High Expression of KIFC1 in Glioma Correlates with Poor Prognosis.

OBJECTIVE: Kinesin family member C1 (KIFC1), a non-essential kinesin-like motor protein, has been found to serve a crucial role in supernumerary centrosome clustering and the progression of several human cancer types. However, the role of KIFC1 in glioma has been rarely reported. Thus, the present study aimed to investigate the role of KIFC1 in glioma progression. METHODS: Online bioinformatics analysis was performed to determine the association between KIFC1 expression and clinical outcomes in glioma. Immunohistochemical staining was conducted to analyze the expression levels of KIFC1 in glioma and normal brain tissues. Furthermore, KIFC1 expression was knocked in the glioma cell lines, U251 and U87MG, and the functional roles of KIFC1 in cell proliferation, invasion and migration were analyzed using cell multiplication, wound healing and Transwell invasion assays, respectively. The autophagic flux and expression levels matrix metalloproteinase-2 (MMP2) were also determined using imaging flow cytometry, western blotting and a gelation zymography assay. RESULTS: The results revealed that KIFC1 expression levels were significantly upregulated in glioma tissues compared with normal brain tissues, and the expression levels were positively associated with tumor grade. Patients with glioma with low KIFC1 expression levels had a more favorable prognosis compared with patients with high KIFC1 expression levels. In vitro, KIFC1 knockdown not only inhibited the proliferation, migration and invasion of glioma cells, but also increased the autophagic flux and downregulated the expression levels of MMP2. CONCLUSION: Upregulation of KIFC1 expression may promote glioma progression and KIFC1 may serve as a potential prognostic biomarker and possible therapeutic target for glioma.

Role of crosstalk between synovial cells and chondrocytes in osteoarthritis (Review).

Osteoarthritis (OA) is a low-grade, nonspecific inflammatory disease that affects the entire joint. This condition is characterized by synovitis, cartilage erosion, subchondral bone defects, and subpatellar fat pad damage. There is mounting evidence demonstrating the significance of crosstalk between synovitis and cartilage destruction in the development of OA. To comprehensively explore the phenotypic alterations of synovitis and cartilage destruction, it is important to elucidate the crosstalk mechanisms between chondrocytes and synovial cells. Furthermore, the updated iteration of single-cell sequencing technology reveals the interaction between chondrocyte and synovial cells. In the present review, the histological and pathological alterations between cartilage and synovium during OA progression are described, and the mode of interaction and molecular mechanisms between synovial cells and chondrocytes in OA, both of which affect the OA process mainly by altering the inflammatory environment and cellular state, are elucidated. Finally, the current OA therapeutic approaches are summarized and emerging therapeutic targets are reviewed in an attempt to provide potential insights into OA treatment.

Application of radiomics model based on lumbar computed tomography in diagnosis of elderly osteoporosis.

A metabolic bone disease characterized by decreased bone formation and increased bone resorption is osteoporosis. It can cause pain and fracture of patients. The elderly are prone to osteoporosis and are more vulnerable to osteoporosis. In this study, radiomics are extracted from computed tomography (CT) images to screen osteoporosis in the elderly. Collect the plain scan CT images of lumbar spine, cut the region of interest of the image and extract radiomics features, use Lasso regression to screen variables and adjust complexity, use python language to model random forests, support vector machines, K nearest neighbor, and finally use receiver operating characteristic curve to evaluate the performance of the model, including precision, recall, accuracy and area under the curve (AUC). For the model, 14 radiolomics features were selected. The diagnosis performance of random forest model and support vector machine is good, all around 0.9. The AUC of K nearest neighbor model in training set and test set is 0.828 and 0.796, respectively. We selected the plain scan CT images of the elderly lumbar spine to build radiomics features model, which has good diagnostic performance and can be used as a tool to assist the diagnosis of osteoporosis in the elderly.

Patterns of Spatial Variation in Rumen Microbiology, Histomorphology, and Fermentation Parameters in Tarim wapiti (Cervus elaphus yarkandensis).

The rumen is divided into multiple rumen sacs based on anatomical structure, and each has its unique physiological environment. Tarim wapiti preserved roughage tolerance after domestication, and adaptation to the desertified environment led to the development of a unique rumen shape and intraruminal environment. In this work, six Tarim wapiti were chosen and tested for fermentation parameters, microbes, and histomorphology in four rumen areas (Dorsal sac, DS; Ventral sac, VS; Caudodorsal blind sac, CDBS; Caudoventral blind sac, CVBS). Tarim wapiti's rumen blind sac had better developed rumen histomorphology, the ventral sac was richer in VFAs, and the dominant bacteria varied most notably in the phylum Firmicutes, which was enriched in the caudoventral blind sac. The ventral sac biomarkers focused on carbohydrate fermentation-associated bacteria, the dorsal sac focused on N recycling, and the caudoventral blind sac identified the only phylum-level bacterium, Firmicutes; we were surprised to find a probiotic bacterium, Bacillus clausii, identified as a biomarker in the ventral sac. This research provides a better understanding of rumen fermentation parameters, microorganisms, and histomorphology in the Tarim wapiti rumen within a unique ecological habitat, laying the groundwork for future regulation targeting the rumen microbiota and subsequent animal production improvement.

Roles of Chemokines in Intervertebral Disk Degeneration.

PURPOSE OF REVIEW: Intervertebral disc degeneration is the primary etiology of low back pain and radicular pain. This review examines the roles of crucial chemokines in different stages of degenerative disc disease, along with interventions targeting chemokine function to mitigate disc degeneration. RECENT FINDINGS: The release of chemokines from degenerated discs facilitates the infiltration and activation of immune cells, thereby intensifying the inflammatory cascade response. The migration of immune cells into the venous lumen is concomitant with the emergence of microvascular tissue and nerve fibers. Furthermore, the presence of neurogenic factors secreted by disc cells and immune cells stimulates the activation of pain-related cation channels in the dorsal root ganglion, potentially exacerbating discogenic and neurogenic pain and intensifying the degenerative cascade response mediated by chemokines. Gaining a deeper comprehension of the functions of chemokines and immune cells in these processes involving catabolism, angiogenesis, and injury detection could offer novel therapeutic avenues for managing symptomatic disc disease.

Urban Versus Lake Impacts on Heat Stress and Its Disparities in a Shoreline City.

Shoreline cities are influenced by both urban-scale processes and land-water interactions, with consequences on heat exposure and its disparities. Heat exposure studies over these cities have focused on air and skin temperature, even though moisture advection from water bodies can also modulate heat stress. Here, using an ensemble of model simulations covering Chicago, we find that Lake Michigan strongly reduces heat exposure (2.75°C reduction in maximum average air temperature in Chicago) and heat stress (maximum average wet bulb globe temperature reduced by 0.86°C) during the day, while urbanization enhances them at night (2.75 and 1.57°C increases in minimum average air and wet bulb globe temperature, respectively). We also demonstrate that urban and lake impacts on temperature (particularly skin temperature), including their extremes, and lake-to-land gradients, are stronger than the corresponding impacts on heat stress, partly due to humidity-related feedback. Likewise, environmental disparities across community areas in Chicago seen for skin temperature are much higher (1.29°C increase for maximum average values per $10,000 higher median income per capita) than disparities in air temperature (0.50°C increase) and wet bulb globe temperature (0.23°C increase). The results call for consistent use of physiologically relevant heat exposure metrics to accurately capture the public health implications of urbanization.

Cu doping in FeP enabling efficient electrochemical nitrate reduction to ammonia in neutral media.

Electrochemical nitrate reduction to ammonia (NH3) not only provides a promising strategy for green NH3 synthesis, but also removes harmful nitrates from water. Herein, a Cu-doped FeP electrocatalyst was prepared for nitrate reduction, which achieved a high NH3 faradaic efficiency of 92.5% and a high NH3 yield of 0.787 mmol h-1 cm-2 in a neutral electrolyte, greatly surpassing its FeP counterpart.

Inactivation of Heterosigma akashiwo under UV/peroxydisulfate advanced disinfection system in marine waters.

Heterosigma akashiwo (H. akashiwo) is recognized as a harmful algal bloom (HABs) species with a global distribution, capable of posing significant threats to marine ecosystems, particularly when spread through ship ballast water. This investigation focused on elucidating the inactivation kinetics and underlying mechanism of H. akashiwo through a combined ultraviolet irradiation and peroxydisulfate (UV/PDS) process. The results demonstrated a strong synergistic effect within the UV/PDS system, resulting in an inactivation of 0.78-ln and 2.67-ln within 40 min of UV and UV/PDS processes. The principal agents accountable for inactivation were identified as sulfate radicals (•SO4-) and hydroxyl radical (•OH), which exhibited a synergistic effect in the UV/PDS process. Furthermore, the study observed a negatively impact of seawater pH and salinity on the efficiency of inactivation. UV/PDS caused oxidative stress on algal cells, initially involving the participation of antioxidant enzymes in counteracting cellular damage, but this protective mechanism diminished as the reaction duration extended. The UV/PDS treatment not only inflicted damage upon H. akashiwo's photosynthetic system but also caused the extracellular release of DNA and algal organic matter (AOM) due to damaged cell membranes. Transcriptome analysis provided a molecular biology perspective on the cellular inactivation process. Upregulation of genes linked to photosynthesis and oxidative phosphorylation suggested a potential elevation in energy metabolism. In contrast, genes associated with cellular and metabolic processes, including glycolysis and the tricarboxylic acid cycle (TCA cycle), exhibited downregulation. Moreover, this treatment exerted an inhibitory influence on RNA polymerase and protein synthesis, resulting in the reduced expression of genetic information.

Indian Ocean glacial deoxygenation and respired carbon accumulation during mid-late Quaternary ice ages.

Reconstructions of ocean oxygenation are critical for understanding the role of respired carbon storage in regulating atmospheric CO2. Independent sediment redox proxies are essential to assess such reconstructions. Here, we present a long magnetofossil record from the eastern Indian Ocean in which we observe coeval magnetic hardening and enrichment of larger, more elongated, and less oxidized magnetofossils during glacials compared to interglacials over the last ~900 ka. Our multi-proxy records of redox-sensitive magnetofossils, trace element concentrations, and benthic foraminiferal Δδ13C consistently suggest a recurrence of lower O2 in the glacial Indian Ocean over the last 21 marine isotope stages, as has been reported for the Atlantic and Pacific across the last glaciation. Consistent multi-proxy documentation of this repeated oxygen decline strongly supports the hypothesis that increased Indian Ocean glacial carbon storage played a significant role in atmospheric CO2 cycling and climate change over recent glacial/interglacial timescales.

Protective effect of TNIP2 on the inflammatory response of microglia after spinal cord injury in rats.

BACKGROUND: Spinal cord injury (SCI) is a devastating disease that can lead to tissue loss and neurological dysfunction. TNIP2 is a negative regulator of NF-κB signaling due to its capacity to bind A20 and suppress inflammatory cytokines-induced NF-κB activation. However, the anti-inflammatory role of TNIP2 in SCI remains unclear. Our study's intention was to evaluate the effect of TNIP2 on the inflammatory response of microglia after spinal cord injury in rats. METHODS: HE staining and Nissl staining were performed on day 3 following SCI to analyze the histological changes. To further investigate the functional changes of TNIP2 after SCI, we performed immunofluorescence staining experiments. The effect of LPS on TNIP2 expression in BV2 cells was examined by western blot. The levels of TNF-α, IL-1ß, and IL-6 in spinal cord tissues of rats with SCI and in BV2 cells with LPS were measured by using qPCR. RESULTS: TNIP2 expression was closely associated with the pathophysiology of SCI in rats, and TNIP2 was involved in regulating functional changes in microglia. TNIP2 expression was increased during SCI in rats and that overexpression of TNIP2 inhibited M1 polarization and pro-inflammatory cytokine production in microglia, which might ultimately protect against inflammatory responses through the MAPK and NF-κB signaling pathways. CONCLUSIONS: The present study provides evidence for a role of TNIP2 in the regulation of inflammation in SCI and suggests that induction of TNIP2 expression alleviated the inflammatory response of microglia.

Coupling Cu doping and oxygen vacancies in Co3O4 for efficient electrochemical nitrate conversion to ammonia.

Electrochemical conversion of nitrate to NH3 not only eliminates nitrate pollution in the environment, but also produces highly valuable NH3. Herein, Cu-doped Co3O4 with abundant oxygen vacancies (Cu-Co3O4-x) was prepared on carbon cloth. The as-fabricated Cu-Co3O4-x can selectively reduce nitrate to NH3 with high Faraday efficiencies (around 90%) and a large NH3 yield of 0.83 mmol h-1 cm-2 in a neutral electrolyte.

Genome-wide association study for the primary feather color trait in a native Chinese duck.

Background: To reveal candidate genes and the molecular genetic mechanism underlying primary feather color trait in ducks, a genome-wide association study (GWAS) for the primary feather color trait was performed based on the genotyping-by-sequencing (GBS) technology for a native Chinese female duck, Longyan Shan-ma ducks. Methods: Blood genomic DNA from 314 female Longyan Shan-ma duck were genotyped using GBS technology. A GWAS for the primary feather color trait with genome variations was performed using an univariate linear mixed model based on all SNPs in autosomes. Results: Seven genome-wide significant single nucleotide polymorphisms (SNPs, Bonferroni-adjusted p-value <8.03 × 10-7) within the introns of the genes STARD9, ZNF106, SLC7A5, and BANP genes were associated with the primary feather color trait. Twenty-two genome-wide suggestive SNPs (Bonferroni-adjusted p-value <1.61 × 10-5) of 17 genes (besides ZNF106 and SLC7A5) were also identified. Seven SNPs were located at one 0.22 Mb region (38.65-38.87 Mb) on chromosome 5, and six SNPs were located at one 0.31 Mb region (19.53-19.84 Mb) on chromosome 11. The functions of STARD9, SLC7A5, BANP, LOC101798015, and IPMK were involved pigmentation and follicle development, especially, STARD9 upregulated expression in black feather (haplotype-CCCC) bulb tissue compared with in pockmarked feather (haplotype-TGTT) bulb tissue, implicating these genes as candidate genes for primary feather color trait. Conclusion: The preliminarily findings suggested candidate genes and regions, and the genetic basis of primary feather color trait in a female duck.

Stereoselective accumulation and biotransformation of chiral fungicide epoxiconazole and oxidative stress, detoxification, and endogenous metabolic disturbance in earthworm (Eisenia foetida).

>80 % of applied pesticides in agriculture will enter the soil and be exposed to soil animals. Little is known about the stereoselective metabolic effects of epoxiconazole (EPO) on soil animals. In this study, EPO-mediated stereoselective enrichment, biotransformation, oxidative stress, detoxification, and global metabolic profiles in earthworms were investigated by exposure to EPO and its enantiomers at 1 mg/kg and 10 mg/kg doses. Preferential enrichment of (-)-EPO was observed, and the five transformation products (TPs) exhibited the chemically specific stereoselective accumulation with inconsistent configurations. Biochemical markers related to reactive oxygen species (ROS) and detoxification (·OH- content, SOD, CAT, GST, and CYP450 enzymes) showed a significant stereoselective activation overall at the low-level exposure (p-value <0.05). Based on untargeted metabolomic analysis, the steroid biosynthesis and ROS-related biotransformation, glutathione metabolism, TCA cycle, amino acid metabolism, purine and pyrimidine metabolism of earthworms were significantly interfered with by EPO and its enantiomer exposure. More pronounced stereoselectivity was observed at the level of the global metabolic profile, while comparable levels of metabolic perturbations were identified at the individual metabolite level. This study provides novel insights into the stereoselective effects of the chiral fungicide EPO, and valuable evidence for soil environmental risk assessments.

Percutaneous vertebral-disc plasty for thoracolumbar very severe osteoporotic vertebral compression fractures: A randomized controlled study.

Purpose: To compare the clinical outcomes and radiological parameters of patients undergoing percutaneous vertebroplasty (PVP) versus those undergoing percutaneous vertebral-disc plasty (PVDP) for back pain, segmental instability, and kyphosis due to thoracolumbar very severe osteoporotic vertebral compression fractures (vsOVCFs). Methods: This prospective randomized controlled study included elderly patients with thoracolumbar vsOVCFs. All the patients were randomly allocated into the PVP group (who underwent conventional PVP) and the PVDP group (who underwent PVP combined percutaneous cement discoplasty). The visual analogue scale (VAS), Oswestry Disability Index (ODI), local kyphosis angle, and disc height were recorded preoperatively and postoperatively. Results: Significant postoperative improvements in the VAS, ODI, and the local kyphosis angle (LKA) were shown, compared with the preoperative values in both groups (p < 0.05). The average VAS, ODI, and LKA for patients in the PVP group were increased compared to those in the PVDP group observed at the last follow-up (p < 0.05). The DHA, DHP, and LKA were seen to be maintained in the PVDP group at the last follow-up (p > 0.05). The change was significantly lower in the PVDP group at the last follow-up in those parameters (p < 0.05). Conclusion: PVDP may be a feasible and effective technique for the treatment of very severe OVCFs, that can restore intervertebral height, provide segmental stabilizing and relieve back pain in the short term.

Ubiquitin ligase Triad1 promotes neurite outgrowth by inhibiting MDM2-mediated ubiquitination of the neuroprotective factor pleiotrophin.

Spinal cord injury (SCI) is the most severe result of spine injury, but no effective therapy exists to treat SCI. We have previously shown that the E3 ubiquitin ligase Two RING fingers and DRIL 1 (Triad1) promotes neurite outgrowth after SCI. However, the mechanism by which Triad1 affects neuron growth and the potential involvement of its ubiquitination activity is unclear. Neuroprotective cytokine pleiotrophin (PTN) can promote microglia proliferation and neurotrophic factor secretion to achieve neuroprotection. We find using immunostaining and behavioral assays in rats that the expression of Triad1 and the PTN was peaked at 1 day after SCI and Triad1 improved motor function and histomorphological injury after SCI. We show using flow cytometry and astrocyte/neuronal coculture assays that Triad1 overexpression promoted PTN protein levels, neurotrophic growth factor (NGF) expression, brain-derived neurotrophic factor (BDNF) expression, astrocyte and neuronal viability, and neurite outgrowth but suppressed astrocyte apoptosis, while shRNA-mediated knockdown of Triad1 and PTN had the opposite effects. Ubiquitin ligase murine double mutant 2 (MDM2) has previously been demonstrated to participate in the process of neurite outgrowth and mediate ubiquitination of p53. Furthermore, we demonstrate overexpression of MDM2 downregulated PTN protein levels, NGF expression and BDNF expression in astrocytes, and inhibited neurite outgrowth of neurons. In addition, MDM2 facilitated PTN ubiquitination, which was reversed by Triad1. Finally, we show simultaneous sh-PTN and MDM2 overexpression attenuated the neurite outgrowth-promoting effect of Triad1 overexpression. In conclusion, we propose Triad1 promotes astrocyte-dependent neurite outgrowth to accelerate recovery after SCI by inhibiting MDM2-mediated PTN ubiquitination.

Environmental behavior of the chiral fungicide epoxiconazole in earthworm-soil system: Enantioselective enrichment, degradation kinetics, chiral metabolite identification, and biotransformation mechanism.

The environmental impact of the chiral fungicide epoxiconazole and its chiral transformation products (TPs) on non-target organisms and the environment has become a significant concern due to its widespread use in agricultural practice. Enantioselectivity studies of parent contaminants cannot adequately assess the complexity of its chiral TPs in the environment. This study aimed to investigate the environmental behavior of epoxiconazole in an earthworm-soil system. 2S,3R-(-)-epoxiconazole was preferentially enriched in earthworms during the accumulation phase (p < 0.05), but no enantioselectivity was observed during the elimination phase. One methoxylated and four hydroxylated chiral TPs were identified in soil, earthworm, and excrement. The epoxy ring hydroxylated TP and methoxylated TP of epoxiconazole were discovered for the first time in the environment. The chemically specific enantioselectivity with enantiomer fraction (EF) > 0.8 was observed for the TPs in different matrices. The CYP450 monooxygenase of earthworm was significant activated. In vitro enzyme metabolism experiments (earthworm microsomes and recombinant CYP450 enzymes CYP2A6, CYP 2C9, and CYP 3A4) were carried out to further explain the biotransformation mechanism of epoxiconazole in earthworm. This study provides new evidence of enantiomeric biotransformation of chiral fungicide epoxiconazole in the earthworm-soil system and could provide valuable insights into their environmental risk assessment.

Simplified Chinese Version of the Spinal Instability Neoplastic Score in Evaluating Patients with Metastatic Spinal Tumor: A Cross-Cultural Adaptation and Validation.

OBJECTIVE: To translate the original English version of the Spinal Instability Neoplastic Score (SINS) into simplified Chinese, adapt it cross-culturally, validate its psychometric properties in measuring spinal instability in patients with metastatic spinal tumors in the Chinese mainland, examine the reliability and validity to demonstrate its accuracy and applicability in clinical practice. METHODS: Patients diagnosed with metastatic spinal disease between January 2016 and January 2020 were recruited. The number of participants was advised to be at least 50 for appropriate analysis of reliability, construct validity, as well as ceiling or floor effects, and recruitment of 100 patients was advised for internal consistency analysis. The study was conducted in two phases: first, the SINS was translated into simplified Chinese; second, the factor structure, internal consistency, test-retest reliability, validity, and floor and ceiling effects of the SC-SINS were assessed. The internationally recognized cross-cultural adaptation guidelines were followed. Internal consistency was evaluated with Cronbach's alpha. Test-retest reliability was examined among the patients with a 4-week interval. The validity of the Chinese version of SINS (SC-SINS) was assessed by examining its relationship with Kostuik classification. Principal component analysis was conducted to confirm the factor structure of each subscale. RESULTS: A total of 160 participants (88 males and 72 females) were enrolled. No major difficulties occurred in the forward and backward translations of SINS. The internal consistency of SC-SINS was excellent (Cronbach's α =0.857, ranging from 0.68 to 0.85). Test-retest reliability was also excellent with a value of 0.89, ranging from 0.86 to 0.95. Validity analyses indicated that the SC-SINS was positively and significantly correlated with Kostuik classification. The correlation between "Posterolateral Involvement of Spinal Elements" and "1-2 Partial Damage" was the highest with a correlation value of 0.792. The correlation between "Pain" and "1-2 Partial Damage" was the lowest with a value of 0.341. All items showed principal component coefficients greater than 0.4. The values of Factor 1 ranged from 0.523 to 0.681; Factor 2 ranged from 0.591 to 0.731; Factor 3 ranged from 0.613 to 0.754; Factor 4 ranged from 0.461 to 0.711; Factor 5 ranged from 0.513 to 0.701; and Factor 6 ranged from 0.501 to 0.668. In addition, neither floor nor ceiling effects were seen in the SC-SINS. CONCLUSION: The SC-SINS demonstrated high internal consistency and test-retest reliability, which has been proven valid and reliable to measure spinal stability in patients from the Chinese mainland with metastatic spinal tumor.

Upregulation of P2Y12 inhibits chondrocyte apoptosis in lumbar osteoarthritis through the PI3K/AKT signaling pathway.

Lumbar facet osteoarthritis (FJOA) is a major cause of severe lower back pain and disability worldwide. However, the mechanism underlying cartilage degeneration in FJOA remains unclear. The purpose of this study was to investigate the regulation and mechanism of P2Y12 on chondrocyte apoptosis in FJOA. The experimental rats were randomly divided into non-operation (n = 20) and operation groups (n = 20). In the operation group, Sodium iodoacetate (MIA, Sigma, 200 mg/mL) was injected into the right L4/5 facet process using a blunt nanoneedle 26 (WPI, Sarasota, FL, USA) under the control of an injection pump. The final injection volume was 5µL and the injection rate was 2µL/min. The facet joint was removed four weeks after surgery. After the operation, samples were stored at -80 °C until further use, whereby the right facet joints in each group were tested. Hematoxylin and eosin (HE) and iron-red solid green staining were used to observe the degeneration of articular chondrocytes in rats. Immunohistochemistry and western blotting were used to observe the expressions of P2Y12, Matrix metalloproteinase 13 (MMP13), Collagen II (COL2), and other cartilage degeneration and apoptosis-related genes. Co-localization of P2Y12-cleaved caspase-3 in the apoptosis model was detected by dual-standard immunofluorescence staining. Apoptosis was also detected by flow cytometry and TUNEL assay.P2Y12 is highly expressed in OA cartilage tissue, and inhibits IL-1ß -induced chondrocyte apoptosis through PI3K/AKT signaling pathway, thus playing a certain protective role on cartilage.

BAG3 protects chondrocytes against lumbar facet joint osteoarthritis by regulating autophagy and apoptosis.

Bcl2-associated athanogene3 (BAG3) protein, mainly induced by stressful stimuli, has been confirmed to participate in apoptosis and autophagy. In recent studies, BAG3 has gradually become a key molecule in tumors. However, the role of BAG3 in the progression of lumbar facet joint osteoarthritis (FJOA) and whether it can regulate chondrocyte apoptosis and autophagy are still unknown. In both human and FJOA rat models, we observed an upregulation of BAG3 and apoptosis and autophagy-related proteins compared with healthy tissues. Then, we established the chondrocytes injury model in vitro by using IL-1ß to stimulate human SW1353 cells. Western blot analysis data showed significant expression of BAG3, apoptosis, and autophagy-related proteins in SW1353 cells. Finally, by knocking down and overexpressing BAG3, we discovered possible anti-apoptotic and autophagy-promoted effects of BAG3 in FJOA through various experimental methods. This study demonstrated that BAG3 actively participates in regulating chondrocyte apoptosis and autophagy in FJOA and may be a highly interesting target for pharmacological interventions.

Integrating high-throughput sequencing and metabolomics to investigate the stereoselective responses of soil microorganisms to chiral fungicide cis-epoxiconazole.

The use of the chiral triazole fungicide cis-epoxiconazole in agricultural production continues to increase; however, little is known about the stereoselective and toxic responses of soil microorganisms to cis-epoxiconazole in the soil microenvironment. High-throughput sequencing and metabolomics were integrated to investigate the stereoselective response of soil microbial community structure, metabolic profile to cis-epoxiconazole exposure, and the correlation between the microbiomes and different metabolites. Soil microbial community structure and soil metabolic profile were significantly altered and exhibited significant enantioselectivity. The alpha diversity (Chao, Shannon, and Simpson diversity) of bacterial and fungus was not significantly affected, whereas the beta diversity (Bray-Curtis dissimilarity and PLS-DA) of bacterial and fungus was significantly altered in treatment of cis-epoxiconazole and its enantiomers (p-value < 0.05). The variation in bacterial and fungus community structure was the highest under (+)-enantiomer exposure, followed by exposure to racemate and (-)-enantiomer. Soil metabolomic analysis revealed that exposure to high or low doses of cis-epoxiconazole and its enantiomers resulted in different degrees of reprogramming of the soil metabolic pool. The 39 significantly changed metabolites mainly included small molecular organic acids, amino acids and their intermediates, and purine and adenosine intermediates. Six metabolic pathways were significantly disrupted. Different correlation patterns were observed between the significantly altered metabolites and microbes (p-value < 0.05) by Pearson correlation-based analysis. In conclusion, as xenobiotic pollutant, epoxiconazole altered the structure and metabolism of soil microorganisms with significant stereoselectivity mainly driven by 2R, 3S-(+)-cis-epoxiconazole. This study provided a more robust assessment of the risks of epoxiconazole exposure to soil microorganisms. Given the importance of the soil environment in agricultural production, characterization of the soil microbiome and metabolome can provide new insights into the ecological risks posed by exposure to the chiral triazole pesticide cis-epoxiconazole and its enantiomers.