Traumatic brain injury (TBI) has increased in rank among traumatic injuries worldwide. Traumatic brain injury is a serious obstacle given that its complex pathology represents a long-term process. Recently, systems biology strategies such as metabolomics to investigate the multifactorial nature of TBI have facilitated attempts to find biomarkers and probe molecular pathways for its diagnosis and therapy.

Axial myopia is the most common type of myopia. However, due to the high incidence of myopia in Chinese children, few studies estimating the physiological elongation of the ocular axial length (AL), which does not cause myopia progression and differs from the non-physiological elongation of AL, have been conducted. The purpose of our study was to construct a machine learning (ML)-based model for estimating the physiological elongation of AL in a sample of Chinese school-aged myopic children.

Microglial inflammation plays an important part in the progression of multiple neurological diseases, including neurodegenerative diseases, stroke, depression, and traumatic encephalopathy. Here, we aimed to explore the role of pterostilbene (PTE) in the microglial inflammatory response and subsequent damage of cocultured neural cells and partially explain the underlying mechanisms. In the coculture system of lipopolysaccharide-activated BV-2 microglia and SH-SY5Y neuroblastoma, PTE (only given to BV-2) exhibited protection on SH-SY5Y cells, evidenced by improved SH-SY5Y morphology and viability and LDH release. It also attenuated SH-SY5Y apoptosis and oxidative stress, evidenced by TUNEL and DCFH-DA staining, as well as MDA, SOD, and GSH levels. Moreover, PTE upregulated SIRT-1 expression and suppressed acetylation of NF-κB p65 subunit in BV-2 microglia, thus decreasing the inflammatory factors, including TNF-α and IL-6. Furthermore, the effects above were reversed by SIRT-1 inhibitor EX527. These results suggest that PTE reduces the microglia-mediated inflammatory response and alleviates subsequent neuronal apoptosis and oxidative injury via increasing SIRT-1 expression and inhibiting the NF-κB signalling pathway.

To accelerate wound healing through promoting vascularization by using reactive oxygen species (ROS)-responsive nanoparticles loaded with stromal cell-derived factor-1α(SDF-1α).

According to previous research studies, warfarin can be detected in human bile after oral administration. Ferulic acid (FA) is the main bioactive component of many Chinese herbs for the treatment of cardiovascular disease. To elucidate the effects of FA on the pharmacokinetics of warfarin in rats after biliary drainage is necessary. Twenty rats were randomly divided into four groups: Group 1 (WN): healthy rats after the administration of warfarin sodium, Group 2 (WO): a rat model of biliary drainage after the administration of warfarin sodium, Group 3 (WFN): healthy rats after the administration of warfarin sodium and FA, and Group 4 (WFO): a rat model of biliary drainage after the administration of warfarin sodium and FA. Blood samples were collected at different time points after administration. The concentrations of blood samples were determined by ultraperformance liquid chromatography-tandem mass spectrometry. Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software. The pharmacokinetic parameters showed a significant difference between the WN and WO groups, the WO group showed a decrease of 51% and 41.6% in area under the curve from 0 to time (AUC0- t ) and peak plasma concentration (C max), respectively, whereas time to C max (T max) was delayed 3.27 folds. There were significant differences between the WFO and WFN groups, the WFO group showed a decrease of 63.8% and 70% in AUC0- t and C max, respectively; the delay in T max between the WN and WFN groups (mean, from 132-432 minutes) was significantly different; the mean retention time from 0 to time (MRT0- t ) between the WO and WFO groups (mean, from 718.31-606.13 minutes) also showed a significant difference. Enterohepatic circulation markedly influences the disposition of warfarin in rats, and FA significantly affected the warfarin disposition in rat plasma.

Peroxisome proliferator-activated receptor γ2 (PPARγ2) is a nuclear hormone receptor of ligand-dependent transcription factor with a key role in adipogenesis and insulin sensitization in diabetes mellitus. In this study, we investigated genetic variants in PPARγ2 promoter, its association with gestational diabetes mellitus (GDM), and its molecular regulation. PPARγ2 promoter and start codon (-2,091 to +82 bp) from 400 pregnancies with GDM and 400 gestational-age matched control pregnancies were sequenced. Association and linkage disequilibrium of the identified polymorphisms with GDM was determined. ChIP-seq, gene silencing, and dual-luciferase reporter assays were performed to confirm transcription factor binding sites and promoter activity of the variants. Transfection experiments were carried out to determine the effects of variants on gene expression and adipogenesis. Among 15 variants identified, 7 known variants were not significantly associated with the risk of GDM (odds ratio: 0.710-1.208, 95% confidence interval: 0.445-0.877 to 1.132-1.664, P > 0.05) while linkage disequilibrium was significant (D' > 0.7, R2 > 0.9). However, T-A-A-T-G haplotype was not significantly associated with GDM (χ2 = 2.461, P = 0.117). Five rare variants and 3 novel variants (rs948820149, rs1553638909, and rs1553638903) were only found in GDM. Transcription factor glucocorticoid receptor β (GRβ) bound to -807A/C (rs948820149) and knockdown of GRβ suppressed PPARγ2 promoter activity. This mutation significantly down-regulated PPARγ2 expression and alleviated adipogenesis. In conclusion, a novel -807A/C in PPARγ2 promoter was identified in Chinese women with GDM and the mutation affected GRβ binding and transcription of PPARγ2 for adipogenesis.

Microfluidic focusing of particles (both synthetic and biological), which enables precise control over the positions of particles in a tightly focused stream, is a prerequisite step for the downstream processing, such as detection, trapping and separation. In this study, we propose a novel hydrodynamic focusing method by taking advantage of open v-shaped microstructures on a glass substrate engraved by femtosecond pulse (fs) laser. The fs laser engraved microstructures were capable of focusing polystyrene particles and live cells in rectangular microchannels at relatively low Reynolds numbers (Re). Numerical simulations were performed to explain the mechanisms of particle focusing and experiments were carried out to investigate the effects of groove depth, groove number and flow rate on the performance of the groove-embedded microchannel for particle focusing. We found out that 10-µm polystyrene particles are directed toward the channel center under the effects of the groove-induced secondary flows in low-Re flows, e.g. Re < 1. Moreover, we achieved continuous focusing of live cells with different sizes ranging from 10 to 15 µm, i.e. human T-cell lymphoma Jurkat cells, rat adrenal pheochromocytoma PC12 cells and dog kidney MDCK cells. The glass grooves fabricated by fs laser are expected to be integrated with on-chip detection components, such as contact imaging and fluorescence lifetime-resolved imaging, for various biological and biomedical applications, where particle focusing at a relatively low flow rate is desirable.

Portulaca oleracea is an important and widely distributed medicinal and edible plant, which has great economic value in the medical and food industries in the whole world. The complete chloroplast genome of Portulaca oleracea was found to possess a total length 156,533 bp and had the circular structure. It was the typical quadripartite structure the same as many plants, including 87,437 bp large single-copy region (LSC), 18,096 bp small single-copy region (SSC) of and a pair of 25,500 bp inverted repeat (IR) regions. The total of 132 genes was successfully annotated, which contained 87 protein-coding genes, 37 transfer RNA genes, and eight ribosomal RNA genes. Nineteen genes were found in one of IR, which included eight protein-coding gene, seven tRNA genes, and four rRNA genes. The overall nucleotide composition of chloroplast genome sequence is: 31.5% (A), 32.1% (T), 18.5% (C), 17.9% (G), and the total GC content of 36.4%. The phylogenetic analysis result showed that Portulaca oleracea was close to Carnegiea gigantean in the phylogenetic relationship by the neighbor-joining (NJ) method in this study.

Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice.

In recent years, many people have shown an excess of fat accumulation. Known as obesity, this lesion poses an increased risk for multiple diseases, such as endocrine disease, diabetes, and cancer, and has reached epidemic proportions. Accompanied by the development of obesity, concern over body image and weight loss behavior is a growing social problem and public health threat, causing concern for many health professionals. However, the consequences of rapid weight loss remain largely unclear. Here, we applied an integrated proteomics and metabolomics analysis to investigate the effects of dieting on the proteins and metabolites in obese rabbits. Our study revealed that 343 differentially expressed proteins (136 upregulated and 207 downregulated) and 150 differentially expressed metabolites (91 upregulated and 59 downregulated) were identified. These molecules are mainly involved in the biological processes, including amino acid metabolism, lipid metabolism, and membrane and cytoskeleton reconstruction. The integrated analysis found that mevalonic acid, arachidonic acid, 15(S)-HpETE, cholecalciferol, hydrocortisone, lipoxin B4, lithocholic acid, etc. were associated with multiple pathways, and they may be the key factors to fight inflammation induced by a high-fat diet (HFD). Overall, this study provides further insight into the consequences of dieting-mediated weight loss and may contribute to the prevention and treatment of obesity.

A high-fat diet (HFD) is widely recognized as a significant modifiable risk for insulin resistance, inflammation, Type 2 diabetes, atherosclerosis and other metabolic diseases. However, the biological mechanism responsible for key metabolic disorders in the PAT of rabbits subject to HFD remains unclear. Here, untargeted metabolomics (LC-MS/MS) combined with liquid chromatography (LC) and high-resolution mass spectrometry (MS) were used to evaluate PAT metabolic changes. Histological observations showed that the adipocytes cells and density of PAT were significantly increased in HFD rabbits. Our study revealed 206 differential metabolites (21 up-regulated and 185 down-regulated); 47 differential metabolites (13 up-regulated and 34 down-regulated), comprising mainly phospholipids, fatty acids, steroid hormones and amino acids, were chosen as potential biomarkers to help explain metabolic disorders caused by HFD. These metabolites were mainly associated with the biosynthesis of unsaturated fatty acids, the arachidonic acid metabolic pathway, the ovarian steroidogenesis pathway, and the platelet activation pathway. Our study revealed that a HFD caused significant lipometabolic disorders. These metabolites may inhibit oxygen respiration by increasing the adipocytes cells and density, cause mitochondrial and endoplasmic reticulum dysfunction, produce inflammation, and finally lead to insulin resistance, thus increasing the risk of Type 2 diabetes, atherosclerosis, and other metabolic syndromes.

A large number of studies have reported that microRNA (miR)‑374c‑5p plays an important role in the occurrence and development of malignant tumors, but there is no research on the role of miR‑374c‑5p in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the role of miR‑374c‑5p in HCC and the underlying molecular mechanism. The expression of miR‑374c‑5p in HCC tissues and HCC cell lines was analyzed via reverse transcription‑quantitative PCR. The association between miR‑374c‑5p and clinical pathology was also analyzed in patients with HCC. Kaplan‑Meier analysis and Cox multivariate analysis were used to evaluate the prognostic significance of miR‑374c‑5p in HCC. The biological functions of miR‑374c‑5p, including cell proliferation, migration and invasion and its potential molecular mechanism were analyzed in vivo and in vitro. In addition, the molecular mechanism of miR‑374c‑5p in HCC was further explored. The results demonstrated that miR‑374c‑5p expression was lower in HCC than in matched adjacent tissue samples. Patients with low expression of miR‑374c‑5p had poor prognosis and short survival time. Overexpression of miR‑374c‑5p inhibited HCC cell proliferation, migration and invasion in vitro. In vivo, it was found that overexpression of miR‑374c‑5p significantly inhibited the growth and proliferation of HCC cells. Dual‑luciferase reporter assays verified that miR‑374c‑5p directly targets the 3'‑untranslated region of pituitary tumor‑transforming 1 (PTTG1) and regulates PTTG1 expression. In general, it was revealed that miR‑374c‑5p regulates the malignant biological behavior of HCC through PTTG1, thereby affecting epithelial‑mesenchymal transition. Thus, miR‑374c‑5p is a potential biological indicator to predict poor prognosis in patients with HCC.

Carotid and vertebral artery dissections are estimated to account for ∼20% of strokes in patients under 45-years-old. This meta-analysis compared the efficacy and safety of treatment with anticoagulants versus antiplatelet agents to determine the optimal therapy. We searched 4 electronic databases for clinical trials published from January 1, 1980 to August 25, 2021 that included patients who received anticoagulant or antiplatelet therapy for carotid and/or vertebral artery dissections. The curative effect was judged by recanalization evaluated by imaging. The primary outcomes were all cause death and ischemic stroke; secondary outcomes included hemorrhage and transient ischemic attack (TIA). Patients who received only a single drug treatment were divided into antiplatelet or anticoagulant groups; all received conservative treatment without surgical intervention. For this investigation, we pooled the available studies to conduct a meta-analysis, which included 7 articles with 1126 patients. The curative effect of vascular recanalization was not significantly different between the 2 treatment groups (odds ratio [OR] = 0.913, 95% confidence interval [CI]: 0.611-1.365, P = .657); similarly, no significant differences were found regarding the primary outcomes all cause death (OR = 1.747, 95%CI: 0.202-15.079, P = .612) and ischemic stroke (OR = 2.289, 95%CI: 0.997-5.254, P = .051). Patients treated with anticoagulants were more likely to experience TIA (OR = 0.517, 95%CI: 0.252-1.060, P = .072) and hemorrhage (OR = 0.468, 95%CI: 0.210-1.042, P = .063), but the differences were not statistically significant. Overall, there were no statistically significant differences between anticoagulant therapy and antiplatelet therapy for the treatment of carotid and vertebral artery dissections.

Large numbers of microbes can be present in seminal fluid, and there are differences in the semen microbiota between normal and abnormal semen samples. To evaluate the semen microbiota in patients with leukocytospermia, 87 seminal fluid samples, including 33 samples with a normal seminal leukocyte count and 54 samples with leukocytospermia, were obtained for a cross-sectional analysis. Twenty samples with a normal seminal leukocyte count had normal sperm parameters (Control group), and 13 samples with a normal seminal leukocyte count were from asthenozoospermia patients (Ast group). However, 32 samples with leukocytospermia were from asthenozoospermia patients (LA group), and only 22 samples with leukocytospermia had normal sperm parameters (Leu group). The 16S ribosomal RNA (rRNA) gene sequencing method was used to sequence the microbiota in the seminal fluid, and multiple bioinformatics methods were utilized to analyze the data. Finally, the results showed that the worse sperm parameters were observed in the leukocytospermia-related groups. Semen microbiota analysis found that there was increased alpha diversity in the leukocytospermia-related groups. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were the primary phyla in the seminal fluid. Two microbiota profiles, namely, Lactobacillus-enriched and Streptococcus-enriched groups, were identified in this study. The majority of the samples in the groups with a normal seminal leukocyte count could be categorized as Lactobacillus-enriched, whereas the majority of the leukocytospermia samples could be categorized as Streptococcus-enriched. Our study indicated that males with leukocytospermia have worse sperm parameters and a different semen microbiota composition compared to males with a normal seminal leukocyte count.

Bone morphogenetic protein 15 (BMP15) is strongly associated with animal reproduction and woman reproductive disease. As a multifunctional oocyte-specific secret factor, BMP15 controls female fertility and follicular development in both species-specific and dosage-sensitive manners. Previous studies found that BMP15 played a critical role in follicular development and ovulation rate in mono-ovulatory mammalian species, especially in sheep and human, but study on knockout mouse model implied that BMP15 possibly has minimal impact on female fertility of poly-ovulatory species. However, this needs to be validated in other poly-ovulatory species. To investigate the regulatory role of BMP15 on porcine female fertility, we generated a BMP15-knockdown pig model through somatic nuclear transfer technology. The BMP15-knockdown gilts showed markedly reduced fertility accompanied by phenotype of dysplastic ovaries containing significantly declined number of follicles, increased number of abnormal follicles, and abnormally enlarged antral follicles resulting in disordered ovulation, which is remarkably different from the unchanged fertility observed in BMP15 knockout mice. Molecular and transcriptome analysis revealed that the knockdown of BMP15 significantly affected both granulosa cells (GCs) and oocytes development, including suppression of cell proliferation, differentiation, and follicle stimulating hormone receptor (Fshr) expression, leading to premature luteinization and reduced estradiol (E2) production in GCs, and simultaneously decreased quality and meiotic maturation of oocyte. Our results provide in vivo evidence of the essential role of BMP15 in porcine ovarian and follicular development, and new insight into the complicated regulatory function of BMP15 in female fertility of poly-ovulatory species.

Heat shock transcription factors (HSF) are divided into classes A, B and C. Class A transcription factors are generally recognized as transcriptional activators, while functional characterization of class B and C heat shock transcription factors have not been fully developed in most plant species. We isolated and characterized a novel HSF transcription factor gene, TrHSFB2a (a class B HSF) gene, from the drought stress-sensitive forage crop species, white clover (Trifolium repens). TrHSFB2a was highly homologous to MtHSFB2b, CarHSFB2a, AtHSFB2b and AtHSFB2a. The expression of TrHSFB2a was strongly induced by drought (PEG6000 15% w/v), high temperature (35 °C) and salt stresses (200 mM L-1 NaCl) in white clover, while subcellular localization analysis showed that it is a nuclear protein. Overexpression of the white clover gene TrHSFB2a in Arabidopsis significantly reduced fresh and dry weight, relative water contents (RWC), maximum photosynthesis efficiency (Fv/Fm) and performance index on the absorption basis (PIABS), while it promoted leaf senescence, relative electrical conductivity (REC) and the contents of malondialdehyde (MDA) compared to a wild type under drought, heat and salt stress conditions of Arabidopsis plants. The silencing of its native homolog (AtHSFB2a) by RNA interference in Arabidopsis thaliana showed opposite trends by significantly increasing fresh and dry weights, RWC, maximum photosynthesis efficiency (Fv/Fm) and performance index on the absorption basis (PIABS) and reducing REC and MDA contents under drought, heat and salt stress conditions compared to wild type Arabidopsis plants. These phenotypic and physiological indicators suggested that the TrHSFB2a of white clover functions as a negative regulator of heat, salt and drought tolerance. The bioinformatics analysis showed that TrHSFB2a contained the core B3 repression domain (BRD) that has been reported as a repressor activator domain in other plant species that might repress the activation of the heat shock-inducible genes required in the stress tolerance process in plants. The present study explores one of the potential causes of drought and heat sensitivity in white clover that can be overcome to some extent by silencing the TrHSFB2a gene in white clover.

Spinal cord injury (SCI) is a serious disorder of the central nervous system with a high disability rate. Long noncoding RNAs (lncRNAs) are reported to mediate many biological processes. The aim of this study was to explore lncRNA and mRNA expression profiles and functional networks after SCI. Differentially expressed genes between SCI model rats and sham controls were identified by microarray assays and analyzed by functional enrichment. Key lncRNAs were identified using a support vector machine- (SVM-) recursive feature elimination (RFE) algorithm. A trans and cis regulation model was used to analyze the regulatory relationships between lncRNAs and their targets. An lncRNA-related ceRNA network was established. We identified 5465 differentially expressed lncRNAs (DE lncRNAs) and 8366 differentially expressed mRNAs (DE mRNAs) in the SCI group compared with the sham group (fold change > 2.0, p < 0.05). Four genes were confirmed by qRT-PCR which were consistent with the microarray data. GSEA analysis showed that most marked changes occurred in pathways related to immune inflammation and nerve cell function, including cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and GABAergic synapse. Enrichment analysis identified 30 signaling pathways, including those associated with immune inflammation response. A total of 40 key lncRNAs were identified using the SVM-RFE algorithm. A key lncRNA-mRNAs coexpression network was generated for 230 951 lncRNA-mRNA pairs with half showing positive correlations. Several key DE lncRNAs were predicted to have "cis"- or "trans"-regulated target genes. The transcription factors, Sp1, JUN, and SOX10, may regulate the interaction between XR_001837123.1 and ETS 1. In addition, five pairs of ceRNA regulatory sequences were constructed. Many mRNAs and lncRNAs were found to be dysregulated after SCI. Bioinformatic analysis showed that DE lncRNAs may play crucial roles in SCI. It is anticipated that these findings will provide new insights into the underlying mechanisms and potential therapeutic targets for SCI.

Quinestrol (QUN), a synthetic estrogen used as an oral contraceptive or emergency contraceptive component, has been shown to be an endocrine-disrupting chemical. To assess the environmental risk of QUN, batch equilibration experiments were conducted to investigate the adsorption-desorption of QUN in five contrasting soils from different areas of China. The leaching properties were also calculated based on the adsorption and degradation data from our previous study with the same soils. The Freundlich and Langmuir models were applied to the sorption-desorption data to examine the affinity towards QUN of the soils, which had varying physical and chemical properties. The Kf and Kfdes values of QUN in the tested soils ranged from 3.72 to 20.47 mg1-n Ln kg-1 and from 1.26 to 7.8 mg1-n Ln kg-1, respectively, and Qm ranged from 28.25 to 126.58 mg/kg. The desorption data showed that hysteresis occurred. The Kf and Kfdes values of QUN were positively correlated with the soil total organic carbon (OC) and cation exchange capacity (CEC), and it may be due to the content of TOC and CEC exhibited a positive correlation. A low mobility potential of QUN in soils was predicted and verified the adsorption results by the groundwater ubiquity score (GUS) and retardation factor (Rf).

Dickkopf-1 (Dkk1) is an inhibitor of Wnt signaling involved in cancer cell proliferation, apoptosis, and migration and angiogenesis. It was previously reported that B cell-specific Moloney mouse leukemia virus integration site 1 (Bmi1) activates the Wnt pathway by inhibiting the expression of DKK1 in breast cancer cell lines and 293T cells. Bmi1 and DKK1 are highly expressed in liver samples taken by biopsy from patients with hepatitis B virus-related hepatocellular carcinoma (HCC), but the effect of both Bmi1 and DKK1 on the carcinogenesis of adult hepatic stem cells (oval cells) has not previously been reported. In this study, we used WB-F344 cells to explore the function and regulation of Dkk1 upon Bmi1 treatment. Overexpression of Dkk1 repressed differentiation, proliferation, and migration induced by Bmi1 but promoted the apoptosis of hepatic WB-F344 oval cells. In addition, Dkk1 reduced the enhancement of β-catenin levels induced by Bmi1. Finally, we used transcriptome sequencing to perform a comprehensive evaluation of the transcriptome-related changes in WB-F344 oval cells induced by Dkk1 and Bmi1. These results may provide evidence for future studies of the pathogenesis of HCC and the design of possible therapies.

LINC00963 is high-expressed in various carcinomas, but its expression and function in colorectal cancer (CRC) have not been explored. This study explored the role and mechanism of LINC00963 in CRC.