Development and validation of a novel prognostic lncRNA signature based on the APOBEC3 family genes in gastric cancer.

Introduction: Gastric Cancer (GC) refers to a prevalent malignant cancer accompanied by a weak prognosis. The APOBEC3 family genes and lncRNAs are linked with cancer progression. Nevertheless, there is still a scarcity of data concerning the prognostic value of APOBEC3-related lncRNAs in GC. Methods: We extracted the data from GC samples, including transcriptome as well as clinical data, obtained from the TCGA database. Then, we screened for lncRNAs that were correlated with the APOBEC3 family genes and constructed an APOBEC3-related lncRNA prognostic signature (LPS) by utilizing univariate Cox and lasso regression analysis. Furthermore, we validated our constructed signature and evaluated it thoroughly, including analysis of its function, immunity, mutations, and clinical applications via multiple methods, including Metascape, GSEA, and analyses including TIC and TME, immune checkpoints, CNV and SNPs, Kaplan-Meier survival curves, nomogram, decision tree and drug prediction analysis. Finally, we overexpressed LINC01094 to evaluate the impacts on the proliferation as well as migration with regards to KATO-2 cells. Results: We selected eight lncRNAs for our APOBEC3-related LPS, which is demonstrated as a valuable tool in predicting the individual GC patients' prognosis. Subsequently, we segregated the samples into subgroups of high-as well as low-risk relying on the risk score with regards to APOBEC3-related LPS. By performing functional analysis, we have shown that immune-as well as tumor-related pathways were enriched in high- and low-risk GC patients. Furthermore, immune analysis revealed a robust correlation between the APOBEC3-related LPS and immunity. We found that immune checkpoints were significantly associated with the APOBEC3-related LPS and were greatly exhibited in GC tumor and high-risk samples. Mutational analysis suggested that the mutational rate was greater in low-risk samples. Furthermore, we predicted small molecular drugs displayed greater sensitivity in patients categorized as high-risk. Moreover, the immune response was also better in high-risk patients. Of these drugs, dasatinib was significant in both methods and might be considered a potential novel drug for treating high-risk GC patients. Finally, we found that LINC01094 has the potential to enhance the migration, proliferation as well as inhibit apoptosis of KATO-2 in GC cells. And Dasatinib has an inhibitory effect on the migration as well as proliferation in GC cells. Conclusion: We created a novel APOBEC3-related LPS in predicting the prognosis with regards to individual GC patients. Importantly, this APOBEC3-related LPS was closely associated with immunity and might guide clinical treatment.

[Changes in protein requirements of elderly people over 5 years assessed using the indicator amino acid oxidation method].

OBJECTIVE: To evaluate the changes in protein requirements of the elderly during the past five years. METHODS: Based on the previous study of protein requirements of 14 elderly in 2017, 4 of these elderly(70-80 y) were included as study participants and protein requirements were re-evaluated using the indicator amino acid oxidation method. There were seven protein levels: 0.1, 0.3, 0.6, 0.9, 1.2, 1.5 and 1.8 g/(kg·d). Maintenance diets were given for the first two days of each protein level. A stable isotope study was conducted on the day 3, using L-~(13)C-phenylalanine as an indicator on the basis of an amino acid rationed diet, which was orally ingested into the body along with the amino acid rationed diet, and breath and urine samples were collected when the metabolism of L-~(13)C-phenylalanine reached steady state in the body. By measuring the kinetic parameters of labeled amino acids in the samples, a nonlinear mixed-effects model was constructed for the protein intake to be tested and the oxidation rate of labeled amino acids. The mean protein requirement of the study population was determined by the protein intake corresponding to the inflection point of the curve. RESULTS: Based on the production rate of ~(13)CO_2 in exhaled breath of four elderly people at different protein levels, the mean protein requirement was 1.05(95%CI 0.51-1.60) g/(kg·d). The protein recommended nutrient intake was 1.31(95%CI 0.64-2.00) g/(kg·d) was estimated by applying the coefficient of variation of the mean protein requirement to derive the recommended nutrient intake. CONCLUSION: Protein requirements in the elderly have increased over a five-year period and sarcopenia may be the main cause of increased protein requirements.

JAML promotes the antitumor role of tumor-resident CD8+ T cells by facilitating their innate-like function in human lung cancer.

Tissue-resident memory CD8+T cells (CD8+TRMs) are thought to play a crucial role in cancer immunosurveillance. However, the characteristics of CD8+TRMs in the tumor microenvironment (TME) of human non-small cell lung cancer (NSCLC) remain unclear. Here, we report that CD8+TRMs accumulate explicitly and exhibit a unique gene expression profile in the TME of NSCLC. Interestingly, these tumor-associated CD8+TRMs uniquely exhibit an innate-like phenotype. Importantly, we found that junction adhesion molecule-like (JAML) provides an alternative costimulatory signal to activate tumor-associated CD8+TRMs via combination with cancer cell-derived CXADR (CXADR Ig-like cell adhesion molecule). Furthermore, we demonstrated that activating JAML could promote the expression of TLR1/2 on CD8+TRMs, inhibit tumor progression and prolong the survival of tumor-bearing mice. Finally, we found that higher CD8+TRMs and JAML expression in the TME could predict favorable clinical outcomes in NSCLC patients. Our study reveals an intrinsic bias of CD8+TRMs for receiving the tumor-derived costimulatory signal in the TME, which sustains their innate-like function and antitumor role. These findings will shed more light on the biology of CD8+TRMs and aid in the development of potential targeted treatment strategies for NSCLC.

High-Performance Contact-Doped WSe2 Transistors Using TaSe2 Electrodes.

Two-dimensional (2D) transitional metal dichalcogenides (TMDs) have garnered significant attention due to their potential for next-generation electronics, which require device scaling. However, the performance of TMD-based field-effect transistors (FETs) is greatly limited by the contact resistance. This study develops an effective strategy to optimize the contact resistance of WSe2 FETs by combining contact doping and 2D metallic electrode materials. The contact regions were doped using a laser, and the metallic TaSe2 flakes were stacked on doped WSe2 as electrodes. Doping the contact areas decreases the depletion width, while introducing the TaSe2 contact results in a lower Schottky barrier. This method significantly improves the electrical performance of the WSe2 FETs. The doped WSe2/TaSe2 contact exhibits an ultralow Schottky barrier height of 65 meV and a contact resistance of 11 kΩ·µm, which is a 50-fold reduction compared to the conventional Cr/Au contact. Our method offers a way on fabricating high-performance 2D FETs.

Flexible Full-Inorganic Ultrathin Films with Stable Circularly Polarized Luminescence Covering the Visible to Near-Infrared Region.

Circularly polarized luminescence (CPL) materials hold significant value in various fields, including information storage, secure communication, three-dimensional displays, biological detection, and optoelectronic devices. Using the Langmuir-Schaeffer (LS) assembly technique, we successfully construct a series of large-area flexible optical ultrathin films. Impressively, the inorganic assembled ultrathin films exhibit excellent CPL optical activity covering the visible to near-infrared (NIR) region, with the luminescence asymmetry factor glum ranging from 0.59 to 0.72. Moreover, such ultrathin films also display outstanding mechanical flexibility, the optical activity of which even after 240 bending cycles shows almost no difference compared to the unbent samples. Owing to the ultra-broadband optical activity and ultra-stable optical activity of such full-inorganic assembled materials on flexible substrates, coupled with their excellent processability and outstanding mechanical flexibility, we anticipate they will find use in many fields such as communication technology and flexible optoelectronics.

Wide Response Range Photoelectrochemical UV Detector Based on Anodized TiO2-Nanotubes@Ti@quartz Structure.

Conventional sandwich structure photoelectrochemical UV detectors cannot detect UV light below 300 nm due to UV filtering problems. In this work, we propose to place the electron collector inside the active material, thus avoiding the effect of electrodes on light absorption. We obtained a TiO2-nanotubes@Ti@quartz photoanode structure by precise treatment of a commercial Ti mesh by anodic oxidation. The structure can absorb any light in the near-UV band and has superior stability to other metal electrodes. The final encapsulated photoelectrochemical UV detectors exhibit good switching characteristics with a response time below 100 ms. The mechanism of the oxidation conditions on the photovoltaic performance of the device was investigated by the electrochemical impedance method, and we obtained the optimal synthesis conditions. Response tests under continuous spectroscopy confirm that the response range of the device is extended from 300-400 nm to 240-400 nm. This idea of a built-in collector is an effective way to extend the response range of a photoelectrochemical detector.

Inflammatory dendritic cells restrain CD11b+CD4+ CTLs via CD200R in human NSCLC.

CD4+ cytotoxic T lymphocytes (CD4+ CTLs) are suggested to play a crucial role in inflammatory diseases, including cancer, but their characteristics in human non-small cell lung cancer (NSCLC) remain unknown. Here, using the cell surface marker CD11b, we identify CD11b+CD4+ CTLs as a cytotoxic subset of CD4+ T cells in multiple tissues of NSCLC patients. In addition, tumor-infiltrating CD11b+CD4+ CTLs show a dysfunctional phenotype with elevated expression of CD200 receptor (CD200R), a negatively immunomodulatory receptor. CD4+ regulatory T (Treg) cells restrain the anti-tumor role of CD11b+CD4+ CTLs via CD200. Mechanistically, inflammatory dendritic cells promote the CD200R expression of CD11b+CD4+ CTLs by secreting interleukin-1ß (IL-1ß). Finally, we demonstrate that CD200 blockade can revive the tumor-killing role of CD11b+CD4+ CTLs and prolong the survival of tumor-bearing mice. Taken together, our study identifies CD11b+CD4+ CTLs in NSCLC with decreased cytotoxicity that can be reinvigorated by CD200 blockade, suggesting that targeting CD200 is a promising immunotherapy strategy in NSCLC.

Effects of allicin on growth performance, antioxidant profile, and microbiota compared to monensin of growing goats.

Allicin is a sulfur-containing compound extracted from raw garlic (Allium sativum L.). We compared the effect of allicin addition on growth performance, serum biochemical parameters, and rumen microbiota of goats compared to monensin. Twenty-four Anhui white goats were assigned randomly to one of three dietary treatments: 1) a basal diet (CON); 2) the basal diet with allicin addition at 750 mg per head per day (AC); 3) the basal diet with monensin addition at 30 mg per kg of diet (MS). Animals were fed for 8 weeks. Results showed the average daily gain, and feed efficiency was increased with allicin and monensin addition. Serum levels of IgG, total superoxide dismutase, and glutathione peroxidase were higher in the AC group than those in the CON and MS groups. The microbiota analysis revealed that monensin addition mainly affected genera related to carbohydrate and protein metabolism, and allicin mainly affected genera related to energy metabolism and intestinal health. In conclusion, allicin could improve growth performance and have advantages over monensin in improving the antioxidant capacity and immune function of goats. Allicin may be a potential alternative to monensin.

Effects of continuous low-speed biogas agitation on anaerobic digestion of high-solids pig manure: Performance and microbial community.

This study aimed to investigate effects of continuous low-speed biogas agitation on the anaerobic digestion (AD) performance and microbial community of high-solids pig manure (total solids content of 10%). Our results reveal that at a biogas agitation intensity of 1.10 L/g feed VS/d, CH4 production increased by 16.67% compared to the non-agitated condition, the removal efficiency of H2S reached 63.18%, and the abundance of Methanosarcina was the highest. The presence of Hungateiclostridiaceae was associated with H2S concentrations. An increasing biogas agitation intensity led to an elevated pH and a decreased oxidation-reduction potential (ORP). Acetate concentrations, pH, and ORP values indicated changes in H2S concentrations. Sedimentibacter demonstrates the potential to indicate biogas agitation intensity and pH. We demonstrate that continuous low-speed biogas agitation effectively increases CH4 production and reduces H2S concentrations in AD of high-solids pig manure, offering a potential technical pathway for developing AD processes for high-solids pig manure, it also demonstrates that AD process can reduce the risk of pathogen and parasite transmission.

p-Toluenesulfonic acid enhanced neutral deep eutectic solvent pretreatment of soybean straw for efficient lignin removal and enzymatic hydrolysis.

Deep eutectic solvent (DES) is a newly-emerged green solvent for efficient pretreatment of lignocellulosic feedstock. To improve the component fractionation performance of neutral DES, p-toluenesulfonic acid (p-TsOH) was employed as catalyst to form a novel ternary DES with benzyltriethylammonium chloride (TEBAC) and glycerol (Gly) for pretreatment of soybean straw. Under the optimum reaction conditions (TEBAC:Gly = 1:12, 1.6 wt% p-TsOH and reacted at 90 °C for 160 min), the lignin and hemicellulose removal from soybean straw were amounted to 92.0 % and 88.2 %, respectively. The pretreated substrate showed satisfactory enzymatic hydrolysis performance, as the glucose and reducing sugar concentrations reached 37.3 g/L and 42.3 g/L, respectively, after 72 h saccharification under the action of cellulase with a relatively low enzyme loading of 10 FPU/g cellulose.This method provides an efficient and mild route for utilization of agricultural waste and production of platform monosaccharides.

Reevaluation of the protein requirement in Chinese elderly adults without sarcopenia with the indicator amino acid oxidation technique.

It is now generally believed that elderly may have slightly higher dietary protein requirements than those of the young-middle-aged adults. We have previously conducted related studies by the indicator amino acid oxidation (IAAO) technique, but more research data are needed to revise the protein requirements of the elderly. The main objective was to reevaluate the dietary protein requirements of healthy Chinese adults (65-80 years) without sarcopenia by using the IAAO technique. Nine healthy adult men and seven healthy adult women participated in the study, with protein intakes ranging from 0·1 to 1·8 g/(kg·d). Diets that delivered energy at a 1·5 resting energy expenditure were isocaloric. The amounts of phenylalanine and tyrosine needed to remain constant for each protein dosage. By applying a nonlinear mixed-effects model analysis on the F13CO2 data, which revealed a breakpoint in F13CO2 in response to graded protein intakes, the mean protein requirement was calculated. The mean estimated average requirement (EAR) for healthy elderly Chinese adults without sarcopenia was determined to be 0·94 g/(kg·d). The protein recommended nutrient intake (RNI) determined using various derivation approaches ranged from 1·13 to 1·36 g/(kg·d). The EAR for Chinese adults without sarcopenia aged 65-80 years in this study is 6·8 % higher than the current recommended EAR (0·88 g/(kg·d)). The RNI derived using various derivation approaches are all greater than the current RNI (0·98 g/(kg·d)). This trial was registered with the Chinese clinical trial registry as ChiCTR2200061382.

A semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening.

High-content imaging for compound and genetic profiling is popular for drug discovery but limited to endpoint images of fixed cells. Conversely, electronic-based devices offer label-free, live cell functional information but suffer from limited spatial resolution or throughput. Here, we introduce a semiconductor 96-microplate platform for high-resolution, real-time impedance imaging. Each well features 4096 electrodes at 25 µm spatial resolution and a miniaturized data interface allows 8× parallel plate operation (768 total wells) for increased throughput. Electric field impedance measurements capture >20 parameter images including cell barrier, attachment, flatness, and motility every 15 min during experiments. We apply this technology to characterize 16 cell types, from primary epithelial to suspension cells, and quantify heterogeneity in mixed co-cultures. Screening 904 compounds across 13 semiconductor microplates reveals 25 distinct responses, demonstrating the platform's potential for mechanism of action profiling. The scalability and translatability of this semiconductor platform expands high-throughput mechanism of action profiling and phenotypic drug discovery applications.

GeoDILI: A Robust and Interpretable Model for Drug-Induced Liver Injury Prediction Using Graph Neural Network-Based Molecular Geometric Representation.

Drug-induced liver injury (DILI) is a significant cause of drug failure and withdrawal due to liver damage. Accurate prediction of hepatotoxic compounds is crucial for safe drug development. Several DILI prediction models have been published, but they are built on different data sets, making it difficult to compare model performance. Moreover, most existing models are based on molecular fingerprints or descriptors, neglecting molecular geometric properties and lacking interpretability. To address these limitations, we developed GeoDILI, an interpretable graph neural network that uses a molecular geometric representation. First, we utilized a geometry-based pretrained molecular representation and optimized it on the DILI data set to improve predictive performance. Second, we leveraged gradient information to obtain high-precision atomic-level weights and deduce the dominant substructure. We benchmarked GeoDILI against recently published DILI prediction models, as well as popular GNN models and fingerprint-based machine learning models using the same data set, showing superior predictive performance of our proposed model. We applied the interpretable method in the DILI data set and derived seven precise and mechanistically elucidated structural alerts. Overall, GeoDILI provides a promising approach for accurate and interpretable DILI prediction with potential applications in drug discovery and safety assessment. The data and source code are available at GitHub repository (https://github.com/CSU-QJY/GeoDILI).

Photoelectrochemical UV Detector Based on High-Temperature Resistant ITO Nanowire Network Transparent Conductive Electrodes: Both the Response Range and Responsivity Are Improved.

UV transparent conductive electrodes based on transferable ITO nanowire networks were prepared to solve the problem of low UV light utilization in conventional photoelectrochemical UV detectors. The mutually cross-linked ITO nanowire network achieved good electrical conductivity and light transmission, and the novel electrode had a transmission rate of more than 80% throughout the near-UV and visible regions. Compared to Ag nanowire electrodes with similar functionality, the chemical stability of the ITO nanowire transparent conductive electrode ensured that the device worked stably in iodine-based electrolytes. More importantly, ITO electrodes composed of oxides could withstand temperatures above 800 °C, which is extremely critical for photoelectrochemical devices. After the deposition of a TiO2 active layer using the high-temperature method, the response range of the photoelectrochemical UV detector was extended from a peak-like response between 300-400 nm to a plateau-like response between 200-400 nm. The responsivity was significantly increased to 56.1 mA/W. The relationship between ITO nanowire properties and device performance, as well as the reasons for device performance enhancement, were intensively investigated.

A semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening.

Profiling compounds and genetic perturbations via high-content imaging has become increasingly popular for drug discovery, but the technique is limited to endpoint images of fixed cells. In contrast, electronic-based devices offer label-free, functional information of live cells, yet current approaches suffer from low-spatial resolution or single-well throughput. Here, we report a semiconductor 96-microplate platform designed for high-resolution real-time impedance "imaging" at scale. Each well features 4,096 electrodes at 25 µm spatial resolution while a miniaturized data interface allows 8× parallel plate operation (768 total wells) within each incubator for enhanced throughputs. New electric field-based, multi-frequency measurement techniques capture >20 parameter images including tissue barrier, cell-surface attachment, cell flatness, and motility every 15 min throughout experiments. Using these real-time readouts, we characterized 16 cell types, ranging from primary epithelial to suspension, and quantified heterogeneity in mixed epithelial and mesenchymal co-cultures. A proof-of-concept screen of 904 diverse compounds using 13 semiconductor microplates demonstrates the platform's capability for mechanism of action (MOA) profiling with 25 distinct responses identified. The scalability of the semiconductor platform combined with the translatability of the high dimensional live-cell functional parameters expands high-throughput MOA profiling and phenotypic drug discovery applications.

Efficacy of PD-1 Inhibitors in First-Line Treatment for Advanced Gastroesophageal Junction and Gastric Cancer by Subgroups: A Systematic Review and Meta-Analysis.

BACKGROUND: PD-1 inhibitors have been approved for the first-line treatment of patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. However, the results of several clinical trials are not entirely consistent, and the dominant population of first-line immunotherapy for advanced gastric/gastroesophageal junction cancer still needs to be precisely determined. OBJECTIVE: This objective of this study is to evaluate the efficacy of anti-PD-1/PD-L1 therapy in advanced gastric/gastroesophageal junction adenocarcinoma patients through a systematic review and meta-analysis of relevant clinical trials. METHOD: The PubMed, Embase, and Cochrane Library electronic databases were searched up to August 1, 2022, for clinical trials of anti-PD-1/PD-L1 immunotherapy for the first-line treatment of advanced gastroesophageal cancer. Hazard ratios and 95% confidence intervals for overall survival, progression-free survival, and objective response rates were extracted and pooled for meta-analysis. Prespecified subgroups included the following: agent type, PD-L1 expression, and high microsatellite instability. RESULTS: This study analyzed 5 RCTs involving 3,355 patients. Compared with the chemotherapy group, the combined immunotherapy group had a significantly higher objective response rate (OR = 0.63, 95% CI: 0.55-0.72, p < 0.00001) and prolonged overall survival (HR = 0.82, 95% CI: 0.76-0.88, p < 0.00001) and progression-free survival (HR = 0.75, 95% CI: 0.69-0.82, p < 0.00001). The combination of immunotherapy and chemotherapy prolonged OS in both MSI-H (HR = 0.38, p = 0.002) and MSS (HR = 0.78, p < 0.00001) populations, but there was a significant difference between groups (p = 0.02). However, in improving ORR, the benefit of ICI combined with chemotherapy in the MSS group and MSI-H group was not significantly different between groups (p = 0.52). Combination therapy with ICIs was more effective than chemotherapy alone in prolonging OS in the subgroup with a high CPS, regardless of the CPS cutoff for PD-L1. However, when the cutoff of CPS was 1, the difference between subgroups did not reach statistical significance (p = 0.12), while the benefit ratio of the MSI-H group was higher when the cutoff was 10 (p = 0.004) than when the cutoff value was 5 (p = 0.002). CONCLUSIONS: For first-line treatment of advanced gastroesophageal cancer, an ICI combination strategy is more effective than chemotherapy. The subgroup of patients with a CPS ≥10 has a more significant benefit, and CPS ≥10 has the potential to be used as an accurate marker of the dominant population of immuno-combined therapy.

MetaSeg: Content-Aware Meta-Net for Omni-Supervised Semantic Segmentation.

Noisy labels, inevitably existing in pseudo-segmentation labels generated from weak object-level annotations, severely hamper model optimization for semantic segmentation. Previous works often rely on massive handcrafted losses and carefully tuned hyperparameters to resist noise, suffering poor generalization capability and high model complexity. Inspired by recent advances in meta-learning, we argue that rather than struggling to tolerate noise hidden behind clean labels passively, a more feasible solution would be to find out the noisy regions actively, so as to simply ignore them during model optimization. With this in mind, this work presents a novel meta-learning-based semantic segmentation method, MetaSeg, that comprises a primary content-aware meta-net (CAM-Net) to serve as a noise indicator for an arbitrary segmentation model counterpart. Specifically, CAM-Net learns to generate pixel-wise weights to suppress noisy regions with incorrect pseudo-labels while highlighting clean ones by exploiting hybrid strengthened features from image content, providing straightforward and reliable guidance for optimizing the segmentation model. Moreover, to break the barrier of time-consuming training when applying meta-learning to common large segmentation models, we further present a new decoupled training strategy that optimizes different model layers in a divide-and-conquer manner. Extensive experiments on object, medical, remote sensing, and human segmentation show that our method achieves superior performance, approaching that of fully supervised settings, which paves a new promising way for omni-supervised semantic segmentation.

Supplementation of feed and water after long-duration road transportation: The effects on welfare and rumen fermentation in goats.

Water and feed are needed for livestock during their long-duration road transportation. However, limited information is available on the need to supply water and feed to livestock at temporary holding stations after road transportation. This study aimed to evaluate the effect of providing water and feed at holding stations on the welfare of goats in mimic surroundings. A total of 24 Guizhou black goats were randomly divided into three groups of eight goats each as follows: deprived of water and feed (TRT0), supplemented with water ad libitum (TRT1), and supplemented with water and feed ad libitum (TRT2). Blood and rumen fluid samples were collected before loading (denoted as "PRE" in this article) and after transport (denoted as "POST" in this article). Statistical analysis was performed via the SAS procedure PROC MIXED. The 10-h road transportation period reduced body weight in TRT0 goats (p < 0.05) but not in TRT1 and TRT2 (p > 0.05). TRT0 and TRT1 goats had POST plasma glucose concentrations above their PRE values (p < 0.05). The PRE-plasma urea nitrogen (PUN) levels were higher in TRT2 compared to TRT0 (p < 0.05) goats, while the POST-PUN levels increased in TRT1 compared to TRT0 goats. The POST non-esterified fatty acid (NEFA) concentration was higher for TRT0 compared to that in TRT1 and TRT2 (p < 0.05) goats. No difference was observed for plasma profiles of malondialdehyde (MDA) and superoxide dismutase (SOD) (p > 0.05). TRT2 goats had higher POST glutathione peroxidase (GSH-Px) activity than TRT0 and TRT1 (p < 0.05) goats. TRT0 goats had higher POST plasma glucagon (GC) compared to TRT2 (p < 0.05) and had increased values compared to their own PRE level as a result of road transportation (p < 0.05). TRT2 goats resulted in a lower POST plasma heat-stressed protein-70 (HSP-70) level than TRT0. There was no difference in ruminal pH (p > 0.05). Ruminal total VFA (acetate, propionate, butyrate), and the NH3-ammonia profiles showed a decrease (p < 0.05) after transportation in all groups. Ruminal microcrystalline cellulose, xylanase, cellobiase, and carboxymethyl cellulose activities were unaffected (p > 0.05). These combined results imply that water and feed supplementation to livestock can effectively alleviate stress responses in goats subjected to road transportation and emphasize the necessity to establish water and feed supplies even at a temporary holding pen.

Excessively Increased Skeletal Muscle Mass of the Bilateral Lower Limbs is Associated with Hyperuricemia in Females with Polycystic Ovarian Syndrome.

This study is aimed at evaluating the correlation between the skeletal muscle mass index (SMI) of different body parts and hyperuricemia in females with polycystic ovary syndrome (PCOS), thus, providing scientific guidance on lifestyle self-management for patients with PCOS. The cross-sectional study included 171 patients with PCOS, which were divided into two distinct sub-groups based on the presence or absence of hyperuricemia. Anthropometric and serological characteristics of the population with PCOS focusing on skeletal muscle mass were conducted. PCOS patients with hyperuricemia had significantly greater SMI in different body parts. Further binary logistic regression analysis revealed that SMI of the bilateral lower limbs was positively associated with hyperuricemia with an adjusted odds ratio (95% confidence interval) of 1.235 (1.103 - 1.384), p < 0.001. The optimal cut-off value of SMI of the bilateral lower limbs in predicting hyperuricemia was 5.11 (Youden index = 0.490). Combined with the mean value of SMI in the bilateral upper limbs, the safe range of SMI of the bilateral lower limbs in patients with PCOS was calculated as 3.64 - 5.11, with the sensitivity and negative predictive values being 83.9% and 65.1%, respectively. Excessively increased SMI of the bilateral lower limbs was correlated with hyperuricemia in patients with PCOS.

Single-Cell Profiling of Tumor Immune Microenvironment Reveals Immune Irresponsiveness in Gastric Signet-Ring Cell Carcinoma.

BACKGROUND & AIMS: Gastric cancer (GC) is a major cancer type characterized by high heterogeneity in both tumor cells and the tumor immune microenvironment (TIME). One intractable GC subtype is gastric signet-ring cell carcinoma (GSRCC), which is associated with poor prognosis. However, it remains unclear what the GSRCC TIME characteristics are and how these characteristics may contribute to clinical outcomes. METHODS: We enrolled 32 patients with advanced GC of diverse subtypes and profiled their TIME using an immune-targeted single-cell profiling strategy, including (1) immune-targeted single-cell RNA sequencing (n = 20 patients) and (2) protein expression profiling by a targeted antibody panel for mass cytometry (n = 12 patients). We also generated matched V(D)J (variable, diversity, and joining gene segments) sequencing of T and B cells along CD45+ immunocytes. RESULTS: We found that compared to non-GSRCC, the GSRCC TIME appears to be quiescent, where both CD4+ and CD8+ T cells are difficult to be mobilized, which further impairs the proper functions of B cells. CXCL13, mainly produced by follicular helper T cells, T helper type 17, and exhausted CD8+ T cells, is a central coordinator of this transformation. We show that CXCL13 expression can predict the response to immune checkpoint blockade in GC patients, which may be related to its effects on tertiary lymphoid structures. CONCLUSIONS: Our study provides a comprehensive molecular portrait of immune cell compositions and cell states in advanced GC patients, highlighting adaptive immune irresponsiveness in GSRCC and a mediator role of CXCL13 in TIME. Our targeted single-cell transcriptomic and proteomic profiling represents a powerful approach for TIME-oriented translational research.