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Osteoarthritis (OA) is a common chronic degenerative disease of articular cartilage in middle-aged and older individuals, which can result in the joint pain and dysfunction, and even cause the joint deformity or disability. With the enhancing process of global aging, OA has gradually become a major public health problem worldwide. Explaining pathogenesis of OA is critical for the development of new preventive and therapeutic interventions. In recent years, gut microbiota (GM) has been generally regarded as a “multifunctional organ,” which is closely relevant with a variety of immune, metabolic and inflammatory functions. Meanwhile, more and more human and animal researches have indicated the existence of gut-bone axis and suggested that GM and its metabolites are closely involved in the pathogenic process of OA, which might become a potential and promising intervention target. Based on the close coordination of gut-bone axis, this review aims to summarize and discuss the mechanisms of GM and its metabolites influencing OA from the aspects of the intestinal mucosal barrier modulation, intestinal metabolites modulation, immune modulation and strategies for the prevention or treatment of OA based on perspectives of GM and its metabolites, thus providing a profound knowledge and recognition of it.

Pardosa pseudoannulata is one of the most common wandering spiders in agricultural fields and a potentially good bioindicator for heavy metal contamination. However, little is known about the mechanisms by which spiders respond to heavy metals at the molecular level. In the present study, high-throughput transcriptome sequencing was employed to characterize the de novo transcriptome of the spiders and to identify differentially expressed genes (DEGs) after cadmium exposure. We obtained 60,489 assembled unigenes, 18,773 of which were annotated in the public databases. A total of 2939 and 2491 DEGs were detected between the libraries of two Cd-treated groups and the control. Functional enrichment analysis revealed that metabolism processes and digestive system function were predominately enriched in response to Cd stress. At the cellular and molecular levels, significantly enriched pathways in lysosomes and phagosomes as well as replication, recombination and repair demonstrated that oxidative damage resulted from Cd exposure. Based on the selected DEGs, certain critical genes involved in defence and detoxification were analysed. These results may elucidate the molecular mechanisms underlying spiders’ responses to heavy metal stress.

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers.Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG.Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort.Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

Background: Programmed cell death is closely related to glioma. As a novel kind of cell death, the mechanism of disulfidptosis in glioma remains unclear. Therefore, it is of great importance to study the role of disulfidptosis-related genes (DRGs) in glioma. Methods: We first investigated the genetic and transcriptional alterations of 15 DRGs. Two consensus cluster analyses were used to evaluate the association between DRGs and glioma subtypes. In addition, we constructed prognostic DRG risk scores to predict overall survival (OS) in glioma patients. Furthermore, we developed a nomogram to enhance the clinical utility of the DRG risk score. Finally, the expression levels of DRGs were verified by immunohistochemistry (IHC) staining. Results: Most DRGs (14/15) were dysregulated in gliomas. The 15 DRGs were rarely mutated in gliomas, and only 50 of 987 samples (5.07 %) showed gene mutations. However, most of them had copy number variation (CNV) deletions or amplifications. Two distinct molecular subtypes were identified by cluster analysis, and DRG alterations were found to be related to the clinical characteristics, prognosis, and tumor immune microenvironment (TIME). The DRG risk score model based on 12 genes was developed and showed good performance in predicting OS. The nomogram confirmed that the risk score had a particularly strong influence on the prognosis of glioma. Furthermore, we discovered that low DRG scores, low tumor mutation burden, and immunosuppression were features of patients with better prognoses. Conclusion: The DRG risk model can be used for the evaluation of clinical characteristics, prognosis prediction, and TIME estimation of glioma patients. These DRGs may be potential therapeutic targets in glioma.

The FORMOSAT-7/COSMIC-2 satellites were launched in 2019, which can provide considerably larger amounts of radio occultation (RO) observations than the FORMOSAT-3/COSMIC satellites. The radio signals emitted from the global navigation satellites system (GNSS) are received by these low Earth orbit (LEO) satellites to provide the so-called bending angle accounting for bending of the rays after penetrating through the atmosphere. Deeper RO observations can be retrieved from FORMOSAT-7/COSMIC-2 for use in RO data assimilation to improve forecasts of tropical cyclones. This study used the global model FV3GFS with the finest grid resolution of about 25 km to simulate five selected typhoons over the western North Pacific, including Hagibis in 2019, Maysak and Haishen in 2020, and Kompasu and Rai in 2021. For each case, two experiments were conducted with and without assimilating FORMOSAT-7/COSMIC-2 RO bending angle. The RO data were assimilated by the GSI 4DEnVar data assimilation system for a total period of 4 days (with 6 h assimilation window) before the typhoon genesis time, followed by a forecast length of 120 h. The RO data assimilation improved the typhoon track forecasts on average of 42 runs. However, no significantly positive impacts, in general, were found on the typhoon intensity forecasts, except for Maysak. Analyses for Maysak attributed the improved intensity forecast mainly to the improved analyses for wind, temperature, and moisture in the mid-upper troposphere after data assimilation. Consequently, the RO data largely enhanced the evolving intensity of the typhoon at a more consistent movement as explained by the wavenumber-one vorticity budget analysis. On the other hand, a noted improvement on the wind analysis, but still with degraded temperature analysis above the boundary layer, also improved track forecast at some specific times for Hagibis. The predictability of typhoon track and intensity as marginally improved by use of the large RO data remains very challenging to be well explored.

The highest risk areas of gastric cancer are currently Japan, Korea and China; Qinghai, a high-altitude area, has one of the highest gastric cancer rates in China. The incidence of gastric cancer is higher in the Tibetan ethnic group compared to that in the Han ethnic group in Qinghai. This study was conducted to determine the clinical characteristics of mitochondrial DNA (mtDNA) mutations and copy numbers among Tibetans with gastric cancer residing at high altitudes and investigate the association between adaptations to hypoxic conditions and oncogenesis. A total of 23 Tibetan gastric cancer patients and 40 matched controls were recruited in this study. Leukocyte mtDNA genes and copy numbers were analyzed. The haplogroups were classified based on mitochondrial gene sequences. A total of 56.5% of the study participants had used alcohol at some point in their lives and 73.9% were positive for Helicobacter pylori (H. pylori). Eight mutations in 8 mitochondrial genes were identified in 43.4% of the Tibetan cancer patient group. There were no significant differences in leukocyte mtDNA copy number levels based on smoking status, alchohol consumption, obesity or H. pylori infection between the control and cancer groups. Statistical differences were also not found between gastric cancer patients with and those without mtDNA mutations. The majority of Tibetan patients with gastric cancer belonged to the mitochondrial haplogroup M9. In conclusion, Tibetans with gastric cancer residing at high altitudes exhibited a wide spectrum of mtDNA mutations. However, leukocyte mtDNA copy numbers in stage II gastric cancer were not statistically different compared to those in healthy Tibetans. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19.Methods: In this retrospective, single-center study, we included all confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function.Results: A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%.Conclusion: Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings.

Past attempts to assimilate precipitation by nudging or variational methods have succeeded in forcing the model precipitation to be close to the observed values. However, the model forecasts tend to lose their additional skill after a few forecast hours. In this study, a local ensemble transform Kalman filter (LETKF) is used to effectively assimilate precipitation by allowing ensemble members with better precipitation to receive higher weights in the analysis. In addition, two other changes in the precipitation assimilation process are found to alleviate the problems related to the non-Gaussianity of the precipitation variable: (a) transform the precipitation variable into a Gaussian distribution based on its climatological distribution (an approach that could also be used in the assimilation of other non-Gaussian observations) and (b) only assimilate precipitation at the location where at least some ensemble members have precipitation. Unlike many current approaches, both positive and zero rain observations are assimilated effectively. Observing system simulation experiments (OSSEs) are conducted using the Simplified Parametrisations, primitivE-Equation DYnamics (SPEEDY) model, a simplified but realistic general circulation model. When uniformly and globally distributed observations of precipitation are assimilated in addition to rawinsonde observations, both the analyses and the medium-range forecasts of all model variables, including precipitation, are significantly improved as compared to only assimilating rawinsonde observations. The effect of precipitation assimilation on the analyses is retained on the medium-range forecasts and is larger in the Southern Hemisphere (SH) than that in the Northern Hemisphere (NH) because the NH analyses are already made more accurate by the denser rawinsonde stations. These improvements are much reduced when only the moisture field is modified by the precipitation observations. Both the Gaussian transformation and the new observation selection criterion are shown to be beneficial to the precipitation assimilation especially in the case of larger observation errors. Assigning smaller horizontal localisation length scales for precipitation observations further improves the LETKF analysis.

Objective To investigate the experience in the clinical management of pregnancy and delivery after split liver transplantation (SLT). Methods Related clinical data were collected from a patient who became pregnant and delivered successfully after SLT in the Organ Transplantation Center of our hospital, and a literature review was also performed. Results The patient underwent allogeneic orthotopic SLT due to decompensated liver cirrhosis after autoimmune hepatitis and developed mild acute rejection after surgery, which was improved after the adjustment of immunosuppressive drugs. The patient became pregnant spontaneously at 2 years after surgery, and due to the medication history of mycophenolate sodium enteric-coated tablets, she decided to terminate pregnancy and withdraw from this drug. The patient became pregnant again at 3 years after surgery and expe-rienced fluctuations in graft function, and a series of treatments were given, such as adjustment of the dose of anti-rejection drugs, liver-protecting symptomatic treatment, and tocolytic therapy for threatened preterm labor. Finally under the guidance of liver transplantation, obstetrics, and neonatology, the patient gave birth to a healthy girl by cesarean section at 35 weeks of gestation. Conclusion Although SLT recipients may experience the situations such as fluctuations in graft function and preterm birth, they can achieve a satisfactory prognosis under multidisciplinary collaboration, scientific medication guidance, and close follow-up monitoring.

Typhoon Morakot produced record-breaking accumulated rainfall over southern Taiwan in August 2009. The combination of several factors resulted in this extreme weather event: the steep terrain in Taiwan, the prevailing south-westerly flow in the monsoon trough, Typhoon Goni over the northern South China Sea, and the slow translation speed of Morakot itself over Taiwan. In this study, the influence of the translation speed is particularly emphasized. Based on the EnKF data assimilation, an innovative method is applied to perform ensemble simulations with several designated translation speeds of Morakot using the WRF model. Thus the influence of the translation speed on the amount of accumulated rainfall over Taiwan can be quantitatively evaluated. In the control simulation with observed translation speed, the maximum amount and geographic pattern of accumulated rainfall during the landfall period of Morakot are generally consistent with the observations, though the detailed overall distributions of accumulated rainfall is mostly underestimated, resulting in the low bias of the frequency distribution of the accumulated rainfall. In a simulation with nearly-doubled translation speed of Morakot, the maximum accumulated rainfall is decreased by 33% than that in the control simulation, while the rainfall distribution over Taiwan remains similar. In addition, the 28 ensemble members can further provide additional information in terms of their spread and other statistics. The results from ensemble members reveal the usefulness of ensemble simulations for the quantitative precipitation forecast.

Aim: To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells., Methods: Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells (HUVECs) were determined by enzyme-linked immunosorbent assay, and proliferation and invasion assays. The angiogenesis of HUVECs through interaction with cancer cells and stromal cells was examined by angiogenesis assay. We eventually investigated activation of PI3K/Akt/mTOR signaling by CXCL12 involved in the metastatic process of colon cancer., Results: CXCL12 was expressed in DLD-1 cancer cells and fibroblasts. The secretion level of CXCL6 by colon cancer cells and HUVECs were significantly promoted by fibroblasts derived from CXCL12. CXCL6 and CXCL2 could significantly enhance HUVEC proliferation and migration ( P < 0.01). CXCL6 and CXCL2 enhanced angiogenesis by HUVECs when cultured with fibroblast cells and colon cancer cells ( P < 0.01). CXCL12 also enhanced the invasion of colon cancer cells. Stromal cell-derived CXCL12 promoted the secretion level of CXCL6 and co-operatively promoted metastasis of colon carcinoma through activation of the PI3K/Akt/mTOR pathway., Conclusion: Fibroblast-derived CXCL12 enhanced the CXCL6 secretion of colon cancer cells, and both CXCL12 and CXCL6 co-operatively regulated the metastasis via the PI3K/Akt/mTOR signaling pathway. Blocking this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests.