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Background: During brain aging, disturbances in neuronal phospholipid metabolism result in impaired cognitive function and dysregulation of neurological processes. Mutations in iPLA2β are associated with neurodegenerative conditions that significantly impact brain phospholipids. iPLA2β deficiency exacerbates mitochondrial dysfunction and abnormal mitochondrial accumulation. We hypothesized that iPLA2β contributes to age-related cognitive decline by disrupting neuronal mitophagy., Methodology: We used aged wild-type (WT) mice and iPLA2β -/- mice as natural aging models to assess cognitive performance, iPLA2β expression in the cortex, levels of chemokines and inflammatory cytokines, and mitochondrial dysfunction, with a specific focus on mitophagy and the mitochondrial phospholipid profile. To further elucidate the role of iPLA2β, we employed adeno-associated virus (AAV)-mediated iPLA2β overexpression in aged mice and re-evaluated these parameters., Results: Our findings revealed a significant reduction in iPLA2β levels in the prefrontal cortex of aged brains. Notably, iPLA2β-deficient mice exhibited impaired learning and memory. Loss of iPLA2β in the PFC of aged mice led to increased levels of chemokines and inflammatory cytokines. This damage was associated with altered mitochondrial morphology, reduced ATP levels due to dysregulation of the parkin-independent mitophagy pathway, and changes in the mitochondrial phospholipid profile. AAV-mediated overexpression of iPLA2β alleviated age-related parkin-independent mitophagy pathway dysregulation in primary neurons and the PFC of aged mice, reduced inflammation, and improved cognitive function., Conclusions: Our study suggests that age-related iPLA2β loss in the PFC leads to cognitive decline through the disruption of mitophagy. These findings highlight the potential of targeting iPLA2β to ameliorate age-related neurocognitive disorders., (© 2024. The Author(s).)

Objective: The aim of this study was to investigate the relationship between circulating levels of B cell activating factor (BAFF) and the presence and severity of coronary artery disease (CAD) and acute myocardial infarction (AMI) in humans, as its biological functions in this context remain unclear., Methods: Serum BAFF levels were measured in a cohort of 723 patients undergoing angiography, including 204 patients without CAD (control group), 220 patients with stable CAD (CAD group), and 299 patients with AMI (AMI group). Logistic regression analyses were used to assess the association between BAFF and CAD or AMI., Results: Significantly elevated levels of BAFF were observed in patients with CAD and AMI compared to the control group. Furthermore, BAFF levels exhibited a positive correlation with the SYNTAX score (r = 0.3002, P < 0.0001) and the GRACE score (r = 0.5684, P < 0.0001). Logistic regression analysis demonstrated that increased BAFF levels were an independent risk factor for CAD (adjusted OR 1.305, 95% CI 1.078-1.580) and AMI (adjusted OR 2.874, 95% CI 1.708-4.838) after adjusting for confounding variables. Additionally, elevated BAFF levels were significantly associated with a high GRACE score (GRACE score 155 to 319, adjusted OR 4.297, 95% CI 1.841-10.030). BAFF exhibited a sensitivity of 75.0% and specificity of 71.4% in differentiating CAD patients with a high SYNTAX score, and a sensitivity of 75.5% and specificity of 72.8% in identifying AMI patients with a high GRACE score., Conclusion: Circulating BAFF levels serve as a valuable diagnostic marker for CAD and AMI. Elevated BAFF levels are associated with the presence and severity of these conditions, suggesting its potential as a clinically relevant biomarker in cardiovascular disease., (© 2024. The Author(s).)

Background: Drought stress restricts the growth, distribution and productivity of alfalfa (Medicago sativa L.). In order to study the response differences of alfalfa cultivars to drought stress, we previously carried out physiological and molecular comparative analysis on two alfalfa varieties with contrasting drought resistance (relatively drought-tolerant Longdong and drought-sensitive Algonquin). However, the differences in proteomic factors of the two varieties in response to drought stress still need to be further studied. Therefore, TMT-based quantitative proteomic analysis was performed using leaf tissues of the two alfalfa cultivars to identify and uncover differentially abundant proteins (DAPs)., Results: In total, 677 DAPs were identified in Algonquin and 277 in Longdong under drought stress. Subsequently, we conducted various bioinformatics analysis on these DAPs, including subcellular location, functional classification and biological pathway enrichment. The first two main COG functional categories of DAPs in both alfalfa varieties after drought stress were 'Translation, ribosomal structure and biogenesis' and 'Posttranslational modification, protein turnover, chaperones'. According to KEGG database, the DAPs of the two alfalfa cultivars after drought treatment were differentially enriched in different biological pathways. The DAPs from Algonquin were enriched in 'photosynthesis' and 'ribosome'. The pathways of 'linoleic acid metabolism', 'protein processing in endoplasmic reticulum' and 'RNA transport' in Longdong were significantly enriched. Finally, we found significant differences in DAP enrichment and expression patterns between Longdong and Algonquin in glycolysis/glycogenesis, TCA cycle, photosynthesis, protein biosynthesis, flavonoid and isoflavonoid biosynthesis, and plant-pathogen interaction pathway after drought treatment., Conclusions: The differences of DAPs involved in various metabolic pathways may explain the differences in the resistance of the two varieties to drought stress. These DAPs can be used as candidate proteins for molecular breeding of alfalfa to cultivate new germplasm with more drought tolerance to adapt to unfavorable environments., (© 2024. The Author(s).)

Background: Despite its prevalence, there is ongoing debate regarding the optimal management strategy for chronic subdural hematoma (CSDH), reflecting the variability in clinical presentation and treatment outcomes. This ambidirectional, nationwide, multicenter registry study aims to assess the efficacy and safety of multimodality treatment approaches for CSDH in the Chinese population., Methods/design: A multicenter cohort of CSDH patients from 59 participating hospitals in mainland China was enrolled in this study. The treatment modalities encompassed a range of options and baseline demographics, clinical characteristics, radiographic findings, and surgical techniques were documented. Clinical outcomes, including hematoma resolution, recurrence rates, neurological status, and complications, were assessed at regular intervals during treatment, 3 months, 6 months, 1 year, and 2 years follow-up., Result: Between March 2022 and August 2023, a comprehensive cohort comprising 2173 individuals who met the criterion was assembled across 59 participating clinical sites. Of those patients, 81.1% were male, exhibiting an average age of 70.12 ± 14.53 years. A historical record of trauma was documented in 48.0% of cases, while headache constituted the predominant clinical presentation in 58.1% of patients. The foremost surgical modality employed was the burr hole (61.3%), with conservative management accounting for 25.6% of cases. Notably, a favorable clinical prognosis was observed in 88.9% of CSDH patients at 3 months, and the recurrence rate was found to be 2.4%., Conclusion: This registry study provides critical insights into the multimodality treatment of CSDH in China, offering a foundation for advancing clinical practices, optimizing patient management, and ultimately, improving the quality of life for individuals suffering from this challenging neurosurgical condition., Trial Registration: ChiCTR2200057179., (© 2024. The Author(s).)

Background: Auxin plays an important role in plant resistance to abiotic stress. The modulation of gene expression by Auxin response factors (ARFs) and the inhibition of auxin/indole-3-acetic acid (Aux/IAA) proteins play crucial regulatory roles in plant auxin signal transduction. However, whether the stress resistance of Masson pine (Pinus massoniana), as a representative pioneer species, is related to Aux/IAA and ARF genes has not been thoroughly studied and explored., Results: The present study provides preliminary evidence for the regulatory role of the PmaIAA27 gene in abiotic stress response in Masson pine. We investigated the effects of drought and hormone treatments on Masson pine by examining the expression patterns of PmaIAA27 and PmaARF15 genes. Subsequently, we conducted gene cloning, functional testing using transgenic tobacco, and explored gene interactions. Exogenous auxin irrigation significantly downregulated the expression of PmaIAA27 while upregulating PmaARF15 in Masson pine seedlings. Moreover, transgenic tobacco with the PmaIAA27 gene exhibited a significant decrease in auxin content compared to control plants, accompanied by an increase in proline content - a known indicator of plant drought resistance. These findings suggest that overexpression of the PmaIAA27 gene may enhance drought resistance in Masson pine. To further investigate the interaction between PmaIAA27 and PmaARF15 genes, we performed bioinformatics analysis and yeast two-hybrid experiments which revealed interactions between PB1 structural region of PmaARF15 and PmaIAA27., Conclusion: The present study provides new insights into the regulatory functions of Aux/IAA and ARF genes in Masson pine. Overexpression of PmaIAA gene may have negative effects on the growth of Masson pine, but may improve the drought resistance. Therefore, this study has great application prospects., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Transcultural capacity is a key component of consolidated global public health assistance cooperation (GPHAC). The aim of this study is to investigate the transcultural capacity perceptions of public health professionals from China's disease control and prevention system after relative training in order to provide a reference for enhancing transcultural capacity during the practice of GPHAC., Methods: A cross sectional qualitative survey in which self-administrated questionnaire with 5 open ended questions was used. The questionnaire was disseminated on the completion of an online training for China's senior public health professions on transcultural capacity in GPHAC. Descriptive statistics, word frequency analysis and content analysis were used to analyze the questionnaire data., Results: Totally, 45 participants took part in this training, 25 of them voluntarily participated in this survey. The participants demonstrated the need for transcultural competence in public health services and suggested improvement in the course content arising from their wealth of knowledge and practical experience in the field. 96% of the participants considered that the training course was "very necessary" and "meaningful". The most interested topics were "Overview of transcultural adaptation and GPHAC", "Transcultural adaptation and response" and "African culture and health". The contents about "Country-specific analysis on cultural factors in public health", "rapid transcultural adaptation" and "more specific practical experiences in diverse cultural backgrounds" were suggested to be added in future training. The participants considered that transcultural capacity ensured the smooth progress of GPHAC and they both could complement each other, transcultural adaptation was the premise of gaining trust and reaching cooperation, it can be conducive to the health assistance professionals to integrate into local cultural life, facilitating their foreign assistance work to be effective and efficient, and impart experiences well. The participants hoped to put the concept into action., Conclusion: The importance of transcultural competence in GPHAC is becoming a consensus of public health professionals. Enhanced transcultural competence reflected in the attitude of public health as well as other health workers would promote GPHAC and would foster efficient emergency health response management among many countries., (© 2023. The Author(s).)

Background: As one of the microelements, nitrogen play essential roles in cereal production. Although the use of chemical fertilizers has significantly improved the yield of wheat, it has also caused increasingly adverse environmental pollution. Revealing the molecular mechanism manipulating wheat nitrogen use efficiency (NUE), and cultivating wheat germplasms with high nitrogen use efficiency has become important goals for wheat researchers. In this study, we investigated the physiological and transcriptional differences of three wheat cultivars with different NUE under low nitrogen stress., Results: The results showed that, under low nitrogen conditions, the activities of nitrogen metabolism-related enzymes (GS, NR, GDH), antioxidant enzymes (SOD, POD, CAT) and soluble protein contents of ZM366 (high NUE cultivar) were higher than those of JD8 (low NUE cultivar). The hybrid cultivar of ZM366 and JD8 showed mid-parent or over-parent heterosis. Transcriptome analysis revealed that 'alanine, aspartate and glutamate metabolism', 'terpenoid backbone biosynthesis' and 'vitamin B6 metabolism' pathways play key roles in nitrogen use efficiency in wheat. The significant enhancement of the 'Calvin cycle' and 'photorespiration' in ZM366 contributed to its higher level of carbon metabolism under low nitrogen stress, which is an important attribute differs from the other two varieties. In addition, the activation of ABA signal transduction and biosynthesis pathways also helps to maintain NUE under low- nitrogen conditions. Moreover, bHLH transcription factors were also found to play a positive role in wheat NUE., Conclusions: In conclusion, these results enriched our knowledge of the mechanism of wheat NUE, and provided a theoretical basis for improving wheat NUE and breeding new cultivars., (© 2022. The Author(s).)

Background: Innate lymphoid cell (ILC) dysfunction is involved in numerous immune diseases, but this has not been demonstrated in Henoch-Schonlein purpura (HSP). This study aimed to investigate whether ILC dysfunction or imbalance participate in the pathogenesis of HSP., Methods: This was a prospective study in patients with HSP who were hospitalized at the Children's Hospital of Soochow University from June to December 2019. Age- and sex-matched controls were also enrolled. ILC subsets and lymphocyte subpopulations were determined by flow cytometry. The transmission immune turbidimetric method also facilitated the exploration of correlations between ILC subset frequency and lymphocyte subpopulation, as well as serum IgA in HSP patients., Results: Fifty-one patients with HSP and 22 control patients were included. There were no differences in age and sex between the two groups. Compared with controls, patients with HSP had higher ILCs in relation to lymphocytes (P = 0.036), higher ILCs in relation to PBMCs (P = 0.026), higher ILC1s (P < 0.001), lower ILC3s (P < 0.05), and higher ILC1/ILC3 ratio (P < 0.001). Sixteen patients underwent routine therapy combined with methylprednisolone for 7-10 days; ILC1s were significantly decreased (P < 0.001) and ILC3s were increased (P = 0.033), and ILC1/ILC3 was significantly decreased (P < 0.001). Compared with the controls, the ratios of ILCs/lymphocytes and ILCs/PBMC were higher in patients in the arthritis and mixed groups (all P < 0.05). ILC1 were elevated in the purpura, arthritis, abdominal, and mixed groups (P = 0.027, P = 0.007, P < 0.001, and P < 0.001, respectively). ILC1/ILCs were positively correlated with CD3 + CD8 + T lymphocytes (r = 0.3701, P = 0.0075). The level of IgA did not correlate with ILCs., Conclusions: Higher circulating ILC1s and lower circulating ILC3s appear to be involved in the pathogenesis of HSP., (© 2022. The Author(s).)

Background: Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH., Methods: The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days., Discussion: This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH., Trial Registration: ChiCTR, ChiCTR1900021659 . Registered on 3 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=36157 ., (© 2021. The Author(s).)

Background: We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy., Methods: Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively., Results: ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA., Conclusions: We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages., (© 2021. The Author(s).)

Background: DNA sequence alignment is a common first step in most applications of high-throughput sequencing technologies. The accuracy of sequence alignments directly affects the accuracy of downstream analyses, such as variant calling and quantitative analysis of transcriptome; therefore, rapidly and accurately mapping reads to a reference genome is a significant topic in bioinformatics. Conventional DNA read aligners map reads to a linear reference genome (such as the GRCh38 primary assembly). However, such a linear reference genome represents the genome of only one or a few individuals and thus lacks information on variations in the population. This limitation can introduce bias and impact the sensitivity and accuracy of mapping. Recently, a number of aligners have begun to map reads to populations of genomes, which can be represented by a reference genome and a large number of genetic variants. However, compared to linear reference aligners, an aligner that can store and index all genetic variants has a high cost in memory (RAM) space and leads to extremely long run time. Aligning reads to a graph-model-based index that includes all types of variants is ultimately an NP-hard problem in theory. By contrast, considering only single nucleotide polymorphism (SNP) information will reduce the complexity of the index and improve the speed of sequence alignment., Results: The SNP-aware alignment tool (SALT) is a fast, memory-efficient, and SNP-aware short read alignment tool. SALT uses 5.8 GB of RAM to index a human reference genome (GRCh38) and incorporates 12.8M UCSC common SNPs. Compared with a state-of-the-art aligner, SALT has a similar speed but higher accuracy., Conclusions: Herein, we present an SNP-aware alignment tool (SALT) that aligns reads to a reference genome that incorporates an SNP database. We benchmarked SALT using simulated and real datasets. The results demonstrate that SALT can efficiently map reads to the reference genome with significantly improved accuracy. Incorporating SNP information can improve the accuracy of read alignment and can reveal novel variants. The source code is freely available at https://github.com/weiquan/SALT ., (© 2021. The Author(s).)

Background: Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to detect the serum levels of Th (T helper) cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α) in cSLE and healthy controls, and then to elucidate their association with clinical manifestations, disease activity and laboratory parameters. In order to provide clues for early diagnosis and timely intervention treatment of cSLE patients., Methods: A total of 33 children with cSLE and 30 healthy children were enrolled in this study. Children in the cSLE group were classified into the inactive or active cSLE group according to their SLE disease activity index 2000 (SLEDAI-2 K) score. Th cytokine profiles in the peripheral blood were detected and analysed., Results: Levels of IL-2, IL-10 and IL-21 in the cSLE group were significantly higher than those in the healthy control group (P < 0.05, P < 0.01 and P < 0.01, respectively). Expression of IL-2, IL-10 and IL-21 in the active cSLE group was significantly higher than that in the healthy control group (P < 0.05, P < 0.01 and P < 0.05, respectively), but that of IL-22 expression was markedly lower in the active cSLE group than in the healthy control group (P < 0.001). IL-21 in the inactive SLE group was significantly higher than that in the healthy control group (P < 0.05), and levels of IL-2 and IL-10 in the active cSLE group were significantly higher than those in the inactive cSLE group (P < 0.01 and P < 0.05). In-depth analysis showed that after excluding age, gender and drug interference, the levels of IL-2 (P < 0.05), IL-6 (P < 0.05) and IL-10 (P < 0.05) were still positively correlated with SLEDAI-2 K scores. However, the levels of IL-6 (P < 0.05) and IFN- γ (P < 0.05) were still negatively correlated with CD4 + /CD8 + , and the concentration of IL-6 (P < 0.05) was still positively correlated with the occurrence of nephritis., Conclusion: This study provides a theoretical basis for the discovery of effective methods to regulate imbalance in T lymphocyte subsets in cSLE, which may lead to new approaches for the diagnosis of cSLE.

Background: Autophagy is a highly conserved homeostatic process in the human body that is responsible for the elimination of aggregated proteins and damaged organelles. Several autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer (PCa). Also, miRNAs have been proven to modulate autophagy by targeting some ARGs. However, their potential role in PCa still remains unclear., Methods: An univariate Cox proportional regression model was used to identify 17 ARGs associated with the overall survival (OS) of PCa. Then, a multivariate Cox proportional regression model was used to construct a 6 autophagy-related prognostic genes signature. Patients were divided into low-risk group and high-risk group using the median risk score as a cutoff value. High-risk patients had shorter OS than low-risk patients. Furthermore, the signature was validated by ROC curves. Regarding mRNA and miRNA, 12 differentially expressed miRNAs (DEMs) and 1073 differentially expressed genes (DEGs) were detected via the GEO database. We found that miR-205, one of the DEMs, was negatively regulated the expression of ARG (NKX2-3). Based on STRING analysis results, we found that the NKX2-3 was moderately related to the part of genes among the 6 autophagy-related genes prognostic signature. Further, NKX 2-3 was significantly correlated with OS and some clinical parameters of PCa by cBioProtal. By gene set enrichment analysis (GSEA). Lastly, we demonstrated that the association between NKX2-3 and tumor mutation burden (TMB) and PDCD1 (programmed cell death 1) of PCa., Results: We identified that the six ARGs expression patterns are independent predictors of OS in PCa patients. Furthermore, our results suggest that ARGs and miRNAs are inter-related. MiR-205 was negatively regulated the expression of ARG (NKX2-3). Further analysis demonstrated that NKX2-3 may be a potential biomarker for predicting the efficacy of anti-PD-1 therapy in PCa., Conclusions: The current study may offer a novel autophagy-related prognostic signature and may identify a promising miRNA-ARG pathway for predicting the efficacy of anti-PD-1 therapy in PCa.

Background: Acute kidney injury (AKI) is independently related to the adverse outcome of septic shock, but it lacks effective early predictors. Renal anginal index (RAI) was used to predict subsequent severe AKI (AKIs) in critically ill patients. The application of RAI in children with septic shock has not been reported. This study aims to evaluate the efficacy of early RAI in predicting subsequent AKIs within 3 days after PICU admission in children with septic shock by comparing with early fluid overload (FO) and early creatinine elevation., Methods: Sixty-six children admitted to PICU aged 1 month to 16 years old, with septic shock from January 2016 to December 2019 were analyzed retrospectively. According to the 2012 Kidney Disease Improving Global outcomes (KDIGO) criteria, AKIs was defined by the KDIGO stage ≥2 within 3 days after PICU admission. Early RAI positive (RAI+) was defined as RAI ≥ 8 within 12 h of PICU admission. Any elevation of serum creatinine (SCr) over baseline within 12 h after PICU admission was denoted as "Early SCr > base". Early FO positive (FO+) was defined as FO > 10% within 24 h of PICU admission., Results: Of 66 eligible cases, the ratio of early RAI+, early SCr > base, early FO+ was 57.57, 59.09 and 16.67% respectively. The incidence of AKIs in early RAI+ group (78.94%) was higher than that in early RAI- group (21.42%) (p = 0.04), and there was no significant difference compared with the early FO+ group (71.79%) and early SCr > base group (81.82%) (P > 0.05). After adjustment for confounders, early RAI+ was independently associated with the occurrence of AKIs within 3 days (OR 10.04, 95%CI 2.39-42.21, p < 0.01). The value of early RAI+ (AUC = 0.78) to identify patients at high risk of AKIs was superior to that of early SCr > base (AUC = 0.70) and early FO+ (AUC = 0.58). A combination of serum lactate with early RAI+ improved the predictive performance for assessing AKIs (AUC = 0.83)., Conclusions: Early RAI could be used as a more convenient and effective index to predict the risk of AKIs in children with septic shock within 3 days. Early RAI+ combined with serum lactate improved the predictive performance for assessing AKIs.

Background: Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear., Methods: CRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils., Results: Our study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition. Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor-β1 (TGF-β1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF-β1 axis., Conclusion: Our study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.

Subdural haematomas (SDHs) are characterized by rapidly or gradually accumulated haematomas between the arachnoid and dura mater. The mechanism of haematoma clearance has not been clearly elucidated until now. The meningeal lymphatic vessel (mLV) drainage pathway is a novel system that takes part in the clearance of waste products in the central nervous system (CNS). This study aimed to explore the roles of the mLV drainage pathway in SDH clearance and its impacting factors. We injected FITC-500D, A488-fibrinogen and autologous blood into the subdural space of mice/rats and found that these substances drained into deep cervical lymph nodes (dCLNs). FITC-500D was also observed in the lymphatic vessels (LYVE+) of the meninges and the dCLNs in mice. The SDH clearance rate in SDH rats that received deep cervical lymph vessel (dCLV) ligation surgery was significantly lower than that in the control group, as evaluated by haemoglobin quantification and MRI scanning. The drainage rate of mLVs was significantly slower after the SDH model was established, and the expression of lymphangiogenesis-related proteins, including LYVE1, FOXC2 and VEGF-C, in meninges was downregulated. In summary, our findings proved that SDH was absorbed through the mLV drainage pathway and that haematomas could inhibit the function of mLVs.

Background: The plant homeodomain (PHD) finger is a Cys 4 HisCys 3 -type zinc finger which promotes protein-protein interactions and binds to the cis-acting elements in the promoter regions of target genes. In Medicago truncatula, five PHD homologues with full-length sequence were identified. However, the detailed function of PHD genes was not fully addressed., Results: In this study, we characterized the function of MtPHD6 during plant responses to drought stress. MtPHD6 was highly induced by drought stress. Ectopic expression of MtPHD6 in Arabidopsis enhanced tolerance to osmotic and drought stresses. MtPHD6 transgenic plants exhibited decreased water loss rate, MDA and ROS contents, and increased leaf water content and antioxidant enzyme activities under drought condition. Global transcriptomic analysis revealed that MtPHD6 reprogramed transcriptional networks in transgenic plants. Expression levels of ABA receptor PYR/PYLs, ZINC FINGER, AP2/EREBP and WRKY transcription factors were mainly up-regulated after transformation of MtPHD6. Interaction network analysis showed that ZINC FINGER, AP2/EREBP and WRKY interacted with each other and downstream stress induced proteins., Conclusions: We proposed that ZINC FINGER, AP2/EREBP and WRKY transcription factors were activated through ABA dependent and independent pathways to increase drought tolerance of MtPHD6 transgenic plants.

Background: Primary cutaneous malignant melanoma is a cancer of the pigment cells of the skin, some of which are accompanied by BRAF mutation. Melanoma incidence and mortality rates have been rising around the world. As the current knowledge about pathogenesis, clinical and genetic features of cutaneous melanoma is not very clear, we aim to use bioinformatics to identify the potential key genes involved in the expression and mutation status of BRAF., Methods: Firstly, we used UCSC public hub datasets of melanoma (Lin et al., Cancer Res 68(3):664, 2008) to perform weighted genes co-expression network analysis (WGCNA) and differentially expressed genes analysis (DEGs), respectively. Secondly, overlapping genes between significant gene modules and DEGs were screened and validated at transcriptional levels and overall survival in TCGA and GTEx datasets. Lastly, the functional enrichment analysis was accomplished to find biological functions on the web-server database., Results: We performed weighted correlation network and differential expression analyses, using gene expression data in melanoma samples. We identified 20 genes whose expression was correlated with the mutation status of BRAF. For further validation, three of these genes (CYR61, DUSP1, and RNASE4) were found to have similar expression patterns in skin tumors from TCGA compared with normal skin samples from GTEx. We also found that weak expression of these three genes was associated with worse overall survival in the TCGA data. These three genes were involved in the nucleic acid metabolic process., Conclusion: In this study, CYR61, DUSP1, and RNASE4 were identified as potential genes of interest for future molecular studies in melanoma, which would improve our understanding of its causes and underlying molecular events. These candidate genes may provide a promising avenue of future research for therapeutic targets in melanoma.

Background: Bone marrow stromal cells (BMSCs) are extensively used in regeneration therapy and cytology experiments simulate how BMSCs respond to radiation. Due to the small number and the heterogeneity of primary isolated BMSCs, extensive in vitro expansion is usually required before application, which affects the cellular characteristics and gene expression of BMSCs. However, whether the radiation response of BMSCs changes during in vitro expansion is unclear., Methods: In this study, BMSCs were passaged in vitro and irradiated at passage 6 (P6) and passage 10 (P10). Then, apoptosis, the cell cycle, senescence, the cytokine secretion and the gene expression profile were analysed for the P6, P10, and non-irradiated (control) BMSCs at different post-irradiation time points., Results: The P6 BMSCs had a lower percentage of apoptotic cells than the P10 BMSCs at 24 and 48 h post-irradiation but not compared to that of the controls at 2 and 8 h post-irradiation. The P6 BMSCs had a lower percentage of cells in S phase and a higher percentage in G1 phase than the P10 BMSCs at 2 and 8 h post-irradiation. The radiation had similar effects on the senescent cell level and impaired immunomodulation capacity of the P6 and P10 BMSCs. Regardless of whether they were irradiated, the P6 and P10 BMSCs always expressed a distinctive set of genes. The upregulated genes were enriched in pathways including the cell cycle, DNA replication and oocyte meiosis. Then, a subset of conserved irradiation response genes across the BMSCs was identified, comprising 12 differentially upregulated genes and 5 differentially downregulated genes. These genes were especially associated with the p53 signaling pathway, DNA damage and DNA repair. Furthermore, validation experiments revealed that the mRNA and protein levels of these conserved genes were different between the P6 and P10 BMSCs after irradiation. Weighted gene co-expression network analysis supported these findings and further revealed the effects of cell passage on the irradiation response in BMSCs., Conclusion: The results indicated that cell passage in vitro affected the irradiation response of BMSCs via molecular mechanisms that mediated differences in apoptosis, the cell cycle, senescence and the cytokine secretion. Thus, accurate cell passage information is not only important for transplantation therapy but also for future studies on the radiation response in BMSCs.

Background: Schizophrenia is a kind of serious mental illness. Due to the lack of an objective physiological data supporting and a unified data analysis method, doctors can only rely on the subjective experience of the data to distinguish normal people and patients, which easily lead to misdiagnosis. In recent years, functional Near-Infrared Spectroscopy (fNIRS) has been widely used in clinical diagnosis, it can get the hemoglobin concentration through the variation of optical intensity., Methods: Firstly, the prefrontal brain networks were constructed based on oxy-Hb signals from 52-channel fNIRS data of schizophrenia and healthy controls. Then, Complex Brain Network Analysis (CBNA) was used to extract features from the prefrontal brain networks. Finally, a classier based on Support Vector Machine (SVM) is designed and trained to discriminate schizophrenia from healthy controls. We recruited a sample which contains 34 healthy controls and 42 schizophrenia patients to do the one-back memory task. The hemoglobin response was measured in the prefrontal cortex during the task using a 52-channel fNIRS system., Results: The experimental results indicate that the proposed method can achieve a satisfactory classification with the accuracy of 85.5%, 92.8% for schizophrenia samples and 76.5% for healthy controls. Also, our results suggested that fNIRS has the potential capacity to be an effective objective biomarker for the diagnosis of schizophrenia., Conclusions: Our results suggested that, using the appropriate classification method, fNIRS has the potential capacity to be an effective objective biomarker for the diagnosis of schizophrenia.

Background: Annexins are an evolutionarily conserved multigene family of calcium-dependent phospholipid binding proteins that play important roles in stress resistance and plant development. They have been relatively well characterized in model plants Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), but nothing has been reported in hexaploid bread wheat (Triticum aestivum) and barely (Hordeum vulgare), which are the two most economically important plants., Results: Based on available genomic and transcriptomic data, 25 and 11 putative annexin genes were found through in silico analysis in wheat and barley, respectively. Additionally, eight and 11 annexin genes were identified from the draft genome sequences of Triticum urartu and Aegilops tauschii, progenitor for the A and D genome of wheat, respectively. By phylogenetic analysis, annexins in these four species together with other monocots and eudicots were classified into six different orthologous groups. Pi values of each of Ann1-12 genes among T. aestivum, T. urartu, A. tauschii and H. vulgare species was very low, with the exception of Ann2 and Ann5 genes. Ann2 gene has been under positive selection, but Ann6 and Ann7 have been under purifying selection among the four species in their evolutionary histories. The nucleotide diversities of Ann1-12 genes in the four species were 0.52065, 0.59239, 0.60691 and 0.53421, respectively. No selective pressure was operated on annexin genes in the same species. Gene expression patterns obtained by real-time PCR and re-analyzing the public microarray data revealed differential temporal and spatial regulation of annexin genes in wheat under different abiotic stress conditions such as salinity, drought, cold and abscisic acid. Among those genes, TaAnn10 is specifically expressed in the anther but fails to be induced by low temperature in thermosensitive genic male sterile lines, suggesting that specific down-regulation of TaAnn10 is associated with conditional male sterility in wheat., Conclusions: This study analyzed the size and composition of the annexin gene family in wheat and barley, and investigated differential tissue-specific and stress responsive expression profiles of the gene family in wheat. These results provided significant information for understanding the diverse roles of plant annexins and opened a new avenue for functional studies of cold induced male sterility in wheat.

Background: Many patients who survive a myocardial infarction (MI) remain at risk of sudden cardiac death despite revascularization and optimal medical treatment. We used the modified moving average (MMA) method to assess the utility of T-wave alternans (TWA) and heart rate turbulence (HRT) as risk markers in MI patients with or without diabetes mellitus (DM)., Methods: We prospectively enrolled 248 consecutive patients: 96 with MI (post-MI patients); 77 MI with DM (post-MI + DM patients); 75 controls without cardiovascular disease (group control). Both TWA and HRT were measured on ambulatory electrocardiograms (AECGs). HRT was assessed by two parameters ─ turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO ≥0% and TS ≤2.5 ms/R-R interval were met. The endpoint was cardiac mortality., Results: TWA values differed significantly between MI and controls. Post-MI + DM patients had higher TWA values than post-MI patients (58 ± 21 μV VS 52 ± 18 μV, P = 0.029). Impaired HRT--increased TO and decreased TS were observed in MI patients with or without DM. During follow-up of 578 ± 146 days, cardiac death occurred in ten patients and three of them suffered sudden cardiac death (SCD). Multivariate analysis determined that a HRT-positive outcome [HR (95% CI): 5.01, 1.33-18.85; P = 0.017], as well as the combination of abnormal TWA (≥47 μV) and positive HRT had significant association with the endpoint [HR (95% CI): 9.08, 2.21-37.2; P = 0.002)]., Conclusion: This study indicates that AECGs-based TWA and HRT can predict cardiac mortality in MI patients with or without DM. Combined analysis TWA and HRT may be a convenient and useful method of identifying patients at high risk for cardiovascular death.

Background: Several studies indicated that Erythropoietin (Epo) may provide remarkable neuroprotection in some neurological diseases. It also showed the significant decrease of Epo immunoreactivity in the cerebral cortex and hippocampus in aged rats, suggesting the role of Epo in the pathogenesis of age-related neurodegenerative diseases such as AD., Methods: The protective effect of Epo was studied in differentiated PC12 cells treated with Abeta. The viability of the cells, the apoptosis of the cells and the level of Bax, Bcl-2, cleaved caspase-3 and cleaved PARP expression were detected by MTT, Hoechst 33258 staining and Western blotting respectively., Results: 20 μM Abeta (25-35) could induce a decreased viability and a increased apoptosis in PC12 cell in a time-dependent manner. However, 20 μM Abeta (35-25) had no effect on cell viability and apoptosis. Western blot analysis also showed that Abeta(25-35) treatment could decrease the expression of Bcl-2 (P < 0.05) and increase the expression of Bax (P < 0.05), Cleaved casapase-3 (P < 0.05), and Cleaved PARP (P < 0.05). The pretreatment of Epo could effectively reverse all the above changes induced by Abeta(25-35) (P < 0.05). Furthermore, the protective effect of Epo could be blocked by PI3K inhibitor LY294002 (P < 0.05)., Conclusions: Epo prevented cell injuries in PC12 cells exposed to the Abeta(25-35) and this effect may depend on the PI3K⁄Akt pathway. Our study provided an important evidence for the potential application of Epo in the therapy of Alzheimer's disease.

Background: China Yangtze Three Gorges Project (TGP) is one of the biggest construction projects in the world. The areas around the Three Gorge Dam has a history of tertian malaria and subtertian malaria epidemic, but there are no overall data about malaria epidemics before the completion of the project. The objective of this study was to get a reliable baseline on malaria infection in the Yangtze River Three Gorges reservoir area and to provide reference data for future studies about the impact of the project on malaria epidemics., Methods: Two surveys of malaria infection were carried out in area, at six-month intervals in May and October 2008. About 3,600 dual specimens blood film samples for parasite diagnosis and filter paper blood spots for serology (using the immunofluorescence antibody test) were collected from the general population, including school populations, whenever possible., Results: The overall percentage of positive response of the same population during post-transmission periods was about twice (1.40/0.72) of that in pre-transmission. Positive individuals under 15 years of age were detected in all the localities., Conclusion: A certain extent of malaria infection existed in this area. Additional studies are needed to determine the length of malaria experience, and chemotherapeutic intervention as well as the distribution of main vectors for transmission in this area.