Defective autophagy of pericytes enhances radiation-induced senescence promoting radiation brain injury.

BACKGROUND: Radiation-induced brain injury (RBI) represents a major challenge for cancer patients undergoing cranial radiotherapy. However, the molecular mechanisms and therapeutic strategies of RBI remain inconclusive. With the continuous exploration of the mechanisms of RBI, an increasing number of studies have implicated cerebrovascular dysfunction as a key factor in RBI-related cognitive impairment. As pericytes are a component of the neurovascular unit, there is still a lack of understanding in current research about the specific role and function of pericytes in RBI. METHODS: We constructed a mouse model of RBI-associated cognitive dysfunction in vivo and an in vitro radiation-induced pericyte model to explore the effects of senescent pericytes on the blood-brain barrier and normal CNS cells, even glioma cells. To further clarify the effects of pericyte autophagy on senescence, molecular mechanisms were explored at the animal and cellular levels. Finally, we validated the clearance of pericyte senescence by using senolytic drug and all-trans retinoic acid to investigate the role of radiation-induced pericyte senescence. RESULTS: Our findings indicated that radiation-induced pericyte senescence plays a key role in blood-brain barrier dysfunction, leading to RBI and subsequent cognitive decline. Strikingly, pericyte senescence also contributes to the growth and invasion of glioma cells. We further demonstrate that defective autophagy in pericytes is a vital regulatory mechanism for pericyte senescence. Moreover, autophagy activated by rapamycin can reverse pericyte senescence. Notably, the elimination of senescent cells by senolytic drugs significantly mitigated radiation-induced cognitive dysfunction. DISSCUSSION: Our results demonstrated that pericyte senescence may be a promising therapeutic target for RBI and glioma progression.

Association of random glucose to albumin ratio with post-contrast acute kidney injury and clinical outcomes in patients with ST-elevation myocardial infarction.

Purpose: Both glucose and albumin are associated with chronic inflammation, which plays a vital role in post-contrast acute kidney injury (PC-AKI). To explore the relationship between random glucose to albumin ratio (RAR) and the incidence of PC-AKI after percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). Patients and methods: STEMI patients who underwent PCI were consecutively enrolled from January, 01, 2010 to February, 28, 2020. All patients were categorized into T1, T2, and T3 groups, respectively, based on RAR value (RAR < 3.377; 3.377 ≤ RAR ≤ 4.579; RAR > 4.579). The primary outcome was the incidence of PC-AKI, and the incidence of major adverse clinical events (MACE) was the second endpoint. The association between RAR and PC-AKI was assessed by multivariable logistic regression analysis. Results: A total of 2,924 patients with STEMI undergoing PCI were finally included. The incidence of PC-AKI increased with the increasing tertile of RAR (3.2% vs 4.8% vs 10.6%, P<0.001). Multivariable regression analysis demonstrated that RAR (as a continuous variable) was associated with the incidence of PC-AKI (adjusted odds ratio (OR) =1.10, 95% confidence interval (CI) =1.04 - 1.16, P<0.001) and in-hospital MACE (OR=1.07, 95% CI=1.02 - 1.14, P=0.012); RAR, as a categorical variable, was significantly associated with PC-AKI (T3 vs. T1, OR=1.70, 95% CI=1.08 - 2.67, P=0.021) and in-hospital MACE (T3 vs. T1, OR=1.63, 95% CI=1.02 - 2.60, P=0.041) in multivariable regression analyses. Receiver operating characteristic curve analysis showed that RAR exhibited a predictive value for PC-AKI (area under the curve (AUC)=0.666, 95% CI=0.625 - 0.708), and in-hospital MACE (AUC= 0.662, 95% CI =0.619 - 0.706). Conclusions: The high value of RAR was significantly associated with the increasing risk of PC-AKI and in-hospital MACE after PCI in STEMI patients, and RAR offers a good predictive value for those outcomes.

Diffusion-based culture and real-time impedance monitoring of tumor spheroids in hydrogel microwells of a suspended membrane under microfluidic conditions.

Tumor spheroids are widely studied for in vitro modeling of tumor growth and responses to anticancer drugs. However, current methods are mostly limited to static and perfusion-based cultures, which can be improved by more accurately mimicking pathological conditions. Here, we developed a diffusion-based dynamic culture system for tumor spheroids studies using a thin membrane of hydrogel microwells and a microfluidic device. This allows for effective exchange of nutrients and metabolites between the tumors and the culture medium flowing underneath, resulting in uniform tumor spheroids. To monitor the growth and drug response of the spheroids in real-time, we performed spectroscopic analyses of the system's impedance, demonstrating a close correlation between the tumor size and the resistance and capacitance of the system. Our results also indicate an enhanced drug effect on the tumor spheroids in the presence of a low AC electric field, suggesting a weakening mechanism of the spheroids induced by external perturbation.

TNKS1BP1 facilitates ubiquitination of CNOT4 by TRIM21 to promote hepatocellular carcinoma progression and immune evasion.

Immune checkpoint inhibitors, particularly PD-1/PD-L1 blockades, have been approved for unresectable hepatocellular carcinoma (HCC). However, high resistance rates still limit their efficacy, highlighting the urgent need to understand the underlying mechanisms and develop strategies for overcoming the resistance. In this study, tankyrasel binding protein 1 (TNKS1BP1) was found to interact with tripartite motif containing 21 (TRIM21) and mediated the ubiquitination of CCR4-NOT transcription complex subunit 4 (CNOT4) at the K239 residue via K48 and K6 linkage, which was essential for its tumorigenesis function. Autophagy and lipid reprogramming were identified as two possible mechanisms underlying the pro-tumor effect of TNKS1BP1. Upregulated TNKS1BP1 inhibited autophagy while induced lipid accumulation by inhibiting the JAK2/STAT3 pathway upon the degradation of CNOT4 in HCC. Importantly, knocking down TNKS1BP1 synergized with anti-PD-L1 treatment by upregulating PD-L1 expression on tumor cells via the JAK2/STAT3 pathway, and remodeling the tumor microenvironment by increasing infiltration of tumor-infiltrating lymphocytes as well as augmenting the effect of cytotoxic T lymphocytes. In conclusion, this study identified TNKS1BP1 as a predictive biomarker for patient prognosis and a promising therapeutic target to overcome anti-PD-L1 resistance in HCC.

Preparation and characterization of polydopamine and n-butyl methacrylate copolymer coatings on titanium-nickel alloy stents.

Cardiovascular diseases pose a significant global health threat, and stents play a crucial role in managing these diseases. However, challenges exist with respect to the poor adhesion of stent coatings. Cardiac stents are often composed of titanium-nickel (TiNi) alloys as the metallic component and poly(n-butyl methacrylate) (PBMA) as the coating. The poor adhesion of PBMA to TiNi alloy surface may cause detachment and subsequent thrombosis post-implantation. This study utilizes Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization to synthesize a novel block copolymer, PBMA-b-PVP, composed of PBMA and poly(N-vinylpyrrolidone) (PVP). TiNi alloy surfaces are functionalized with polydopamine (PDA) to enhance polymer coating adhesion. PBMA-b-PVP exhibits a remarkable improvement in adhesion from class 5 to class 0 and high coating stability after a 15 days immersion in a phosphate buffer solution. The corrosion current density is reduced by 44% with the incorporation of PDA into PBMA-b-PVP coatings, suggesting high corrosion resistance. PDA-functionalized coatings promote cell viability without cytotoxicity, suggesting high biocompatibility. This study provides a robust strategy for preparing stent coatings with high adhesion, corrosion resistance, and biocompatibility.

Serum Albumin-to-Creatinine Ratio: A Novel Predictor of Pulmonary Infection in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

AIM: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), a low serum albumin-to-creatinine ratio (sACR) is associated with elevated risk of poor short- and long-term outcomes. However, the relationship between sACR and pulmonary infection during hospitalization in patients with STEMI undergoing PCI remains unclear. METHODS: A total of 4,507 patients with STEMI undergoing PCI were enrolled and divided into three groups according to sACR tertile. The primary outcome was pulmonary infection during hospitalization, and the secondary outcome was in-hospital major adverse cardiovascular events (MACE) including stroke, in-hospital mortality, target vessel revascularization, recurrent myocardial infarction, and all-cause mortality during follow-up. RESULTS: Overall, 522 (11.6%) patients developed pulmonary infections, and 223 (4.9%) patients developed in-hospital MACE. Cubic spline models indicated a non-linear, L-shaped relationship between sACR and pulmonary infection (P=0.039). Receiver operating characteristic curve analysis indicated that sACR had good predictive value for both pulmonary infection (area under the ROC curve [AUC]=0.73, 95% CI=0.70-0.75, P＜0.001) and in-hospital MACE (AUC=0.72, 95% CI=0.69-0.76, P＜0.001). Kaplan-Meier survival analysis indicated that higher sACR tertiles were associated with a greater cumulative survival rate (P＜0.001). Cox regression analysis identified lower sACR as an independent predictor of long-term all-cause mortality (hazard ratio [HR]=0.96, 95% CI=0.95-0.98, P＜0.001). CONCLUSIONS: A low sACR was significantly associated with elevated risk of pulmonary infection and MACE during hospitalization, as well as all-cause mortality during follow-up among patients with STEMI undergoing PCI. These findings highlighted sACR as an important prognostic marker in this patient population.

Co-delivery of fucoxanthin and Twist siRNA using hydroxyethyl starch-cholesterol self-assembled polymer nanoparticles for triple-negative breast cancer synergistic therapy.

INTRODUCTION: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer with an extremely dismal prognosis and few treatment options. As a desmoplastic tumor, TNBC tumor cells are girdled by stroma composed of cancer-associated fibroblasts (CAFs) and their secreted stromal components. The rapidly proliferating tumor cells, together with the tumor stroma, exert additional solid tissue pressure on tumor vasculature and surrounding tissues, severely obstructing therapeutic agent from deep intratumoral penetration, and resulting in tumor metastasis and treatment resistance. OBJECTIVES: Fucoxanthin (FX), a xanthophyll carotenoid abundant in marine algae, has attracted widespread attention as a promising alternative candidate for tumor prevention and treatment. Twist is a pivotal regulator of epithelial to mesenchymal transition, and its depletion has proven to sensitize antitumor drugs, inhibit metastasis, reduce CAFs activation and the following interstitial deposition, and increase tumor perfusion. The nanodrug delivery system co-encapsulating FX and nucleic acid drug Twist siRNA (siTwist) was expected to form a potent anti-TNBC therapeutic cyclical feedback loop. METHODS AND RESULTS: Herein, our studies constituted a novel self-assembled polymer nanomedicine (siTwist/FX@HES-CH) based on the amino-modified hydroxyethyl starch (HES-NH2) grafted with hydrophobic segment cholesterol (CH). The MTT assay, flow cytometry apoptosis analysis, transwell assay, western blot, and 3D multicellular tumor spheroids growth inhibition assay all showed that siTwist/FX@HES-CH could kill tumor cells and inhibit their metastasis in a synergistic manner. The in vivo anti-TNBC efficacy was demonstrated that siTwist/FX@HES-CH remodeled tumor microenvironment, facilitated interstitial barrier crossing, killed tumor cells synergistically, drastically reduced TNBC orthotopic tumor burden and inhibited lung metastasis. CONCLUSION: Systematic studies revealed that this dual-functional nanomedicine that targets both tumor cells and tumor microenvironment significantly alleviates TNBC orthotopic tumor burden and inhibits lung metastasis, establishing a new paradigm for TNBC therapy.

Heterosis of endophytic microbiomes in hybrid rice varieties improves seed germination.

Seed endophytic microbiomes are shaped by host and environmental factors and play a crucial role in their host growth and health. Studies have demonstrated that host genotype, including hybridization, affects seed microbiomes. Heterosis features are also observed in root-associated microbiomes. It remains unclear, however, whether heterosis exists in seed endophytic microbiomes and whether hybrid microbiota provide noticeable advantages to host plant growth, especially to seed germination. Here, we investigated the structure of seed endophytic bacterial and fungal communities from three hybrid rice varieties and their respective parents using amplicon sequencing targeting 16S rRNA and ITS2 genes. Heterosis was found in diversity and composition of seed endophytic microbiomes in hybrids, which hosted more diverse communities and significantly higher abundances of plant growth-promoting taxa, such as Pseudomonas and Rhizobium genera compared with their parental lines. Co-occurrence network analysis revealed that there are potentially tighter microbial interactions in the hybrid seeds compared with their parent seeds. Finally, inoculation of seed-cultivable endophytes, isolated from hybrids, resulted in a greater promotion of seed germination compared with those isolated from parent lines. These findings suggest that heterosis exists not only in plant traits but also in seed endophytic microbiota, the latter in turn promotes seed germination, which offers valuable guidance for microbiome-assisted rice breeding.IMPORTANCEGenetic and physiological changes associated with plant hybridization have been studied for many crop species. Still, little is known about the impact of hybridization on the seed microbiota. In this study, we indicate that hybridization has a significant impact on the endophytic bacterial and fungal communities in rice seeds. The seed endophytic microbiomes of hybrids displayed distinct characteristics from those of their parental lines and exhibited potential heterosis features. Furthermore, the inoculation of seed-cultivable endophytes isolated from hybrids exhibited a greater promotion effect on seed germination compared with those isolated from the parents. Our findings make a valuable contribution to the emerging field of microbiome-assisted plant breeding, highlighting the potential for a targeted approach that aims to achieve not only desired plant traits but also plant-beneficial microbial communities on the seeds.

Pan-cancer transcriptional atlas of minimal residual disease links DUSP1 to chemotherapy persistence.

Chemotherapy is a commonly effective treatment for most types of cancer. However, many patients experience a relapse due to minimal residual disease (MRD) after chemotherapy. Previous studies have analyzed the changes induced by chemotherapy for specific types of cancer, but our study is the first to comprehensively analyze MRD across various types of cancer. We included both bulk and single-cell RNA sequencing datasets. We compared the expression of the entire genome and calculated scores for canonical pathway signatures and immune infiltrates before and after chemotherapy across different types of cancer. Our findings revealed that DUSP1 was the most significantly and widely enriched gene in pan-cancer MRD. DUSP1 was found to be essential for MRD formation and played a role in T cell-fibroblast communications and the cytotoxic function of CD4 + T cells. Overall, our analysis provides a comprehensive understanding of the changes caused by chemotherapy and identifies potential targets for preventing and eliminating MRD, which could lead to long-term survival benefits for patients.

Evaluation of bidirectional causal association between cardiovascular diseases and pneumonia: A Mendelian randomization study.

AIMS: Observational evidence suggests a bidirectional relationship between cardiovascular diseases (CVDs) and pneumonia. However, the causality between CVDs and pneumonia remains undetermined. Thus, we aimed to investigate the bidirectional causality between CVDs and pneumonia using Mendelian randomization (MR) analysis. METHODS: Global genetic correlation analysis and bidirectional two-sample MR analysis were performed to infer the genetic correlation and causality between CVDs and pneumonia by using genome-wide association study (GWAS) summary data from GWAS meta-analysis study, FinnGen or UK Biobank consortium. Post-hoc power calculation was conducted to assess the power for detecting the causality. RESULTS: The linkage disequilibrium score regression analysis suggested a positive significant genetic correlation between CVDs and pneumonia. In the MR analysis, only genetically predicted ischemic stroke was causally associated with any pneumonia (odds ratio [OR]: 1.119, 95% confidence interval [CI]: 1.031-1.393), bacterial pneumonia (OR: 1.251, 95% CI: 1.032-1.516), and pneumococcal pneumonia (OR: 1.308, 95% CI: 1.093-1.565), but the causality was attenuated to non-significance after adjusting for deep venous thrombosis. However, the causal effects of pneumonia on CVDs were not detected. Post-hoc power calculations supported strong power (more than 80%) to detect the causality. CONCLUSIONS: Ischemic stroke is causally associated with an increased risk of pneumonia, but there is no evidence for the causal effect of pneumonia on CVDs. Our findings have important implications as they provide further support for the thrombosis risk screening as a strategy to reduce the incidence of pneumonia in patients with ischemic stroke.

This Mendelian randomization analysis aimed to investigate the bidirectional causality between cardiovascular diseases and pneumonia. Our findings support the causal association of ischemic stroke on pneumonia, but indicate no evidence for the causal effects of pneumonia on cardiovascular diseases. The causal association of ischemic stroke on pneumonia was revealed to rely on deep venous thrombosis, which provided further support for the thrombosis risk screening as a strategy to reduce the incidence of pneumonia in patients with ischemic stroke.

Ticagrelor alleviates pyroptosis of myocardial ischemia reperfusion-induced acute lung injury in rats: a preliminary study.

Pulmonary infection is highly prevalent in patients with acute myocardial infarction undergoing percutaneous coronary intervention. However, the potential mechanism is not well characterized. Myocardial ischemia-reperfusion injury (MIRI) induces acute lung injury (ALI) related to pulmonary infection and inflammation. Recent studies have shown that pyroptosis mediates ALI in several human respiratory diseases. It is not known whether MIRI induces pyroptosis in the lungs. Furthermore, ticagrelor is a clinically approved anti-platelet drug that reduces ALI and inhibits the expression levels of several pyroptosis-associated proteins, but the effects of ticagrelor on MIRI-induced ALI have not been reported. Therefore, we investigated whether ticagrelor alleviated ALI in the rat MIRI model, and its effects on pyroptosis in the lungs. Sprague-Dawley rats were randomly divided into four groups: control, MIRI, MIRI plus low ticagrelor (30 mg/kg), and MIRI plus high ticagrelor (100 mg/kg). Hematoxylin and Eosin (HE) staining was performed on the lung sections, and the HE scores were calculated to determine the extent of lung pathology. The wet-to-dry ratio of the lung tissues were also determined. The expression levels of pyroptosis-related proteins such as NLRP3, ASC, and Cleaved caspase-1 were estimated in the lung tissues using the western blot. ELISA was used to estimate the IL-1ß levels in the lungs. Immunohistochemistry was performed to determine the levels of MPO-positive neutrophils as well as the total NLRP3-positive and Cleaved caspase-1-positive areas in the lung tissues. The lung tissues from the MIRI group rats showed significantly higher HE score, wet-to-dry ratio, and the MPO-positive area compared to the control group, but these effects were attenuated by pre-treatment with ticagrelor. Furthermore, lung tissues of the MIRI group rats showed significantly higher expression levels of pyroptosis-associated proteins, including NLRP3 (2.1-fold, P < 0.05), ASC (3.0-fold, P < 0.01), and Cleaved caspase-1 (9.0-fold, P < 0.01). Pre-treatment with the high-dose of ticagrelor suppressed MIRI-induced upregulation of NLRP3 (0.46-fold, P < 0.05), ASC (0.64-fold, P < 0.01), and Cleaved caspase-1 (0.80-fold, P < 0.01). Immunohistochemistry results also confirmed that pre-treatment with ticagrelor suppressed MIRI-induced upregulation of pyroptosis in the lungs. In summary, our data demonstrated that MIRI induced ALI and upregulated pyroptosis in the rat lung tissues. Pre-treatment with ticagrelor attenuated these effects.

Association between cerebrovascular disease and perioperative neurocognitive disorders: a retrospective cohort study.

BACKGROUND: Previous studies have shown that patients with cerebrovascular disease (CVD) have a significantly increased risk of cognitive decline or dementia; however, the association between preoperative CVD and perioperative neurocognitive disorders (PNDs) remains unclear. This study aimed to explore the correlation between preoperative CVD and PNDs, as well as combine logistic regression and receiver operating characteristic (ROC) curves to construct a clinical prediction PND model. MATERIALS AND METHODS: This retrospective cohort study evaluated 13 899 surgical patients of a large-scale comprehensive hospital between January 2021 and January 2022 to explore the association between preoperative CVD and PNDs, with follow-up to monitor postoperative survival until 28 February 2023, unless the patient died. The study participants comprised all inpatients from the Bone and Joint Surgery, Spine Surgery, Urology, Hepatobiliary Surgery, Gastrointestinal Surgery, and Thoracic Surgery departments. Patients were classified into two groups: the CVD group with a confirmed diagnosis and the noncerebrovascular disease group. The incidence of PNDs was measured, and potential associations between patient demographic information, preoperative comorbidities, and CVD, as well as the correlation between preoperative CVD and PNDs, were investigated by multivariate logistic regression analysis. Next, the authors constructed a clinical prediction PND model by drawing the ROC curve. The postoperative survival of all patients was tracked, and a survival curve was constructed and incorporated into the Cox proportional hazard regression model to analyze the relationship between preoperative CVD and the overall postoperative survival rate. RESULTS: Of the included 13 899 patients, propensity score matching yielded 1006 patient pairs. Multivariate logistic regression analysis revealed that CVD was an independent risk factor for PNDs [odds ratio: 10.193; 95% CI: 7.454-13.938; P <0.001]. Subsequently, the authors developed a clinical prediction model for PNDs by multivariate logistic regression analysis. The area under the ROC curve was 0.798 (95% CI: 0.765-0.830). The survival of 11 702 patients was followed up. Multivariate Cox hazard ratio regression analysis revealed that CVD affected the overall postoperative survival rate (hazard ratio, 1.398; 95% CI: 1.112-1.758; P <0.001). CONCLUSION: CVD was an independent risk factor for PNDs and affected the overall postoperative survival rate of surgical patients with preoperative CVD.

Convergent gene pair dSH3 and irr regulate Pi and Fe homeostasis in Bradyrhizobium diazoefficiens USDA110 and symbiotic nitrogen fixation efficiency.

The nitrogen-fixing bacteroids inhabit inside legume root nodules must manage finely the utilization of P and Fe, the two most critical elements, due to their antagonistic interactions. While the balance mechanism for them remains unclear. A double SH3 domain-containing protein (dSH3) in the Bradyrhizobium diazoefficiens USDA110 was found to inhibit the alkaline phosphatase activity, thereby reducing P supply from organophosphates. The dSH3 gene is adjacent to the irr gene, which encodes the iron response repressor and regulates Fe homeostasis under Fe-limited conditions. Their transcription directions converge to a common intergenic sequence (IGS) region, forming a convergent transcription. Extending the IGS region through Tn5 transposon or pVO155 plasmid insertion significantly down-regulated expression of this gene pair, leading to a remarkable accumulation of P and an inability to grow under Fe-limited conditions. Inoculation of soybean with either of the insertion mutants resulted in N2-fixing failure. However, the IGS-deleted mutant showed no visible changes in N2-fixing efficiency on soybean compared to that inoculated with wild type. These findings reveal a novel regulative strategy in the IGS region and its flanking convergent gene pair for antagonistic utilization of P and Fe in rhizobia and coordination of N2-fixing efficiency.

Protocol for the PORT study: short-term perioperative rehabilitation to improve outcomes in cardiac valvular surgery - a randomised control trial.

INTRODUCTION: Perioperative rehabilitation (PORT) has shown a positive effect on patients undergoing cardiac surgery. However, there are minimal data on the impact of short-term PORT in cardiac surgery, which is associated with higher postoperative morbidity and mortality. The trial will assess the efficacy of short-term PORT in reducing in-hospital mortality, postoperative pulmonary complications and length of stay, compared with the usual care in cardiac surgical patients. METHODS AND ANALYSIS: This is a single-centre prospective, randomised, open, controlled trial with a 1:1 ratio. Consecutive 800 adult patients undergoing elective valve surgery will be randomised to either usual care or in-hospital short-term PORT that consists of education, inspiratory muscle training, active cycle of breathing techniques and early mobilisation. The primary outcome of this study will be a composite of in-hospital all-cause mortality, incidence of postoperative pulmonary complications and the ratio of postoperative hospitalisation >7 days. ETHICS AND DISSEMINATION: The PORT study was granted by the Medical Research Ethics Committee of Guangdong Provincial People's Hospital in August 2018. Findings will be disseminated to patients, clinicians and commissioning groups through peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03709511.

[Effects of Aeration Methods on Microbial Diversity and Community Structure in Rice Rhizosphere].

To explore the effects of different aeration methods on the abundance of microorganisms and microorganism community structure in rice rhizosphere soil, two rice varieties, Miyang 46(MY) and Zhenshan 97B(ZS), were used with three aeration treatments:alternate wetting and drying(AWD), continuous flooding and aeration(CFA), and continuous flooding(CF). The diversity of bacterial and fungal communities in rice rhizosphere soil was analyzed using Illumina MiSeq high-throughput sequencing. Soil physical and chemical factors were also analyzed. The results showed that the dominant bacterial communities in rice rhizosphere soil were Chloroflexi, Actinobaciota, Acidobacteria, Proteobacteria, and Firmicutes, and the dominant fungal communities were Ascomycota and Basidiomycota in rice rhizosphere soil. At each growth stage, the relative abundance of Chloroflexi and Acidobacteria was higher in the AWD treatment than in the other treatments, and the relative abundance of Actinobaciota was higher in the CFA treatment than in the other treatments. The relative abundance of Firmicutes was lower in the AWD treatment than in the other treatments. Aeration methods affected the diversity and richness of rhizosphere microbial species. For example, the diversity of bacterial species was higher, and the richness of bacterial species was lower in the AWD treatment than that in the other treatments. The diversity and richness of fungal species were higher in the AWD and CFA treatments than those in the CF treatment. The physical and chemical properties of rhizosphere soil were also affected by aeration method. The soil redox potential(Eh) was the highest in AWD, followed by that in CFA and CF, and significant differences were observed among treatments. The NO3--N content was significantly higher, and the NH4+-N content was significantly lower in the AWD and CFA treatments than in the CF treatment in rhizosphere soil at all growth stages. Correlation analysis showed that the pH and Eh of rhizosphere soil were positively correlated with the diversity of bacterial species, negatively correlated with the richness of bacterial species, and positively correlated with the diversity and richness of fungal species. Redundancy analysis indicated that the relative abundance of Chloroflexi was positively correlated with the pH and NH4+-N content at each period, positively correlated with the Eh and NO3--N content at the tillering and heading stages, and negatively correlated with Eh and NO3--N content at the maturity stage. At each growth stage, the pH and Eh were positively correlated with the relative abundance of Acidobacteria, Proteobacteria, and Basidiomycota and negatively correlated with the relative abundance of Firmicutes and Ascomycota. During the entire growth period, the relative abundance of Ascomycota was negatively correlated with the NO3--N content and positively correlated with the NH4+-N content, and the opposite patterns were observed for the relative abundance of Basidiomycota. In summary, rhizosphere oxygenation enhanced the soil oxygen environment, altered soil physical and chemical properties, and affected microbial community diversity and richness to optimize microbial community structure.

Variants of WFS1 identified by whole exome sequencing in a boy with Wolfram syndrome 1: A case report.

Wolfram syndrome 1 (WS1) is a rare autosomal recessive neurodegenerative disease. The condition is also known as 'diabetes insipidus, diabetes mellitus (DM), optic atrophy (OA) and deafness', with early onset DM and OA as the usual initial manifestations in childhood. The present study reports a case of WS1 in a 3.5-year-old boy. The clinical characteristics of the patient were collected from medical records. Based on the clinical findings, a diagnosis of renal failure, moderate ammonia and congenital heart disease was considered. A diagnosis of WS1 was also suspected, as an abnormal plasma glucose level and retinitis pigmentosa were found. Whole exome sequencing was therefore performed for the differential diagnosis. Two homozygous variants in the wolframin endoplasmic reticulum transmembrane glycoprotein (WFS1) gene, which were classified as likely pathogenic variants, were found and then confirmed by Sanger sequencing. The variants in WFS1 were the molecular basis of WS1. This study shows the importance of genetic diagnosis in such cases.

Association between admission-blood-glucose-to-albumin ratio and clinical outcomes in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention.

Introduction: It is unclear whether admission-blood-glucose-to-albumin ratio (AAR) predicts adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who are treated with percutaneous coronary intervention (PCI). Here, we performed a observational study to explore the predictive value of AAR on clinical outcomes. Methods: Patients diagnosed with STEMI who underwent PCI between January 2010 and February 2020 were enrolled in the study. The patients were classified into three groups according to AAR tertile. The primary outcome was in-hospital all-cause mortality, and the secondary outcomes were in-hospital major adverse cardiac events (MACEs), as well as all-cause mortality and MACEs during follow-up. Logistic regression, Kaplan-Meier analysis, and Cox proportional hazard regression were the primary analyses used to estimate outcomes. Results: Among the 3,224 enrolled patients, there were 130 cases of in-hospital all-cause mortality (3.9%) and 181 patients (5.4%) experienced MACEs. After adjustment for covariates, multivariate analysis demonstrated that an increase in AAR was associated with an increased risk of in-hospital all-cause mortality [adjusted odds ratio (OR): 2.72, 95% CI: 1.47-5.03, P = 0.001] and MACEs (adjusted OR: 1.91, 95% CI: 1.18-3.10, P = 0.009), as well as long-term all-cause mortality [adjusted hazard ratio (HR): 1.64, 95% CI: 1.19-2.28, P = 0.003] and MACEs (adjusted HR: 1.58, 95% CI: 1.16-2.14, P = 0.003). Receiver operating characteristic (ROC) curve analysis indicated that AAR was an accurate predictor of in-hospital all-cause mortality (AUC = 0.718, 95% CI: 0.675-0.761) and MACEs (AUC = 0.672, 95% CI: 0.631-0.712). Discussion: AAR is a novel and convenient independent predictor of all-cause mortality and MACEs, both in-hospital and long-term, for STEMI patients receiving PCI.

Comparative analysis of the effects of conventional and biodegradable plastic mulching films on soil-peanut ecology and soil pollution.

In agricultural production, biodegradable plastic mulching film (Bio-PMF) has the potential to replace conventional plastic mulching film (CPMF) due to its degradability, but their impacts on soil-crop ecology are controversial. In this study, from 2019 to 2021, effects of CPMF and Bio-PMF on the soil-crop ecology and soil pollution were evaluated on a peanut farm. Compared to the Bio-PMF, an overall improvement in the soil-peanut ecology under the CPMF was observed, including an increase of 10.77 ± 4.8% in peanut yield, an amelioration of four soil physicochemical properties (total P and available P in the flowering stage, total P and temperature in the mature stage), an increase of rhizobacterial relative abundances in class level (Bacteroidia, Blastocatellia, Thermoleophilia and Vicinamibacteria in the flowering stage, Nitrospira and Bacilli in the mature stage) and genus level (RB41 and Bacillus in the flowering stage, Bacillus and Dongia in the mature stage), and an enhancement of soil nitrogen metabolism abilities (ureolysis, nitrification and aerobic ammonia in the flowering stage, nitrate reduction and nitrite ammonification in the mature stage). These preserved soil nutrients and temperature, reshaped rhizobacterial communities, and enhanced soil nitrogen metabolism abilities in the mature stage were obviously correlated with peanut yield under CPMF. However, such remarkable relations were not existed under Bio-PMF. In addition, compared with Bio-PMF, CPMF significantly increased the contents of dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP) and microplastics (MPs) in soil by 79.93, 44.55, 138.72 and 14.1%, respectively. Thus, CPMF improved soil-peanut ecology and caused serious soil pollution, while Bio-PMF introduced little pollutants into the soil and had little impact on soil-peanut ecology. Based on these, the degradation ability of CPMF or the ecological improvement capacity of Bio-PMF should be improved to obtain the environmentally and soil-crop ecology friendly plastic film in the future.

Incorporating Bioaccessibility into Inhalation Exposure Assessment of Emamectin Benzoate from Field Spraying.

The inhalation exposure of pesticide applicators and residents who live close to pesticide-treated fields is a worldwide concern in public health. Quantitative assessment of exposure to pesticide inhalation health risk highlights the need to accurately assess the bioaccessibility rather than the total content in ambient air. Herein, we developed an in vitro method to estimate the inhalation bioaccessibility of emamectin benzoate and validated its applicability using a rat plasma pharmacokinetic bioassay. Emamectin benzoate was extracted using the Gamble solution, with an optimized solid-to-liquid ratio (1/250), extraction time (24 h), and agitation (200 rpm), which obtained in vitro inhalation bioaccessibility consistent with its inhalation bioavailability in vivo (32.33%). The margin of exposure (MOE) was used to assess inhalation exposure risk. The inhalation unit exposures to emamectin benzoate of applicators and residents were 11.05-28.04 and 0.02-0.04 ng/m3, respectively, varying markedly according to the methods of application, e.g., formulations and nozzles. The inhalation risk assessment using present application methods appeared to be acceptable; however, the MOE of emamectin benzoate might be overestimated by 32% without considering inhalation bioaccessibility. Collectively, our findings contribute insights into the assessment of pesticide inhalation exposure based on bioaccessibility and provide guidance for the safe application of pesticides.

Positive association between stress hyperglycemia ratio and pulmonary infection in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: Previous studies have shown that the stress hyperglycemia ratio (SHR), a parameter of relative stress-induced hyperglycemia, is an excellent predictive factor for all-cause mortality and major adverse cardiovascular events (MACEs) among patients with ST-segment elevation myocardial infarction (STEMI). However, its association with pulmonary infection in patients with STEMI during hospitalization remains unclear. METHODS: Patients with STEMI undergoing percutaneous coronary intervention (PCI) were consecutively enrolled from 2010 to 2020. The primary endpoint was the occurrence of pulmonary infection during hospitalization, and the secondary endpoint was in-hospital MACEs, composed of all-cause mortality, stroke, target vessel revascularization, or recurrent myocardial infarction. RESULTS: A total of 2,841 patients were finally included, with 323 (11.4%) developing pulmonary infection and 165 (5.8%) developing in-hospital MACEs. The patients were divided into three groups according to SHR tertiles. A higher SHR was associated with a higher rate of pulmonary infection during hospitalization (8.1%, 9.9%, and 18.0%, P < 0.001) and in-hospital MACEs (3.7%, 5.1%, and 8.6%, P < 0.001). Multivariate logistic regression analysis demonstrated that SHR was significantly associated with the risk of pulmonary infection during hospitalization (odds ratio [OR] = 1.46, 95% confidence interval [CI] 1.06-2.02, P = 0.021) and in-hospital MACEs (OR = 1.67, 95% CI 1.17-2.39, P = 0.005) after adjusting for potential confounding factors. The cubic spline models demonstrated no significant non-linear relationship between SHR and pulmonary infection (P = 0.210) and MACEs (P = 0.743). In receiver operating characteristic curve, the best cutoff value of SHR for pulmonary infection was 1.073. CONCLUSIONS: The SHR is independently associated with the risk of pulmonary infection during hospitalization and in-hospital MACEs for patients with STEMI undergoing PCI.