response to the three Xoo strains. The expression of several hub genes was validated to be induced by all three Xoo strains, suggesting its role in bacterial blight disease response to Xoo strains. Genomic analysis of the Xoo strains belonging to pathotypes IV, V, and IX, identification of effectors and genes related to Xoo virulence in rice plants will provide insights into understanding the molecular mechanism underlying rice-Xoo interaction and the gene expression pattern in response to Xoo infection. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors have improved the objective response rate and survival of melanoma patients. However, there are still many melanoma patients suffering from disease progression due to primary or secondary immune checkpoint inhibitor resistance, as is observed in the failure of anti-PD1/PD-L1 therapy. While the expression of valuable markers, such as TMB, MSI, and PD-L1, could serve as effective predictors of anti-checkpoint inhibitor therapies, tumor cell PD-L1 expression and its regulating mechanism would significantly affect the anti-PD-1 immunotherapy response and efficacy. Therefore, it is urgent to determine the function of PD-1/PD-L1 expression in melanoma and its associated pathways to enhance the efficacy of anti-PD-1 therapies. Methods: A cohort of 133 patients with histologically confirmed melanoma from Tianjin Medical University Cancer Institute & Hospital were included in this study. We performed immunohistochemical staining to detect the expression of Migration and invasion inhibitory protein (MIIP), HDAC6 and PD-L1. Kaplan–Meier and log-rank test were used for survival analysis. As for vitro, Western blot was used in melanoma cell lines to verify the signaling pathway that MIIP regulates PD-L1 expression. Results: MIIP expression was decreased in melanoma and that the negative expression of MIIP was correlated with worse overall survival. The positive expression of HDAC6, a molecule that is downstream of MIIP, had a positive trend with decreased overall survival. At the same time, the positive expression of PD-L1, a crucial costimulatory molecule, was associated with decreased overall survival. Furthermore, there was a positive association between HDAC6 and PD-L1 protein expression (p < 0.01), and this correlation is more prominent in cutaneous melanoma than acral melanoma. In cutaneous melanoma cell lines, we found that increasing MIIP led to decreased HDAC6, pSTAT3, and PD-L1 expression. Knocking down MIIP led to increased HDAC6, pSTAT3, and PD-L1 expression. Combining the published results, showing that HDAC6 can regulate PD-L1 expression through STAT3, our present data suggest that MIIP inhibits the expression of PD-L1 by downregulating HDAC6 in melanoma. Most importantly, methods for targeting MIIP-HDAC6-PD-L1 pathways, such as treatment with HDAC6 inhibitors, might indicate a new therapeutic approach for enhancing immune checkpoint inhibitor therapies in melanoma. Conclusions: Our findings highlight the immunomodulatory effects of MIIP in the inhibition of PD-L1 expression by downregulating HDAC6 in melanoma. Methods for targeting MIIP-HDAC6-PD-L1 pathways might be new therapeutic approaches for enhancing immune checkpoint inhibitor therapies in melanoma. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is strongly associated with type 2 diabetes (T2D) that results in serious complications and mortality. However, the pathogenic role of periodontitis in the development of T2D and the underlain mechanism have not been fully elucidated. Methods: A Mendelian randomization (MR) was performed to estimate the causality between two diseases. Bioinformatics tools, including gene ontology and pathway enrichment analyses, were employed to analyze the common differentially expressed genes (DEGs) in periodontitis and T2D. MR and colocalization analyses were then utilized to investigate the causal associations between potential pathogenic gene expression and the risk of T2D. Single cell-type expression analysis was further performed to detect the cellular localization of these genes. Results: Genetically predicted periodontitis was associated with a higher risk of T2D (OR, 1.469; 95% CI, 1.117–1.930; P = 0.006) and insulin resistance (OR 1.034; 95%CI 1.001–1.068; P = 0.041). 79 common DEGs associated with periodontitis and T2D were then identified and demonstrated enrichment mainly in CXC receptor chemokine receptor binding and interleutin-17 signaling pathway. The integration of GWAS with the expression quantitative trait locis of these genes from the peripheral blood genetically prioritized 6 candidate genes, including 2 risk genes (RAP2A, MCUR1) and 4 protective genes (WNK1, NFIX, FOS, PANX1) in periodontitis-related T2D. Enriched in natural killer cells, RAP2A (OR 4.909; 95% CI 1.849–13.039; P = 0.001) demonstrated high risk influence on T2D, and exhibited strong genetic evidence of colocalization (coloc.abf-PPH4 = 0.632). Conclusions: This study used a multi-omics integration method to explore causality between periodontitis and T2D, and revealed molecular mechanisms using bioinformatics tools. Periodontitis was associated with a higher risk of T2D. MCUR1, RAP2A, FOS, PANX1, NFIX and WNK1 may play important roles in the pathogenesis of periodontitis-related T2D, shedding light on the development of potential drug targets. [ABSTRACT FROM AUTHOR]

Background: The tea plant (Camellia sinensis (L.) O. Kuntze) is one of the most economically important woody crops. Plastic greenhouse covering cultivation has been widely used in tea areas of northern China. Chlorophyll is not only the crucial pigment for green tea, but also plays an important role in the growth and development of tea plants. Currently, little is known about the effect of plastic greenhouse covering cultivation on chlorophyll in tea leaves. Results: To investigate the effect of plastic greenhouse covering cultivation on chlorophyll in tea leaves, color difference values, chlorophyll contents, gene expression, enzyme activities and photosynthetic parameters were analyzed in our study. Sensory evaluation showed the color of appearance, liquor and infused leaves of greenhouse tea was greener than field tea. Color difference analysis for tea liquor revealed that the value of ∆L, ∆b and b/a of greenhouse tea was significantly higher than field tea. Significant increase in chlorophyll content, intracellular CO2, stomatal conductance, transpiration rate, and net photosynthetic rate was observed in greenhouse tea leaves. The gene expression and activities of chlorophyll-metabolism-related enzymes in tea leaves were also activated by greenhouse covering. Conclusion: The higher contents of chlorophyll a, chlorophyll b and total chlorophyll in greenhouse tea samples were primarily due to higher gene expression and activities of chlorophyll-metabolism-related enzymes especially, chlorophyll a synthetase (chlG), pheophorbide a oxygenase (PAO) and chlorophyllide a oxygenase (CAO) in tea leaves covered by greenhouse. In general, our results revealed the molecular basis of chlorophyll metabolism in tea leaves caused by plastic greenhouse covering cultivation, which had great significance in production of greenhouse tea. [ABSTRACT FROM AUTHOR]

Background: Populus simonii, a notable native tree species in northern China, demonstrates impressive resistance to stress, broad adaptability, and exceptional hybridization potential. DOF family is a class of specific transcription factors that only exist in plants, widely participating in plant growth and development, and also playing an important role in abiotic stress response. To date, there have been no reported studies on the DOF gene family in P. simonii, and the expression levels of this gene family in different tissues of poplar, as well as its expression patterns under cold, heat, and other stress conditions, remain unclear. Methods: In this study, DOF gene family were identified from the P. simonii genome, and various bioinformatics data on the DOF gene family, gene structure, gene distribution, promoters and regulatory networks were analyzed. Quantitative real time PCR technology was used to verify the expression patterns of the DOF gene family in different poplar tissues. Results: This research initially pinpointed 41 PSDOF genes in P. simonii genome. The chromosomal localization results revealed that the PSDOF genes is unevenly distributed among 19 chromosomes, with the highest number of genes located on chromosomes 4, 5, and 11. A phylogenetic tree was constructed based on the homology between Arabidopsis thaliana and P. simonii, dividing the 41 PSDOF genes into seven subgroups. The expression patterns of PSDOF genes indicated that specific genes are consistently upregulated in various tissues and under different stress conditions, suggesting their pivotal involvement in both plant development and response to stress. Notably, PSDOF35 and PSDOF28 serve as pivotal hubs in the interaction network, playing a unique role in coordinating with other genes within the family. Conclusion: The analysis enhances our comprehension of the functions of the DOF gene family in tissue development and stress responses within P. simonii. These findings provide a foundation for future exploration into the biological roles of DOF gene family. [ABSTRACT FROM AUTHOR]

Pinus sibirica is primarily distributed in Siberia. Owing to its excellent cold resistance and development potential, it has become an important introduced tree species in the Greater Xing'an area of China. Pine wilt disease, triggered by the pine wood nematode (PWN, Bursaphelenchus xylophilus), constitutes a profoundly critical affliction within forest ecosystems. Its incidence has extended to the northeastern region of China in recent years. To explore the potential host status of P. sibirica in the Greater Xing'an area for PWN and to elucidate the responses following inoculation, artificial inoculation, transcriptomics, and metabolomics methods were used. In the artificial inoculation experiments, quantitative analysis of nematode populations within the trees demonstrated that PWN exhibited normal growth and reproductive capabilities within P. sibirica. Subsequently, transcriptome and metabolome sequencing were conducted at four time points before disease onset (3-, 5-, 7-, and 9-days post inoculation). Gene trend analysis and differentially expressed gene screening were employed and the results indicated that genes associated with the flavonoid biosynthesis pathway exhibited predominant enrichment among the upregulated genes. Metabolome analysis showed that the abundance of flavonoidrelated metabolites in P. sibirica increased after inoculation with PWN. Integrated analysis of transcriptome and metabolome revealed that after PWN inoculation in P. sibirica, two chalcone synthase (chs) genes and a chalcone isomerase (chi) gene were significantly upregulated, and the upregulation should accumulate naringenin, pinocembrin, and apigenin to help P. sibirica resist infection of PWN. The results suggested that flavonoid biosynthesis pathway continued to respond after P. sibirica was infected with PWN and played an important role in the interaction between P. sibirica and PWN. [ABSTRACT FROM AUTHOR]

Simple Summary: Shitou geese are the exclusive representative of a large-sized goose breed in China, typically exhibiting gray feathers but also possessing a recessive white plumage. However, the precise mechanism underlying the formation of this white plumage coloration in Shitou geese remains unclear. Here, a transcriptome sequencing analysis was conducted to identify candidate genes and microRNAs (miRNAs) that may be associated with the white plumage color in Shitou geese. A number of pigmentation genes and miRNAs were identified as candidates that may regulate white plumage color formation in Shitou geese. This result may be important for understanding the genetic mechanism underlying the formation of white plumage color in Shitou geese. The Shitou goose, a highly recognized indigenous breed with gray plumage originating from Chaozhou Raoping in Guangdong Province, China, is renowned for being the largest goose species in the country. Notably, during the pure breeding process of Shitou geese, approximately 2% of the offspring in each generation unexpectedly exhibited white plumage. To better understand the mechanisms underlying white plumage color formation in Shitou geese, we conducted a comparative transcriptome analysis between white and gray feather follicles, aiming to identify key genes and microRNAs that potentially regulate white plumage coloration in this unique goose breed. Our results revealed a number of pigmentation genes, encompassing TYR, TYRP1, EDNRB2, MLANA, SOX10, SLC45A2, GPR143, TRPM1, OCA2, ASIP, KIT, and SLC24A5, which were significantly down-regulated in the white feather follicles of Shitou geese. Among these genes, EDNRB2 and KIT emerged as the most promising candidate genes for white plumage coloration in Shitou geese. Additionally, our analysis also uncovered 46 differentially expressed miRNAs. Of these, miR-144-y may play crucial roles in the regulation of feather pigmentation. Furthermore, the expression of novel-m0086-5p, miR-489-y, miR-223-x, miR-7565-z, and miR-3535-z exhibits a significant negative correlation with the expression of pigmentation genes including TYRP1, EDNRB2, MLANA, SOX10, TRPM1, and KIT, suggesting these miRNAs may indirectly regulate the expression of these genes, thereby influencing feather color. Our findings provide valuable insights into the genetic mechanisms underlying white plumage coloration in Shitou geese and contribute to the broader understanding of avian genetics and coloration research. [ABSTRACT FROM AUTHOR]

Background Intestinal metaplasia (IM) and intraepithelial neoplasia (IEN) are considered precursors of gastric cardia cancer (GCC). Here, we investigated the histopathologic and molecular profiles of precancerous gastric cardia lesions (PGCLs) and biomarkers for risk stratification of gastric cardia IM. Methods We conducted a hospital-based evaluation (n   =   4578) for PGCL profiles in high-incidence and non-high-incidence regions for GCC in China. We next performed 850K methylation arrays (n   =   42) and RNA-seq (n   =   44) in tissues with PGCLs. We then examined the protein expression of candidate biomarker using immunohistochemistry. Results Of the 4578 participants, 791 were diagnosed with PGCLs (600 IM, 62 IM with IEN, and 129 IEN). We found that individuals from high-incidence regions (26.7%) were more likely to develop PGCLs than those from non-high-incidence areas (13.5%). DNA methylation and gene expression alterations, indicated by differentially methylated probes (DMPs) and differentially expressed genes (DEGs), exhibited a progressive increase from type I IM (DMP = 210, DEG = 24), type II IM (DMP = 3402, DEG = 129), to type III IM (DMP = 3735, DEG = 328), peaking in IEN (DMP = 47 373, DEG = 2278). Three DEGs with aberrant promoter methylation were identified, shared exclusively by type III IM and IEN. Of these DEGs, we found that OLFM4 expression appears in IMs and increases remarkably in IENs (P  <  .001). Conclusions We highlight that type III IM and IEN share similar epigenetic and transcriptional features in gastric cardia and propose biomarkers with potential utility in risk prediction. [ABSTRACT FROM AUTHOR]