Wafer-Recyclable, Eco-Friendly, and Multiscale Dry Transfer Printing by Transferable Photoresist for Flexible Epidermal Electronics.

Flexible electronics have been of great interest in the past few decades for their wide-ranging applications in health monitoring, human-machine interaction, artificial intelligence, and biomedical engineering. Currently, transfer printing is a popular technology for flexible electronics manufacturing. However, typical sacrificial intermediate layer-based transfer printing through chemical reactions results in a series of challenges, such as time consumption and interface incompatibility. In this paper, we have developed a time-saving, wafer-recyclable, eco-friendly, and multiscale transfer printing method by using a stable transferable photoresist. Demonstration of photoresist with various, high-resolution, and multiscale patterns from the donor substrate of silicon wafer to different flexible polymer substrates without any damage is conducted using the as-developed dry transfer printing process. Notably, by utilizing the photoresist patterns as conformal masks and combining them with physical vapor deposition and dry lift-off processes, we have achieved in situ fabrication of metal patterns on flexible substrates. Furthermore, a mechanical experiment has been conducted to demonstrate the mechanism of photoresist transfer printing and dry lift-off processes. Finally, we demonstrated the application of in situ fabricated electrode devices for collecting electromyography and electrocardiogram signals. Compared to commercially available hydrogel electrodes, our electrodes exhibited higher sensitivity, greater stability, and the ability to achieve long-term health monitoring.

Pushing the thinness limit of silver films for flexible optoelectronic devices via ion-beam thinning-back process.

Reducing the silver film to 10 nm theoretically allows higher transparency but in practice leads to degraded transparency and electrical conductivity because the ultrathin film tends to be discontinuous. Herein, we developed a thinning-back process to address this dilemma, in which silver film is first deposited to a larger thickness with high continuity and then thinned back to a reduced thickness with an ultrasmooth surface, both implemented by a flood ion beam. Contributed by the shallow implantation of silver atoms into the substrate during deposition, the thinness of silver films down to 4.5 nm can be obtained, thinner than ever before. The atomic-level surface smooth permits excellent visible transparency, electrical conductivity, and the lowest haze among all existing transparent conductors. Moreover, the ultrathin silver film exhibits the unique robustness of mechanical flexibility. Therefore, the ion-beam thinning-back process presents a promising solution towards the excellent transparent conductor for flexible optoelectronic devices.

GSDMD induces hepatocyte pyroptosis to trigger alcoholic hepatitis through modulating mitochondrial dysfunction.

BACKGROUND: Mechanisms and consequences of Gasdermin D (GSDMD) activation in alcoholic hepatitis (AH) are unclear. In the present study, we investigated whether GSDMD induces hepatocyte pyroptosis by regulating mitochondrial dysfunction in AH. RESULTS: Liver damage in AH mice was assessed by HE staining, serum levels of AST, ALT, TC, and TG. The levels of IL-1ß, IL-18, LDH, inflammasome-associated proteins and hepatocyte death were assessed to determine pyroptosis. Mitochondrial dysfunction was assessed through various parameters including mitochondrial DNA (mtDNA) levels, ROS generation, mitochondrial membrane potential, ATP contents, levels of mitochondrial function-related proteins and morphological changes of mitochondria. AH induced gasdermin D (GSDMD) activation, leading to increased protein expression of N-terminal GSDMD (GSDMD-N), NLRP3, and Caspase 11 in liver tissues. Downregulation of GSDMD alleviated alcohol-induced hepatocyte pyroptosis. Alcohol also causes mitochondrial dysfunction in hepatocytes in AH, which was improved by inhibiting GSDMD. Furthermore, enhancing mitochondrial function suppressed alcohol-induced hepatocyte pyroptosis. Further, knockdown of GSDMD or dynamin-related protein 1 (Drp1) improved AH-induced liver injury, accompanied by a decrease in hepatocyte pyroptosis. CONCLUSION: GSDMD induces hepatocyte pyroptosis by modulating mitochondrial dysfunction during AH-induced inflammation and liver injury. These findings may pave the way to develop new therapeutic treatments for AH.

Maximizing Polysaccharides and Phycoerythrin in Porphyridium purpureum via the Addition of Exogenous Compounds: A Response-Surface-Methodology Approach.

Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) and polypeptides (BT), and their optimal amounts were determined using the response surface methodology (RSM) based on three single-factor experiments. The optimal concentrations of CG, MG, and BT were determined to be 4, 12, and 2 g L-1, respectively. The RSM-based models indicated that biomass and phycoerythrin production were significantly affected only by MG and BT, respectively. However, polysaccharide production was significantly affected by the interactions between CG and BT and those between MG and BT, with no significant effect from BT alone. Using the optimized culture conditions, the maximum biomass (5.97 g L-1), phycoerythrin (102.95 mg L-1), and polysaccharide (1.42 g L-1) concentrations met and even surpassed the model-predicted maximums. After optimization, biomass, phycoerythrin, and polysaccharides concentrations increased by 132.3%, 27.97%, and 136.67%, respectively, compared to the control. Overall, this study establishes a strong foundation for the highly efficient production of phycoerythrin and polysaccharides using P. purpureum.

Engineering APOBEC3A deaminase for highly accurate and efficient base editing.

Cytosine base editors (CBEs) are effective tools for introducing C-to-T base conversions, but their clinical applications are limited by off-target and bystander effects. Through structure-guided engineering of human APOBEC3A (A3A) deaminase, we developed highly accurate A3A-CBE (haA3A-CBE) variants that efficiently generate C-to-T conversion with a narrow editing window and near-background level of DNA and RNA off-target activity, irrespective of methylation status and sequence context. The engineered deaminase domains are compatible with PAM-relaxed SpCas9-NG variant, enabling accurate correction of pathogenic mutations in homopolymeric cytosine sites through flexible positioning of the single-guide RNAs. Dual adeno-associated virus delivery of one haA3A-CBE variant to a mouse model of tyrosinemia induced up to 58.1% editing in liver tissues with minimal bystander editing, which was further reduced through single dose of lipid nanoparticle-based messenger RNA delivery of haA3A-CBEs. These results highlight the tremendous promise of haA3A-CBEs for precise genome editing to treat human diseases.

Targeted Gene Insertion: The Cutting Edge of CRISPR Drug Development with Hemophilia as a Highlight.

The remarkable advance in gene editing technology presents unparalleled opportunities for transforming medicine and finding cures for hereditary diseases. Human trials of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9)-based therapeutics have demonstrated promising results in disrupting or deleting target sequences to treat specific diseases. However, the potential of targeted gene insertion approaches, which offer distinct advantages over disruption/deletion methods, remains largely unexplored in human trials due to intricate technical obstacles and safety concerns. This paper reviews the recent advances in preclinical studies demonstrating in vivo targeted gene insertion for therapeutic benefits, targeting somatic solid tissues through systemic delivery. With a specific emphasis on hemophilia as a prominent disease model, we highlight advancements in insertion strategies, including considerations of DNA repair pathways, targeting site selection, and donor design. Furthermore, we discuss the complex challenges and recent breakthroughs that offer valuable insights for progressing towards clinical trials.

Tibial transverse transport induces mobilization of endothelial progenitor cells to accelerate angiogenesis and ulcer wound healing through the VEGFA/CXCL12 pathway.

BACKGROUND: Tibial transverse transport (TTT) can promote the healing of chronic foot ulcers, but the specific cellular and molecular mechanisms by which TTT promotes wound healing remain unclear. METHODS: New Zealand White rabbits were selected to induce foot ulcer models. The treatment included unilateral TTT surgery and bilateral TTT surgery. Observation of tissue neovascularization structure by HE staining and CD31 immunofluorescence detection. Collagen fiber formation was detected through the Masson staining. The mobilization of endothelial progenitor cell (EPCs) were analyzed by VEGFR2 immunofluorescence detection and flow cytometry detection of the number of VEGFR2/Tie-2-positive cells in peripheral blood. ELISA and qPCR assay were performed to detect VEGFA and CXCL12 levels. RESULTS: The complete healing time of ulcer surfaces in sham, unilateral and bilateral TTT groups was about 22 days, 17 days and 13 days, respectively. TTT treatment significantly increased the deposition of granulation tissue and epithelialization of wounds. It also led to an increase in collagen fiber content and the level of the microvascular marker CD31. Furthermore, TTT treatment upregulated the levels of VEGFA and CXCL12 in peripheral blood and wound tissues, as well as increased the expression of VEGFR2 in wound tissues and the proportion of VEGFR2/Tie-2 in peripheral blood. Moreover, these effects of TTT treatment in the bilateral group was more significant than that in the unilateral group. CONCLUSIONS: TTT may facilitate wound fibroblasts to release VEGFA and CXCL12, causing EPC mobilization, thus promoting angiogenesis and ulcer wound healing.

A predictive model for intraabdominal infection after radical gastrectomy in elderly patients.

Gastric cancer (GC) is one of the most common malignant tumors worldwide and the fourth leading cause of cancer-related deaths, with a relatively high incidence among the elderly population. Surgical resection is the mainstay treatment for GC and is currently the only cure. However, the incidence of postoperative intraabdominal infections remains high and seriously affects the prognosis. This study aimed to explore the risk factors for intraabdominal infections after radical gastrectomy in elderly patients and to establish and validate a risk prediction model. We collected the clinical data of 322 GC patients, who underwent radical gastrectomy at the General Surgery Department of China Medical University Dandong Central Hospital from January 2016 to January 2023. The patients were divided into an infected group (n = 27) and a noninfected group (n = 295) according to whether intraabdominal infections occurred postoperatively. A nomogram risk prediction model for the occurrence of postoperative intraabdominal infections was developed. All patients were randomized into a training set (n = 225) and a validation set (n = 97) in a 7:3 ratio, and the model was internally validated. Of the 322 patients, 27 (8.3%) experienced postoperative intraabdominal infections. Single-factor analysis revealed associations of intraabdominal infection with body mass index, glucose, hemoglobin, albumin, and other factors. The multifactorial analysis confirmed that body mass index, glucose, hemoglobin, albumin, surgical duration, and bleeding volume were independent risk factors for intraabdominal infections. The nomogram constructed based on these factors demonstrated excellent performance in both the training and validation sets. A nomogram model was developed and validated to predict the risk of intraabdominal infection after radical gastrectomy. The model has a good predictive performance, which could help clinicians prevent the occurrence of intraabdominal infections after radical gastrectomy in elderly patients.

Survival after minimally invasive radical hysterectomy with protective colpotomy for early-stage cervical cancer: A systematic review and meta-analysis.

Minimally invasive surgery on treatment of early-stage cervical cancer is debatable. Traditional approaches of colpotomy are considered responsible for an inferior oncological outcome. Evidence on whether protective colpotomy could optimize minimally invasive technique and improve prognoses of women with early-stage cervical cancer remains limited. We produced a systematic review and meta-analysis to compare oncological outcomes of the patients treated by minimally invasive radical hysterectomy with protective colpotomy to those treated by open surgery according to existing literature. We explored PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception to December 2022. Inclusion criteria were: (1) randomized controlled trials or observational studies published in English, (2) studies comparing minimally invasive radical hysterectomy with protective colpotomy to abdominal radical hysterectomy in early-stage cervical cancer, and (3) studies comparing survival outcomes. Two reviewers performed the screening, data extraction, and quality assessment independently. A total of 8 retrospective cohort studies with 2020 women were included in the study, 821 of whom were in the minimally invasive surgery group, and 1199 of whom were in the open surgery group. The recurrence-free survival and overall survival in the minimally invasive surgery group were both similar to that in the open surgery group (pooled hazard ratio, 0.88 and 0.78, respectively; 95% confidence interval, 0.56-1.38 and 0.42-1.44, respectively). Minimally invasive radical hysterectomy with protective colpotomy on treatment of early-stage cervical cancer had similar recurrence-free survival and overall survival compared to abdominal radical hysterectomy. Protective colpotomy could be a guaranteed approach to modifying minimally invasive technique.

Explaining differences in self-focused and other-involved public health preventive behaviors between the US and China: the role of self- construal and health locus of control.

Background: This study examined national similarities and differences in people's engagement in health preventive behaviors during a public health crisis, as well as investigated the underlying individual-level psychological mechanisms. A conceptual distinction was made between self-focused and other-involved preventive behaviors in response to public health crises. Method: Two cross-sectional surveys were conducted in the United States (N = 888) and China (N = 844) during the early stage of the COVID-19 pandemic. Hayes' PROCESS was utilized to assess national differences in seven preventive behaviors, along with the mediating effects of self-construal and health locus of control. Results: The results showed that American participants reported greater engagement in self-focused preventive behaviors than Chinese, whereas Chinese participants reported greater engagement in other-involved preventive behaviors than Americans. Chinese participants also engaged more in other-involved than self-focused preventive behaviors. Self-construal and health locus of control partially explained the observed differences in engagement in preventive behaviors. Discussion: This study introduces a culture-sensitive approach to provide insights for crafting communication interventions that can enhance the effectiveness of health campaigns in the context of a public health crisis.

Subtle Structural Changes across the Boundary between A2AR/A2BR Dual Antagonism and A2BR Antagonism: A Novel Class of 2-Aminopyrimidine-Based Derivatives.

Aberrantly elevated adenosine in the tumor microenvironment exerts its immunosuppressive functions through adenosine receptors A2AR and A2BR. Antagonism of A2AR and A2BR has the potential to suppress tumor growth. Herein, we report a systemic assessment of the effects of an indole modification at position 4, 5, 6, or 7 on both A2AR/A2BR activity and selectivity of novel 2-aminopyrimidine compounds. Substituting indole at the 4-/5-position produced potent A2AR/A2BR dual antagonism, whereas the 6-position of indole substitution gave highly selective A2BR antagonism. Molecular dynamics simulation showed that the 5-cyano compound 7ai had a lower binding free energy than the 6-cyano compound 7aj due to water-bridged hydrogen bond interactions with E169 or F168 in A2AR. Of note, dual A2AR/A2BR antagonism by compound 7ai can profoundly promote the activation and cytotoxic function of T cells. This work provided a strategy for obtaining novel dual A2AR/A2BR or A2BR antagonists by fine-tuning structural modification.

Exploring the potential prompting role of cervical human papilloma virus detection in vulvar lesions: a cross-sectional study in China.

Introduction: The etiology and clinical presentation of vulvar carcinomas, especially vulvar lesions, are not fully understood. Because the vulva and cervix are anatomically connected, human papillomavirus (HPV) is the main cause of cervical lesions. Thus, this study explored the potential characteristics and effects of specific HPV infection types across vulvar lesions and concurrent cervical lesions. Methods: This retrospective, cross-sectional study analyzed patients with cervical HPV or cytological results and concurrent vulvar biopsy who were seen in our hospital colposcopy clinic in Shanxi Province, China, between 2013 and 2023. Data on age, menopause status, vulvar manifestations, and cytology and HPV infection testing results were collected. Attributable fractions and multinominal logistic models were used to evaluate HPV genotyping and clinical characteristics across vulvar lesions. Results: Among the 1,027 participants, 83 (8.1%) had vulvar intraepithelial neoplasia (VIN) of high grade or worse (VIN2+), and 127 (12.4%) had non-neoplastic epithelial disorders of the vulva (NNEDV). A total of 175 patients had either VIN2+ or cervical intraepithelial neoplasia (CIN) lesions of grade 2 or worse (CIN2+). The most common HPV genotypes for VIN2+ or concurrent VIN2+/CIN2+ were HPV16, HPV52, and HPV58, although attributable fractions differed among lesions. Patients with normal cytological or histopathological result were more likely to have NNEDV detected, while abnormal cervical diagnosis was associated with higher detection of VIN2+. Multinominal logistic modeling showed that age and HPV16 infection were risk factors for VIN2+ or concurrent VIN2+/CIN2+; however, only vulvar presentation with depigmentation was a risk factor for NNEDV. Among patients with low-grade CIN1/VIN1, compared with those who were HPV16 negative, those who were HPV16 positive were at 6.63-fold higher risk of VIN2+/CIN2+ [95% confidence interval (CI): 3.32, 13.21]. Vulvar depigmentation was also associated with increased risk of NNEDV (odds ratio: 9.98; 95% CI: 3.02, 33.04). Conclusions: Chinese women may be at specific, high risk for HPV infection types associated with VIN or CIN. The use of cervical cell HPV detection along with vulvar presentation during cervical cancer screening may also contribute to vulvar lesion detection.

The effects of low-dose IL-2 on Th17/Treg cell imbalance in primary biliary cholangitis mouse models.

BACKGROUND/AIMS: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. Low-dose IL-2 can alleviate disease severity through modulating CD4 + T cell subsets in patients with autoimmune diseases. Hence, the present study aimed to examine the effects and mechanism of low-dose IL-2 in PBC mouse models. METHODS: PBC models were induced in female C57BL/6 mice by two immunizations with 2OA-BSA at two-week intervals, and poly I: C every three days. PBC mouse models were divided into the IL-2 treated and untreated groups and low-dose IL-2 was injected at three different time points. Th17 and Tregs were analyzed by flow cytometry, and the related cytokines were analyzed by ELISA. Liver histopathology was examined by H&E and immunohistochemical staining. RESULTS: Twelve weeks after modeling, the serum AMA was positive and the ALP was significantly increased in PBC mouse models (P<0.05). The pathology showed lymphocyte infiltration in the portal area, damage, and reactive proliferation of the small bile duct (P<0.05). The flow cytometric showed the imbalance of Th17/Treg cells in the liver of PBC mouse models, with decreased Treg cells, increased Th17 cells, and Th17/Treg ratio (P < 0.05). After the low-dose IL-2 intervention, biochemical index and liver pathologies showed improvement at 12 weeks. Besides, the imbalance of Th17 and Treg cells recovered. Public database mining showed that Th17 cell differentiation may contribute to poor response in PBC patients. CONCLUSION: Low-dose IL-2 can significantly improve liver biochemistry and pathology by reversing the imbalance of Th17 and Treg cells, suggesting that it may be a potential therapeutic target for PBC.

Tailored Exfoliation of Polymeric Carbon Nitride for Photocatalytic H2O2 Production and CH4 Valorization Mediated by O2 Activation.

The exfoliation of bulk C3N4 (BCN) into ultrathin layered structure is an effective strategy to boost photocatalytic efficiency by exposing interior active sites and accelerating charge separation and transportation. Herein, we report a novel nitrate anion intercalation-decomposition (NID) strategy that is effective in peeling off BCN into few-layer C3N4 (fl-CN) with tailored thickness down to bi-layer. This strategy only involves hydrothermal treatment of BCN in diluted HNO3 aqueous solution, followed by pyrolysis at various temperatures. The decomposition of the nitrate anions not only exfoliates BCN and changes the band structure, but also incorporates oxygen species onto fl-CN, which is conducive to O2 adsorption and hence relevant chemical processes. In photocatalytic O2 reduction under visible light irradiation, the H2O2 production rate over the optimal fl-CN-530 catalyst is 952 µmol g-1 h-1, which is 8.8 times that over BCN. More importantly, under full arc irradiation and in the absence of hole scavenger, CH4 can be photocatalytically oxidized by on-site formed H2O2 and active oxygen species to generate value-added C1 oxygenates with high selectivity of 99.2 % and record-high production rate of 1893 µmol g-1 h-1 among the metal-free C3N4-based photocatalysts.

The remediation of polycyclic aromatic hydrocarbon contaminated soil by immobilized microorganisms using distiller's grains.

Polycyclic aromatic hydrocarbons are a persistent organic pollutant, and their biodegradation in the soil is often limited due to the limited degradation ability of indigenous bacteria and the low activity of exogenous PAH degrading bacteria. Immobilized microbial technology can protect microorganisms from the impact of harsh environments, and distiller's grains have the potential as carriers for microbial immobilization. This study aims to use distiller's grains as a microbial carrier, investigate the feasibility of immobilized microorganisms using distiller's grains for remediation of PAH contaminated soil; explore the relationship between soil nutrient content, consumption, and PAH degradation rate; and reveal the mechanism of bioremediation from the perspective of soil enzyme activity and microbial community composition. The results showed that after 72 days of remediation, the removal rates of phenanthrene and pyrene in the treatment of immobilized microorganisms in distiller grains reached 91.78% and 58.59%, respectively. Distiller grains can serve as a carrier for microorganisms, providing them with shelter and nutrients to enhance their chance of survival. Additionally, they can regulate the composition of soil particles and improve aeration, thereby increasing the efficiency of PAH degradation in soil.

The role of differentially expressed genes and immune cell infiltration in the progression of nonalcoholic steatohepatitis (NASH) to hepatocellular carcinoma (HCC): a new exploration based on bioinformatics analysis.

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver disease characterized. The condition ranges from isolated excessive hepatocyte triglyceride accumulation and steatosis (nonalcoholic fatty liver (NAFL), to hepatic triglyceride accumulation plus inflammation and hepatocyte injury (nonalcoholic steatohepatitis (NASH)) and finally to hepatic fibrosis and cirrhosis and/or hepatocellular carcinoma (HCC). However, the mechanism driving this process is not yet clear. Obtain sample microarray from the GEO database. Extract 6 healthy liver samples, 74 nonalcoholic hepatitis samples, 8 liver cirrhosis samples, and 53 liver cancer samples from the GSE164760 dataset. We used the GEO2R tool for differentially expressed genes (DEGs) analysis of disease progression (nonalcoholic hepatitis healthy group, cirrhosis nonalcoholic hepatitis group, and liver cancer cirrhosis group) and necroptosis gene set. Gene set variation analysis (GSVA) is used to evaluate the association between biological pathways and gene features. The STRING database and Cytoscape software were used to establish and visualize protein-protein interaction (PPI) networks and identify the key functional modules of DEGs, drawn factor-target genes regulatory network. Gene Ontology (GO) and KEGG pathway enrichment analyses of DEGs were also performed. Additionally, immune infiltration patterns were analyzed using the cibersort, and the correlation between immune cell-type abundance and DEGs expression was investigated. We further screened and obtained a total of 152 intersecting DEGs from three groups. 23 key genes were obtained through the MCODE plugin. Transcription factors regulating common differentially expressed genes were obtained in the hTFtarget database, and a TF target network diagram was drawn. There are 118 nodes, 251 edges, and 4 clusters in the PPI network. The key genes of the four modules include METAP2, RPL14, SERBP1, EEF2; HR4A1; CANX; ARID1A, UBE2K. METAP2, RPL14, SERBP1 and EEF2 was identified as the key hub genes. CREB1 was identified as the hub TF interacting with those gens by taking the intersection of potential TFs. The types of key gene changes were genetic mutations. It can be seen that the incidence of key gene mutations is 1.7% in EEF2, 0.8% in METAP2, and 0.3% in RPL14, respectively. Finally, We found that the most significant expression differences of the immune infiltrating cells among the three groups, were Tregs and M2, M0 type macrophages. We identified four hub genes METAP2, RPL14, SERBP1 and EEF2 being the most closely with the process from NASH to cirrhosis to HCC. It is beneficial to examine and understand the interaction between hub DEGs and potential regulatory molecules in the process. This knowledge may provide a novel theoretical foundation for the development of diagnostic biomarkers and gene-related therapy targets in the process.

Dissection of a novel major stable QTL on chromosome 7D for grain hardness and its breeding value estimation in bread wheat.

Grain hardness (Gh) is important for wheat processing and end-product quality. Puroindolines polymorphism explains over 60% of Gh variation and the novel genetic factors remain to be exploited. In this study, a total of 153 quantitative trait loci (QTLs), clustered into 12 genomic intervals (C1-C12), for 13 quality-related traits were identified using a recombinant inbred line population derived from the cross of Zhongkemai138 (ZKM138) and Chuanmai44 (CM44). Among them, C7 (harboring eight QTLs for different quality-related traits) and C8 (mainly harboring QGh.cib-5D.1 for Gh) were attributed to the famous genes, Rht-D1 and Pina, respectively, indicating that the correlation of involved traits was supported by the pleotropic or linked genes. Notably, a novel major stable QTL for Gh was detected in the C12, QGh.cib-7D, with ZKM138-derived allele increasing grain hardness, which was simultaneously mapped by the BSE-Seq method. The geographic pattern and transmissibility of this locus revealed that the increasing-Gh allele is highly frequently present in 85.79% of 373 worldwide wheat varieties and presented 99.31% transmissibility in 144 ZKM138-derivatives, indicating the non-negative effect on yield performance and that its indirect passive selection has happened during the actual breeding process. Thus, the contribution of this new Gh-related locus was highlighted in consideration of improving the efficiency and accuracy of the soft/hard material selection in the molecular marker-assisted process. Further, TraesCS7D02G099400, TraesCS7D02G098000, and TraesCS7D02G099500 were initially deduced to be the most potential candidate genes of QGh.cib-7D. Collectively, this study provided valuable information of elucidating the genetic architecture of Gh for wheat quality improvement.

Discovery of a Highly Potent Oxysterol Receptor GPR183 Antagonist Bearing the Benzo[d]thiazole Structural Motif for the Treatment of Inflammatory Bowel Disease (IBD).

Accumulating evidence has demonstrated a critical pathological role of oxysterol receptor GPR183 in various inflammatory and autoimmune diseases, including inflammatory bowel disease (IBD). However, the currently reported GPR183 antagonists are very limited and not qualified for in vivo studies due to their inferior druglike properties. Herein, we conducted a structural elaboration focusing on improving its PK and safety profile based on a reference antagonist NIBR189. Of note, compound 33, bearing an aminobenzothiazole motif, exhibited reduced hERG inhibition, improved PK properties, and robust antagonistic activity (IC50 = 0.82 nM) with high selectivity against GPR183. Moreover, compound 33 displayed strong in vitro antimigration and anti-inflammatory activity in monocytes. Oral administration of compound 33 effectively improved the pathological symptoms of DSS-induced experimental colitis. All of these findings demonstrate that compound 33 is a novel and promising GPR183 antagonist suitable for further investigation to treat IBD.