Genome-wide analysis reveals transcriptional and translational changes during diapause of the Asian corn borer (Ostrinia furnacalis).

BACKGROUND: Diapause, a pivotal phase in the insect life cycle, enables survival during harsh environmental conditions. Unraveling the gene expression profiles of the diapause process helps uncover the molecular mechanisms that underlying diapause, which is crucial for understanding physiological adaptations. In this study, we utilize RNA-seq and Ribo-seq data to examine differentially expressed genes (DEGs) and translational efficiency during diapause of Asian corn borer (Ostrinia furnacalis, ACB). RESULTS: Our results unveil genes classified as "forwarded", "exclusive", "intensified", or "buffered" during diapause, shedding light on their transcription and translation regulation patterns. Furthermore, we explore the landscape of lncRNAs (long non-coding RNAs) during diapause and identify differentially expressed lncRNAs, suggesting their roles in diapause regulation. Comparative analysis of different types of diapause in insects uncovers shared and unique KEGG pathways. While shared pathways highlight energy balance, exclusive pathways in the ACB larvae indicate insect-specific adaptations related to nutrient utilization and stress response. Interestingly, our study also reveals dynamic changes in the HSP70 gene family and proteasome pathway during diapause. Manipulating HSP protein levels and proteasome pathway by HSP activator or inhibitor and proteasome inhibitor affects diapause, indicating their vital role in the process. CONCLUSIONS: In summary, these findings enhance our knowledge of how insects navigate challenging conditions through intricate molecular mechanisms.

Carbon Dots-Mediated Photodynamic Treatment Reduces Postharvest Senescence and Decay of Grapes by Regulating the Antioxidant System.

Grapes are susceptible to mold and decay during postharvest storage, and developing new technologies to extend their storage period has important application value. Photodynamic technology (PDT) in concurrence with carbon dots (CDs) proposes an innovative and eco-friendly preservation strategy. We examined the effects of carbon dots combined with photodynamic treatment on postharvest senescence and antioxidant system of table grape. The compounding of photodynamic technology with a 0.06 g L-1 CDs solution could possibly extend the postharvest storage period of grape berries. Through this strategy, we achieved a decreased rate of fruit rotting and weight loss alongside the delayed deterioration of fruit firmness, soluble solids, and titratable acid. As paired with photodynamic technology, CDs considerably decreased the postharvest storage loss of phenols, flavonoids, and reducing sugars as compared to the control group. Concurrently, it remarkably postponed the build-up of hydrogen peroxide (H2O2), superoxide anion (O2∙-), and malondialdehyde (MDA); elevated the levels of reduced ascorbic acid (AsA) and reduced glutathione (GSH); lowered the levels of dehydroascorbic acid (DHA) and oxidized glutathione (GSSG); raised the ratios of AsA/DHA and GSSH/GSSG; encouraged the activities of superoxide dismutase (SOD) and phenylalanine ammonia-lyase (PAL); and inhibited the activities of polyphenol oxidase (PPO) and lipoxygenase (LOX). Furthermore, it enhanced the iron reduction antioxidant capacity (FRAP) and DPPH radical scavenging capacity of grape berries. CDs combined with photodynamic treatment could efficiently lessen postharvest senescence and decay of grape berry while extending the storage time.

A Study on the Effect of Pd Layer Thickness on the Properties of Cu-Ag Intermetallic Compounds at the Bonding Interface.

This paper conducted a high-temperature storage test (HTST) on bonded samples made of Pd100 (Pd-coated Cu wire with a Pd layer thickness of 100 nm) and Pd120, and studied the growth law of Cu-Ag intermetallic compounds and the inhibitory mechanism of Pd thickness on Cu-Ag intermetallic compounds. The results show that the Kirkendall effect at the bonding interface of the Pd100-bonded sample is more obvious after the HTST, the sizes of voids and cracks are larger, and the thickness of intermetallic compounds is uneven. But, the bonding interface of the Pd120-bonded sample has almost no microcracks, the Kirkendall voids are small, and the intermetallic compound size is uniform and relatively thin. The formation sequence of intermetallic compounds is as follows: Cu atoms diffuse into the Ag layer to form Ag-rich compounds such as CuAg4 or CuAg2, and then the CuAg forms with the increase in diffused Cu elements. Pd can significantly reduce the Kirkendall effect and slow down the growth of Cu-Ag intermetallic compounds. The growth rate of intermetallic compounds is too fast when the Cu bonding wire has a thin Pd layer, which results in holes and microcracks in the bonding interface and lead to the peeling of the bonding interface. Voids and cracks will hinder the continuous diffusion of Cu and Ag atoms, resulting in the growth of intermetallic compounds being inhibited.

Time interval distribution of hepatitis B vaccine immunization among infants in China from 2017 to 2021.

Infant hepatitis B vaccine coverage in China is high, with over 95% of infants immunized; however, high vaccine coverage can often mask low timeliness. The vaccination interval between the second and third doses is not clearly defined by immunization guidelines in China. This retrospective cohort study assessed the time interval distribution of hepatitis B vaccination among a cohort of randomly selected live births from the Centers for Disease Control and Prevention across four provinces or municipalities in China between January 2017 and December 2021. Among the infants analyzed, 163,224 received the first dose of hepatitis B vaccine with 146,905 (90.0%) and 135,757 (83.2%) infants receiving the second and third doses, respectively. A total of 132,577 (90.2%) infants received the second dose between 28 and 61 days after the first dose. Of the 119,437 (88.0%) infants that completed the hepatitis B series between 61 and 214 days after the second dose 87,067 (64.1%) infants were vaccinated with the third dose between 151 and 180 days after the second dose. The time interval distribution varied across the four provinces or municipalities (p < .001). Of the 58,077 infants who completed the hepatitis B vaccine series, 36,377 (62.6%) infants used the same type of hepatitis B vaccine for all three doses. Overall, the timeliness of hepatitis B vaccination for infants was lower than expected, with regional disparities observed. This highlights the need for improved timeliness through the introduction of a defined timeframe for the last two doses of vaccine and training for obstetricians and related personnel.

Association Between Psychological Empowerment and Intent to Stay Among Military Hospital Nurses: The Mediating Effects of the Practice Environment and Burnout.

AIMS: To explore the impact of psychological empowerment on nurses' intent to stay in military hospitals as well as the mediating effects of the practice environment and burnout in this context. DESIGN: This study employed a cross-sectional survey approach and followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting. METHODS: A total of 1225 nurses from nine military hospitals were recruited via convenience sampling. Questionnaires were distributed and collected via the Questionnaire Star platform. The study variables, including psychological empowerment, the practice environment, burnout and intent to stay, were assessed via self-report questionnaires. SPSS 23.0 software was used to conduct descriptive and correlation analyses. Additionally, PROCESS Model 6 was employed to examine the mediating effects. RESULTS: Psychological empowerment is positively associated with nurses' intent to stay. Mediation analysis revealed that the practice environment, burnout and the chain mediating effect of the practice environment and burnout accounted for 54.5%, 2.8% and 1.5% of the total effect respectively. CONCLUSION: Psychological empowerment affects nurses' intent to stay not only directly but also indirectly via the practice environment and burnout. IMPLICATIONS FOR THE PROFESSION: Nursing managers may consider utilising psychological empowerment as a management strategy to enhance nurses' perceived practice environment, reduce burnout and ultimately increase nurses' intent to stay. This approach has the potential to lower turnover rates among nurses. PATIENT OR PUBLIC CONTRIBUTION: Questionnaires completed by nurses were used to explore the relationships among psychological empowerment, the practice environment, burnout and intent to stay in this context.

Nine months of bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine chemotherapy for rifampicin/multidrug-resistant tuberculosis: a multicenter, randomized, open-label non-inferiority trial in China.

BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Treatment Outcomes and Associated Influencing Factors Among Patients with Rifampicin-Resistant Tuberculosis: A Multicenter, Retrospective, Cohort Study in China.

Objective: Rifampin-resistant tuberculosis (RR-TB) remains a serious global public health concern. We assessed treatment outcomes and associated influencing factors among RR-TB patients in China. Methods: This research enrolled 1339 patients who started RR-TB treatment between May 2018 and April 2020 in China retrospectively. Data were collected from the electronic medical records. Multivariable logistic regression analysis was used to identify the influencing factors related to unfavorable outcomes. Results: Of the 1339 RR-TB patients, 78.8% (1055/1339) achieved treatment success (cured or treatment completed), 5.1% (68/1339) experienced treatment failure, 1.1% (15/1339) died during treatment, 10.1% (135/1339) were lost to follow-up, and 4.9% (66/1339) were not evaluated. About 67.7% (907/1339) of patients experienced at least one adverse event (AE). The most common AE was hypohepatia (507/1339, 37.9%), followed by hyperuricemia (429/1339, 32.0%), anemia (368/1339, 27.5%), electrolyte disturbance (318/1339, 23.7%), peripheral neuritis (245/1339, 18.3%), and gastrointestinal reactions (203/1339, 15.2%). Multivariate analysis showed that age ≥60 years [adjusted odds ratio (aOR): 1.96, 95% confidence interval (CI): 1.39-2.77], national minority (aOR: 2.36, 95% CI: 1.42-3.93), smoking (aOR: 1.50, 95% CI: 1.10-2.04), cardiopathy (aOR: 2.90, 95% CI: 1.33-6.31), tumors (aOR: 9.84, 95% CI: 2.27-42.67), immunocompromise (aOR: 2.17, 95% CI: 1.21-3.91), re-treated TB (aOR: 1.46, 95% CI: 1.08-1.97), and experienced gastrointestinal reactions (aOR: 2.27, 95% CI: 1.52-3.40) were associated with unfavorable outcomes. Body mass index (BMI) ≥18.5 kg/m2, regimens containing bedaquiline and experienced adverse events (AEs) such as hypohepatia, leukopenia, peripheral neuritis, and optic neuritis were associated with favorable outcomes. Conclusion: High rates of treatment success were achieved for RR-TB patients at tertiary tuberculosis hospitals in China. Age ≥60 years, national minority, smoking status, comorbidities, re-treated TB, and experienced gastrointestinal reactions were independent prognostic factors for unfavorable treatment outcomes.

Transition Metal-Nitrogen-Carbon Single-Atom Catalysts Enhanced CO2 Electroreduction Reaction: A Review.

As the global energy crisis and environmental challenges worsen, CO2 conversion has emerged as a focal point in international research. CO2 electroreduction reaction (CO2ER) is a green and sustainable technology that converts CO2 into high-value chemicals, thereby achieving the recycling of carbon resources. However, the activity and selectivity are constrained by the performance of the catalyst. Although traditional N-doped carbon-based catalysts exhibit excellent performance toward CO2ER, the atomic utilization rate in these materials is far from 100%. Single atom catalysts (SACs) can attain nearly 100% atomic utilization efficiency because of the fully exposing metal atoms. Therefore, SACs have emerged as one of the hot research materials in the field of CO2ER. Recently, transition metal-nitrogen-carbon single-atom catalysts (TM-N-C SACs) have flourished because of their extraordinary catalytic activity, low cost, and excellent stability, demonstrating enormous application prospects in CO2ER. In this review, we concentrate on TM-N-C SACs that electrochemically reduce CO2 to high value products. A comprehensive and detailed discussion were conducted on the synthesis method, chemical structure, chemical characterization of TM-N-C SACs, as well as their catalytic performance, active sources, and mechanism exploration for CO2ER. Finally, challenges and prospects for commercial application of TM-N-C SACs catalysts suitable for CO2ER are proposed.

Mutation of tomato xyloglucan transglucosylase/hydrolase5 increases fruit firmness and contributes to prolonged shelf life.

Fruit ripening in tomato is a highly coordinated developmental process accompanied with fruit softening, which is closely associated with cell wall degradation and remodeling. Xyloglucan endotransglucosylase/hydrolases (XTHs) are known to play an essential role in cell wall xyloglucan metabolism. Tomato XTH5 exhibits xyloglucan endotransglucosylase (XET) activity in vitro, but the understanding of its biological role in fruit ripening remains unclear. In this study, we revealed that SlXTH5 is highly expressed in mature fruits. Knockout mutant plants of SlXTH5 were generated by CRISPR/Cas9 gene editing strategy in tomato cultivar Micro-Tom. The mutant fruits showed accelerated transition from unripe to ripe process and earlier ethylene accumulation compared to wild type fruits. Although the mutation of SlXTH5 did not affect the size, weight and number of fruits, it indeed increased fruit firmness and extended shelf life, which is probably attributed to the increased cell layer and cell wall thickness of pericarp tissue. Pathogen infection experiment showed the enhanced resistance of mutant fruits to Botrytis cinerea. These results revealed the role of SlXTH5 in fruit ripening process, and provide new insight into how cell wall metabolism and remodeling regulate fruit softening and shelf life.

Carbon chain elongation characterizations of electrode-biofilm microbes in electro-fermentation.

The higher efficiency of electro-fermentation in synthesizing medium-chain fatty acids (MCFAs) compared to traditional fermentation has been acknowledged. However, the functional mechanisms of electrode-biofilm enhancing MCFAs synthesis remain research gaps. To address this, this study proposed a continuous flow electrode-biofilm reactor for chain elongation (CE). After 225 days of operation, stable electrode-biofilms formed and notably improved caproate yield by more than 38 %. The electrode-biofilm was enriched with more CE microorganisms and electroactive bacteria compared to the suspended sludge microorganisms, including Caproicibacterium, Oscillibacter and Pseudoramibacter. Besides, the upregulated CE pathways were evaluated by metagenomic analysis, and the results indicated that the pathways such as acetyl-CoA and malonyl-[acp] formation, reverse beta-oxidation, and fatty acid biosynthesis pathway were all markedly enhanced in cathodic biofilm, more than anodic biofilm and suspended microorganisms. Moreover, microbial community regulated processes like bacterial chemotaxis, flagellar assembly and quorum sensing, crucial for electrode-biofilm formation. Electron transfer, energy metabolism, and microbial interactions were found to be prominently upregulated in the cathodic biofilm, surpassing levels observed in anodic biofilm and suspended sludge microorganisms, which further enhanced CE efficiency. In addition, the statistical analyses further highlighted key microbial functions and interactions within the cathodic biofilm. Oscillospiraceae_bacterium was identified to be the most active microbe, alongside pivotal roles played by Caproiciproducens_sp._NJN-50, Clostridiales_bacterium, Prevotella_sp. and Pseudoclavibacter_caeni. Eventually, the proposed microbial collaboration mechanisms of cathodic biofilm were ascertained. Overall, this study uncovered the biological effects of the electrode-biofilm on MCFAs electrosynthesis, thereby advancing biochemicals production and filling the knowledge gaps in CE electroactive biofilm reactors.

Patient Participation in Medication Safety for Noncommunicable Diseases: A Qualitative Study of General Practitioners, Pharmacists, and Outpatients' Perspectives in Beijing.

Purpose: Our study aimed to explore the current status of patient participation in medication safety from the perspectives of general practitioners (GPs), pharmacists, and outpatients in Beijing, China. Patients and Methods: A qualitative study using semi-structured in-depth individual interviews with GPs, pharmacists, and outpatients. Subjects were identified by purposive sampling until code saturation. Semi-structured qualitative interviews were conducted with GPs, pharmacists, and patients from community health service centers in three urban districts of Beijing, China. The interviews were transcribed verbatim and the text was analysed using thematic analysis techniques including familiarising with data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report. Results: A total of eight GPs, seven pharmacists, and 18 outpatients were interviewed. Data analysis led to the generation of five key themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. Patients participated in medication safety in multiple ways. However, insufficient knowledge about medication safety, lack of awareness of the patient's role in ensuring medication safety, shortage of consultation lengths, and being misled by some information were problems with patient participation in medication safety. Conclusion: This exploratory study contributes to our initial understanding of patient participation in medication safety. There were still many issues and barriers in the process of patient participation. Appropriate policies and measures, such as providing various forms of patient education, ensuring sufficient physician-patient communication, giving full play to the role of pharmacists, and making judicious use of digital health tools should be taken to improve medication safety by fully utilising the role of patients.

Medication safety is a significant concern around the world. Patient participation in the medication process is effective in reducing the incidence of medication errors and improving medication safety. However, the role of outpatients with chronic conditions in ensuring medication safety is often neglected. This study aims to explore the perspectives and experiences of GPs, pharmacists, and outpatients by qualitative interviews in Beijing, China. The study involved a series of interviews with eight GPs, seven pharmacists, and 18 outpatients living with noncommunicable diseases. The interview revealed five themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. The findings might help propose suggestions for patient participation in medication safety. Integrating these findings into future studies can help healthcare professionals formulate interventions and better support patients in participating in the medication process.

Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis.

Background: Emergence agitation (EA) is a behavioural disturbance encountered during the recovery phase of patients following general anaesthesia. It is characterised by restlessness, involuntary limb movements, and drainage tube withdrawal and may significantly harm patients and medical staff. The mechanism of EA has not been fully understood and is still a challenging subject for researchers. Methods: We extracted relevant publications published between 1 January 2001 and 31 December 2023 on the Web of Science Core Collection platform. VOSviewer software was utilised to analyse the retrieved literature and predict the development trends and hotspots in the field. Results: The results show that the number of publications grew annually, with China contributing the most, followed by the United States and South Korea. The co-occurrence of keywords "children," "propofol," "risk factors" are current research hotspots. Owing to its self-limiting and short-duration characteristics, EA lacks standardised clinical time guidelines and objective assessment tools, which may be the focus of future research in this field. Conclusions: Understanding the research hotspots and the latest progress in this field, this study will help to continuously improve the clinical understanding and management of EA, and help to timely identify environmental risk factors for EA in clinical practice.

Mitochondria-Targeting AIEgens as Pyroptosis Inducers for Boosting Type-I Photodynamic Therapy of Tongue Squamous Cell Carcinoma.

The development of a photosensitizer (PS) that induces pyroptosis could be a star for photodynamic therapy (PDT), particularly with type-I PSs that produce reactive oxygen species (ROS) in a hypoxic tumor microenvironment. Since pyroptosis is a recently characterized cell death pathway, it holds promise for advancing PDT in oncology, with PSs playing a critical role. Herein, we develop a PS named Th-M with aggregation-induced emission (AIE) characteristics for type-I PDT against tongue squamous cell carcinoma (TSCC). Th-M stands out for its exceptional mitochondrial-targeting ability, which triggers mitochondrial dysfunction and leads to Caspase-3 and Gasdermin E (GSDME) cleavage under white light irradiation, inducing pyroptosis in TSCC cells. Our studies verify the effectiveness of Th-M in destroying cancer cells in vitro and suppressing tumor growth in vivo while also demonstrating a favorable biosafety profile. This work pioneers the application of Th-M as a mitochondria-targeted, type-I PS that leverages the mechanism of pyroptosis, offering a potent approach for the treatment of TSSC with promising implications for future PDT of cancers.

Protocol for detecting lysosome quantity and membrane permeability in acute myeloid leukemia cell lines.

Lysosomal function and activity are essential to support cellular adaptation to multiple stresses. For example, certain drugs can induce increased lysosomal membrane permeability to exert their anti-cancer effects. Here, we present a protocol to evaluate the lysosome alterations induced by drug treatment. We first describe the steps for inducing lysosomal alterations in cultured cells. We then show how to quantify the number of lysosomes, assess the integrity of lysosomal membranes, and determine lysosomal membrane permeabilization by using galectin puncta assay. For complete details on the use and execution of this protocol, please refer to Jiang et al.1.

Observation of Hot Carrier Localization Affected by A Cations in Hybrid Perovskites.

Organic-inorganic lead halide perovskites (OLHPs) have demonstrated exceptional properties in high-performance photoelectric devices. However, the impact of A-site cations, specifically formamidinium and methylammonium (MA), on the optoelectronic properties of OLHPs, particularly in the context of hot carrier utilization, remains a topic of debate. In this study, we propose a method for characterizing hot carrier transportation by measuring the hot carrier mobility and momentum-dependent transient photocurrent influenced by A-site cations in OLHPs. Our findings reveal that the direction of photon drag current is reversed upon substitution of the MA cation, suggesting the strong localization of hot carriers by the MA cation dipole. Furthermore, the correlation between the hot carrier photoconductivity and the electronic structure in different A-site cation samples indicates that hot carrier mobility in OLHPs can be reduced by >50% due to the influence of A-site cations.

Development of a magnetic separation method for rapid isolation and enrichment of bacteria in raw pork using chitosan functionalized magnetic Fe3O4@MIL-100(Fe) composites.

In this study, a pretreatment method based on a magnetic capture probe for the rapid isolation and enrichment of bacteria from raw pork was developed. The chitosan immobilized Fe3O4@MIL-100(Fe) was prepared as a capture probe for total bacterial counts through the electrostatic interaction of positively charged chitosan and the negatively charged substances on the surface of bacteria. The interference of matrix in pork samples on this method was studied and removed by differential centrifugation. The results showed the capture probe had a great selectivity binding and magnetic separation properties for the tested six common bacteria in pork. Under the optimal conditions, the capture efficiency of the bacteria (105 CFU mL-1) from pork surface samples was all above 90%. The capture efficiency of the bacteria in a homogenate system was greatly decreased due to the interference of sarcoplasmic protein and myofibrillar protein in pork. The matrix effect was mitigated by a differential centrifugation method, and the capture efficiency of all six bacteria was >80%. The developed magnetic separation method took 40 min and showed good isolation and enrichment properties of bacteria. Thus, the proposed method is expected to provide a simple, convenient, and time-saving pretreatment method for the detection of total bacterial counts in pork.

Variants in tubule epithelial regulatory elements mediate most heritable differences in human kidney function.

Kidney failure, the decrease of kidney function below a threshold necessary to support life, is a major cause of morbidity and mortality. We performed a genome-wide association study (GWAS) of 406,504 individuals in the UK Biobank, identifying 430 loci affecting kidney function in middle-aged adults. To investigate the cell types affected by these loci, we integrated the GWAS with human kidney candidate cis-regulatory elements (cCREs) identified using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq). Overall, 56% of kidney function heritability localized to kidney tubule epithelial cCREs and an additional 7% to kidney podocyte cCREs. Thus, most heritable differences in adult kidney function are a result of altered gene expression in these two cell types. Using enhancer assays, allele-specific scATAC-seq and machine learning, we found that many kidney function variants alter tubule epithelial cCRE chromatin accessibility and function. Using CRISPRi, we determined which genes some of these cCREs regulate, implicating NDRG1, CCNB1 and STC1 in human kidney function.

Genome-wide analysis of the AP2/ERF gene family in Pennisetum glaucum and the negative role of PgRAV_01 in drought tolerance.

APETALA2/ethylene-responsive (AP2/ERF) plays crucial roles in resisting diverse stresses and in regulating plant growth and development. However, little is known regarding the structure and function of the AP2/ERF genes in pearl millet (Pennisetum glaucum). The AP2/ERF gene family may be involved in the development and maintenance of P. glaucum resilience to abiotic stresses, central to its role as a vital forage and cereal crop. In this study, PgAP2/ERF family members were identified and comprehensive bioinformatics analyses were performed, including determination of phylogenetic relationships, gene structures, conserved motifs, chromosomal localization, gene duplication, expression pattern, protein interaction network, and functional characterization of PgRAV_01 (Related to ABI3/VP1). In total, 78 PgAP2/ERF members were identified in the P. glaucum genome and classified into five subfamilies: AP2, ERF, DREB, RAV, and soloist. Members within the same clade of the PgAP2/ERF family showed similar gene structures and motif compositions. Six duplication events were identified in the PgAP2/ERF family; calculation of Ka/Ks values showed that purification selection dominated the evolution of PgAP2/ERFs. Subsequently, a potential interaction network of PgAP2/ERFs was generated to predict the interaction relationships. Additionally, abiotic stress expression analysis showed that most PgAP2/ERFs were induced in response to drought and heat stresses. Furthermore, overexpression of PgRAV_01 negatively regulated drought tolerance in Nicotiana benthamiana by reducing its antioxidant capacity and osmotic adjustment. Taken together, these results provide valuable insights into the characteristics and functions of PgAP2/ERF genes, with implications for abiotic stress tolerance, and will ultimately contribute to the genetic improvement of cereal crop breeding.

Cxcl10 and Cxcr3 regulate self-renewal and differentiation of hematopoietic stem cells.

BACKGROUND: The function of hematopoietic stem cells (HSC) is regulated by HSC internal signaling pathways and their microenvironment. Chemokines and chemokine ligands play important roles in the regulation of HSC function. Yet, their functions in HSC are not fully understood. METHODS: We established Cxcr3 and Cxcl10 knockout mouse models (Cxcr3-/- and Cxcl10-/-) to analyze the roles of Cxcr3 or Cxcl10 in regulating HSC function. The cell cycle distribution of LT-HSC was assessed via flow cytometry. Cxcr3-/- and Cxcl10-/- stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. To study the effects of Cxcr3 or Cxcl10 deficient bone marrow microenvironment, we transplanted CD45.1 donor cells into Cxcr3-/-or Cxcl10-/- recipient mice (CD45.2) and examined donor-contributed hematopoiesis. RESULTS: Deficiency of Cxcl10 and its receptor Cxcr3 led to decreased BM cellularity in mice, with a significantly increased proportion of LT-HSC. Cxcl10-/- stem/progenitor cells showed reduced self-renewal capacity in the secondary transplantation assay. Notably, Cxcl10-/- donor-derived cells preferentially differentiated into B lymphocytes, with skewed myeloid differentiation ability. Meanwhile, Cxcr3-deficient HSCs demonstrated a reconstitution disadvantage in secondary transplantation, but the lineage bias was not significant. Interestingly, the absence of Cxcl10 or Cxcr3 in bone marrow microenvironment did not affect HSC function. CONCLUSIONS: The Cxcl10 and Cxcr3 regulate the function of HSC, including self-renewal and differentiation, adding to the understanding of the roles of chemokines in the regulation of HSC function.