Mendelian randomization reveals the impact of diet on infertility in men and women.

Background: Although studies on the effects of diet on fertility has progressed, some cumulative evidence has piled against popular hypotheses. The aim of our study was to investigate the effects of 31 diets including 23 individual dietary intakes and 8 dietary habits on infertility in men and women. Methods: The datas of diets and infertility were collected from genome-wide association studies (GWAS). Mendelian randomization (MR) methods were used to analyze causal relationships. Multivariate MR (MVMR) adjusted for the effects of other exposures on causality. And MR-Egger, Cochran's Q, radial MR, and MR-PRESSO tests were employed to assess heterogeneity and horizontal pleiotropy. Results: Our study found that coffee intake (OR, 3.6967; 95% CI, 1.0348 - 13.2065; P = 0.0442) and cooked vegetable intakes (OR, 54.7865; 95% CI, 2.9011 - 1030.5500; P = 0.0076) increased the risk of male infertility. For women, beer was a risk factor for infertility (OR, 4.0932; 95% CI, 1.8728 - 8.9461; P = 0.0004); but processed meat was negatively associated with infertility (OR, 0.5148; 95% CI, 0.2730 - 0.9705; P = 0.0401). MVMR demonstrated selenium as a protective factor against female infertility (OR, 7.4474e-12; 95% CI, 5.4780e-22 - 1.0125e-01; P = 0.0314). Conclusion: We found the causal relationships between four diets and infertility. We look forward to more high-quality epidemiologic studies to prove our conclusions.

A bidirectional causal relationship study between mental disorders and male and female infertility.

Background: The relation between mental disorders (MDs) and infertility can be reciprocal. But exactly which MD affects infertility remains controversial. Our aim was to use Mendelian randomization (MR) to explore bidirectional causality between 15 MDs and male infertility and female infertility. Methods: The data of MDs, male infertility, and female infertility were derived from published genome-wide association studies (GWAS). The inverse variance weighted method was considered to be the main analytical approach. Sensitivity analysis was performed using MR-Egger, Cochran's Q, radial MR, and MR-PRESSO tests. Results: Our results found that mood disorders (OR, 1.4497; 95% CI, 1.0093 - 2.0823; P = 0.0444) and attention deficit hyperactivity disorder (OR, 1.3921; 95% CI, 1.0943 - 1.7709; P = 0.0071) were positively correlated with male infertility, but obsessive-compulsive disorder (OR, 0.8208; 95% CI, 0.7146 - 0.9429; P = 0.0052) was negatively associated with male infertility. For females, anorexia nervosa (OR, 1.0898; 95% CI, 1.0070 - 1.1794; P = 0.0329), attention deficit hyperactivity disorder (OR, 1.1013; 95% CI, 1.0041 - 1.2079; P = 0.0406), and major depressive disorder (OR, 1.1423; 95% CI, 1.0213 - 1.2778; P = 0.0199) increased risk of infertility. In reverse relationship, female infertility increased the incidence of bipolar disorder (OR, 1.0009; 95% CI, 1.0001 - 1.0017; P = 0.0281). Conclusion: We demonstrated the association between five MDs and male or female infertility. Female infertility was also found to be associated with an increased risk of one MD. We look forward to better designed epidemiological studies to support our results.

Amorphous Bismuth-Tin Oxide Nanosheets with Optimized C-N Coupling for Efficient Urea Synthesis.

Closing the carbon and nitrogen cycles by electrochemical methods using renewable energy to convert abundant or harmful feedstocks into high-value C- or N-containing chemicals has the potential to transform the global energy landscape. However, efficient conversion avenues have to date been mostly realized for the independent reduction of CO2 or NO3-. The synthesis of more complex C-N compounds still suffers from low conversion efficiency due to the inability to find effective catalysts. To this end, here we present amorphous bismuth-tin oxide nanosheets, which effectively reduce the energy barrier of the catalytic reaction, facilitating efficient and highly selective urea production. With enhanced CO2 adsorption and activation on the catalyst, a C-N coupling pathway based on *CO2 rather than traditional *CO is realized. The optimized orbital symmetry of the C- (*CO2) and N-containing (*NO2) intermediates promotes a significant increase in the Faraday efficiency of urea production to an outstanding value of 78.36% at -0.4 V vs RHE. In parallel, the nitrogen and carbon selectivity for urea formation is also enhanced to 90.41% and 95.39%, respectively. The present results and insights provide a valuable reference for the further development of new catalysts for efficient synthesis of high-value C-N compounds from CO2.

Ultra-High Proportion of Grain Boundaries in Zinc Metal Anode Spontaneously Inhibiting Dendrites Growth.

Aqueous Zn-ion batteries are an attractive electrochemical energy storage solution for their budget and safe properties. However, dendrites and uncontrolled side reactions in anodes detract the cycle life and energy density of the batteries.Grain boundaries in metals are generally considered as the source of the above problems but we present a diverse result. This study introduces an ultra-high proportion of grain boundaries on zinc electrodes through femtosecond laser bombardment to enhance stability of zinc metal/electrolyte interface.The ultra-high proportion of grain boundaries promotes the homogenization of zinc growth potential, to achieve uniform nucleation and growth, thereby suppressing dendrite formation. Additionally, the abundant active sites mitigate the side reactions during the electrochemical process. Consequently, the 15-µm-Fs-Zn||MnO2 pouch cell achieves an energy density of 249.4 Wh kg-1 and  operates for over 60 cycles at a depth-of-discharge of 23%. The recognition of the favorable influence exerted by UP-GBs paves a new way for other metal batteries.

Glycyrrhizin attenuates renal inflammation in a mouse Con A-hepatitis model via the IL-25/M2 axis.

Glycyrrhizin (GL) has immunoregulatory effects on various inflammatory diseases including hepatitis and nephritis. However, the mechanisms underlying the anti-inflammatory effect of GL on renal inflammation are not fully understood. Hepatorenal syndrome (HRS) is a functional acute renal impairment that occurs in severe liver disease, and we found that kidney injury also occurs in Con A-induced experimental hepatitis in mice. We previously found that GL can alleviate Con A-induced hepatitis by regulating the expression of IL-25 in the liver. We wanted to investigate whether GL can alleviate Con A-induced nephritis by regulating IL-25. IL-25 regulates inflammation by modulating type 2 immune responses, but the mechanism by which IL-25 affects kidney disease remains unclear. In this study, we found that the administration of GL enhanced the expression of IL-25 in renal tissues; the latter promoted the generation of type 2 macrophages (M2), which inhibited inflammation in the kidney caused by Con A challenge. IL-25 promoted the secretion of the inhibitory cytokine IL-10 by macrophages but inhibited the expression of the inflammatory cytokine IL-1ß by macrophages. Moreover, IL-25 downregulated the Con A-mediated expression of Toll-like receptor (TLR) 4 on macrophages. By comparing the roles of TLR2 and TLR4, we found that TLR4 is required for the immunoregulatory effect of IL-25 on macrophages. Our data revealed that GL has anti-inflammatory effects on Con A-induced kidney injury and that the GL/IL-25/M2 axis participates in the anti-inflammatory process. This study suggested that GL is a potential therapeutic for protecting against acute kidney injury.

Mn(II)-Based Metal Halide with Near-Unity Quantum Yield for White LEDs and High-Resolution X-ray Imaging.

Metal halides have drawn great interest as luminescent materials and scintillators due to their outstanding optical properties. Exploring new types of phosphors with easy production processes, excellent photophysical properties, high light yields, and environmentally friendly compositions is crucial and quite challenging. Herein, a novel Mn(II)-based metal halide (4-BTP)2MnBr4 was produced using a facile solvent evaporation method, which exhibited a strong green emission peaking at 524 nm from the d-d transition of tetrahedral-coordinated Mn2+ ion and a near-unity quantum yield. The prepared white light-emitting diode device has a wide color gamut of 100.7% NTSC with CIE chromaticity coordinates of (0.32, 0.32). In addition, (4-BTP)2MnBr4 demonstrates excellent characteristics in X-ray scintillation, including a high light yield of 98 000 photons/MeV, a sensitive detection limit of 37.4 nGy/s, excellent resistance to radiation damage, and successful demonstration of X-ray imaging with high resolution at 21.3 lp/mm, revealing the potential for application in diagnostic X-ray medical imaging and industry radiation detection.

Accessing Early Differentiation of Virus-Specific Follicular Helper CD4+ T Cell in Acute LCMV-Infected Mice.

Follicular Helper T (TFH) cells are perceived as an independent CD4+ T cell lineage that assists cognate B cells in producing high-affinity antibodies, thus establishing long-term humoral immunity. During acute viral infection, the fate commitment of virus-specific TFH cells is determined in the early infection phase, and investigations of the early-differentiated TFH cells are crucial in understanding T cell-dependent humoral immunity and optimizing vaccine design. In the study, using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection and the TCR-transgenic SMARTA (SM) mouse with CD4+ T cells specifically recognizing LCMV glycoprotein epitope I-AbGP66-77, we described procedures to access the early fate commitment of virus-specific TFH cells based on flow cytometry stainings. Furthermore, by exploiting retroviral transduction of SM CD4+ T cells, methods to manipulate gene expression in early-differentiated virus-specific TFH cells are also provided. Hence, these methods will help in studies exploring the mechanism(s) underlying the early commitment of virus-specific TFH cells.

Achieving Negatively Charged Pt Single Atoms on Amorphous Ni(OH)2 Nanosheets with Promoted Hydrogen Absorption in Hydrogen Evolution.

Single-atom (SA) catalysts with nearly 100% atom utilization have been widely employed in electrolysis for decades, due to the outperforming catalytic activity and selectivity. However, most of the reported SA catalysts are fixed through the strong bonding between the dispersed single metallic atoms with nonmetallic atoms of the substrates, which greatly limits the controllable regulation of electrocatalytic activity of SA catalysts. In this work, Pt-Ni bonded Pt SA catalyst with adjustable electronic states was successfully constructed through a controllable electrochemical reduction on the coordination unsaturated amorphous Ni(OH)2 nanosheet arrays. Based on the X-ray absorption fine structure analysis and first-principles calculations, Pt SA was bonded with Ni sites of amorphous Ni(OH)2, rather than conventional O sites, resulting in negatively charged Ptδ-. In situ Raman spectroscopy revealed that the changed configuration and electronic states greatly enhanced absorbability for activated hydrogen atoms, which were the essential intermediate for alkaline hydrogen evolution reaction. The hydrogen spillover process was revealed from amorphous Ni(OH)2 that effectively cleave the H-O-H bond of H2O and produce H atom to the Pt SA sites, leading to a low overpotential of 48 mV in alkaline electrolyte at -1000 mA cm-2 mg-1Pt, evidently better than commercial Pt/C catalysts. This work provided new strategy for the controllable modulation of the local structure of SA catalysts and the systematic regulation of the electronic states.

A New Dataset and Comparative Study for Aphid Cluster Detection and Segmentation in Sorghum Fields.

Aphid infestations are one of the primary causes of extensive damage to wheat and sorghum fields and are one of the most common vectors for plant viruses, resulting in significant agricultural yield losses. To address this problem, farmers often employ the inefficient use of harmful chemical pesticides that have negative health and environmental impacts. As a result, a large amount of pesticide is wasted on areas without significant pest infestation. This brings to attention the urgent need for an intelligent autonomous system that can locate and spray sufficiently large infestations selectively within the complex crop canopies. We have developed a large multi-scale dataset for aphid cluster detection and segmentation, collected from actual sorghum fields and meticulously annotated to include clusters of aphids. Our dataset comprises a total of 54,742 image patches, showcasing a variety of viewpoints, diverse lighting conditions, and multiple scales, highlighting its effectiveness for real-world applications. In this study, we trained and evaluated four real-time semantic segmentation models and three object detection models specifically for aphid cluster segmentation and detection. Considering the balance between accuracy and efficiency, Fast-SCNN delivered the most effective segmentation results, achieving 80.46% mean precision, 81.21% mean recall, and 91.66 frames per second (FPS). For object detection, RT-DETR exhibited the best overall performance with a 61.63% mean average precision (mAP), 92.6% mean recall, and 72.55 on an NVIDIA V100 GPU. Our experiments further indicate that aphid cluster segmentation is more suitable for assessing aphid infestations than using detection models.

An oncolytic virus delivering tumor-irrelevant bystander T cell epitopes induces anti-tumor immunity and potentiates cancer immunotherapy.

Tumor-specific T cells are crucial in anti-tumor immunity and act as targets for cancer immunotherapies. However, these cells are numerically scarce and functionally exhausted in the tumor microenvironment (TME), leading to inefficacious immunotherapies in most patients with cancer. By contrast, emerging evidence suggested that tumor-irrelevant bystander T (TBYS) cells are abundant and preserve functional memory properties in the TME. To leverage TBYS cells in the TME to eliminate tumor cells, we engineered oncolytic virus (OV) encoding TBYS epitopes (OV-BYTE) to redirect the antigen specificity of tumor cells to pre-existing TBYS cells, leading to effective tumor inhibition in multiple preclinical models. Mechanistically, OV-BYTE induced epitope spreading of tumor antigens to elicit more diverse tumor-specific T cell responses. Remarkably, the OV-BYTE strategy targeting human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory efficiently inhibited tumor progression in a human tumor cell-derived xenograft model, providing important insights into the improvement of cancer immunotherapies in a large population with a history of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination.

Melatonin alleviates endoplasmic reticulum stress and follicular granulosa cell apoptosis by regulating ATF4 to activate mTOR signaling pathway in chickens.

Follicular atresia in chickens reduces the number of follicles that can further develop, leading to decrease egg laying. Endoplasmic reticulum stress (ERS) can initiate a unique pathway inducing the apoptosis of follicular granulosa cells, thus reducing egg laying. Melatonin (MEL) is involved in the regulation of follicle development, ovulation, and oocyte maturation, and is closely related to follicle fate. Mammalian target of Rapamycin (mTOR) signaling pathway plays an important role in cell growth regulation, and that there is a possible crosstalk between melatonin and mTOR activity in granular cells maturation and ovulation. This study aimed to investigate whether MEL inhibits ERS and follicular granulosa cell apoptosis by regulating ATF4 to activate mTOR signaling pathway in chickens. Frist, we established an in vitro ERS cell model using tunicamycin (TM). The results showed that different concentrations of TM exhibited dose-dependent inhibition of cell activity and induction of granulosa cells (P<0.01). Therefore, we chose 5 µg/mL of TM and a treatment time for 6 h as the optimal concentration for the following experiments. Then we investigate whether melatonin can inhibit ERS. TM treatment decreased the cell viability and Bcl-2 expression, increasing ROS levels and the mRNA expression of Grp78, ATF4, CHOP, PERK, eIF-2α, and BAX (P<0.01), whereas TM+MEL treatment significantly inhibited these changes (P<0.01). Then we explored whether melatonin protects follicular granulosa cells from ERS-induced apoptosis through the mammalian target of rapamycin (mTOR) signaling pathway by regulating ATF4, we found that ATF4 knockdown inhibited ERS by decreasing the expression of ERS-related genes and proteins and activating mTOR signaling pathway by increasing the protein expression of p4E-BP1 and pT389-S6K (P<0.001), while these changes were promoted by TM+si-ATF4+MEL treatment (P<0.01). These results indicate that MEL could alleviate TM-induced ERS by regulating ATF4 to activate mTOR signaling pathway in follicular granulosa cells, thus providing a new perspective for prolonging the laying cycle in chickens.

Integrated analysis of transcriptional changes in major depressive disorder: Insights from blood and anterior cingulate cortex.

Background: Major depressive disorder (MDD) was involved in widely transcriptional changes in central and peripheral tissues. While, previous studies focused on single tissues, making it difficult to represent systemic molecular changes throughout the body. Thus, there is an urgent need to explore the central and peripheral biomarkers with intrinsic correlation. Methods: We systematically retrieved gene expression profiles of blood and anterior cingulate cortex (ACC). 3 blood datatsets (84 MDD and 88 controls) and 6 ACC datasets (100 MDD and 100 controls) were obtained. Differential expression analysis, RobustRankAggreg (RRA) analysis, functional enrichment analysis, immune associated analysis and protein-protein interaction networks (PPI) were integrated. Furthermore, the key genes were validated in an independent ACC dataset (12 MDD and 15 controls) and a cohort with 120 MDD and 117 controls. Results: Differential expression analysis identified 2211 and 2021 differential expressed genes (DEGs) in blood and ACC, respectively. RRA identified 45 and 25 robust DEGs in blood and ACC based on DEGs, and all of them were closely associated with immune cells. Functional enrichment results showed both the robust DEGs in blood and ACC were enriched in humoral immune response. Furthermore, PPI identified 8 hub DEGs (CD79A, CD79B, CD19, MS4A1, PLP1, CLDN11, MOG, MAG) in blood and ACC. Independent ACC dataset showed the area under the curve (AUC) based on these hub DEGs was 0.77. Meanwhile, these hub DEGs were validated in the serum of MDD patients, and also showed a promising diagnostic power. Conclusions: The biomarker panel based on hub DEGs yield a promising diagnostic efficacy, and all of these hub DEGs were strongly correlated with immunity. Humoral immune response may be the key link between the brain and blood in MDD, and our results may provide further understanding for MDD.

Analysis of Pickled Cucumber Products, Based on Microbial Diversity and Flavor Substance Detection.

Changes to the microbial community during pickled cucumber fermentation were studied using the 16S rDNA technique. The changes of volatile organic compounds (VOCs) during pickled cucumber fermentation were studied by gas chromatograph-ion mobility spectrometry. At the phylum level, Cyanophyta and Proteobacteria were the dominant flora in the natural fermentation group, and Firmicutes were the dominant flora in the added-bacteria fermentation group. At the generic level, the addition of Lactobacillus led to changes in the community of the bacteria in the added-bacterial fermentation group and decreased the species abundance of other bacteria. In total, 75 volatile organic compounds were identified from naturally fermented pickled cucumber, and 60 volatile organic compounds were identified from fermented pickled cucumber with bacterial addition. The main metabolites were esters, aldehydes, acids, alcohols, ketones, alkanes, nitriles, and alkenes. These metabolites will bring their unique aroma components to the pickled cucumber. Metabolomic analysis of the O2PLS model showed that Weissella and Lactobacillus were closely and positively correlated with nine alcohols, six esters, five aldehydes, four acids, three ketones, and one pyrazine. Pseudomonas and norank_f_Mitochondria show a close positive correlation with four kinds of alcohols, two kinds of esters, one kind of aldehyde, and one kind of nitrile.

The significance of detecting HBV pgRNA and HBcrAg in HBV patients treated with NAs.

The value of detecting hepatitis B virus (HBV), pregenomic RNA (pgRNA), and hepatitis B core-related antigen (HBcrAg), both separately and jointly, in the management of HBV patients undergoing treatment with Nucleotide Analog was investigated. A total of 149 HBV patients who were being treated with Nucleotide Analog were enrolled in this study. The quantitative levels of HBV pgRNA and HBcrAg in the sera of these patients were determined, aiming to comprehend their replication levels and expression during the course of antiviral therapy. The patients were separated into 3 groups based on treatment duration: treatment time ≤ 12 months, treatment time ranging from 12 months to <60 months, and treatment time ≥ 60 months. Significantly different levels of HBcrAg and HBV pgRNA were observed among 3 groups (P < .05). In the group of patients with positive hepatitis B e antigen, both HBcrAg and pgRNA levels were higher compared to the group with negative hepatitis B e antigen, and this difference between the 2 groups was found to be statistically significant. Stratified analysis based on levels of hepatitis B surface antigen (HBsAg) revealed that the group with HBsAg levels < 100 IU/mL had lower levels of both HBcrAg and pgRNA compared to the group with HBsAg levels ≥ 100 IU/mL (P < .001). Following antiviral therapy, various degrees of transcription of covalently closed circular DNA continue to exist within the liver of HBV patients. The levels of serum HBcrAg and HBV pgRNA vary among patients with different treatment durations, indicating their efficacy in evaluating disease conditions during antiviral therapy.

Astragaloside IV combined with ligustrazine ameliorates abnormal mitochondrial dynamics via Drp1 SUMO/deSUMOylation in cerebral ischemia-reperfusion injury.

OBJECTIVES: Astragaloside IV (AST IV) and ligustrazine (Lig), the main ingredients of Astragali Radix and Chuanxiong Rhizoma respectively, have demonstrated significant benefits in treatment of cerebral ischemia -reperfusion injury (CIRI); however, the mechanisms underlying its benificial effects remain unclear. SUMO-1ylation and deSUMO-2/3ylation of dynamin-related protein 1 (Drp1) results in mitochondrial homeostasis imbalance following CIRI, which subsequently aggravates cell damage. This study investigates the mechanisms by which AST IV combined with Lig protects against CIRI, focusing on the involvement of SUMOylation in mitochondrial dynamics. METHODS: Rats were administrated AST IV and Lig for 7 days, and middle cerebral artery occlusion was established to mimic CIRI. Neural function, cerebral infarction volume, cerebral blood flow, cognitive function, cortical pathological lesions, and mitochondrial morphology were measured. SH-SY5Y cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury. Mitochondrial membrane potential and lactic dehydrogenase (LDH), reactive oxygen species (ROS), and adenosine triphosphate (ATP) levels were assessed with commercial kits. Moreover, co-immunoprecipitation (Co-IP) was used to detect the binding of SUMO1 and SUMO2/3 to Drp1. The protein expressions of Drp1, Fis1, MFF, OPA1, Mfn1, Mfn2, SUMO1, SUMO2/3, SENP1, SENP2, SENP3, SENP5, and SENP6 were measured using western blot. RESULTS: In rats with CIRI, AST IV and Lig improved neurological and cognitive functions, restored CBF, reduced brain infarct volume, and alleviated cortical neuron and mitochondrial damage. Moreover, in SH-SY5Y cells, the combination of AST IV and Lig enhanced cellular viability, decreased release of LDH and ROS, increased ATP content, and improved mitochondrial membrane potential. Furthermore, AST IV combined with Lig reduced the binding of Drp1 with SUMO1, increased the binding of Drp1 with SUMO2/3, suppressed the expressions of Drp1, Fis1, MFF, and SENP3, and increased the expressions of OPA1, Mfn1, Mfn2, SENP1, SENP2, and SENP5. SUMO1 overexpression promoted mitochondrial fission and inhibited mitochondrial fusion, whereas SUMO2/3 overexpression suppressed mitochondrial fission. AST IV combined with Lig could reverse the effects of SUMO1 overexpression while enhancing those of SUMO2/3 overexpression. CONCLUSIONS: This study posits that the combination of AST IV and Lig has the potential to reduce the SUMO-1ylation of Drp1, augment the SUMO-2/3ylation of Drp1, and thereby exert a protective effect against CIRI.

Urocortin-1 promotes colorectal cancer cell migration and proliferation and inhibits apoptosis via inhibition of the p53 signaling pathway.

PURPOSE: To investigate the effect of urocortin-1 (UCN-1) on growth, migration, and apoptosis in colorectal cancer (CRC) in vivo and vitro and the mechanism by which UCN-1 modulates CRC cells in vitro. METHODS: The correlation between UCN-1 and CRC was evaluated using The Cancer Genome Atlas (TCGA) database and a tissue microarray. The expression of UCN-1 in CRC cells was assessed using quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting. In vitro, the influence of UCN-1 on the proliferation, apoptosis, and migration of HT-29, HCT-116, and RKO cells was explored using the celigo cell counting assay or cell counting kit-8 (CCK8), flow cytometry, and wound healing or Transwell assays, respectively. In vivo, the effect of UCN-1 on CRC growth and progression was evaluated in nude mice. The downstream pathway underlying UCN-1-mediated regulation of CRC was determined using the phospho-kinase profiler array in RKO cells. Lentiviruses were used to knockdown or upregulate UCN-1 expression in cells. RESULTS: Both the TCGA and tissue microarray results showed that UCN-1 was strongly expressed in the tissues of patients with CRC. Furthermore, the tissue microarray results showed that the expression of UCN-1 was higher in male than in female patients, and high expression of UCN-1 was associated with higher risk of lymphatic metastasis and later pathological stage. UCN-1 knockdown caused a reduction in CRC cell proliferation, migration, and colony formation, as well as an increase in apoptosis. In xenograft experiments, tumors generated from RKO cells with UCN-1 knockdown exhibited reduced volumes and weights. A reduction in the expression of Ki-67 in xenograft tumors indicated that UCN-1 knockdown curbed tumor growth. The human phospho-kinase array showed that the p53 signaling pathway participated in UCN-1-mediated CRC development. The suppression in migration and proliferation caused by UCN-1 knockdown was reversed by inhibitors of p53 signal pathway, while the increase in cell apoptosis was suppressed. On the other hand, overexpression of UCN-1 promoted proliferation and migration and inhibited apoptosis in CRC cells. Overexpression of p53 reversed the effect of UCN-1 overexpression on CRC development. CONCLUSION: UCN-1 promotes migration and proliferation and inhibits apoptosis via inhibition of the p53 signaling pathway.

Integrated Electrochemical Aptasensor Array toward Monitoring Anticancer Drugs in Sweat.

In the realm of clinical practice, the concurrent utilization of anticancer medications can enhance their overall therapeutic efficacy. However, it is crucial to acknowledge that the interactions among these anticancer drugs can potentially yield detrimental consequences on their intended outcomes. Consequently, the assessment of both anticancer potency and potential toxic side effects is greatly refined when multiple anticancer drugs are simultaneously detected and evaluated. Here, we designed a wearable electrochemical aptasensor array for monitoring multiple anticancer drugs in sweat. The integrated sensor array consists of three working electrodes modified with three different aptamers (Apt1, Apt2, and Apt3), a Au counter electrode, and a Ag/AgCl reference electrode. Molecular docking simulations were performed to show the binding affinities between three anticancer drugs and their corresponding aptamers. Various eigenvalues were derived from the square-wave voltammetry electrochemical signals, and these data sets were subjected to rigorous analysis through multivariate data analysis techniques. This analytical approach demonstrated exceptional performance by achieving flawless 100% accuracy in the precise identification of nine anticancer drugs consistently at uniform concentrations. Furthermore, the integrated wearable sensor array exhibited impressive capabilities, correctly recognizing all nine anticancer drugs with 100% accuracy and successfully distinguishing between these drugs in artificial sweat samples. The proposed sensor array presents good stability for 15 days. Flexibility tests showed stable device performance after 500 twisting cycles. This innovative wearable sensing array represents a novel approach for achieving real-time monitoring and precise adjustment of drug dosages. It offers invaluable insights for tailoring the treatment of anticancer drugs to individual patients, predicting both drug efficacy and potential adverse reactions within the field of clinical medicine.

Effects of 28 h ahemeral light cycle on production performance, egg quality, blood parameters, and uterine characteristics of hens during the late laying period.

This study aimed to systematically determined the effect of 28 h ahemeral light cycle on production performance, egg quality, blood parameters, uterine morphological characteristics, and gene expression of hens during the late laying period. At 74 wk, 260 Hy-Line Brown layers were randomly divided into 2 groups of 130 birds each and in duplicates. Both a regular (16L:8D) and an ahemeral light cycle (16L:12D) were provided to the hens. The oviposition pattern in an ahemeral cycle shifted into darkness, with oviposition mostly occurring 3 to 5 h after light out. Production performance was unaffected by light cycle (P > 0.05). Nonetheless, compared to the normal group, the ahemeral group exhibited increased egg weight, eggshell weight, eggshell percentage, yolk percentage, eggshell thickness, and eggshell strength (P < 0.05). There were rhythmic changes in the uterine morphological structure in both cycles, however, the ahemeral group maintained a longer duration and had more uterine folds than the normal group. In the ahemeral cycle, the phases of the CLOCK and PER2 genes were phase-advanced for 3.96 h and 4.54 h compared to the normal cycle. The PHLPP1 gene, which controls clock resetting, exhibited a substantial oscillated rhythm in the ahemeral group (P < 0.05), while the expression of genes presenting biological rhythm, such as CRY2 and FBXL3, was rhythmically oscillated in normal cycle (P < 0.05). The ITPR2 gene, which regulates intracellular Ca2+ transport, displayed a significant oscillated rhythm in ahemeral alone (P < 0.05), while the CA2 gene, which presents biomineralization, rhythmically oscillated in both cycles (P < 0.05). The ahemeral cycle caused 2.5 h phase delays in the CA2 gene compared to the normal cycle. In conclusion, the 28 h ahemeral light cycle preserved the high condition of the uterine folds and changed the uterine rhythms of CLOCK, PER2, ITPR2, and CA2 gene expression to improve ion transport and uterine biomineralization.

Toll-like receptor 2 deficiency promotes the generation of alloreactive γδT17 cells after cardiac transplantation in mice.

Homograft rejection is the main cause of heart transplantation failure. The role of TLR2, a major member of the toll-like receptor (TLR) family, in transplantation rejection is has yet to be elucidated. In this study, we used a mouse model of acute cardiac transplantation rejection to investigate whether the TLR2 signalling pathway can regulate cardiac transplantation rejection by regulating alloreactive IL-17+γδT (γδT17) cells. We found that the expression of TLR2 on the surface of dendritic cells (DCs) and macrophages increased during acute transplantation rejection. In addition, our investigation revealed that γδT17 cells exert a significant influence on acute cardiac transplantation rejection. TLR2 gene knockout resulted in an increase in alloreactive γδT17 cells in the spleen and heart grafts of recipient mice compared with wild-type recipient mice and an increase in the mRNA expression of IL-17, IL-1ß, CCR6, and CCL20 in the heart grafts. In an in vitro experiment, a mixed lymphocyte reaction was conducted to assess the impact of TLR2 deficiency on the generation of γδT17 cells, which further substantiated a significant increase compared to that in wild-type controls. Furthermore, the mixed lymphocyte reaction showed that TLR2 regulated the production of γδT17 cells by regulating the ability of DCs to secrete IL-1ß. These results suggest that TLR2 signalling is important for regulating the generation of γδT17 cells after cardiac allograft transplantation.

Identification of Shared Signature Genes and Immune Microenvironment Subtypes for Heart Failure and Chronic Kidney Disease Based on Machine Learning.

Background: A complex interrelationship exists between Heart Failure (HF) and chronic kidney disease (CKD). This study aims to clarify the molecular mechanisms of the organ-to-organ interplay between heart failure and CKD, as well as to identify extremely sensitive and specific biomarkers. Methods: Differentially expressed tandem genes were identified from HF and CKD microarray datasets and enrichment analyses of tandem perturbation genes were performed to determine their biological functions. Machine learning algorithms are utilized to identify diagnostic biomarkers and evaluate the model by ROC curves. RT-PCR was employed to validate the accuracy of diagnostic biomarkers. Molecular subtypes were identified based on tandem gene expression profiling, and immune cell infiltration of different subtypes was examined. Finally, the ssGSEA score was used to build the ImmuneScore model and to assess the differentiation between subtypes using ROC curves. Results: Thirty-three crosstalk genes were associated with inflammatory, immune and metabolism-related signaling pathways. The machine-learning algorithm identified 5 hub genes (PHLDA1, ATP1A1, IFIT2, HLTF, and MPP3) as the optimal shared diagnostic biomarkers. The expression levels of tandem genes were negatively correlated with left ventricular ejection fraction and glomerular filtration rate. The CIBERSORT results indicated the presence of severe immune dysregulation in patients with HF and CKD, which was further validated at the single-cell level. Consensus clustering classified HF and CKD patients into immune and metabolic subtypes. Twelve immune genes associated with immune subtypes were screened based on WGCNA analysis, and an ImmuneScore model was constructed for high and low risk. The model accurately predicted different molecular subtypes of HF or CKD. Conclusion: Five crosstalk genes may serve as potential biomarkers for diagnosing HF and CKD and are involved in disease progression. Metabolite disorders causing activation of a large number of immune cells explain the common pathogenesis of HF and CKD.