Dynamic fecal microenvironment properties enable predictions and understanding of peripartum blood oxidative status and nonesterified fatty acids in dairy cows.

The transition period in dairy cows is a critical stage and peripartum oxidative status, negative energy balance (NEB), and inflammation are highly prevalent. Fecal microbial metabolism is closely associated with blood oxidative status and nonesterified fatty acids (NEFA) levels. Here, we investigated dynamic changes in total oxidative status markers and NEFA in blood, fecal microbiome, and metabolome of 30 dairy cows during transition (-21, -7, +7, +21 d relative to calving). Then the Bayesian network and 9 machine-learning algorithms were applied to dismantle their relationship. Our results show that the oxidative status indicator (OSI) of -21, -7, +7 d was higher than +21 d. The plasma concentration of NEFA peaked on +7 d. For fecal microenvironment, a decline in bacterial α diversity was observed at postpartum and in bacterial interactions at +7 d. Conversely, microbial metabolites involved in carbohydrate, lipid, and energy metabolism increased on +7 d. A correlation analysis revealed that 11 and 10 microbial metabolites contributed to OSI and NEFA variations, respectively (arc strength >0.5). The support vector machine (SVM) radial model showed the highest average predictive accuracy (100% and 88.9% in the test and external data sets) for OSI using 1 metabolite and 3 microbiota. The SVM radial model also showed the highest average diagnostic accuracy (100% and 91% in the test and external data sets) for NEFA with 2 metabolites and 3 microbiota. Our results reveal a relationship between variation in the fecal microenvironment and indicators of oxidative status, NEB, and inflammation, which provide a theoretical basis for the prevention and precise regulation of peripartum oxidative status and NEB.

HKDC1 upregulation promotes glycolysis and disease progression, and confers chemoresistance onto gastric cancer.

There is increasing evidence that hexokinase is involved in cell proliferation and migration. However, the function of the hexokinase domain containing protein-1 (HKDC1) in gastric cancer (GC) remains unclear. Immunohistochemistry analysis and big data mining were used to evaluate the correlation between HKDC1 expression and clinical features in GC. In addition, the biological function and molecular mechanism of HKDC1 in GC were studied by in vitro and in vivo assays. Our study indicated that HKDC1 expression was upregulated in GC tissues compared with adjacent nontumor tissues. High expression of HKDC1 was associated with worse prognosis. Functional experiments demonstrated that HKDC1 upregulation promoted glycolysis, cell proliferation, and tumorigenesis. In addition, HKDC1 could enhance GC invasion and metastasis by inducing epithelial-mesenchymal transition (EMT). Abrogation of HKDC1 could effectively attenuate its oncogenic and metastatic function. Moreover, HKDC1 promoted GC proliferation and migration in vivo. HKDC1 overexpression conferred chemoresistance to cisplatin, oxaliplatin, and 5-fluorouracil (5-Fu) onto GC cells. Furthermore, nuclear factor kappa-B (NF-κB) inhibitor PS-341 could attenuate tumorigenesis, metastasis, and drug resistance ability induced by HKDC1 overexpression in GC cells. Our results highlight a critical role of HKDC1 in promoting glycolysis, tumorigenesis, and EMT of GC cells via activating the NF-κB pathway. In addition, HKDC1-mediated drug resistance was associated with DNA damage repair, which further activated NF-κB signaling. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.

Microbiota-host crosstalk in the newborn and adult rumen at single-cell resolution.

BACKGROUND: The rumen is the hallmark organ of ruminants, playing a vital role in their nutrition and providing products for humans. In newborn suckling ruminants milk bypasses the rumen, while in adults this first chamber of the forestomach has developed to become the principal site of microbial fermentation of plant fibers. With the advent of single-cell transcriptomics, it is now possible to study the underlying cell composition of rumen tissues and investigate how this relates the development of mutualistic symbiosis between the rumen and its epithelium-attached microbes. RESULTS: We constructed a comprehensive cell landscape of the rumen epithelium, based on single-cell RNA sequencing of 49,689 high-quality single cells from newborn and adult rumen tissues. Our single-cell analysis identified six immune cell subtypes and seventeen non-immune cell subtypes of the rumen. On performing cross-species analysis of orthologous genes expressed in epithelial cells of cattle rumen and the human stomach and skin, we observed that the species difference overrides any cross-species cell-type similarity. Comparing adult with newborn cattle samples, we found fewer epithelial cell subtypes and more abundant immune cells, dominated by T helper type 17 cells in the rumen tissue of adult cattle. In newborns, there were more fibroblasts and myofibroblasts, an IGFBP3+ epithelial cell subtype not seen in adults, while dendritic cells were the most prevalent immune cell subtype. Metabolism-related functions and the oxidation-reduction process were significantly upregulated in adult rumen epithelial cells. Using 16S rDNA sequencing, fluorescence in situ hybridization, and absolute quantitative real-time PCR, we found that epithelial Desulfovibrio was significantly enriched in the adult cattle. Integrating the microbiome and metabolome analysis of rumen tissues revealed a high co-occurrence probability of Desulfovibrio with pyridoxal in the adult cattle compared with newborn ones while the scRNA-seq data indicated a stronger ability of pyroxidal binding in the adult rumen epithelial cell subtypes. These findings indicate that Desulfovibrio and pyridoxal likely play important roles in maintaining redox balance in the adult rumen. CONCLUSIONS: Our integrated multi-omics analysis provides novel insights into rumen development and function and may facilitate the future precision improvement of rumen function and milk/meat production in cattle.

A method of assessing the depth of contaminated sediments that should be removed in lakes: a case study of Tangxun Lake, China.

The depth of contaminated sediments constrains the water environment of large shallow lakes and can affect shallow lake water quality through sediment resuspension and nutrient release. Although such effects can be avoided by sediment dredging methods, we still cannot precisely quantify the depth of sediment dredging. Therefore, we used organic index method, pollution index method and potential ecological risk evaluation to evaluate the contamination status of split samples of in situ sediments layer by layer, and established a comprehensive contamination index evaluation method for layer-by-layer sediments, then combined with the contamination release characteristics of split samples to assess the contamination degree of the sediments obtained. The results show that the content of nitrogen and phosphorus in the surface layer of Lake Townsend sediments is generally higher than that in the middle and bottom sediments, and the heavy metals also satisfy this pattern, which is consistent in the sediments of both east and west regions. We also simulated the release process of nitrogen and phosphorus nutrients in the in situ sediment of Tangxun Lake in 2019, and the experimental results showed that the risk of nitrogen and phosphorus nutrient release in the sediment was mainly concentrated in the surface and middle layers, and the risk of elemental nitrogen release was significantly greater than that of phosphorus release. Finally, a comprehensive evaluation was carried out to obtain the desilting depth of the sediments in Lake Townsend, and it can be determined that the recommended desilting depth is about 20 cm for West Lake and 30 cm for East Lake. The results show that the recommended dredging depth can be determined based on this method, which provides an important scientific basis for sediment dredging in Tangxun Lake and even provides a new paradigm for sediment dredging depth estimation in similar large shallow lakes.

Pulses outweigh cumulative effects of water diversion from river to lake on lacustrine phytoplankton communities.

Due to the allochthonous input of nutrients and species, the cumulative effects of water diversion on water-receiving lakes deserve attention. Taking the water diversion project from the Yangtze River to Lake Taihu (WDYT) as an example, we explored the temporal effects of WDYT on the phytoplankton community and physicochemical habitat of Lake Taihu in autumn and winter from 2013 to 2018. Although the short-term diversion significantly increased the risk of importing nutrients, the relatively high quality of the diversion water compared with other inflow rivers had improved the water quality of the water-receiving lake region. The seasonal water diversion significantly increased phytoplankton diversity and community network complexity and reshaped the lacustrine community to be diatom-dominated with their relative proportions of 24.1-64.9% during water diversion periods. The contributions of physicochemical habitat changes induced by water diversion to variations in phytoplankton communities were 24.0-28.0%. The differences in phytoplankton diversity, community composition and physicochemical habitat in the water-receiving lake region between the diversion and non-diversion years were more evident than those between the non-diversion years in the same season, when comparing the multivariate dispersion indices among them. However, the lacustrine phytoplankton community during non-diversion periods still has not been essentially altered after several years of diversion, so the pulse effects of short-term water diversion were more obvious than the long-term cumulative impacts. Better control of allochthonous nutrients, appropriate increase in inflow water, adhering to the long-term operation, should be effective to enhance ecological benefits of such water diversion projects.

Limited Lymph Node Resection Does Not Decrease Postoperative Mortality After Esophagectomy in Octogenarians With Thoracic Esophageal Cancer.

BACKGROUND: Octogenarians with esophageal cancer typically have a poor physical condition, reduced physiological reserves, and high postoperative mortality (POM). Extensive lymph node dissection increases surgical trauma and postoperative complications. The purpose of this study was to examine the associations between the number of dissected lymph nodes and short-term and long-term postoperative outcomes in octogenarians with thoracic esophageal cancer. METHODS: We examined the data of patients from the Surveillance, Epidemiology, and End Results database. We divided the patients into two groups in accordance with the number of lymph nodes dissected: patients with <15 examined lymph nodes (eLNs) and patients with ≥15 eLNs. Mortality was quantified at 30, 60, and 90 d after surgery. Univariable and multivariable logistic regression analyses were performed to identify predictors of 90-day mortality. Kaplan-Meier analysis and the log-rank test were used to analyze the overall survival and cause-specific survival of the patients. RESULTS: A total of 208 octogenarians with thoracic esophageal cancer were included in the analysis. The 30-day POM rates were 10.3% and 6.9%, the 60-day POM rates were 16.9% and 13.9%, and the 90-day POM rates were 21.3% and 19.4% for patients with <15 eLNs and ≥15 eLNs, respectively. However, the differences in POM between the two groups were statistically nonsignificant (all P > 0.05). In accordance with the multivariable logistic regression analysis, age and marital status were significantly associated with 90-day POM. Furthermore, no significant difference was found between the groups in terms of long-term survival. The 5-year overall survival rates were 29% and 26.8% (P = 0.719) and the 5-year cause-specific survival rates were 43.2% and 34.1% (P = 0.446) in patients with <15 eLNs and ≥15 eLNs, respectively. CONCLUSIONS: We have demonstrated that octogenarians undergoing esophagectomy are associated with an unacceptably high POM, and less extensive lymph node resection does not decrease POM. Octogenarians may not benefit from esophagectomy with lymphadenectomy. Additional studies need to be conducted to further guide clinicians performing highly selective esophagectomy.

Prognostic significance and function of MCM10 in human hepatocellular carcinoma.

Aim: To investigate the role of MCM10, a conserved replication factor, in hepatocellular carcinoma (HCC). Methods: We used data from 364 HCC patients in the Cancer Genome Atlas database and conducted in vitro experiments to confirm the role of MCM10. Results: High MCM10 expression correlated with poor HCC patient outcome and was an independent prognosticator for HCC. Time-dependent receiver operating characteristic curve analysis found that the sequential trend of MCM10 for survival was not inferior to that of the tumor node metastasis stage. The MCM10 model had a higher C-index than the non-MCM10 model, indicating that incorporating MCM10 into a multivariate model improves the model's prognostic accuracy for HCC. Genetic alterations of MCM10 prominently correlated with an unfavorable HCC outcome. Conclusion: Our findings strongly suggest using the MCM10 gene as a prognostic indicator in HCC.

Lay abstract Hepatocellular carcinoma is one of the most aggressive malignant cancers globally. Our study investigated the role of a conserved replication factor, MCM10, in hepatocellular carcinoma. We performed some bioinformatics analysis and in vitro experiments, and successfully found that MCM10 has a good predictive value for survival in patients with hepatocellular carcinoma.

Diagnostic and prognostic value of HOXC family members in gastric cancer.

Aims: HOX clusters encode proteins that play pivotal roles in regulating transcription factors and many other proteins during embryogenesis. However, little is known about the diagnostic and prognostic values of HOXC family members in gastric cancer (GC). Materials and methods: The authors evaluated the data in patients with GC based on bioinformatics analysis. Results: HOXC6/8/9/10/11/13 were overexpressed in GC and associated with a poor prognosis. HOXC4/5 were downregulated in GC tissues. Receiver operating characteristic curve analysis demonstrated that they have high diagnostic value. In addition, HOXC4/5/6/9/10/11/13 were negatively correlated with DNA methylation level. The gene set enrichment analysis results implied that they play essential roles in multiple biological processes underlying tumorigenesis. Conclusion: HOXC family members are potential targets for diagnosis and may work as prognostic biomarkers of GC.

Lay abstracts Gastric cancer (GC) remains one of the most common malignant tumors of the digestive system and the third most common cause of death from cancer. Since GC is usually diagnosed at an advanced stage, despite advances in comprehensive treatment strategies, its mortality rate is still very high. GC is a disease that is highly heterogeneous in terms of genotype and phenotype. Therefore, a more complete understanding of the molecular mechanism of GC carcinogenesis and identification of reliable molecular targets for the diagnosis and prognosis of GC are highly valued. It is well known that the HOXC gene family expression is upregulated in most solid tumor types, such as lung cancer, colon cancer and prostate cancer. The authors explore the role of the HOXC gene family in GC. Results demonstrated that HOXC family members are potential targets for diagnosis and may work as prognostic biomarkers of GC.

HOTAIR plays an oncogenic role in gastric cancer through microRNA and SNP.

HOX transcript antisense intergenic RNA (HOTAIR) is a lncRNA with a length of 2,158 nucleotides and its two terminal domains could combine with different complexes to function at the level of transcription and translation. It overexpresses in many cancers including gastric cancer. HOTAIR could play an oncogenic role in the initiation and progression of gastric cancer through interaction with microRNAs, such as miR-330/618/126 in the PI3K/Akt signaling pathways. HOTAIR single nucleotide polymorphisms (SNPs) may have genotype-function and allele-specific effect on gastric cancer by a mechanism that specific SNP could give rise to a variation of HOTAIR and alter the binding site of microRNAs. Both rs920778 T allele and rs4759314 G allele will enhance the susceptibility to gastric cancer in the Chinese populations. In a word, the suppression of HOTAIR and overexpression of downstream microRNAs may be potential therapeutic strategies of gastric cancer related to HOTAIR.

Lacustrine micro-ecosystem responses to the inflow discharge gradient of water diversion from Yangtze River to Lake Taihu.

Water diversion project is always taken as the emergency and effective engineering measure to deal with the cyanobacterial blooms in eutrophic lakes. The inflow discharge and duration are the critical parameters influencing the effects and costs of the water diversion activities. Due to the impacts of meteorological and hydrological factors such as precipitation and wind-wave currents, the environmental influence of water diversion on shallow eutrophic lakes is always unclear. To explore the quantitative relationships among inflow discharges, duration and ecological parameters in water-receiving lakes, the typical water diversion engineering-Water Diversion Project from Yangtze River to Lake Taihu was taken as an example and the mesocosm experiment modeling the micro-ecosystem of the water-receiving Meiliang Bay in Lake Taihu was conducted with five groups of inflow discharges according to the practical discharges of the main river channel-Wangyu River. Each micro-ecosystem had a volume of 15 L and was studied for a period of 30 days (25 days for the water diversion period and 5 days for the stop period). The results showed that the inflow discharges had different extents of impact on the physicochemical and biological characteristics of the micro-ecosystems. The concentrations of total dissolved solids, total nitrogen, nitrate, active silicate and bacterial abundance in the experimental groups (inflow discharges > 100 m3/s) were all decreased compared with the control group, with the lowest values in the period of 10-15 days. During the stop period, the concentrations of sensitive biotic and abiotic parameters were all recovered with different extents and different from the initial state of this experiment, which revealed that the effects of the short-term water diversion on lake ecosystems were resilient and durable. There were quantitative relationships among the inflow discharge, content interpolation and variation in water nutrients, with different relationships in different periods of the water diversion. The influence of water diversion on lake ecosystems was not only related to the direct impacts of allochthonous inputs, but also with the indirect effects of internal habitat variation in lakes.

Exploring and quantifying the impact of climate change on surface water temperature of a high mountain lake in Central Europe.

Lake surface water temperature (LSWT) is a key indicator which drives ecosystem structure and function. Quantifying the impact of climate change on LSWT variations is thus of great significance. In this study, observed data of LSWT during the period 1969-2018 in a high mountain lake (Morskie Oko Lake, Central Europe) were analyzed. The results showed that the prominent warming of the LSWT and air temperature began around 1997. A logistic non-linear S-curve function was used to model monthly average LSWT. The non-linear model performed well to capture monthly average LSWT and air temperature relationships (Nash-Sutcliffe efficiency coefficient 0.86 and the root mean squared error 1.63 °C). Using the 2009-2018 period as base scenario, a sensitivity analysis was conducted. The results showed that the annual mean LSWT will likely increase about + 1.29 °C and + 2.64 °C with air temperature increases of + 2 °C and + 4 °C respectively at the end of the twenty-first century. If realized, such a scenario will cause serious consequences on lake ecosystem.

HOXC10 promotes gastric cancer cell invasion and migration via regulation of the NF-κB pathway.

Homeobox gene C10 (HOXC10), known to regulate cell differentiation and proliferation, is upregulated in gastric cancer (GC). The mechanism underlying HOXC10 involvement in GC metastasis is unclear. Herein, we found that HOXC10 is overexpressed in GC relative to normal controls. In the 73 GC patients tissue microarrays (TMA) tested, HOXC10 expression was closely related with tumor-node-metastasis (TNM) stage, lymph node metastasis, and distant metastasis. HOXC10 overexpression tended to associate with low 5-year cumulative survival. Cox regression analysis identified HOXC10 as an independent prognostic factor for poor patient survival. HOXC10 promoted GC cell invasion and migration, regulated the expression of activated ATM and markers of NF-κB signaling. HOXC10 may promote invasion and migration of GC by regulating ATM/NF-κB signaling pathway. HOXC10 should be explored as a clinical marker of GC prognosis.

Overexpression of NKX6.1 is closely associated with progressive features and predicts unfavorable prognosis in human primary hepatocellular carcinoma.

The homeobox gene NKX6.1 was recently identified in cervical tumors. This study was designed to explore the clinical and prognostic significance of NKX6.1 further in patients with primary hepatocellular carcinoma (HCC). The expression levels of NKX6.1 were examined using real-time PCR, Western blotting, and immunohistochemistry in HCC cell lines and HCC tissues. The invasion capability of cell lines following silencing or overexpression of NKX6.1 was investigated by Transwell assay. Cells proliferation was tested by MTT assays. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to NKX6.1 expression. Correlation between NKX6.1 immunohistochemical staining, clinicopathologic parameters, and follow-up data of HCC patients was analyzed statistically. NKX6.1 expression was higher in HCC tissues compared to the adjacent noncancerous tissue. NKX6.1 overexpression was significantly correlated with tumor size, tumor differentiation, clinical stage, metastasis, and relapse. Kaplan-Meier analysis revealed that NKX6.1 overexpression was related to unfavorable 5-year disease-free survival and overall survival. Importantly, multivariate analysis indicated that NKX6.1 overexpression was an independent unfavorable marker for overall survival. Moreover, a significant relationship was observed between NKX6.1 and EMT marker expression levels, and NKX6.1 knockdown inhibited cell invasion, and overexpression of NKX6.1 promotes cell proliferation in vitro. NKX6.1 is upregulated in HCC and is a reliable prognostic marker for patients with HCC.

Low expression of BARX2 in human primary hepatocellular carcinoma correlates with metastasis and predicts poor prognosis.

AIM: The homeobox gene Barx2 was recently identified as a regulator of ovarian and breast cancer; however, the expression level of BARX2 and its significance in hepatocellular carcinoma (HCC) remain unknown. METHODS: Protein and mRNA expression levels of Barx2 were examined using Western blotting and real-time PCR respectively, in paired HCC tissue and matched adjacent non-cancerous tissue from 12 patients. The expression levels of epithelial-mesenchymal transition (EMT) markers were also detected in relation to BARX2 expression. Lastly, immunohistochemistry for BARX2 was also performed on a tissue microarray containing 231 HCC tissue samples. RESULTS: We observed that BARX2 expression was lower in HCC tissues compared to matching adjacent non-cancerous tissue. The low expression level of BARX2 was significantly correlated with metrics of tumor size, tumor differentiation, clinical stage, metastasis and relapse. Furthermore, the patients with low BARX2 expression had adverse survival outcomes. Importantly, multivariate Cox regression analysis revealed that low BARX2 expression was an independent marker for lower overall survival (P = 0.007). Moreover, a significant negative relationship was observed between the expression of BARX2 and markers of EMT. CONCLUSION: These findings provide evidence that the low expression level of BARX2 in HCC is significantly correlated with tumor metastasis, and that BARX2 may be an independent prognostic biomarker for patients with HCC.

Modelling selenium behavior in aquatic systems: a review of status, challenges, and opportunities.

Selenium (Se) is an essential element for aquatic organisms as well as humans. It can be toxic to organisms depending on its concentration and chemical speciation; thus, considerable efforts have been made to unravel the biogeochemical cycling of Se in aquatic systems. Mathematical models provide an important tool to better understand the fate of Se in different environment compartments. However, a comprehensive review of modeling Se in aquatic systems with current challenges and opportunities is missing. To fill this gap, we firstly summarize the processes governing Se cycling in aquatic systems, including particle adsorption and desorption, diffusion, biological uptake, redox reactions, and volatilization. Then, we critically review the available models, identifying the compartments modelled, environmental factors considered, and the Se species and geochemical processes used in each model, providing an assessment of their advantages and limitations. Data availability for modeling studies is investigated, highlighting how to better quantify the redox reactions, estimate of Se loadings, and mass balance. For the modeling of Se cycling in aquatic systems, the ability of the models to link sources to biota concentrations under a range of hydrodynamic conditions and with mechanistic representations of transport, transformation, and uptake processes is required. The majority of the current models can conduct this task; however, to better present the uptake processes of Se in the food web, two-way coupling of the Se cycling model with a food web model is recommended.

Assessing and predicting water quality index with key water parameters by machine learning models in coastal cities, China.

The water quality index (WQI) is a widely used tool for comprehensive assessment of river environments. However, its calculation involves numerous water quality parameters, making sample collection and laboratory analysis time-consuming and costly. This study aimed to identify key water parameters and the most reliable prediction models that could provide maximum accuracy using minimal indicators. Water quality from 2020 to 2023 were collected including nine biophysical and chemical indicators in seventeen rivers in Yancheng and Nantong, two coastal cities in Jiangsu Province, China, adjacent to the Yellow Sea. Linear regression and seven machine learning models (Artificial Neural Network (ANN), Self-Organizing Maps (SOM), K-Nearest Neighbor (KNN), Support Vector Machines (SVM), Random Forest (RF), Extreme Gradient Boosting (XGB) and Stochastic Gradient Boosting (SGB)) were developed to predict WQI using different groups of input variables based on correlation analysis. The results indicated that water quality improved from 2020 to 2022 but deteriorated in 2023, with inland stations exhibiting better conditions than coastal ones, particularly in terms of turbidity and nutrients. The water environment was comparatively better in Nantong than in Yancheng, with mean WQI values of approximately 55.3-72.0 and 56.4-67.3, respectively. The classifications "Good" and "Medium" accounted for 80 % of the records, with no instances of "Excellent" and 2 % classified as "Bad". The performance of all prediction models, except for SOM, improved with the addition of input variables, achieving R2 values higher than 0.99 in models such as SVM, RF, XGB, and SGB. The most reliable models were RF and XGB with key parameters of total phosphorus (TP), ammonia nitrogen (AN), and dissolved oxygen (DO) (R2 = 0.98 and 0.91 for training and testing phase) for predicting WQI values, and RF using TP and AN (accuracy higher than 85 %) for WQI grades. The prediction accuracy for "Medium" and "Low" water quality grades was highest at 90 %, followed by the "Good" level at 70 %. The model results could contribute to efficient water quality evaluation by identifying key water parameters and facilitating effective water quality management in river basins.

An optimized NARX-based model for predicting thermal dynamics and heatwaves in rivers.

The thermal dynamics within river ecosystems represent critical areas of study due to their profound impact on overall aquatic health. With the rising prevalence of heatwaves in rivers, a consequence of climate change, it is imperative to deepen our understanding through comprehensive research efforts. Despite this urgency, there remains a noticeable dearth in studies aimed at refining modeling techniques to precisely characterize the duration and intensity of these events. In response to this gap, the present study endeavors to augment the NARX-based model (Nonlinear Autoregressive network with Exogenous Inputs) to enhance predictive capabilities regarding thermal dynamics and river heatwaves. The optimized NARX-based model included the Bayesian Optimization (BO) algorithm, which allows fine-tuning the number of NARX hidden nodes and lagged input/target values, and the Bayesian Regularization (BR) backpropagation algorithm to improve the NARX calibration process. A long-term dataset spanning from 1991 to 2021, encompassing 18 rivers across the expansive Vistula River Basin, one of Europe's largest river systems, was employed for this study. The performance of the BO-NARX-BR model was compared with that of the widely utilized air2stream model for modeling river water temperature (RWT). The results unequivocally demonstrated the superior performance of the NARX-based model across the calibration and validation periods, and four heatwave years. In the context of river heatwaves, the study revealed an escalating frequency and intensity within the Vistula River Basin. Furthermore, the NARX-based model exhibited superior proficiency in characterizing river heatwaves compared to the air2stream model. This study, as the inaugural examination of river heatwaves in Poland and one of the few globally, furnishes crucial reference points for subsequent research endeavors on this phenomenon.

HSPA4 upregulation induces immune evasion via ALKBH5/CD58 axis in gastric cancer.

INTRODUCTION: Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Recently, targeted therapies including PD1 (programmed cell death 1) antibodies have been used in advanced GC patients. However, identifying new biomarker for immunotherapy is still urgently needed. The objective of this study is to unveil the immune evasion mechanism of GC cells and identify new biomarkers for immune checkpoint blockade therapy in patients with GC. METHODS: Coimmunoprecipitation and meRIP were performed to investigate the mechanism of immune evasion of GC cells. Cocuture system was established to evaluate the cytotoxicity of cocultured CD8+ T cells. The clinical significance of HSPA4 upregulation was analyzed by multiplex fluorescent immunohistochemistry staining in GC tumor tissues. RESULTS: Histone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. The cytotoxicity of CD8+ T cells are impaired and PD1/PDL1 axis is activated when CD8+ T cells are cocultured with HSPA4 overexpressed GC cells. HSPA4 upregulation is associated with worse 5-year overall survival of GC patients receiving only surgery. It is an independent prognosis factor for worse survival of GC patients. In GC patients receiving the combined chemotherapy with anti-PD1 immunotherapy, HSPA4 upregulation is observed in responders compared with non-responders. CONCLUSION: HSPA4 upregulation causes the decrease of CD58 in GC cells via HSPA4/ALKBH5/CD58 axis, followed by PD1/PDL1 activation and impairment of CD8+ T cell's cytotoxicity, finally induces immune evasion of GC cells. HSPA4 upregulation is associated with worse overall survival of GC patients with only surgery. Meanwhile, HSPA4 upregulation predicts for better response in GC patients receiving the combined immunotherapy.

Single-cell transcriptomics across 2,534 microbial species reveals functional heterogeneity in the rumen microbiome.

Deciphering the activity of individual microbes within complex communities and environments remains a challenge. Here we describe the development of microbiome single-cell transcriptomics using droplet-based single-cell RNA sequencing and pangenome-based computational analysis to characterize the functional heterogeneity of the rumen microbiome. We generated a microbial genome database (the Bovine Gastro Microbial Genome Map) as a functional reference map for the construction of a single-cell transcriptomic atlas of the rumen microbiome. The atlas includes 174,531 microbial cells and 2,534 species, of which 172 are core active species grouped into 12 functional clusters. We detected single-cell-level functional roles, including a key role for Basfia succiniciproducens in the carbohydrate metabolic niche of the rumen microbiome. Furthermore, we explored functional heterogeneity and reveal metabolic niche trajectories driven by biofilm formation pathway genes within B. succiniciproducens. Our results provide a resource for studying the rumen microbiome and illustrate the diverse functions of individual microbial cells that drive their ecological niche stability or adaptation within the ecosystem.

Analysis of IGFBP7 expression characteristics in pan-cancer and its clinical relevance to stomach adenocarcinoma.

Background: Insulin-like growth factor (IGF) binding proteins (IGFBPs) are involved in tumorigenesis and cancer progression. IGFBP7 has been shown to act as either a tumor suppressive gene or an oncogene in many tumors, including stomach adenocarcinoma (STAD). To provide a more systematic and comprehensive understanding of IGFBP7 gene, we performed an integrative pan-cancer analysis and explored further with the case of STAD. Methods: We compared the expression data of IGFBP7 in various cancer and normal tissues obtained from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database. The TISIDB web portal was used to analyze the associations of IGFBP7 with cancer molecular subtypes and immune subtypes. We also analyzed the predictive ability and prognostic values of IGFBP7 in pan-cancer, as well as explored its targeted binding proteins and their biological functions. Additionally, we examined the relationship between IGFBP7 and the clinical characteristics of STAD, investigated the co-expression genes and biological functions of differentially expressed genes (DEGs), and validated the mRNA and protein expression levels of IGFBP7 using gastric cancer (GC) and adjacent normal tissues in a small self-case-control study. Results: IGFBP7 was found to be overexpressed in STAD and downregulated in many other cancers. The mRNA and protein expression levels of IGFBP7 were also significantly higher in the collected GC tissues compared with adjacent tissues. Expression of IGFBP7 varied significantly across molecular subtypes of nine different cancer types and immune subtypes of eight types, with the highest expression observed in the genomically stable molecular subtype and C3 inflammatory immune subtype in STAD. IGFBP7 demonstrated an area under the curve (AUC) >0.7 for predicting 16 cancer types, and an AUC >0.9 for seven types. Patients in the higher IGFBP7 expression group showed a poorer prognosis for adrenal cortical carcinoma (ACC) and low-grade glioma (LGG), while demonstrating a more favorable prognosis for kidney renal clear cell carcinoma (KIRC). IGFBP7 expression in STAD was significantly associated with T stage, pathological stage, histologic grade, and Helicobacter pylori infection. Conclusions: IGFBP7 showed promise as a biomarker for prediction and prognosis in pan-cancer. IGFBP7 was found to be overexpressed in STAD, and its expression was closely associated with the clinical characteristics of STAD.