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Abstract Background Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbiosis. However, it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets. Results In this study, we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score, and elevated levels of lipopolysaccharide (LPS) and D-lactate (D-LA) compared to healthy piglets. Subsequently, we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets. Diarrheal piglets demonstrated intestinal microbiota dysbiosis, characterized primarily by a higher Firmicutes to Bacteroidota ratio, a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri, and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron. Functional profiling of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data was performed, and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diarrhea. Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets. Furthermore, we explored the effects of dietary indole-3-aldehyde (IAld), a key tryptophan metabolite, on intestinal development and gut barrier function in weaned piglets. Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell (ISC) expansion in piglets. The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids. Conclusions These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intestinal development by promoting ISC expansion in weaned piglets.

Abstract Background Cardiovascular function and metabolic homeostasis are closely linked, but the underlying mechanisms are not fully understood. Corin is a protease that activates atrial natriuretic peptide (ANP), an essential hormone for normal blood pressure and cardiac function. The goal of this study is to investigate a potential corin and ANP function in regulating liver glycogen metabolism and glucose homeostasis. Methods Liver glycogen and blood glucose levels were analyzed in Corin or Nppa (encoding ANP) knockout (KO) mice. ANP signaling was examined in livers from Corin and Nppa KO mice and in cultured human and mouse hepatocytes by western blotting. Results We found that Corin and Nppa KO mice had reduced liver glycogen contents and increased blood glucose levels. By analyzing conditional KO mice lacking either cardiac or renal Corin, we showed that cardiac corin and ANP act in an endocrine manner to enhance cGMP-protein kinase G (PKG)-AKT-GSK3 signaling in hepatocytes. In cultured hepatocytes, ANP treatment stimulated PKG signaling, glucose uptake, and glycogen production, which could be blocked by small molecule PKG and AKT inhibitors. Conclusions Our results indicate that corin and ANP are important regulators in liver glycogen metabolism and glucose homeostasis, suggesting that defects in the corin and ANP pathway may contribute to both cardiovascular and metabolic diseases.

Abstract Purpose In the Zhejiang region, research on Helicobacter pylori is lacking. The purpose of this study was to assess the extent of antibiotic resistance in H. pylori in this region, explore alternative methods for predicting the resistance patterns of H. pylori, and investigate the colonization of native gastric mucosa by other clades of H. pylori in the structure population of this bacterium. Methods Strains were cultured under microaerobic conditions, and antimicrobial susceptibility testing (AST) was performed via agar dilution. Whole-genome sequencing (WGS) was performed via next-generation sequencing (NGS) technology. Epidemiological data including data from this study and reported articles from Zhejiang, China, were included. Further analyses based on AST, WGS, and epidemiological date include virulence genes, antibiotic resistance-related mutations, and phylogenetic trees based on 7 housekeeping genes and core-genome single nucleotide polymorphisms (SNPs). Results The bacterial isolates in this study presented higher antibiotic resistance rates than previously reported, especially against levofloxacin and clarithromycin. The point mutation A2147G in 23 S rRNA is specific to clarithromycin resistance. Mutations at position/s 87 and/or 91 of the gyrA gene amino acid sequence are highly consistent with levofloxacin resistance highly. The point mutations C1707T in 23 S rRNA and E463K in the gyrB gene have not been previously documented in China. All the bacterial isolates belong to Asian branches in the structure population. The resistance rate to clarithromycin of isolates from hosts born after January 1, 1977 is statistically higher than that of hosts born before 1977. Conclusion Eradication therapy based on AST results is urgently needed in Zhejiang. The point mutation A2147G in 23 S rRNA and point mutations in the gyrA gene at amino acid/s 87 and/or 91 are sufficient for predicting resistance to clarithromycin and levofloxacin, respectively. The isolate with the mutation E463K in the gyrB gene represents a significant contribution to the field. Mutations in 23 S rRNA may offer valuable insights into the dynamics of H. pylori transmission among hosts.

Abstract Corin is a protease that activates atrial natriuretic peptide (ANP), a hormone in cardiovascular homeostasis. Structurally, ANP is similar to C-type natriuretic peptide (CNP) crucial in bone development. Here, we examine the role of corin and ANP in chondrocyte differentiation and bone formation. We show that in Corin and Nppa (encoding ANP) knockout (KO) mice, chondrocyte differentiation is impaired, resulting in shortened limb long bones. In adult mice, Corin and Nppa deficiency impairs bone density and microarchitecture. Molecular studies in cartilages from newborn Corin and Nppa KO mice and in cultured chondrocytes indicate that corin and ANP act in chondrocytes via cGMP-dependent protein kinase G signaling to inhibit mitogen-activated protein kinase phosphorylation and stimulate glycogen synthase kinase-3β phosphorylation and β-catenin upregulation. These results indicate that corin and ANP signaling regulates chondrocyte differentiation in bone development and homeostasis, suggesting that enhancing ANP signaling may improve bone quality in patients with osteoporosis.

Androgen‐regulated DNA damage response (DDR) is one of the essential mechanisms in prostate cancer (PCa), a hormone‐sensitive disease. The heterogeneous nuclear ribonucleoprotein K (hnRNPK)‐homology splicing regulatory protein known as far upstream element‐binding protein 2 (KHSRP) is an RNA‐binding protein that can attach to AU‐rich elements in the 3′ untranslated region (3′‐UTR) of messenger RNAs (mRNAs) to mediate mRNA decay and emerges as a critical regulator in the DDR to preserve genome integrity. Nevertheless, how KHSRP responds to androgen‐regulated DDR in PCa development remains unclear. This study found that androgen can significantly induce acetylation of KHSRP, which intrinsically drives tumor growth in xenografted mice. Moreover, enhanced KHSRP acetylation upon androgen stimuli impedes KHSRP‐regulated DDR gene expression, as seen by analyzing RNA sequencing (RNA‐seq) and Gene Set Enrichment Analysis (GSEA) datasets. Additionally, NAD‐dependent protein deacetylase sirtuin‐7 (SIRT7) is a promising deacetylase of KHSRP, and androgen stimuli impairs its interaction with KHSRP to sustain the increased KHSRP acetylation level in PCa. We first report the acetylation of KHSRP induced by androgen, which interrupts the KHSRP‐regulated mRNA decay of the DDR‐related genes to promote the tumorigenesis of PCa. This study provides insight into KHSRP biology and potential therapeutic strategies for PCa treatment, particularly that of castration‐resistant PCa.

In order to exploit new botanic fungicide, the antifungal activities of the ethanol extracts of stem-leaf and rhizoid of P. commune were studied by the mycelia growth rate method and the spore germination method based on the determination of their mycelia growth inhibition rates, spore germination inhibition rates and median inhibition concentration values (EC50) on B. cinerea, F. solani f. sp. batatas, F. solani and A. brassicicola. The results showed that the antifungal activities of the ethanol extracts of P. commune against the four plant pathogenic fungi were extremely significant (P

ObjectiveTo understand the awareness of breast cancer knowledge and its influencing factors among medical staff in maternal and child health hospitals of all levels in Ordos city. MethodsFrom April to June 2023, a convenient sampling method was used to select 886 medical staff from maternal and child health hospitals at all levels in Ordos city, Inner Mongolia Autonomous Region to conduct a questionnaire survey using Questionnaire Star online platform with a self-designed questionnaire on general demographic information and core knowledge of breast cancer prevention and treatment health education introduced in the national “Breast Cancer Screening Work Plan”, and the willingness to recommend to women to have breast cancer screening at an appropriate age. SPSS 19.0 software was used for multivariate logistic regression model analysis. ResultsA total of 862 valid questionnaires were collected, with an effective response rate of 97.3%. The mean score of the respondents' knowledge of breast cancer prevention and treatment was 15.08 ± 5.88 out of a total score of 24. The results of multivariate analysis showed that the respondents with medical majors (clinical medicine: odds ratio [OR] = 7.50, 95% confidence interval [95%CI]: 2.90 – 19.42; nursing: OR = 4.93, 95%CI: 1.92 – 12.66; other medical majors: OR = 4.70, 95%CI: 1.82 – 12.11), working in ultrasound/imaging departments (OR = 2.01, 95%CI: 1.03 – 3.92), and with a professional title of associate senior or higher (senior physician: OR = 3.54, 95%CI: 1.30 – 9.63; associate senior: OR = 2.56, 95%CI: 1.35 – 4.86) had better awareness of breast cancer prevention and treatment knowledge (all P < 0.05). Among the typical symptoms of breast cancer, the awareness rates of "breast lump" (82.48%), "axillary lymph node enlargement" (74.71%), and "breast skin depression or wrinkling" (74.48%) were higher; among the risk factors for breast cancer, the awareness rates of "long-term use of exogenous estrogen" (64.39%) and "family history of breast or ovarian cancer" (61.14%) were higher; among the common breast cancer screening methods, the awareness rates of clinical breast examination, breast ultrasound, and breast x-ray were all around 90%; the awareness rate of the recommended screening age in the breast cancer screening work plan was 74.71%, but the awareness rate of the screening time interval was only 24.25%. The awareness rates of screening age and screening time interval among breast cancer screening personnel (88.36%, 33.33%) were higher than those of non-breast cancer screening personnel (70.88%, 21.69%) (P < 0.001). Of the respondents, 689 (79.93%) and 684 (79.35%) agreed that breast cancer screening can improve the early detection rate and reduce the mortality rate of breast cancer, respectively, and 831 (96.40%) were willing to recommend regular breast cancer screening to women of appropriate age. ConclusionThe awareness of breast cancer screening and the willingness to recommend breast cancer screening to women of appropriate age among medical staff in maternal and child health hospitals in Ordos city are relatively high, but the awareness of breast cancer prevention and treatment knowledge needs to be improved. Professional training in breast related knowledge should be strengthened for local medical staff.

ObjectiveTo understand the structural variation in hospitalization costs for patients with cervical cancer and to investigate the reasons for these variations. MethodsUsing the degree of structural variation (DSV) analysis and grey relational analysis methods, we analyzed the hospitalization data of 5 654 cervical cancer patients from three class A tertiary hospitals in northern China from 2013 to 2022. The DSV was used to describe the overall characteristics and dynamic trends of the hospitalization cost composition, while gray relational analysis assessed the correlation between hospitalization costs and individual cost items. ResultsDuring this period, the average individual total cost of hospitalization for all patients studied showed an upward trend with a low overall DSV and an average annual DSV of 18.60%. Diagnostic fees and drug costs were two significant factors influencing cost changes. In particular, the structural variation values of diagnostic fees and drug costs showed positive changes during this period. The top three cost items contributing to the change in hospital cost structure were other fees (contribution rate: 35.87%), diagnostic fees (32.09%), and drug costs (16.44%), with a cumulative structural contribution rate of 84.40%. The proportion of diagnostic fees has increased significantly, contributing to the structural variation, indicating that diagnostic fees are a major component of hospitalization costs. Although the proportion of drug costs has decreased in recent years, it remains an important factor influencing cost changes. Gray relation analysis showed that from 2013 to 2022, other fees had the highest correlation with hospitalization costs (correlation coefficient: 0.855), followed by diagnostic fees (0.824) and drug costs (0.781). ConclusionFor the hospitalization costs of cervical cancer patients from tertiary hospitals in northern China, diagnostic fees, drug costs, and other fees contribute significantly to the cost structure and have the highest correlation with hospitalization costs, which are significant factors influencing the fluctuation of hospitalization costs. The structural contribution rates of comprehensive medical service fees and treatment fees are relatively low, and their correlation with hospitalization costs is also lower, so they have minimal impact on the structure and changing trends of hospitalization costs.

Background: The association between problematic mobile phone use (PMPU) and negative emotions in university students is not well understood in terms of causality and directionality. This study aims to clarify whether negative emotions trigger PMPU or whether the PMPU itself leads to increased negative emotions over time. Methods: A two-wave longitudinal study was conducted involving 5568 Chinese freshmen who were surveyed at baseline and followed up after one academic year. PMPU, social media use, online game use, fear of missing out, loneliness, social anxiety, and academic burnout were measured. Cross-sectional and longitudinal connections between these variables were examined using network analysis techniques. Results: The variable with the strongest influence in both contemporaneous networks was “Productivity loss” of MAPI. Moreover, “Academic burnout” at baseline significantly predicted higher levels of problematic smartphone use and negative emotions at follow-up, suggesting that it may serve as a catalyst for addictive tendencies. Furthermore, we observed bidirectional relationships between “Escapism” and “Social anxiety”, as well as between “Social anxiety” and “Inability to control craving”, suggesting a potential self-perpetuating cycle. Conclusion: These findings highlight the role of academic burnout in initiating cycles of PMPU and negative emotions. In order to effectively tackle PMPU, it is crucial to consider the underlying drivers such as academic burnout and emotional states. This is important due to the complex and reciprocal associations uncovered through our longitudinal network analysis.

IntroductionWith its distinctive evolutionary rate and inheritance patterns separate from the nuclear genome, mitochondrial genome analysis has become a prominent focus of current research. Dendrobium hancockii Rolfe, a species of orchid with both medicinal and horticultural value, will benefit from the application of the fully assembled and annotated mitochondrial genome. This will aid in elucidating its phylogenetic relationships, comparative genomics, and population genetic diversity.MethodsBased on sequencing results from Illumina combined with PacBio and Nanopore, the mitochondrial genome map of D. hancockii was constructed. Comparative analysis was conducted from the perspectives of phylogeny across multiple species, selection pressure on protein-coding genes, and homologous segments. The population diversity of D. hancockii was analyzed using single nucleotide polymorphism (SNP) data from the mitochondrial genome and single-copy nuclear genes.Results and discussionThis research constructed a circular mitochondrial map for D. hancockii, spanning 523,952 bp, containing 40 unique protein-coding genes, 37 transfer RNA genes, and 4 ribosomal RNA genes. Comparative analysis of mitochondrial genes from 26 land plants revealed a conserved gene cluster, "rpl16-ccmFn-rps3-rps19," particularly within the Dendrobium genus. The mitochondrial genome of D. hancockii exhibits a lower point mutation rate but significant structural variation. Analysis of 103 resequencing samples identified 19,101 SNP sites, dividing D. hancockii into two major groups with limited gene flow between them, as supported by population diversity, genetic structure analysis, principal component analysis, and phylogenetic trees. The geographical distribution and genetic differentiation of D. hancockii into two major groups suggest a clear phytogeographical division, likely driven by ancient geological or climatic events. The close alignment of mitochondrial data with nuclear gene data highlights the potential of the mitochondrial genome for future studies on genetic evolution in this species.

ObjectiveTo understand the status and influencing factors of human papillomavirus (HPV) vaccination knowledge and recommendation behaviors among healthcare workers and teachers in Ordos city, Inner Mongolia Autonomous Region. MethodsUsing a typical sampling method and a self-designed questionnaire, we conducted an online survey among 415 healthcare workers and teachers recruited in one district and one banner of Ordos City, Inner Mongolia Autonomous Region in July 2023. Participants′ information on knowledge of HPV and its vaccines, and beliefs about HPV vaccination based on the health belief model (HBM) were collected. Univariate logistic regression and unconditional multivariate logistic regression were used to analyze the factors influencing HPV vaccination recommendation behavior. ResultsOf the 243 health care workers and 86 teachers ultimately included in the analysis, 201 and 56, respectively, had recommended HPV vaccination. The median of HPV knowledge score was 7 out of a total score of 11 for healthcare workers and 6 for teachers. Multivariate unconditional logistic regression model analysis showed that among healthcare workers, those with the following characteristics were more likely to recommend HPV vaccination: living in the banner (odds ratio [OR] = 17.042, 95% confidence interval [95%CI]: 2.778 – 104.544), having a higher HPV knowledge score (OR = 10.194, 95%CI: 3.076 – 33.778), having a higher HPV vaccination knowledge score (OR = 4.510, 95%CI: 1.451 – 14.015), having a higher score of perceived favorable factors for recommending HPV vaccination (OR = 17.492, 95% CI: 3.054 – 100.178), and having a high perception of susceptibility to HPV infection (OR = 100.407, 95%CI: 15.087 – 668.239); while those who were married were less likely to recommend HPV vaccination (OR = 0.050, 95%CI: 0.006 – 0.404); the teachers with high perception of susceptibility to HPV infection were more likely to recommend HPV vaccination (OR = 4.947, 95%CI: 1.322 – 18.516). ConclusionHealthcare workers and teachers in Ordos city had good knowledge of HPV vaccination. Region of residence, marital status, HPV knowledge, perceived favorable factors for recommending HPV vaccination, and perceived susceptibility to HPV infection were the main factors influencing the recommendation behavior of healthcare workers, while perceived susceptibility to HPV infection was the main factor influencing the recommendation behavior of teachers.

Abstract Although asymmetric molecular design has been widely demonstrated effective for organic photovoltaics (OPVs), the correlation between asymmetric molecular geometry and their optoelectronic properties is still unclear. To access this issue, we have designed and synthesized several symmetric-asymmetric non-fullerene acceptors (NFAs) pairs with identical physical and optoelectronic properties. Interestingly, we found that the asymmetric NFAs universally exhibited increased open-circuit voltage compared to their symmetric counterparts, due to the reduced non-radiative charge recombination. From our molecular-dynamic simulations, the asymmetric NFA naturally exhibits more diverse molecular interaction patterns at the donor (D):acceptor (A) interface as compared to the symmetric ones, as well as higher D:A interfacial charge-transfer state energy. Moreover, it is observed that the asymmetric structure can effectively suppress triplet state formation. These advantages enable a best efficiency of 18.80%, which is one of the champion results among binary OPVs. Therefore, this work unambiguously demonstrates the unique advantage of asymmetric molecular geometry, unveils the underlying mechanism, and highlights the manipulation of D:A interface as an important consideration for future molecular design.

Abstract Ribose-5-phosphate (R5P) is a precursor for nucleic acid biogenesis; however, the importance and homeostasis of R5P in the intracellular parasite Toxoplasma gondii remain enigmatic. Here, we show that the cytoplasmic sedoheptulose-1,7-bisphosphatase (SBPase) is dispensable. Still, its co-deletion with transaldolase (TAL) impairs the double mutant’s growth and increases 13C-glucose-derived flux into pentose sugars via the transketolase (TKT) enzyme. Deletion of the latter protein affects the parasite’s fitness but is not lethal and is correlated with an increased carbon flux via the oxidative pentose phosphate pathway. Further, loss of TKT leads to a decline in 13C incorporation into glycolysis and the TCA cycle, resulting in a decrease in ATP levels and the inability of phosphoribosyl-pyrophosphate synthetase (PRPS) to convert R5P into 5′-phosphoribosyl-pyrophosphate and thereby contribute to the production of AMP and IMP. Likewise, PRPS is essential for the lytic cycle. Not least, we show that RuPE-mediated metabolic compensation is imperative for the survival of the ΔsbpaseΔtal strain. In conclusion, we demonstrate that multiple routes can flexibly supply R5P to enable parasite growth and identify catalysis by TKT and PRPS as critical enzymatic steps. Our work provides novel biological and therapeutic insights into the network design principles of intracellular parasitism in a clinically-relevant pathogen.

IntroductionA multitude of variables influence the healing of tooth extraction wounds, and delayed or non-healing extraction wounds might complicate later prosthodontic therapy. In this research, we analyzed the effects of systemic clopidogrel and aspirin alone or in combination on the healing of tooth extraction wounds in mice in order to provide experimental evidence for the healing of extraction wounds in patients who are clinically treated with the two medicines.Methods7-week-old ICR mice were randomly divided into four groups: control group (CON), clopidogrel group (CLOP), aspirin group (ASP), and clopidogrel combined with aspirin group (CLOP + ASP); left upper first molar was extracted, after which mice in 1 week of adaptive feeding, CLOP/ASP/CLOP + ASP groups were respectively administered with clopidogrel (10 mg/kg/d), aspirin (15 mg/kg/d), clopidogrel (10 mg/kg/d)+aspirin (15 mg/kg/d), and the control group was given an equal amount of 0.9% saline by gavage. Mice in each group were euthanized at 14 and 28 days postoperatively, and the maxilla was extracted. The tissues in the extraction sockets were examined using MicroCT and sectioned for HE staining, Masson staining, and TRAP staining, and immunohistochemistry staining (for TRAP, RANKL and osteoprotegerin).ResultsMicroCT analysis showed that at day 14, BS/BV was significantly lower in CLOP and CLOP + ASP groups compared to control and ASP groups, while BV/TV, Tb.Th was significantly higher. At day 28, BV/TV was significantly higher in the CLOP + ASP group compared to the CLOP group, with p < 0.05 for all results. HE staining and Masson trichrome staining findings revealed that at day 28, the mesenchyme in the bone was further decreased compared to that at day 14, accompanied with tightly arranged and interconnected bone trabeculae. In the quantitative analysis of Masson, the fraction of newly formed collagen was significantly higher in the CLOP group in comparison with that in the CON group (p < 0.05). At day 14, the ASP group had substantially more TRAP-positive cells than the CLOP and CLOP + ASP groups (p < 0.05). In immunohistochemical staining, RANKL expression was found to be significantly higher in the ASP group than those in the other three groups at day 28 (p < 0.05); OPG expression was significantly higher in the CLOP group and the CLOP + ASP group compared with that at day 14, and was higher than that in the ASP group at day 14 and day 28. OPG/RANKL was significantly higher in the CLOP and the CLOP + ASP groups than in the ASP group (p < 0.05).ConclusionClopidogrel alone promotes osteogenesis in the extraction wound, whereas aspirin alone inhibits alveolar bone healing. When the two drugs were combined, the healing effect of the extraction wound was more similar to that of the clopidogrel alone group. These results indicated that clopidogrel could promote the healing of the tooth extraction wound, and neutralize the adverse effect of ASP on osteogenesis when the two drugs were used in combination.

Plant-derived natural compounds are significant resources for the discovery of potential anticancer drugs. While research in the plant-based anticancer field has surged in recent years, systematic bibliometric analyses covering a longer period and containing up-to-date publications remain scarce. Here, we conducted a bibliometric analysis of literature on the anticancer properties of plant natural compounds over the past three decades, leveraging the bibliometric framework and open-access platform, KNIME. Our findings showed that the number of plant anticancer-related publications underwent an accelerating growth from 1992 to 2023. The country and institution analyses revealed that countries with traditional medical systems contributed a large portion of publications in the plant anticancer field, such as India, China, and South Korea. This study also highlighted the top ten eminent researchers and publications, assisting researchers in identifying pivotal literature. The primary publications were domains of chemistry and biology-related fields, such as Pharmacology & Pharmacy, Plant Sciences, and Biochemistry & Molecular Biology. Additionally, we noted that flavonoids have been focal plant compounds in anticancer, with strong anticancer potential. Our study provides new insights into the progress and trends in the plant anticancer field and will assist researchers in grasping the future research direction.

ObjectiveThe circulating tumor cells (CTCs) could be captured by the peptide functionalized magnetic nanoparticles (Pep@MNP) detection system in pancreatic ductal adenocarcinoma (PDAC). CTCs and the CXCR4 expression were detected to explore their clinical significance. The CXCR4+ CTCs, this is highly metastatic-prone stem cell-like subsets of CTCs (HM-CTCs), were found to be associated with the early recurrence and metastasis of PDAC.MethodsCTCs were captured by Pep@MNP. CTCs were identified via immunofluorescence with CD45, cytokeratin antibodies, and the CXCR4 positive CTCs were assigned to be HM-CTCs.ResultsThe over-expression of CXCR4 could promote the migration of pancreatic cancer cell in vitro and in vivo. In peripheral blood (PB), CTCs were detected positive in 79.0% of all patients (49/62, 9 (0–71)/2mL), among which 63.3% patients (31/49, 3 (0–23)/2mL) were HM-CTCs positive. In portal vein blood (PVB), CTCs were positive in 77.5% of patients (31/40, 10 (0–40)/2mL), and 67.7% of which (21/31, 4 (0–15)/2mL) were HM-CTCs positive CTCs enumeration could be used as diagnostic biomarker of pancreatic cancer (AUC = 0.862), and the combination of CTCs positive and CA19–9 increase shows improved diagnostic accuracy (AUC = 0.963). in addition, PVB HM-CTCs were more accurate to predict the early recurrence and liver metastasis than PB HM-CTCs (AUC 0.825 vs. 0.787 and 0.827 vs. 0.809, respectively).ConclusionsThe CTCs identified by Pep@MNP detection system could be used as diagnostic and prognostic biomarkers of PDAC patients. We identified and defined the CXCR4 over-expressed CTC subpopulation as highly metastatic-prone CTCs, which was proved to identify patients who were prone to suffering from early recurrence and metastasis.

IntroductionPlumbagin is an important phytochemical and has been reported to exhibit potent larvicidal activity against several insect pests, However, the insecticidal mechanism of plumbagin against pests is still poorly understood. This study aimed to investigate the insecticidal activities of plumbagin and the underlying molecular mechanisms against a devastating agricultural pest, the fall armyworm Spodoptera frugiperda.MethodsThe effects of plumbagin on S. frugiperda larval development and the activities of two detoxification enzymes were initially examined. Next, transcriptomic changes in S. frugiperda after plumbagin treatment were investigated. Furthermore, RNA-seq results were validated by qPCR.ResultsPlumbagin exhibited a high larvicidal activity against the second and third instar larvae of S. frugiperda with 72 h LC50 of 0.573 and 2.676 mg/g, respectively. The activities of the two detoxification enzymes carboxylesterase and P450 were significantly increased after 1.5 mg/g plumbagin treatment. Furthermore, RNA-seq analysis provided a comprehensive overview of complex transcriptomic changes in S. frugiperda larvae in response to 1.5 mg/g plumbagin exposure, and revealed that plumbagin treatment led to aberrant expression of a large number of genes related to nutrient and energy metabolism, humoral immune response, insect cuticle protein, chitin-binding proteins, chitin synthesis and degradation, insect hormone, and xenobiotic detoxification. The qPCR results further validated the reproducibility and reliability of the transcriptomic data.DiscussionOur findings provide a valuable insight into understanding the insecticidal mechanism of the phytochemical plumbagin.

Terpene synthases (TPSs), key gatekeepers in the biosynthesis of herbivore-induced terpenes, are pivotal in the diversity of terpene chemotypes across and within plant species. Here, we constructed a gene-based pangenome of the Gossypium genus by integrating the genomes of 17 diploid and 10 tetraploid species. Within this pangenome, 208 TPS syntelog groups (SGs) were identified, comprising 2 core SGs (TPS5 and TPS42) present in all 27 analyzed genomes, 6 softcore SGs (TPS11, TPS12, TPS13, TPS35, TPS37, and TPS47) found in 25 to 26 genomes, 131 dispensable SGs identified in 2 to 24 genomes, and 69 private SGs exclusive to a single genome. The mutational load analysis of these identified TPS genes across 216 cotton accessions revealed a great number of splicing variants and complex splicing patterns. The nonsynonymous/synonymous Ka/Ks value for all 52 analyzed TPS SGs was less than one, indicating that these genes were subject to purifying selection. Of 208 TPS SGs encompassing 1795 genes, 362 genes derived from 102 SGs were identified as atypical and truncated. The structural analysis of TPS genes revealed that gene truncation is a major mechanism contributing to the formation of atypical genes. An integrated analysis of three RNA-seq datasets from cotton plants subjected to herbivore infestation highlighted nine upregulated TPSs, which included six previously characterized TPSs in G. hirsutum (AD1_TPS10, AD1_TPS12, AD1_TPS40, AD1_TPS42, AD1_TPS89, and AD1_TPS104), two private TPSs (AD1_TPS100 and AD2_TPS125), and one atypical TPS (AD2_TPS41). Also, a TPS-associated coexpression module of eight genes involved in the terpenoid biosynthesis pathway was identified in the transcriptomic data of herbivore-infested G. hirsutum. These findings will help us understand the contributions of TPS family members to interspecific terpene chemotypes within Gossypium and offer valuable resources for breeding insect-resistant cotton cultivars.

Summary: Embryos, originating from fertilized eggs, undergo continuous cell division and differentiation, accompanied by dramatic changes in transcription, translation, and metabolism. Chromatin regulators, including transcription factors (TFs), play indispensable roles in regulating these processes. Recently, the trophoblast regulator TFAP2C was identified as crucial in initiating early cell fate decisions. However, Tfap2c transcripts persist in both the inner cell mass and trophectoderm of blastocysts, prompting inquiry into Tfap2c’s function in post-lineage establishment. In this study, we delineate the dynamics of TFAP2C during the mouse peri-implantation stage and elucidate its collaboration with the key lineage regulators CDX2 and NANOG. Importantly, we propose that de novo formation of H3K9me3 in the extraembryonic ectoderm during implantation antagonizes TFAP2C binding to crucial developmental genes, thereby maintaining its lineage identity. Together, these results highlight the plasticity of the chromatin environment in designating the genomic binding of highly adaptable lineage-specific TFs and regulating embryonic cell fates.

Summary: Ferroptosis and ferritinophagy play critical roles in various disease contexts. Herein, we observed that ferroptosis and ferritinophagy were induced both in the brains of mice with diabetes mellitus (DM) and neuronal cells after high glucose (HG) treatment, as evidenced by decreases in GPX4, SLC7A11, and ferritin levels, but increases in NCOA4 levels. Interestingly, melatonin administration ameliorated neuronal damage by inhibiting ferroptosis and ferritinophagy both in vivo and in vitro. At the molecular level, we found that not only the ferroptosis inducer p53 but also the ferritinophagy mediator NCOA4 was the potential target of miR-214-3p, which was downregulated by DM status or HG insult, but was increased after melatonin treatment. However, the inhibitory effects of melatonin on ferroptosis and ferritinophagy were blocked by miR-214-3p downregulation. These findings suggest that melatonin is a potential drug for improving diabetic brain damage by inhibiting p53-mediated ferroptosis and NCOA4-mediated ferritinophagy through regulating miR-214-3p in neurons.

This study aims to investigate the effect of berberine on necroptosis in cervical H8 cells. CCK-8 assay was used to assess cell proliferation activity. The expression levels of necroptosis key markers Receptor-interacting protein kinase 1 (RIPK1), MLKL, p-MLKL, and apoptosis-related caspase-8, caspase-3 were analyzed through qRT-PCR, western blot, and immunofluorescence. Mechanistic studies were conducted using the RIPK1 kinase inhibitor necrostatin-1 (Nec-1). The results showed that berberine could inhibit H8 cell proliferation in a time- and dose-dependent manner (p

Background: The hypoglycemic effects of Chinese bayberry leaves proanthocyanidins (BLPs) have been demonstrated. It is unclear, nevertheless, whether BLPs reduced postprandial blood glucose levels by regulating glucose uptake and glucose transport.Method: This study investigated the effect of BLPs (25, 50, and 100 μg/mL) on glucose uptake and glucose transport in human intestinal epithelial cells (Caco-2 cells). The uptake of 2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose (2-NBDG) and disaccharidases activity in Caco-2 cells were measured. The glucose transport ability across the cell membrane was determined using the established Caco-2 monolayer model. The transcript and protein levels of key glucose transporters were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively.Results: The results showed that BLPs significantly decreased glucose uptake and disaccharidases activity (p < 0.05). Otherwise, BLPs treatment obviously inhibited glucose transport across the Caco-2 monolayer in both simulated-fast (5 mM glucose) and simulated-fed (25 mM glucose) conditions. It was attributed to the suppression of glucose transporter2 (GLUT2) and sodium-dependent glucose cotransporter 1 (SGLT1) by BLPs. BLPs were found to significantly downregulated the transcript level and protein expression of glucose transporters (p < 0.05). Meanwhile, the mRNA expression of phospholipase C (PLC) and protein kinase C (PKC) involved in the signaling pathway associated with glucose transport were decreased by BLPs.Conclusion: These results suggested that BLPs inhibited intestinal glucose transport via inhibiting the expression of glucose transporters. It indicated that BLPs could be potentially used as a functional food in the diet to modulate postprandial hyperglycemia.

Abstract Background Mitochondrial genomes are essential for deciphering the unique evolutionary history of seed plants. However, the rules of their extreme variation in genomic size, multi-chromosomal structure, and foreign sequences remain unresolved in most plant lineages, which further hindered the application of mitogenomes in phylogenetic analyses. Results Here, we took Dendrobium (Orchidaceae) which shows the great divergence of morphology and difficulty in species taxonomy as the study focus. We first de novo assembled two complete mitogenomes of Dendrobium wilsonii and Dendrobium henanense that were 763,005 bp and 807,551 bp long with multichromosomal structures. To understand the evolution of Dendrobium mitogenomes, we compared them with those of four other orchid species. The results showed great variations of repetitive and chloroplast-derived sequences in Dendrobium mitogenomes. Moreover, the intergenic content of Dendrobium mitogenomes has undergone expansion during evolution. We also newly sequenced mitogenomes of 26 Dendrobium species and reconstructed phylogenetic relationships of Dendrobium based on genomic mitochondrial and plastid data. The results indicated that the existence of chloroplast-derived sequences made the mitochondrial phylogeny display partial characteristics of the plastid phylogeny. Additionally, the mitochondrial phylogeny provided new insights into the phylogenetic relationships of Dendrobium species. Conclusions Our study revealed the evolution of Dendrobium mitogenomes and the potential of mitogenomes in deciphering phylogenetic relationships at low taxonomic levels.

Under the background of building a "maritime power" and developing Hainan Free Trade Zone (Port), the marine fishery in Hainan Province has developed rapidly. But at the same time, there have been a series of problems such as the destruction of ecological environment and excessive consumption of resources. Thus, to study the ecological efficiency of marine fishery in Hainan Province is of great significance to the sustainable development of Hainan Province. Based on the total sewage discharge of mariculture is taken as the undesired output, the spatial-temporal evolution characteristics of marine fishery eco-efficiency in Hainan Province from 1998 to 2019 were analyzed by using SBM model, standard deviation and coefficient of variation, and classifying the level of ecological efficiency in the coastal cities and countries of Hainan Province. The results showed that during the study period, the average value of marine fishery eco-efficiency in Hainan, which had taken into account the undesired output, was at a moderate level and fluctuating downward. While the regional differences showed a trend of fluctuating and expansion. The marine fishery eco-efficiency level in Hainan was divided into three categories: high-efficiency, medium-efficiency and low-efficiency. The efficiency categories of cities and counties are different during the same period, such as Haikou belongs to high-efficiency in the "ninth Five-Year" and "eleventh Five-Year" period, but in the "twelfth Five-Year" belongs to medium-efficiency, in the "thirteenth Five-Year" belongs to low-efficiency. It was mainly affected by the diminishing marginal benefit and the lag of ecological restoration. According to the different types of ecological efficiency in Hainan, the differentiated development strategy of the marine fishery was put forward to realize the high-quality development of the marine fishery ecological and economic system.

In the intelligent manufacturing environment, modern industry is developing at a faster pace, and there is an urgent need for reasonable production scheduling to ensure an organized production order and a dependable production guarantee for enterprises. Additionally, production cooperation between enterprises and different branches of enterprises is increasingly common, and distributed manufacturing has become a prevalent production model. In light of these developments, this paper presents the research background and current state of distributed shop scheduling. It summarizes relevant research on issues that align with the new manufacturing model, explores hot topics and concerns and focuses on the classification of distributed parallel machine scheduling, distributed flow shop scheduling, distributed job shop scheduling and distributed assembly shop scheduling. The paper investigates these scheduling problems in terms of single-objective and multi-objective optimization, as well as processing constraints. It also summarizes the relevant optimization algorithms and their limitations. It also provides an overview of research methods and objects, highlighting the development of solution methods and research trends for new problems. Finally, the paper analyzes future research directions in this field.

Abstract Super-enhancers (SEs) consist of multiple typical enhancers enriched at high density with transcription factors, histone-modifying enzymes and cofactors. Oncogenic SEs promote tumorigenesis and malignancy by altering protein-coding gene expression and noncoding regulatory element function. Therefore, they play central roles in the treatment of cancer. Here, we review the structural characteristics, organization, identification, and functions of SEs and the underlying molecular mechanism by which SEs drive oncogenic transcription in tumor cells. We then summarize abnormal SE complexes, SE-driven coding genes, and noncoding RNAs involved in tumor development. In summary, we believe that SEs show great potential as biomarkers and therapeutic targets.

Highlights A solid additive-assisted layer-by-layer (SAA-LBL) processing was developed to facilitate the inter-diffusion between polymer donor and acceptor and optimize the morphology of quasi-planar heterojunction for high-performance organic solar cells (OSCs). The pre-phase separation between fatty acid and polymer donor, easily tuned via controlling the cohesive energy, is critical to form the desired vertical phase-separation morphology. The SAA-LBL is generally applicable to various OSC systems, and enables the record efficiency of 19.02% among the binary OSCs.

Previous studies have demonstrated that L. delbrueckii plays beneficial roles in modulating the gut microbiota, enhancing the intestinal barrier, and promoting animal growth. Postbiotics have a similar or even superior effect in protecting intestinal health compared to probiotics due to their excellent stability, extended shelf life, and safety. However, the protective effects and underlying mechanism of postbiotics from L. delbrueckii in intestinal inflammation remain unclear. In this study, we demonstrated the beneficial impact of postbiotics from L. delbrueckii on intestinal health by establishing a S. Typhimurium-induced intestinal inflammation model in mice, which included inactivated bacteria and supernatant. The results revealed that the probiotics and postbiotics from L. delbrueckii increased the survival rate and body weight of S. Typhimurium-induced mice, increased the level of IL-10, and decreased the levels of TNF-α and IL-6, thereby alleviating intestinal inflammation. Meanwhile, treatment with postbiotics decreased the levels of D-LA, DAO, and LPS and promoted the expression of Occludin, ZO-1, and Claudin-1 in the serum and jejunum, suggesting an improvement in intestinal barrier function by postbiotics. Additionally, the postbiotics modulated gut microbial diversity, increased the ratio of Firmicutes and Bacteroidetes, and restored the abundance of Muribaculaceae, Lachnospiraceae_NK4a136_groups, and Alloprevotella in S. Typhimurium-infected mice. Moreover, postbiotics from L. delbrueckii promoted the expansion of intestinal stem cells (ISCs) and increased the numbers of Paneth and Goblet cells. Taken together, these data revealed the beneficial role of postbiotics from L. delbrueckii in protecting against intestinal inflammation by promoting the expansion of ISCs.

Dendrobium brymerianum Rchb. f. is a species of orchid with pharmacological interest for its potential to inhibit the growth of human lung cancer cells. The identification of the Dendrobium species is a notable problem due to morphological similarities and the limitations of universal DNA barcodes. To overcome these difficulties, this study employed complete chloroplast (cp) genome sequences as useful resources for the identification of D. brymerianum. Based on Illumina sequencing, the complete cp genomes of five D. brymerianum individuals were assembled. These genomes were in the quadripartite structure, diverse in length between 151,832 and 152,189 bp, and comprised 126 genes. Moreover, significant differences were found in the Small Single-Copy (SSC) and Large Single-Copy (LSC) regions in comparison to the Inverted Repeat (IR) regions. This study recognized hotspot regions and simple sequence repeat (SSR) loci, providing valuable insights into genetic markers. The phylogenetic relationship of Dendrobium species was discovered, highlighting the need for more precise differentiation practices. To address this, ARMS-specific primers, mainly AAob1/AAob2, confirmed strong specificity, permitting the accurate identification of D. brymerianum from other species through ARMS-qPCR. Overall, this study of D. brymerianum chloroplast genomes has generated valuable data about sequence variations, phylogenetics, and mutation dynamics. These perceptions will be valuable in future research on population genetics, taxonomy, and species identification within the Dendrobium genus.

This review provides an overview of the solid oxide fuel cell/gas turbine (SOFC/GT) hybrid system, highlighting its potential as a highly efficient and low-emission power generation technology. The operating principles and components of the SOFC/GT system, as well as the various configurations and integration strategies, are discussed. This review also examines the performance, advantages, and challenges of the SOFC/GT system, and discusses the research and development efforts aimed at improving its efficiency, reliability, and cost-effectiveness. This work provides an overview of the research conducted in the area of SOFC-based hybrid systems, which is expected to be beneficial for researchers who are interested in this area.

COVID-19 is a disease caused by a virus named SARS-CoV-2. SARS-CoV-2 is a single-stranded positive-sense RNA virus. Reverse transcription quantitative PCR (RT–qPCR) assays are the gold standard molecular test for detection of RNA viruses. The aim of this study was to construct an RNA-positive control based on MS2 phage-like particles (MS2 VLPs) to detect SARS-CoV-2 RNA. pCDFDuet-1 was used as a one-plasmid double-expression system to construct MS2 VLPs containing ssRNA of SARS-CoV-2. The sequence encoding one copy of maturase, His-tag and coat protein dimer was cloned and inserted into MCS1 of the plasmid; the fragment encoding protein N and ORF1ab from SARS-CoV-2 was cloned and inserted into MCS2. The prepared plasmid was transformed into Escherichia coli strain BL2 (DE3), and expression of the construct was induced by 1 mM isopropyl-L-thio-D-galactopyranoside (IPTG) at 30°C for 12 hours. MS2 VLPs were purified and collected with Ni-NTA affinity chromatography columns. The size and shape of the MS2 VLPs were verified by transmission electron microscopy, and the stability of MS2 VLP packaged RNA was evaluated by treatment with RNase A. Effects of storage temperature and buffer on MS2 VLP stability were also investigated. The results showed that SARS-CoV-2 MS2 VLPs could be successfully produced by this one-plasmid double-expression system. MS2 VLPs showed high stability and may be used as a positive control in molecular diagnosis of COVID-19.

As a typical chlorophenol, 2,4,6-trichlorophenol (2,4,6-TCP) is highly toxic and difficult to degrade. Here, we prepared a novel material (Cu/HAP@sBC) by combining copper-based hydroxyapatite with biochar, which removes 2,4,6-TCP via activated persulfate (PS). Cu/HAP@sBC was tested using various characterization methods. In addition, the removal of 2,4,6-TCP was up to 100% after 60 min, and the Cu/HAP@sBC/PS system had a broad pH application range (3−10). Based on the results, SO4−•, •OH, •O2−, and 1O2 were the main reactive species. Finally, the possible degradation pathways of 2,4,6-TCP were explored based on the intermediates identified by high-performance liquid chromatography-mass spectrometry (LC-MS).

Abstract Background To assess the accuracy of contrast sensitivity function (CSF) in detecting dysthyroid optic neuropathy (DON) at an early stage in thyroid-associated ophthalmopathy (TAO) patients and to examine potential factors that may be linked to early visual impairments in these individuals. Methods A total of 81 TAO patients (50 non-DON and 31 DON), and 24 control subjects participated in the study. CSF was measured with the quick CSF (qCSF) method. Optical coherence tomography angiography (OCTA) images of the ganglion cell complex layer (GCCL), superficial and deep retinal capillary plexuses (SRCP and DRCP) in a 3 mm diameter area around the macula were evaluated. Results Compared with the controls, the area under the log contrast sensitivity function (AULCSF) and SRCP density were significantly reduced in non-DON and DON patients (all P

Abstract Malnutrition is a common complication in the dialysis population, both hemodialysis and peritoneal dialysis (PD). We report our exploratory study on the characteristics of intestinal microbiota and nutritional status in PD patients. The nutritional status of our PD patients were evaluated, and their feces were collected for 16S rRNA gene V3-V4 regions amplification and high-throughput sequencing. The characteristics and differences of microbiota between the well-nourished (W) and malnourished (M) groups were compared. We studied the genera and the operational taxonomic units (OTUs) within the genus of our patients, initially comparing the malnourished and the well- nourished groups and later on reanalyzing the whole group using these OTUs. At the OTU level, 6 bacteria were significantly correlated with the serum albumin level. The abundances of 2 OTUs (OTU208 Lachnospiraceae_incertae_sedi and OTU4 Bacteroides) were more in W group. Meanwhile, 4 OTUs (OTU225 Akkermansia, OTU87 Megasphaera, OTU31 Peptostreptococcaceae_incertae_sedi and OTU168 Clostridium_sensu_strictu) displayed higher abundance among individuals in M group. Notably, the OTU168 Clostridium_sensu_stricto was the only bacteria that significantly correlated with serum albumin (r = − 0.356, P = 0.05), pre-albumin (r = − 0.399, P = 0.02), and SGA (r = 0.458, P = 0.01). The higher the OTU168 Clostridium_sensu_strictu, the lower serum albumin and pre-albumin and a higher score of SGA signifying a worse nutritional status. Our preliminary findings suggested a relationship between the nutrition status and microbiota in PD patients. Our results provide a basis for further exploration of the interactions between malnutrition and intestinal flora in PD patients with potential interventions using probiotics and prebiotics.

Abstract Autophagy dysfunction is one of the common causes of tumor formation and plays an important role in uveal melanoma (UM). However, little is known about the regulatory mechanisms of autophagy in UM. Here, we show that PTK6 can promote the proliferation, migration, and invasion of UM cells by inhibiting autophagy. SOCS3 can inhibit the proliferation, migration, and invasion of UM cells. Overexpression of SOCS3 can partially rescue the PTK6-induced promotion of UM cell proliferation, migration, and invasion. Mechanistically, PTK6 can bind to SOCS3, and SOCS3 can downregulate the expression of PTK6. Furthermore, PTK6 can upregulate the phosphorylation of mTOR to inhibit autophagy. Taken together, our findings demonstrate the functions of PTK6 and SOCS3 in UM cells and targeting the SOCS3-PTK6 signaling axis might be a novel and promising therapeutic strategy for patients with UM.

Abstract Background The widespread use of antibiotics has led to the emergence of many drug-resistant strains; thus, the development of new antibacterial drugs is essential with antimicrobial peptides becoming the focus of research. This study assessed the antibacterial effect of a novel antimicrobial peptide, named LL-1 on Escherichia coli (E.coli) by determining the minimum inhibitory concentration (MIC) and the antibacterial curve. The interaction between LL-1 and E. coli DNA was then detected by nucleic acid gel electrophoresis. The effect of LL-1 on the E. coli cell membrane was assessed by detecting the leakage of β-galactosidase, nucleic acid and protein. The influence of LL-1 on the intracellular ATP of E. coli was analysed by determining the concentration of intracellular ATP. Finally, the bacteria and colonies of E. coli treated with LL-1 were observed using scanning and transmission electron microscopy. Results The results suggested that the MIC value was 3.125 µg/ml, and the antibacterial effect was dose-dependent. LL-1 dose-dependently combined with E. coli DNA. LL-1 resulted in the leakage of intracellular β-galactosidase, nucleic acid and protein, and decreased intracellular ATP concentrations of E. coli. Two MIC of LL-1 caused E. coli to shrink, resulting in a rough surface, plasmolysis, and bacterial adhesion. Conclusion This study indicated that LL-1 had a good bactericidal effect on E. coli by mainly increasing the permeability of the cell membrane, leading to leakage of the intracellular content. This will lay the foundation for an in-depth study on the antibacterial mechanism of LL-1 against E. coli and its clinical application.

IntroductionHeavy metal-associated isoprenylated plant proteins (HIPPs) play vital roles in metal absorption, transport and accumulation in plants. However, so far, only several plant HIPPs have been functionally analyzed. In this study, a novel HIPP member OsHIPP17, which was involved in the tolerance to copper (Cu) was functionally characterized.MethodsIn this study, qRT-PCR, Yeast transgenic technology, Plant transgenic technology, ICP-MS and so on were used for research.ResultsOsHIPP17 protein was targeted to the nucleus. The Cu concentration reached 0.45 mg/g dry weight due to the overexpression of OsHIPP17 in yeast cells. Meanwhile, the overexpression of OsHIPP17 resulted in the compromised growth of Arabidopsis thaliana (Arabidopsis) under Cu stress. The root length of Oshipp17 mutant lines was also significantly reduced by 16.74- 24.36% under 25 mM Cu stress. The roots of Oshipp17 rice mutant showed increased Cu concentration by 7.25%-23.32%. Meanwhile, knockout of OsHIPP17 decreased the expression levels of OsATX1, OsZIP1, OsCOPT5 or OsHMA5, and increased the expression levels of OsCOPT1 or OsHMA4. Antioxidant enzyme activity was also reduced in rice due to the knockout of OsHIPP17. Moreover, the expression levels of cytokinin-related genes in plants under Cu stress were also affected by overexpression or knockout of OsHIPP17.DiscussionThese results implied that OsHIPP17 might play a role in plant Cu toxic response by affecting the expression of Cu transport genes or cytokinin-related genes. Simultaneously, our work may shed light on the underlying mechanism of how heavy metals affect the plant growth and provide a novel rice genetic source for phytoremediation of heavy metal-contaminated soil.

Liver fibrosis, a critical pathological feature of chronic liver diseases, arises from a multitude of pathogenic factors. Consequently, establishing an appropriate animal model to simulate liver fibrosis holds immense significance for comprehending its underlying pathogenesis. Despite the numerous methodologies available for generating liver fibrosis models, they often deviate substantially from the spontaneous age-related liver fibrosis process. In this study, compared with young (12 weeks) and middle-aged NOD/SCID mice (32 weeks), there were a large number of fibrous septum and collagen in the liver tissue of old NOD/SCID mice (43 weeks, 43 W). Immunohistochemical analysis unequivocally indicated heightened α-SMA content within the liver tissue of the 43 W mice, thereby underscoring aging’s role in triggering the epithelial-to-mesenchymal transition. In addition, SA-β-gal staining as well as P21 expression were increased, and SIRT1 and SIRT3 expression were decreased in 43 W mice. A comprehensive evaluation encompassing transmission electron microscopy and fluorescence quantitative analysis elucidated compromised mitochondrial function and reduced antioxidant capacity in hepatocytes of the 43 W mice. Furthermore, the aging process activated the pro-fibrotic TGF-β-SMAD pathway, concurrently inducing hepatocellular inflammation. The results of the present study not only validate the successful construction of a spontaneous liver fibrosis mouse model through natural aging induction but also provide initial insights into the mechanisms underpinning age-induced liver fibrosis.

Abstract Background Because chloroplast (cp) genome has more conserved structures than nuclear genome and mitochondrial genome, it is a useful tool in estimating the phylogenetic relationships of plants. With a series of researches for cp genomes, there have been comprehensive understandings about the cp genome features. The genus Bulbophyllum widely distributed in Asia, South America, Australia and other places. Therefore, it is an excellent type genus for studying the effects of geographic isolation. Results In this study, the cp genomes of nine Bulbophyllum orchids were newly sequenced and assembled using the next-generation sequencing technology. Based on 19 Asian (AN) and eight South American (SA) Bulbophyllum orchids, the cp genome features of AN clade and SA clade were compared. Comparative analysis showed that there were considerable differences in overall cp genome features between two clades in three aspects, including basic cp genome features, SSC/IRB junctions (JSBs) and mutational hotspots. The phylogenetic analysis and divergence time estimation results showed that the AN clade has diverged from the SA clade in the late Oligocene (21.50–30.12 mya). After estimating the occurrence rates of the insertions and deletions (InDels), we found that the change trends of cp genome structures between two clades were different under geographic isolation. Finally, we compared selective pressures on cp genes and found that long-term geographic isolation made AN and SA Bulbophyllum cp genes evolved variably. Conclusion The results revealed that the overall structural characteristics of Bulbophyllum cp genomes diverged during the long-term geographic isolation, and the crassulacean acid metabolism (CAM) pathway may play an important role in the Bulbophyllum species evolution.

Abstract Background Bone fibrous dysplasia is a benign disease of bone tissue dysplasia. Vision impairment is the commonest neurological complication of craniofacial fibrous dysplasia. Most of the vision loss caused by craniofacial fibrous dysplasia is usually a gradual process. Very few present with acute visual impairment as described in our case. Case presentation We report a patient with fibrous dysplasia presenting rapidly progressive visual loss in the left eye secondary to bone cyst formation. Transnasal endoscopic surgery guided by navigation with drainage and curettage of this bone cyst and orbital decompression resulted in progressive improvement in visual acuity that returned to normal 1 month post-operatively. Conclusions In cases with acute visual loss due to fibrous dysplasia, emergency surgical treatment should be considered to preserve vision. In the surgical approach, navigation-guided nasal endoscopic surgery may be preferred because of its advantages.

Abstract Background Ferula persica is one of the most important traditional medicinal plants that is used to treat various diseases such as diabetes, backache and rheumatism. The aim of the present study was to evaluate the anti‐inflammatory and wound healing potential of F. persica using stereological and molecular methods in experimental models. Methods In the present study, two wound models (circular excision and linear incision) were used. Male Wistar rats were divided into four groups (n = 16), including control, vehicle treated, treated with F. persica extract ointment (5% w/w) and treated with the reference drug (Madecassol). All the animals were treated topically once a day. The circular and linear wounds were treated for 9 and 17 days, respectively. At the end of the study, samples from wounds area were harvested for histology, stereology, immunohistochemistry and molecular assessments to determine the in vivo healing potential and anti‐inflammatory activity. Results We observed significant recovery in macroscopic evaluation of wound healing in the F. persica extract treated group compared with the control and vehicle treated groups (p 0.05, p

ObjectiveTo study the dynamic changes of local metrics in patients with toothache (TA, Toothache) in the resting state, in order to further understand the changes of central neural mechanism in patients with dental pain and its effect on cognition and emotion.MethodsThirty patients with TA and thirty matched healthy (HC) control volunteers were recruited, and resting-state functional magnetic resonance (rs-MRI) scans were performed on all subjects, and data were analyzed to compare group differences in three dynamic local indices: dynamic regional homogeneity (dReHO), dynamic low-frequency fluctuation amplitude (dALFF) and dynamic fractional low-frequency fluctuation amplitude (dfALFF). In addition, the association between dynamic local metrics in different brain regions of TA patients and scores on the Visual Analog Scale (VAS) and the Hospital Anxiety and Depression Scale (HADS) was investigated by Pearson correlation analysis.ResultsIn this study, we found that The local metrics of TA patients changed with time Compared with the HC group, TA patients showed increased dReHo values in the left superior temporal gyrus, middle frontal gyrus, precentral gyrus, precuneus, angular gyrus, right superior frontal gyrus, middle temporal gyrus, postcentral gyrus and middle frontal gyrus, increased dALFF values in the right superior frontal gyrus, and increased dfALFF values in the right middle temporal gyrus, middle frontal gyrus and right superior occipital gyrus (p < 0.01, cluster level P < 0.05). Pearson correlation analysis showed that dReHo values of left precuneus and left angular gyrus were positively correlated with VAS scores in TA group. dReHo value of right posterior central gyrus was positively correlated with HADS score (P < 0.05).ConclusionThere are differences in the patterns of neural activity changes in resting-state brain areas of TA patients, and the brain areas that undergo abnormal changes are mainly pain processing brain areas, emotion processing brain areas and pain cognitive modulation brain areas, which help to reveal their underlying neuropathological mechanisms. In the hope of further understanding its effects on cognition and emotion.

Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves proanthocyanidins (BLPs) were natural bioactive compounds in the treatment of obesity and diabetes with a unique structural characteristic. This study aimed to investigate the effect of BLPs on hepatic glucose metabolism in insulin-resistant HepG2 cells and elucidate the underlying mechanism. With the supplementation of BLPs, the glucose consumption and glucose uptake in IR-HepG2 cells were increased. BLPs promoted glycogen synthesis via up-regulating p-GSK3β and GYS2 expression, and attenuated gluconeogenesis by down-regulating PEPCK and G6Pase expression. It was attributed to the activation of PI3K/AKT signal pathway by BLPs, which was confirmed using the PI3K inhibitor LY294002. Moreover, BLPs remarkably reduced the expression of miR-29a, miR-423 and miR-122, which involved in hepatic glucose metabolism. Our results provide an insight of the hypoglycemic potential of BLPs on the hepatic glucose metabolism, suggesting that BLPs can be further used as a novel ingredient in functional food.

During the traumatic brain injury (TBI), improved expression of circulatory miR-21 serves as a diagnostic feature. Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and blood–brain barrier (BBB) permeability, reduce nerve apoptosis, restore neural function and ameliorate TBI. We evaluated the role of macrophage derived exosomes-miR-21 (M-Exos-miR-21) in disrupting BBB, deteriorating TBI, and Rg1 interventions. IL-1β-induced macrophages (IIM)-Exos-miR-21 can activate NF-κB signaling pathway and induce the expressions of MMP-1, -3 and -9 and downregulate the levels of tight junction proteins (TJPs) deteriorating the BBB. Rg1 reduced miR-21-5p content in IIM-Exos (RIIM-Exos). The interaction of NMIIA–HSP90 controlled the release of Exos-miR-21, this interaction was restricted by Rg1. Rg1 could inhibit the Exos-miR-21 release in peripheral blood flow to brain, enhancing TIMP3 protein expression, MMPs proteolysis, and restricting TJPs degradation thus protected the BBB integrity. Conclusively, Rg1 can improve the cerebrovascular endothelial injury and hold the therapeutic potential against TBI disease.

(E)-β-ocimene, a ubiquitous monoterpene volatile in plants, is emitted from flowers to attract pollinators and/or from vegetative tissues as part of inducible defenses mediated by complex signaling networks when plants are attacked by insect herbivores. Wild pear species Pyrus betuleafolia used worldwide as rootstock generally displays valuable pest-resistant traits and is a promising genetic resource for pear breeding. In the current study, transcriptional changes in this wild pear species infested with a polyphagous herbivore Spodoptera litura and the underlying molecular mechanisms were fully investigated. A total of 3,118 differentially expressed genes (DEGs) were identified in damaged pear leaf samples. Spodoptera litura larvae infestation activated complex phytohormonal signaling networks in which jasmonic acid, ethylene, brassinosteroids, cytokinin, gibberellic acid and auxin pathways were induced, whereas salicylic acid and abscisic acid pathways were suppressed. All DEGs associated with growth-related photosynthesis were significantly downregulated, whereas most DEGs involved in defense-related early signaling events, transcription factors, green leaf volatiles and volatile terpenes were significantly upregulated. The PbeOCS (GWHGAAYT028729), a putative (E)-β-ocimene synthase gene, was newly identified in P. betuleafolia transcriptome. The upregulation of PbeOCS in S. litura-infested pear leaves supports a potential role for PbeOCS in herbivore-induced plant defenses. In enzyme-catalyzed reaction, recombinant PbeOCS utilized only geranyl pyrophosphate but not neryl diphosphate, farnesyl pyrophosphate or geranylgeranyl diphosphate as a substrate, producing (E)-β-ocimene as the major product and a trace amount of (Z)-β-ocimene. Moreover, as a catalytic product of PbeOCS, (E)-β-ocimene showed repellent effects on larvae of S. litura in dual-choice bioassays. What is more, (E)-β-ocimene increased mortalities of larvae in no-choice bioassays. These findings provide an overview of transcriptomic changes in wild pears in response to chewing herbivores and insights into (E)-β-ocimene biosynthesis in pear plants, which will help elucidate the molecular mechanisms underlying pear-insect interactions.

PurposeTo quantify the retinal vessel density in thyroid-associated ophthalmology (TAO) patients with visual field (VF) defect and examine its associations with mechanical and system vascular risk factors for underlying pathogenesis of VF defect in TAO.MethodsThe cohort was composed of 62 TAO eyes (39 with VF defect and 23 without VF defect). The pulse pressure (PP), intraocular pressure (IOP), ophthalmic rectus muscular index (MI), superficial retinal capillary plexus (SRCP), radial peripapillary capillary (RPC) density, and other related parameters were measured. The associations among these factors and VF mean deviation (MD) were analyzed.ResultsIn TAO patients with VF defect, reduced RPC density, higher PP, and larger horizontal and vertical MI were found (all P < 0.03) when compared to TAO patients without VF defect. The RPC density was correlated with VF MD value (r = 0.242, P = 0.029), while SRCP density was not (P = 0.419). In univariable general estimating equation (GEE) analysis with RPC density as the outcome, PP and its fluctuation showed a significant association (both P < 0.04). In the final RPC model with multivariable GEE analysis, only PP (β = -0.082, P = 0.029) showed significance while PP fluctuation (P = 0.080) did not.ConclusionsThe elevated PP was correlated with reduced retinal peripapillary perfusion in TAO resulting in VF defect. These data suggested that the system vascular factor may be important in the pathogenesis of reduced retinal perfusion resulting in visual impairment in TAO.

PurposeWe explored whether thyroid-associated ophthalmopathy (TAO) patients without clinical signs of dysthyroid optic neuropathy (DON) would have a selective deficit mediated by S-cone.MethodsThirty-two TAO patients without clinical signs of DON (non-DON, 42.03 ± 9.59 years old) and 27 healthy controls (41.46 ± 6.72 years old) participated in this prospective, cross-sectional study. All observers were tested psychophysically after passing color screening tests and a comprehensive ocular examination. Isolated L-, M-, and S-cone contrast thresholds were measured at 0.5 cyc/deg using Gabor patches. We calculated the area under the receiver operating characteristic (ROC) curve to quantify the ability of chromatic contrast sensitivity to detect the early visual function changes in non-DON patients.ResultsS-cone contrast sensitivity in non-DON patients was found to be lower than that of healthy controls (P < 0.001), whereas the sensitivities to L- and M-cone Gabor patches were similar between these two groups (P = 0.297, 0.666, respectively). Our analysis of the ROC curve revealed that the sensitivity to S-cone had the highest index to discriminate non-DON patients from healthy controls (AUC = 0.846, P < 0.001). The deficit of S-cone was significantly correlated with muscle index in non-DON patients (R = 0.576, P = 0.001).ConclusionThere is a selective S-cone deficit in the early stage of TAO. S-cone contrast sensitivity could serve as a sensitive measure of visual impairments associated with early DON in patients with TAO.