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.

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.

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.

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.

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.

A novel optimized model based on NARX networks for predicting thermal anomalies in Polish lakes during heatwaves, with special reference to the 2018 heatwave.

In 2018, Europe experienced one of the most severe heatwaves ever recorded. This extreme event's impact on lake surface water temperature (LSWT) in Polish lakes has largely remained unknown. In this study, the impact of the 2018 European heatwave on LSWT in 24 Polish lakes was investigated based on a long-term observed dataset (1987-2020). To capture the LSWT dynamics during the heatwave period and reproduce lake heatwaves, a novel BO-NARX-BR model was developed and evaluated. This model combines the capabilities of the Nonlinear Autoregressive network with Exogenous Inputs (NARX) neural network, the Bayesian Optimization (BO) algorithm for optimizing the number of NARX hidden nodes and lagged input/target values, and the Bayesian Regularization (BR) backpropagation algorithm for the NARX training. The results showed that from April to October 2018, the mean and maximum LSWTs were 2.35 and 3.38 °C warmer than the base-period average (1987-2010) due to the impact of the extreme heatwave. The NARX-based model outperformed another widely used model called air2water in calibration and validation periods. The results also revealed that the BO-NARX-BR model produced significantly better results in capturing lake heatwaves, with computed duration and intensity of lake heatwaves close to the in-situ data. Additionally, LSWT anomaly significantly impacted the duration and intensity of heatwaves that occurred in lakes. Extreme climatic events are gaining increasing importance for the functioning of various elements of the hydrosphere. Such a situation encourages the search for more accurate methods and tools for their prediction. The model applied in the paper corresponds with these assumptions, and its good performance allows for its adaptation to lakes in other regions.

A stacked machine learning model for multi-step ahead prediction of lake surface water temperature.

Lake surface water temperature is one of the most important physical and ecological indices of lakes, which has frequently been used as the indicator to evaluate the impact of climate change on lakes. Knowing the dynamics of lake surface water temperature is thus of great significance. The past decades have witnessed the development of different modeling tools to forecast lake surface water temperature, yet, simple models with fewer input variables, while maintaining high forecasting accuracy are scarce. Impact of forecast horizons on model performance has seldom been investigated. To fill the gap, in this study, a novel machine learning algorithm by stacking multilayer perceptron and random forest (MLP-RF) was employed to forecast daily lake surface water temperature using daily air temperature as the exogenous input variable, with the Bayesian Optimization procedure applied for tuning the hyperparameters. Prediction models were developed using long-term observed data from eight Polish lakes. The MLP-RF stacked model showed very good forecasting capabilities for all lakes and forecast horizons, far better than shallow multilayer perceptron neural network, a model coupling wavelet transform and multilayer perceptron neural network, non-linear regression and air2water models. A reduction in model performance was observed as the forecast horizon increased. However, the model also performs well with a forecast horizon of several days (e.g., 7 days ahead, testing stage: R2 - [0.932, 0.990], RMSE °C - [0.77, 1.83], MAE °C - [0.55, 1.38]). In addition, the MLP-RF stacked model has proven to be reliable for both intermediate temperatures and minimum and maximum peaks. The model proposed in this study will be useful to the scientific community in predicting lake surface water temperature, thus contributing to studies on such sensitive aquatic ecosystems as lakes.

The hindgut microbiome contributes to host oxidative stress in postpartum dairy cows by affecting glutathione synthesis process.

BACKGROUND: Dairy cows are susceptible to postpartum systemic oxidative stress (OS), which leads to significant production loss and metabolic disorders. The gut microbiota has been linked to host health and stress levels. However, to what extent the gut microbiota is associated with postpartum OS remains unknown. In this study, the contribution of the fecal microbiota to postpartum systemic OS and its underlying mechanisms were investigated by integrating 16S rRNA gene sequencing, metagenomics, and metabolomics in postpartum dairy cattle and by transplanting fecal microbiota from cattle to mice. RESULTS: A strong link was found between fecal microbial composition and postpartum OS, with an explainability of 43.1%. A total of 17 significantly differential bacterial genera and 19 species were identified between cows with high (HOS) and low OS (LOS). Among them, 9 genera and 16 species showed significant negative correlations with OS, and Marasmitruncus and Ruminococcus_sp._CAG:724 had the strongest correlations. The microbial functional analysis showed that the fecal microbial metabolism of glutamine, glutamate, glycine, and cysteine involved in glutathione synthesis was lower in HOS cows. Moreover, 58 significantly different metabolites were identified between HOS and LOS cows, and of these metabolites, 19 were produced from microbiota or cometabolism of microbiota and host. Furthermore, these microbial metabolites were enriched in the metabolism of glutamine, glutamate, glycine, and cysteine. The mice gavaged with HOS fecal microbiota had significantly higher OS and lower plasma glutathione peroxidase and glutathione content than those orally administered saline or LOS fecal microbiota. CONCLUSIONS: Integrated results suggest that the fecal microbiota is responsible for OS and that lower glutathione production plays a causative role in HOS. These findings provide novel insights into the mechanisms of postpartum OS and potential regulatory strategies to alleviate OS in dairy cows. Video Abstract.

Age- and Microbiota-Dependent Cell Stemness Plasticity Revealed by Cattle Cell Landscape.

Newborn ruminants are considered functionally monogastric animals. The poor understanding of cellular differences between newborn and mature ruminants prevents the improvement of health and performance of domestic ruminants. Here, we performed the single-cell RNA sequencing on the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, rectum, liver, salivary gland, and mammary gland from newborn and adult cattle. A comprehensive single-cell transcriptomic atlas covering 235,941 high-quality single cells and 78 cell types was deciphered. A Cattle Cell Landscape database (http://cattlecelllandscape.zju.edu.cn) was established to elaborately display the data and facilitate effective annotation of cattle cell types and subtypes for the broad research community. By measuring stemness states of epithelial cells in each tissue type, we revealed that the epithelial cells from newborn forestomach (rumen, reticulum, and omasum) were more transcriptionally indistinct and stochastic compared with the adult stage, which was in contrast to those of abomasum and intestinal tissues. The rapid forestomach development during the early life of calves was driven by epithelial progenitor-like cells with high DNA repair activities and methylation. Moreover, in the forestomach tissues of newborn calves, the Megasphaera genus was involved in regulating the transcriptional plasticity of the epithelial progenitor-like cells by DNA methylation regulation. A novel cell type, the STOML3+ cell, was found to be newborn-specific. It apparently plays a crucial role in stemness maintenance of its own and cholangiocytes in the hepatic microenvironment. Our results reveal that the age- and microbiota-dependent cell stemness plasticity drives the postnatal functional maturity of ruminants.

Gut microbiome is linked to functions of peripheral immune cells in transition cows during excessive lipolysis.

BACKGROUND: Postpartum dairy cows experiencing excessive lipolysis are prone to severe immunosuppression. Despite the extensive understanding of the gut microbial regulation of host immunity and metabolism, its role during excessive lipolysis in cows is largely unknown. Herein, we investigated the potential links between the gut microbiome and postpartum immunosuppression in periparturient dairy cows with excessive lipolysis using single immune cell transcriptome, 16S amplicon sequencing, metagenomics, and targeted metabolomics. RESULTS: The use of single-cell RNA sequencing identified 26 clusters that were annotated to 10 different immune cell types. Enrichment of functions of these clusters revealed a downregulation of functions in immune cells isolated from a cow with excessive lipolysis compared to a cow with low/normal lipolysis. The results of metagenomic sequencing and targeted metabolome analysis together revealed that secondary bile acid (SBA) biosynthesis was significantly activated in the cows with excessive lipolysis. Moreover, the relative abundance of gut Bacteroides sp. OF04 - 15BH, Paraprevotella clara, Paraprevotella xylaniphila, and Treponema sp. JC4 was mainly associated with SBA synthesis. The use of an integrated analysis showed that the reduction of plasma glycolithocholic acid and taurolithocholic acid could contribute to the immunosuppression of monocytes (CD14+MON) during excessive lipolysis by decreasing the expression of GPBAR1. CONCLUSIONS: Our results suggest that alterations in the gut microbiota and their functions related to SBA synthesis suppressed the functions of monocytes during excessive lipolysis in transition dairy cows. Therefore, we concluded that altered microbial SBA synthesis during excessive lipolysis could lead to postpartum immunosuppression in transition cows. Video Abstract.

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.

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.

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.

Heavy metals in lake surface sediments in protected areas in Poland: concentration, pollution, ecological risk, sources and spatial distribution.

This paper presents the state and spatial distribution of surface sediment contamination of 77 lakes in Poland by Cr, Ni, Cd, Pb, Zn, and Cu. The analyzed lakes were located within a network of nature protection areas in the territory of the European Union (EU). Spatial distribution of the heavy metals (HMs), factors favoring the delivery/accumulation of HMs in surface sediments, and pollution sources were analyzed. The results indicate the contamination of lake sediments by HMs, but the potentially toxic effects of HMs are only found in single lakes. The spatial distribution of Cr indicates predominant impacts of point sources, while for Pb, Ni, and Zn, the impact of non-point sources. The analysis showed the presence of areas with very high values of particular HMs (hot spots) in the western part of Poland, while a group of 5 lakes with very low values of Ni, Pb, and Zn (cold spots) was identified in the central part of Poland. Principal component analysis showed that presence of wetlands is a factor limiting HMs inflow to lakes. Also, lower HMs concentrations were found in lake surface sediments located in catchments with a higher proportion of national parks and nature reserves. Higher HMs concentrations were found in lakes with a high proportion of Special Protection Areas designated under the EU Birds Directive. The positive matrix factorization analysis identified four sources of HMs. High values of HMs concentrations indicate their delivery from industrial, urbanized, and agricultural areas. However, these impacts overlap, which disturbs the characteristic quantitative profiles assigned to these pollution sources.

Clinical features of capsule endoscopy in young adults: A single-center retrospective study.

Background and Aim: Capsule endoscopy (CE) has been used in clinical examination among people of various ages, while few studies exclusively focused on the young. We aimed to explore its clinical features in young adults and those with obscure gastrointestinal bleeding (OGIB). Methods: A total of 479 young adults aged 18-44 years were analyzed, with median age of 33 years. Primary positive findings of patients were classified into four kinds of lesions, and potential risk of bleeding among patients with OGIB was assessed based on Saurin classification (P0-2 lesions). Results: The overall completion rate and diagnostic yield of CE among young adults were 89.77 and 77.04%, respectively. Significant differences were found among overall completion rate/diagnostic yield and inpatient status/CE brand. Positive diagnostic yield among 157 patients with OGIB was 51.59% (P1-2 lesions), and the significant risk of bleeding was 37.04% (P2 lesions). Among patients with OGIB in which 134 patients with a total of 216 lesions, ulceration was the commonest P2 lesions, followed by angioectasia and telangiectasia. Inpatient rate, completion rate, and diagnostic yield were higher among patients with overt OGIB, and disease categories of overt OGIB were different compared with occult OGIB. Conclusion: CE is an optimal tool for discovering lesions in young adults and could play a role in evaluating the bleeding risk of young adults with OGIB.

An Age Effect of Rumen Microbiome in Dairy Buffaloes Revealed by Metagenomics.

Age is an important factor in shaping the gut microbiome. However, the age effect on the rumen microbial community for dairy buffaloes remains less explored. Using metagenomics, we examined the microbial composition and functions of rumen microbiota in dairy Murrah buffaloes of different ages: Y (1 year old), M (3−5 years old), E (6−8 years old), and O (>9 years old). We found that Bacteroidetes and Firmicutes were the predominant phyla, with Prevotella accounting for the highest abundance at the genus level. The proportion of Bacteroides and Methanobrevibacter significantly increased with age, while the abundance of genus Lactobacillus significantly decreased with age (LDA > 3, p < 0.05). Most differed COG and KEGG pathways were enriched in Y with carbohydrate metabolism, while older buffaloes enriched more functions of protein metabolism and the processing of replication and repair (LDA > 2, p < 0.05). Additionally, the functional contribution analysis revealed that the genera Prevotella and Lactobacillus of Y with more functions of CAZymes encoded genes of glycoside hydrolases and carbohydrate esterases for their roles of capable of metabolizing starch and sucrose-associated oligosaccharide enzyme, hemicellulase, and cellulase activities than the other three groups (LDA > 2, p < 0.05), thus affecting the 1-year-old dairy buffalo rumen carbohydrate metabolism. This study provides comprehensive dairy buffalo rumen metagenome data and assists in manipulating the rumen microbiome for improved dairy buffalo production.

The efficiency of MSC-based targeted AIE nanoparticles for gastric cancer diagnosis and treatment: An experimental study.

Mesenchymal stem cells (MSCs), due to their tumor tropism, are strongly recruited by various solid tumors and mobilized by inflammatory signals in the tumor microenvironment. However, effective cellular uptake is critical for MSC-based drug delivery. In this study, we synthesized a spherical copolymer, polyethylenimine-poly(ε-caprolactone), with aggregation-induced emission (AIE) material and the anticancer drug, paclitaxel, coloaded onto its inner core. This was followed by the addition of a transactivator of transcription (TAT) peptide, a type of cell-penetrating peptide, to modify the nanoparticles (NPs). Finally, the MSCs were employed to carry the TAT-modified AIE-NPs drug to the tumor sites and assist in simultaneous cancer diagnosis and targeted tumor therapy. In vitro, the TAT-modified AIE-NPs showed good biocompatibility, targeting, and stability in an aqueous solution besides high drug-loading and encapsulation efficiency. In vitro, the AIE-NPs exhibited a controllable release under a mildly acidic environment. The in vivo and in vitro studies showed high antitumor efficacy and low cytotoxicity of the AIE-NP drug, whereas biodistribution confirmed the tumor tropism of MSCs. To summarize, the MSC-based AIE-NP drugs loaded with TAT possessed good biocompatibility and high antitumor efficacy via the enhanced NP-drug uptake. In addition, the tumor tropism of MSCs provided selective drug uptake by the tumor cells and thus reduced the systemic side effects.

Cross-tissue single-cell transcriptomic landscape reveals the key cell subtypes and their potential roles in the nutrient absorption and metabolism in dairy cattle.

Introduction: Dairy cattle are a vitally important ruminant in meeting the demands for high-quality animal protein production worldwide. The complicated biological process of converting human indigestible biomass into highly digestible and nutritious milk is orchestrated by various tissues. However, poorly understanding of the cellular composition and function of the key metabolic tissues hinders the improvement of health and performance of domestic ruminants. Objectives: The cellular heterogeneity, metabolic features, interactions across ten tissue types of lactating dairy cattle were studied at single-cell resolution in the current study. Methods: Unbiased single-cell RNA-sequencing and analysis were performed on the rumen, reticulum, omasum, abomasum, ileum, rectum, liver, salivary gland, mammary gland, and peripheral blood of lactating dairy cattle. Immunofluorescences and fluorescence in situ hybridization were performed to verify cell identity. Results: In this study, we constructed a single-cell landscape covering 88,013 high-quality (500 < genes < 4,000, UMI < 50, 000, and mitochondrial gene ratio < 40% or 15%) single cells and identified 55 major cell types in lactating dairy cattle. Our systematic survey of the gene expression profiles and metabolic features of epithelial cells related to nutrient transport revealed cell subtypes that have preferential absorption of different nutrients. Importantly, we found that T helper type 17 (Th17) cells (highly expressing CD4 and IL17A) were specifically enriched in the forestomach tissues and predominantly interacted with the epithelial cell subtypes with high potential uptake capacities of short-chain fatty acids through IL-17 signaling. Furthermore, the comparison between IL17RAhighIL17RChigh cells (epithelial cells with IL17RA and IL17RC expression levels both greater than 0.25) and other cells explained the importance of Th17 cells in regulating the epithelial cellular transcriptional response to nutrient transport in the forestomach. Conclusion: The findings enhance our understanding of the cellular biology of ruminants and open new avenues for improved animal production of dairy cattle.

Sediment phosphate release flux under hydraulic disturbances in the shallow lake of Chaohu, China.

Quantifying the effect of hydraulic disturbances on sediment phosphate release is a key issue in the water quality assessment of lakes, especially for the shallow lakes which are susceptible to winds and waves. Here, we sampled the original sediment columns from 12 positions in the eastern, central, and western areas of the Chaohu Lake, a representative shallow lake in China, and observed phosphate release under three levels of hydraulic disturbances in the laboratory. When the disturbance was weak and sediment on the surface of bottom mud moved individually (the Individual Motion Mode), sediment phosphate release rate was insignificant (0.24 mg/m2/day). When the disturbance was medium and only a small percentage (< 16%) of surface sediment started to move (the Small Motion Mode), the phosphate release rate sharply increased to 4.81 mg/m2/day. When the disturbance was further strengthened and most (≥ 16%) of the surface sediment moved (the General Motion Mode), the phosphate release rate was more than doubled (10.23 mg/m2/day). With the increase in hydraulic disturbance intensity, the variation range of phosphate release also became wider. Spatial distribution showed that the release rate varies the most in the western area, followed by the eastern and the central areas. By extrapolating the experimental results to the real scale, it was found that the phosphate release fluxes would probably fall within a wide range between 203.43 to 7311.01 kg/day under different levels of hydrodynamic disturbances which considerably affects phosphate release from shallow lakes. This study also has implications for the pollutant management in other shallow lakes.