C2H2-type zinc-finger protein BCL11B suppresses avian Leukosis virus subgroup J replication by regulating apoptosis.

Apoptosis plays a crucial role in host antiviral defense. The avian leukosis virus subgroup J (ALV-J), an avian oncogenic retrovirus, has been shown to suppress apoptosis while promoting its own replication. ALV-J induces myeloid tumors and hemangiomas in chickens resulting in significant economic losses for commercial layer and meat-type chicken production. B-cell lymphoma/leukemia 11B (Bcl11b) encodes a C2H2-type zinc finger protein-BCL11B, that exerts critical functions in cell proliferation, differentiation, and plays an essential role in the immune system. Previous study has been shown that Bcl11b is associated with ALV-J infection. In this study, we further investigated the pathological changes in ALV-J infected cells and examined the role and expression regulation of chicken Bcl11b. Our results demonstrate that Bcl11b, as an interferon-stimulated gene (ISG), encodes C2H2-type zinc finger protein BCL11B that promotes apoptosis to inhibit ALV-J infection. Additionally, gga-miR-1612 and gga-miR-6701-3p regulate apoptosis and are involved in ALV-J infection by targeting Bcl11b, thus revealing immune response strategies between the host and ALV-J. Although the underlying mechanisms require further validation, Bcl11b and its regulatory miRNAs are the first to demonstrate inhibition of ALV-J replication via apoptosis. BCL11B can a valuable target for treating diseases triggered by ALV-J infection.

Establishment of an ovarian cancer exhausted CD8+T cells-related genes model by integrated analysis of scRNA-seq and bulk RNA-seq.

Ovarian cancer (OC) was the fifth leading cause of cancer death and the deadliest gynecological cancer in women. This was largely attributed to its late diagnosis, high therapeutic resistance, and a dearth of effective treatments. Clinical and preclinical studies have revealed that tumor-infiltrating CD8+T cells often lost their effector function, the dysfunctional state of CD8+T cells was known as exhaustion. Our objective was to identify genes associated with exhausted CD8+T cells (CD8TEXGs) and their prognostic significance in OC. We downloaded the RNA-seq and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD8TEXGs were initially identified from single-cell RNA-seq (scRNA-seq) datasets, then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were utilized to calculate risk score and to develop the CD8TEXGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in the risk groups were used to figure out the closely correlated pathways with the risk group. The role of risk score has been further explored in the homologous recombination repair deficiency (HRD), BRAC1/2 gene mutations and tumor mutation burden (TMB). A risk signature with 4 CD8TEXGs in OC was finally built in the TCGA database and further validated in large GEO cohorts. The signature also demonstrated broad applicability across various types of cancer in the pan-cancer analysis. The high-risk score was significantly associated with a worse prognosis and the risk score was proven to be an independent prognostic biomarker. The 1-, 3-, and 5-years ROC values, nomogram, calibration, and comparison with the previously published models confirmed the excellent prediction power of this model. The low-risk group patients tended to exhibit a higher HRD score, BRCA1/2 gene mutation ratio and TMB. The low-risk group patients were more sensitive to Poly-ADP-ribose polymerase inhibitors (PARPi). Our findings of the prognostic value of CD8TEXGs in prognosis and drug response provided valuable insights into the molecular mechanisms and clinical management of OC.

Highly Selective Drug-Derived Fluorescent Probes for the Cannabinoid Receptor Type 1 (CB1R).

The cannabinoid receptor type 1 (CB1R) is pivotal within the endocannabinoid system regulating various signaling cascades with effects in appetite regulation, pain perception, memory formation, and thermoregulation. Still, understanding of CB1R's cellular signaling, distribution, and expression dynamics is very fragmentary. Real-time visualization of CB1R is crucial for addressing these questions. Selective drug-like CB1R ligands with a defined pharmacological profile were investigated for the construction of CB1R fluorescent probes using a reverse design-approach. A modular design concept with a diethyl glycine-based building block as the centerpiece allowed for the straightforward synthesis of novel probe candidates. Validated by computational docking studies, radioligand binding, and cAMP assay, this systematic approach allowed for the identification of novel pyrrole-based CB1R fluorescent probes. Application in fluorescence-based target-engagement studies and live cell imaging exemplify the great versatility of the tailored CB1R probes for investigating CB1R localization, trafficking, pharmacology, and its pathological implications.

Machine Learning-Assisted Optimization of Mixed Carbon Source Compositions for High-Performance Denitrification.

Appropriate mixed carbon sources have great potential to enhance denitrification efficiency and reduce operational costs in municipal wastewater treatment plants (WWTPs). However, traditional methods struggle to efficiently select the optimal mixture due to the variety of compositions. Herein, we developed a machine learning-assisted high-throughput method enabling WWTPs to rapidly identify and optimize mixed carbon sources. Taking a local WWTP as an example, a mixed carbon source denitrification data set was established via a high-throughput method and employed to train a machine learning model. The composition of carbon sources and the types of inoculated sludge served as input variables. The XGBoost algorithm was employed to predict the total nitrogen removal rate and microbial growth, thereby aiding in the assessment of the denitrification potential. The predicted carbon sources exhibited an enhanced denitrification potential over single carbon sources in both kinetic experiments and long-term reactor operations. Model feature analysis shows that the cumulative effect and interaction among individual carbon sources in a mixture significantly enhance the overall denitrification potential. Metagenomic analysis reveals that the mixed carbon sources increased the diversity and complexity of denitrifying bacterial ecological networks in WWTPs. This work offers an efficient method for WWTPs to optimize mixed carbon source compositions and provides new insights into the mechanism behind enhanced denitrification under a supply of multiple carbon sources.

CT-determined low skeletal muscle index predicts poor prognosis in patients with colorectal cancer.

BACKGROUND: Sarcopenia is highly prevalent among patients with colorectal cancer (CRC). Computed tomography (CT)-based assessment of low skeletal muscle index (SMI) is widely used for diagnosing sarcopenia. However, there are conflicting findings on the association between low SMI and overall survival (OS) in CRC patients. The objective of this study was to investigate whether CT-determined low SMI can serve as a valuable prognostic factor in CRC. METHODS: We collected data from patients with CRC who underwent radical surgery at our institution between June 2020 and November 2021. The SMI at the third lumbar vertebra was calculated using CT scans, and the cutoff values for defining low SMI were determined using receiver operating characteristic curves. Univariate and multivariate analyses were performed to assess the associations between clinical characteristics and postoperative major complications. RESULTS: A total of 464 patients were included in the study, 229 patients (46.7%) were classified as having low SMI. Patients with low SMI were older and had a lower body mass index (BMI), a higher neutrophil to lymphocyte ratio (NLR), and higher nutritional risk screening 2002 (NRS2002) scores compared to those with normal SMI. Furthermore, patients with sarcopenia had a higher rate of major complications (10.9% vs. 1.3%; p < 0.001) and longer length of stay (9.09 ± 4.86 days vs. 8.25 ± 3.12 days; p = 0.03). Low SMI and coronary heart disease were identified as independent risk factors for postoperative major complications. Moreover, CRC patients with low SMI had significantly worse OS. Furthermore, the combination of low SMI with older age or TNM stage II + III resulted in the worst OS in each subgroup analysis. CONCLUSIONS: CT-determined low SMI is associated with poor prognosis in patients with CRC, especially when combined with older age or advanced TNM stage.

Vermicompost Supply Enhances Fragrant-Rice Yield by Improving Soil Fertility and Eukaryotic Microbial Community Composition under Environmental Stress Conditions.

Heavy-metal contamination in agricultural soil, particularly of cadmium (Cd), poses serious threats to soil biodiversity, rice production, and food safety. Soil microbes improve soil fertility by regulating soil organic matter production, plant nutrient accumulation, and pollutant transformation. Addressing the impact of Cd toxicity on soil fungal community composition, soil health, and rice yield is urgently required for sustainable rice production. Vermicompost (VC) is an organic fertilizer that alleviates the toxic effects of Cd on soil microbial biodiversity and functionality and improves crop productivity sustainably. In the present study, we examined the effects of different doses of VC (i.e., 0, 3, and 6 tons ha-1) and levels of Cd stress (i.e., 0 and 25 mg Cd kg-1) on soil biochemical attributes, soil fungal community composition, and fragrant-rice grain yield. The results showed that the Cd toxicity significantly reduced soil fertility, eukaryotic microbial community composition and rice grain yield. However, the VC addition alleviated the Cd toxicity and significantly improved the soil fungal community; additionally, it enhanced the relative abundance of Ascomycota, Chlorophyta, Ciliophora, Basidiomycota, and Glomeromycta in Cd-contaminated soils. Moreover, the VC addition enhanced the soil's chemical attributes, including soil pH, soil organic carbon (SOC), available nitrogen (AN), total nitrogen (TN), and microbial biomass C and N, compared to non-VC treated soil under Cd toxicity conditions. Similarly, the VC application significantly increased rice grain yield and decreased the Cd uptake in rice. One possible explanation for the reduced Cd uptake in plants is that VC amendments influence the soil's biological properties, which ultimately reduces soil Cd bioavailability and subsequently influences the Cd uptake and accumulation in rice plants. RDA analysis determined that the leading fungal species were highly related to soil environmental attributes and microbial biomass C and N production. However, the relative abundance levels of Ascomycota, Basidiomycota, and Glomeromycta were strongly associated with soil environmental variables. Thus, the outcomes of this study reveal that the use of VC in Cd-contaminated soils could be useful for sustainable rice production and safe utilization of Cd-polluted soil.

Bitter taste TAS2R14 activation by intracellular tastants and cholesterol.

Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents1,2. TAS2R14 is also widely expressed in extragustatory tissues, suggesting its extra roles in diverse physiological processes and potential therapeutic applications3. Here we present cryogenic electron microscopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G-protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A G-protein-coupled receptors. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis and molecular dynamic simulation studies, elucidate the broad-spectrum ligand recognition and activation of the receptor by means of intricate multiple ligand-binding sites. Our study also uncovers the specific coupling modes of TAS2R14 with gustducin and Gi1 proteins. These findings should be instrumental in advancing knowledge of bitter taste perception and its broader implications in sensory biology and drug discovery.

Flipping the GPCR Switch: Structure-Based Development of Selective Cannabinoid Receptor 2 Inverse Agonists.

We report a blueprint for the rational design of G protein coupled receptor (GPCR) ligands with a tailored functional response. The present study discloses the structure-based design of cannabinoid receptor type 2 (CB2R) selective inverse agonists (S)-1 and (R)-1, which were derived from privileged agonist HU-308 by introduction of a phenyl group at the gem-dimethylheptyl side chain. Epimer (R)-1 exhibits high affinity for CB2R with Kd = 39.1 nM and serves as a platform for the synthesis of a wide variety of probes. Notably, for the first time these fluorescent probes retain their inverse agonist functionality, high affinity, and selectivity for CB2R independent of linker and fluorophore substitution. Ligands (S)-1, (R)-1, and their derivatives act as inverse agonists in CB2R-mediated cAMP as well as G protein recruitment assays and do not trigger ß-arrestin-receptor association. Furthermore, no receptor activation was detected in live cell ERK1/2 phosphorylation and Ca2+-release assays. Confocal fluorescence imaging experiments with (R)-7 (Alexa488) and (R)-9 (Alexa647) probes employing BV-2 microglial cells visualized CB2R expressed at endogenous levels. Finally, molecular dynamics simulations corroborate the initial docking data in which inverse agonists restrict movement of toggle switch Trp2586.48 and thereby stabilize CB2R in its inactive state.

Study on changing disciplinarian of beak colors in ducks and the regulation network based on transcriptome sequencing.

Beak color in ducks is a primary characteristic of local breeds and genetic resources. Among them, black beaks, a rare packaging trait of high-quality duck products, have attracted much attention. In this study, Runzhou White Created ducks (black beak) and white-feathered Putian black ducks (yellow beak) were used to construct the F2 generation resource population to study the changing discipline of beak color combined with the beak color statistics of gray-beaked ducklings of Runzhou White Created ducks. Subsequently, transcriptome sequencing was performed to identify genetic markers related to beak color. To explore the rules of beak color change and its regulatory network, trends, and trend analysis and weighted gene co-expression network analysis（WGCNA）were performed. The screening results were verified by real-time quantitative polymerase chain reaction. A large difference was observed between the beak colors of birds from the F1 generation at 0 and 42 d of age. The F2 generation results show that nearly half of the black-beaked ducklings become green-beaked; the proportion of black spots for gray- and patterned-beaked ducklings increases with age, with most becoming green-beaked. Moreover, the beak color darkened from the first day, and the gray color value decreased significantly from the second day. Transcriptome sequencing indicated that TYR was differentially expressed between black and yellow beaks at 4 to 6 wk of age, and trend and WGCNA analyses showed that EDNRB signaling pathway genes and MITF were highly expressed in the first week, and TYR, TYRP1, and DCT were highly expressed at 4 to 6 wk of age. Therefore, there is melanin synthesis and deposition after hatching for gray- and patterned-beaked ducklings, while the yellow pigment might be deposited in the epidermis of beaks for black-beaked ducklings. The EDNRB signaling pathway is probably involved in early melanosome maturation and melanin formation in duck beaks, and genes such as TYR can maintain the black-beak phenotype.

Effect of exogenous hydrogen sulfide on hypoxia/reoxygenation injury in glomerular mesangial cells and its mechanism / 中国药理学通报

Aim To explore the effect of exogenous hydrogen sulfide ( H2 S ) on hypoxia/reoxygenation ( H/R) injury in glomerular mesangial cells and elucidate its relevant mechanism. Methods H/R induced mouse mesangial cell line ( SV40MES13 ) to establish cell damage model. Cell viability was detected by cell proliferation kit ( CCK8 ), the content of H

Substation of vermicompost mitigates Cd toxicity, improves rice yields and restores bacterial community in a Cd-contaminated soil in Southern China.

Cadmium (Cd) contamination in agricultural soil is a global concern for soil health and food sustainability because it can cause Cd accumulation in cereal grains. An in-situ stabilizing technology (using organic amendments) has been widely used for Cd remediation in arable lands. Therefore, the current study examined the influence of vermicompost (VC) on soil biochemical traits, bacterial community diversity and composition, Cd uptake and accumulation in rice plants and grain yield in a Cd-contaminated soil during the late growing season in 2022. Different doses of VC (i.e., V1 = 0 t ha-1, V2 = 3 t ha-1 and V3 = 6 t ha-1) and two concentrations of Cd (i.e., Cd1 = 0 and Cd2 = 50 mg Cd Kg-1 were used. We performed high-throughput sequencing of 16S ribosomal RNA gene amplicons to characterize soil bacterial communities. The addition of VC considerably affected the diversity and composition of the soil bacterial community; and increased the relative abundance of phyla Chloroflexi, Proteobacteria, Acidobacteriota, Plantomycetota, Gemmatimonadota, Patescibacteria and Firmicute. In addition, VC application, particularly High VC treatment, exhibited the highest bacterial diversity and richness (i.e., Simpson, Shannon, ACE, and Chao 1 indexes) of all treatments. Similarly, the VC application increased the soil chemical traits, including soil pH, soil organic carbon (SOC), available nitrogen (AN), total nitrogen (TN), total potassium (TK), total phosphorous (TP) and enzyme activities (i.e., acid phosphatase, catalase, urease and invertase) compared to non-VC treated soil under Cd stress. The average increase in SOC, TN, AN, TK and TP were 5.75%, 41.15%, 18.51%, 12.31%, 25.45% and 29.67%, respectively, in the High VC treatment (Pos-Cd + VC3) compared with Cd stressed soil. Redundancy analysis revealed that the leading bacterial phyla were associated with SOC, AN, TN, TP and pH, although the relative abundance of Firmicutes, Proteobacteria, Bacteroidata, and Acidobacteria on a phylum basis and Actinobacteria, Gammaproteobacteria and Myxococcia on a class basis, were highly correlated with soil environmental factors. Moreover, the VC application counteracted the adverse effects of Cd on plants and significantly reduced the Cd uptake and accumulation in rice organs, such as roots, stem + leaves and grain under Cd stress conditions. Similarly, applying VC significantly increased the fragrant rice grain yield and yield traits under Cd toxicity. The correlation analysis showed that the increased soil quantities traits were crucial in obtaining high rice grain yield. Generally, the findings of this research demonstrate that the application of VC in paddy fields could be useful for growers in Southern China by sustainably enhancing soil functionality and crop production.

Evaluation of early effectiveness of local infiltration anesthesia with compound betamethasone in total knee arthroplasty / 中国修复重建外科杂志

OBJECTIVE@#To evaluate the early effectiveness of local infiltration anesthesia (LIA) with compound betamethasone in total knee arthroplasty (TKA).@*METHODS@#The clinical data of 102 patients with knee osteoarthritis who were treated by TKA and met the selection criteria between May 2022 and March 2023 were retrospectively analyzed. They were divided into control group and study group according to whether LIA preparation was added with compound betamethasone, with 51 cases in each group. There was no significant difference of baseline data, such as age, gender, body mass index, operative side, preoperative range of motion (ROM), Knee Society Score (KSS), white blood cell (WBC), and hematocrit between the two groups ( P>0.05). The intraoperative total blood loss and hidden blood loss were recorded, and WBC was recorded on the 1st, 2nd, and 3rd days after operation. Pain was assessed by visual analogue scale (VAS) score on the 1st, 2nd, and 3rd days after operation and morphine intake milligrames equivalent within 48 hours after operation. Passive ROM, maximum extension and flexion angles of knee joint were measured on the 3rd day after operation; the early postoperative complications were recorded.@*RESULTS@#There was no significant difference in total blood loss and hidden blood loss between the two groups ( P>0.05). The postoperative pain levels in both groups were relatively mild, and there was no significant difference in VAS scores in the first 3 days after operation and in morphine intake milligrams equivalent within 48 hours after operation between the two groups ( P>0.05). The WBC in the first 3 days after operation was significantly improved in both groups ( P<0.05). The WBC in the study group was significantly higher than that in the control group on the 1st and 2nd days after operation ( P<0.05), but there was no significant difference between the two groups on the 3rd day after operation ( P>0.05). On the 3rd day after operation, the maximum extension angle of knee joint in the study group was smaller than that in the control group, while the maximum flexion angle and passive ROM of knee joint in the study group were larger than those in the control group, and the differences were significant ( P<0.05). There were 6 cases of fever and 17 cases of deep venous thrombosis in the control group, and 1 case and 14 cases in the study group, respectively. There was no poor wound healing and periprosthetic joint infection in the two groups, and there was no significant difference in the incidence of complications between the two groups ( P>0.05).@*CONCLUSION@#The application of compound betamethasone in LIA during TKA is a safe and optimal strategy to promote the early postoperative rehabilitation of patients.

[Novel CD19-KIRS2/Dap12-BB CAR-T Treatment for 3 Patients with Relapsed and Refractory B-Cell Tumors].

OBJECTIVE: To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM). METHODS: Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed. RESULTS: After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively. CONCLUSION: The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.

Prognostic significance of organ failure and infected pancreatic necrosis in acute pancreatitis: An updated systematic review and meta-analysis.

OBJECTIVES: In patients with acute pancreatitis (AP), minimally invasive treatment and the step-up approach have been widely used to deal with infected pancreatic necrosis (IPN) in the last decade. It is unclear whether IPN has become a less important determinant of mortality relative to organ failure (OF). We aimed to statistically aggregate recent evidence from published studies to determine the relative importance of IPN and OF as determinants of mortality in patients with AP (PROSPERO: CRD42020176989). METHODS: Relevant studies were sourced from MEDLINE and EMBASE databases. Relative risk (RR) or weighted mean difference (WMD) was analyzed as outcomes. A two-sided P value of less than 0.05 was regarded as statistical significance. RESULTS: Forty-three studies comprising 11 601 patients with AP were included. The mortality was 28% for OF patients and 24% for those with IPN. Patients with OF without IPN had a significantly higher risk of mortality compared to those with IPN but without OF (RR 3.72, P < 0.0001). However, patients with both OF and IPN faced the highest risk of mortality. Additionally, IPN increased length of stay in hospital for OF patients (WMD 28.75, P = 0.032). CONCLUSION: Though IPN remains a significant concern, which leads to increased morbidity and longer hospital stay, it is a less critical mortality determinant compared to OF in AP.

Long-term analysis of cellular immunity in patients with RRMM treated with CAR-T cell therapy.

Chimeric antigen receptor T (CAR-T) cell therapy exhibits remarkable efficacy against refractory or relapsed multiple myeloma (RRMM); however, the immune deficiency following CAR-Ts infusion has not been well studied. In this study, 126 patients who achieved remission post-CAR-Ts infusion were evaluated for cellular immunity. Following lymphodepletion (LD) chemotherapy, the absolute lymphocyte count (ALC) and absolute counts of lymphocyte subsets were significantly lower than baseline at D0. Grade ≥ 3 lymphopenia occurred in 99% of patients within the first 30 days, with most being resolved by 180 days. The median CD4+ T-cell count was consistently below baseline and the lower limit of normal (LLN) levels at follow-up. Conversely, the median CD8+ T-cell count returned to the baseline and LLN levels by D30. The median B-cell count remained lower than baseline level at D60 and returned to baseline and LLN levels at D180. In the first 30 days, 27 (21.4%) patients had 29 infections, with the majority being mild to moderate in severity (21/29; 72.4%). After day 30, 44 (34.9%) patients had 56 infections, including 20 severe infections. One patient died from bacteremia at 3.8 months post-CAR-Ts infusion. In conclusion, most patients with RRMM experienced cellular immune deficiency caused by LD chemotherapy and CAR-Ts infusion. The ALC and most lymphocyte subsets gradually recovered after day 30 of CAR-Ts infusion, except for CD4+ T cells. Some patients experience prolonged CD4+ T-cell immunosuppression without severe infection.

Design and Synthesis of Novel GPR139 Agonists with Therapeutic Effects in Mouse Models of Social Interaction and Cognitive Impairment.

The GPR139 receptor is an orphan G-protein-coupled receptor (GPCR) mainly found in the central nervous system and is a potential therapeutic target for the treatment of schizophrenia and drug addiction. Guided by the reported structure of GPR139, we conducted medicinal chemistry optimizations of TAK-041, the GPR139 agonist in clinical trials. New compounds with three different core structures were designed and synthesized, and their activity at GPR139 was evaluated. Among them, compounds 15a (EC50 = 31.4 nM) and 20a (EC50 = 24.7 nM) showed potent agonist activity at GPR139 and good pharmacokinetic properties. In murine schizophrenia models, both compounds rescued the social interaction deficits observed in BALB/c mice. Compound 20a also alleviated cognitive deficits in mice with a pharmacologically induced model of schizophrenia. These findings further demonstrated the potential of GPR139 agonists in alleviating the negative symptoms and cognitive deficits of schizophrenia. Compound 20a is worth further evaluation as an antischizophrenia drug candidate.

Identification of SNPs in MITF associated with beak color of duck.

Introduction: Beak color-a pigment-related trait-is an important feature of duck breeds. Recently, little research has addressed genetic mechanism of the beak colors in poultry, whereas the process and the regulation factors of melanin deposition have been well described. Methods: To investigate the genetic mechanism of beak colors, we conducted an integrated analysis of genomic selection signatures to identify a candidate site associated with beak color. For this, we used black-billed (Yiyang I meat duck synthetic line H1, H2, H3&HF) and yellow-billed ducks (Cherry Valley ducks and white feather Putian black duck). Quantitative real-time PCR and genotyping approaches were used to verify the function of the candidate site. Results: We identified 3,895 windows containing 509 genes. After GO and KEGG enrichment analysis, nine genes were selected. Ultimately, MITF was selected by comparing the genomic differentiation (FST). After loci information selection, 41 extreme significantly different loci were selected, which are all located in intron regions of MITF and are in almost complete linkage disequilibrium. Subsequently, the site ASM874695v1:10:g.17814522T > A in MITF was selected as the marker site. Furthermore, we found that MITF expression is significantly higher in black-beaked ducks than in yellow-beaked ducks of the F2 generation (p < 0.01). After genotyping, most yellow-billed individuals are found with homozygous variant; at the same time, there are no birds with homozygous variant in black-billed populations, while the birds with homozygous and heterozygous variant share the same proportion. Conclusion: MITF plays a very critical role in the melanogenesis and melanin deposition of duck beaks, which can effectively affect the beak color. The MITF site, ASM874695v1:10:g.17814522T > A could be selected as a marker site for the duck beak color phenotype.

Exogenous TiO2 Nanoparticles Alleviate Cd Toxicity by Reducing Cd Uptake and Regulating Plant Physiological Activity and Antioxidant Defense Systems in Rice (Oryza sativa L.).

Cadmium (Cd) is a potentially hazardous element with significant biological toxicity, negatively affecting plant growth and physio-biochemical metabolism. Thus, it is necessary to examine practical and eco-friendly approaches to reduce Cd toxicity. Titanium dioxide nanoparticles (TiO2-NPs) are growth regulators that help in nutrient uptake and improve plant defense systems against abiotic and biological stress. A pot experiment was performed in the late rice-growing season (July-November) 2022 to explore the role of TiO2-NPs in relieving Cd toxicity on leaf physiological activity, biochemical attributes, and plant antioxidant defense systems of two different fragrant rice cultivars, i.e., Xiangyaxiangzhan (XGZ) and Meixiangzhan-2 (MXZ-2). Both cultivars were cultivated under normal and Cd-stress conditions. Different doses of TiO2-NPs with and without Cd-stress conditions were studied. The treatment combinations were: Cd-, 0 mg/kg CdCl2·2.5 H2O; Cd+, 50 mg/kg CdCl2·2.5 H2O; Cd + NP1, 50 mg/kg Cd + 50 TiO2-NPs mg/L; Cd + NP2, 50 mg/kg Cd + 100 TiO2-NPs mg/L; Cd + NP3, 50 mg/kg Cd + 200 TiO2-NPs mg/L; Cd + NP4, 50 mg/kg Cd + 400 TiO2-NPs mg/L. Our results showed that the Cd stress significantly (p < 0.05) decreased leaf photosynthetic efficiency, stomatal traits, antioxidant enzyme activities, and the expression of their encoding genes and protein content. Moreover, Cd toxicity destabilized plant metabolism owing to greater accretion of hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels at vegetative and reproductive stages. However, TiO2-NPs application improved leaf photosynthetic efficacy, stomatal traits, and protein and antioxidant enzyme activities under Cd toxicity. Application of TiO2-NPs decreased the uptake and accumulation of Cd in plants and levels of H2O2 and MDA, thereby helping to relieve Cd-induced peroxidation damage of leaf membrane lipids by enhancing the activities of different enzymes like ascorbate peroxidase (APX), catalase (CAT), peroxidase (POS), and superoxide dismutase (SOD). Average increases in SOD, APX, CAT, and POS activities of 120.5 and 110.4%, 116.2 and 123.4%, 41.4 and 43.8%, and 36.6 and 34.2% in MXZ-2 and XGZ, respectively, were noted in Cd + NP3 treatment across the growth stages as compared with Cd-stressed plants without NPs. Moreover, the correlation analysis revealed that the leaf net photosynthetic rate is strongly associated with leaf proline and soluble protein content, suggesting that a higher net photosynthetic rate results in higher leaf proline and soluble protein content. Of the treatments, the Cd + NP3 (50 mg/kg Cd + 200 mg/L TiO2-NPs) performed the best for both fragrant rice cultivars under Cd toxicity. Our results showed that TiO2-NPs strengthened rice metabolism through an enhanced antioxidant defense system across the growth stages, thereby improving plant physiological activity and biochemical characteristics under Cd toxicity.

A Sensitivity-Optimized Flexible Capacitive Pressure Sensor with Cylindrical Ladder Microstructural Dielectric Layers.

Flexible capacitive pressure sensors have attracted extensive attention due to their dynamic response and good sensing capability for static and small pressures. Using microstructural dielectric layers is an effective method for improving performance. However, the current state of microstructure design is primarily focused on basic shapes and is largely limited by simulation results; there is still a great deal of potential for further innovation and improvement. This paper innovatively proposes to increase the ladder structure based on the basic microstructures, for example, the long micro-ridge ladder, the cuboid ladder, and cylindrical ladder microstructures. By comparing 9 kinds of microstructures including ladder structure through finite element simulation, it is found that the sensor with a cylindrical ladder microstructure dielectric layer has the highest sensitivity. The dielectric layers with various microstructures are obtained by 3D printed molds, and the sensor with cylindrical ladder microstructure dielectric layer has the sensitivity of 0.12 kPa-1, which is about 3.9 times higher than that without microstructure. The flexible pressure sensor developed by us boasts sensitivity-optimized and operational stability, making it an ideal solution for monitoring rainfall frequency in real time.