A receptor kinase senses sterol by coupling with elicitins in auxotrophic Phytophthora.

Sterols are vital nutrients and signals for eukaryotic organisms. Mammalian cells are known to sense and respond to sterol status changes to maintain them within strict limits, a process associated with various human diseases. However, this process is not understood in oomycete pathogens, most of which are sterol auxotrophic and must obtain sterols from host plants. Here, we report that Phytophthora sojae SSRK1 (sterol-sensing receptor kinase 1) detects host sterols by coupling with elicitins, thereby controlling signaling and sterol absorption. Sterols are recruited by extracellular soluble elicitins, and these complexes then bind to SSRK1 to form trimolecular complexes. These complexes subsequently trigger downstream calcium influx, activation of mitogen-activated protein kinase, and transcriptome reprogramming through the receptor's kinase activity. Our data demonstrate a unique sterol sensing pathway where elicitins and a transmembrane receptor kinase SSRK1 act as coreceptors for extracellular sterols. These findings also portray a sterol-based war between oomycetes and plants, providing a unique perspective on how a pathogen detects host signals during infection.

Mediation effect of illness acceptance between perceived social support and self-management behaviors in rural elderly with coronary heart disease.

OBJECTIVE: To explore the relationship between perceived social support, acceptance of illness, and self-management behaviors and the mediating role of acceptance of illness in perceived social support and self-management behaviors. METHODS: Between August 2022 and February 2023, 731 rural older adults with coronary heart disease in Feicheng City participated in this study. Correlation analysis was used to analyze the relationship between variables, and mediating effects were analyzed using AMOS 23.0 software. RESULTS: Perceived social support and acceptance of illness were positively correlated with self-management behaviors. Acceptance of illness mediated the relationship between the perceived social support and the three dimensions of self-management behavior. CONCLUSION: These findings contribute to the understanding that increased perceived social support and acceptance of illness are more likely to improve self-management behaviors.

A Pythium myriotylum Small Cysteine-Rich Protein Triggers Immune Responses in Diverse Plant Hosts.

The oomycete Pythium myriotylum is a necrotrophic pathogen that infects many crop species worldwide, including ginger, soybean, tomato, and tobacco. Here, we identified a P. myriotylum small cysteine-rich protein, PmSCR1, that induces cell death in Nicotiana benthamiana by screening small, secreted proteins that were induced during infection of ginger and did not have a predicted function at the time of selection. Orthologs of PmSCR1 were found in other Pythium species, but these did not have cell death-inducing activity in N. benthamiana. PmSCR1 encodes a protein containing an auxiliary activity 17 family domain and triggers multiple immune responses in host plants. The elicitor function of PmSCR1 appears to be independent of enzymatic activity, because the heat inactivation of PmSCR1 protein did not affect PmSCR1-induced cell death or other defense responses. The elicitor function of PmSCR1 was also independent of BAK1 and SOBIR1. Furthermore, a small region of the protein, PmSCR186-211, is sufficient for inducing cell death. A pretreatment using the full-length PmSCR1 protein promoted the resistance of soybean and N. benthamiana to Phytophthora sojae and Phytophthora capsici infection, respectively. These results reveal that PmSCR1 is a novel elicitor from P. myriotylum, which exhibits plant immunity-inducing activity in multiple host plants. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Spliceosomal protein U2B″ delays leaf senescence by enhancing splicing variant JAZ9ß expression to attenuate jasmonate signaling in Arabidopsis.

The regulatory framework of leaf senescence is gradually becoming clearer; however, the fine regulation of this process remains largely unknown. Here, genetic analysis revealed that U2 small nuclear ribonucleoprotein B (U2B″), a component of the spliceosome, is a negative regulator of leaf senescence. Mutation of U2B″ led to precocious leaf senescence, whereas overexpression of U2B″ extended leaf longevity. Transcriptome analysis revealed that the jasmonic acid (JA) signaling pathway was activated in the u2b″ mutant. U2B″ enhances the generation of splicing variant JASMONATE ZIM-DOMAIN 9ß (JAZ9ß) with an intron retention in the Jas motif, which compromises its interaction with CORONATINE INSENSITIVE1 and thus enhances the stability of JAZ9ß protein. Moreover, JAZ9ß could interact with MYC2 and obstruct its activity, thereby attenuating JA signaling. Correspondingly, overexpression of JAZ9ß rescued the early senescence phenotype of the u2b″ mutant. Furthermore, JA treatment promoted expression of U2B″ that was found to be a direct target of MYC2. Overexpression of MYC2 in the u2b″ mutant resulted in a more pronounced premature senescence than that in wild-type plants. Collectively, our findings reveal that the spliceosomal protein U2B″ fine-tunes leaf senescence by enhancing the expression of JAZ9ß and thereby attenuating JA signaling.

An F-box protein attenuates fungal xylanase-triggered immunity by destabilizing LRR-RLP NbEIX2 in a SOBIR1-dependent manner.

Receptor-like proteins (RLPs) lacking the cytoplasmic kinase domain play crucial roles in plant growth, development and immunity. However, what remains largely elusive is whether RLP protein levels are fine-tuned by E3 ubiquitin ligases, which are employed by receptor-like kinases for signaling attenuation. Nicotiana benthamiana NbEIX2 is a leucine-rich repeat RLP (LRR-RLP) that mediates fungal xylanase-triggered immunity. Here we show that NbEIX2 associates with an F-box protein NbPFB1, which promotes NbEIX2 degradation likely by forming an SCF E3 ubiquitin ligase complex, and negatively regulates NbEIX2-mediated immune responses. NbEIX2 undergoes ubiquitination and proteasomal degradation in planta. Interestingly, NbEIX2 without its cytoplasmic tail is still associated with and destabilized by NbPFB1. In addition, NbPFB1 also associates with and destabilizes NbSOBIR1, a co-receptor of LRR-RLPs, and fails to promote NbEIX2 degradation in the sobir1 mutant. Our findings reveal a distinct model of NbEIX2 degradation, in which an F-box protein destabilizes NbEIX2 indirectly in a SOBIR1-dependent manner.

Transcriptome analysis and the identification of genes involved in the metabolic pathways of fenoxaprop-P-ethyl in rice treated with isoxadifen-ethyl hydrolysate.

Fenoxaprop-P-ethyl (FE) is a highly effective weed control agent for rice fields, but it causes phytotoxicity in crops. A whole-plant bioassay has revealed that isoxadifen-ethyl hydrolysate (IH) can significantly improve the tolerance of rice to FE, but the molecular mechanisms underlying this phenomenon are still unclear. In this study, we performed RNA-Seq analysis using rice seedlings treated with FE and IH to determine the IH-regulated candidate genes involved in metabolic resistance to FE. We also analyzed spatiotemporal expression using quantitative reverse transcription polymerase chain reaction to reveal the expression patterns of these genes under different treatments. The results showed that genes encoding metabolic enzymes, such as cytochrome P450 monooxygenases, glutathione-s-transferases, UDP-glycosyltransferase, carboxylesterase, and ATP-binding cassette transporter, were influenced by the application of IH. Most of these genes were upregulated, and their products were involved in various stages of FE metabolism. Tolerance to FE was primarily mediated by CarE15, CYP86A1, GSTU6, GST4, UGT13248, UGT79, and ABCC4, all of which played a vital role in regulating the detoxification process of FE. Our findings elucidated the protective mechanisms of IH, which can help alleviate the phytotoxic effects of FE and expand its potential for application in agriculture.

Morphologic analysis of alveolar bone in maxillary and mandibular incisors on sagittal views.

PURPOSE: The aim of this study was to analyze the morphologic features of alveolus in relatively healthy maxillary and mandibular incisors using cone-beam-computed tomography (CBCT). METHODS: CBCT images of 318 patients were retrospectively acquired. Alveolar bone in incisive area was divided into: type 1 (thick), type 2 (relatively thick with mono-plate concavity), type 3 (thin with double-plate concavities), and type 4 (vulnerably thin). Alveolus prevalence and widths were analyzed statistically relative to age, gender, and molar relationship. RESULTS: Prevalence of type 1 alveolus was 78.9% in maxillary central incisors, 15.1% in maxillary lateral incisors, 24.1% in mandibular central incisors, and 5.0% in mandibular lateral incisors. Type 2 alveolus was commonly observed in the maxillary lateral incisors (82.2%), mandibular central incisors (66.2%), and mandibular lateral incisors (87.9%). Prevalence of type 3 and 4 alveoli ranged from 0.0 to 9.4%. As for maxillary central incisors, type 1 was the widest both at the alveolar crest (7.77 ± 0.58 mm) and apical area (9.05 ± 1.86 mm), while type 3 had the lowest width at the apical region (4.08 ± 0.51 mm). Among maxillary central incisors, prevalence of type 1 tended to decrease with age. At all maxillary and mandibular incisor sites, alveolus widths were significantly thicker in males than in females. At maxillary lateral incisor and mandibular incisor sites, prevalence of alveolus type was significantly different among three molar relationships. CONCLUSION: A 4-type classification system was suggested for alveolus morphology in incisive region. Identification of alveolus type might aid in the corresponding treatment.

Protective effect of Specnuezhenide on islet ß cell of rats with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) refers to diabetes mellitus and impaired glucose tolerance first diagnosed during pregnancy without previous history of the disease. Usually, GDM has a high risk of inducing type 2 diabetes mellitus. The incidence of GDM is increasing year by year worldwide, and it seriously affects the quality of life of patients, and increases the risk to pregnancy. Specnuezhenide (SPZ) is a characteristic active component of Ligustrum lucidum, a plant which exerts a variety of pharmacological effects. In this study, the protective effect of SPZ on ß cells in gestational diabetes mellitus rats was investigated in a rat model of gestational diabetes. Based on oral glucose tolerance test, ELISA, qRT-PCR and western blotting assays, It was found that SPZ effectively improved blood sugar control and glucose tolerance in gestational diabetic rats, inhibited inflammation in islet tissue, and reduced inflammation-mediated insulin resistance.

Evaluation of Parotid Gland Function Before and After Endoscopy-Assisted Stone Removal.

PURPOSE: To quantify gland function before and after endoscopy-assisted lithectomy for patients with parotid stones and to analyze correlations among different evaluation modalities. MATERIALS AND METHODS: This study investigated 58 patients (27 men and 31 women) with a stone larger than 5 mm or multiple parotid stones who underwent successful endoscopy-assisted surgery at the authors' center from August 2007 through September 2017. Meticulous postoperative manipulations were administered routinely for 3 to 6 months to promote functional recovery of the affected gland. Gland function was evaluated preoperatively and 6 to 36 months (mean, 12 months) postoperatively by sialography, scintigraphy, and sialometry. Statistical analyses were conducted to quantify gland function recovery and to distinguish correlations among the 3 objective tests. RESULTS: Preoperative sialograms exhibited ductal ectasia at the stone site with ductal stenosis anterior to the stone (n = 53) or duct interruption at the stone site (n = 5). Postoperative sialograms of 45 patients without stones were categorized as approximately normal (type I; n = 17); showing ectasia or stenosis of the main duct without persistent contrast on the functional film (type II; n = 16); showing ectasia or stenosis of the main duct with mild contrast retention (type III; n = 6); or showing poor ductal shape with evident contrast retention (type IV; n = 6). Scintigraphy of 23 preoperative and 12 postoperative patients and sialometry of 24 preoperative and 12 postoperative patients indicated severe preoperative impairment and postoperative improvement of gland function. Postoperatively, although no relevant differences in saliva flow rate were found between the 2 sides, scintigraphy showed lower function of the affected gland compared with the control side. Statistical data showed positive correlations among the 3 methods. Sialography intuitively reflected the ductal shape, whereas sialometry and scintigraphy were more sensitive for evaluating gland function. CONCLUSION: For patients with parotid stones, minimally invasive endoscopic surgery and meticulous postoperative manipulations help preserve the glands and facilitate recovery of gland function. The 3 evaluating modalities have certain positive correlations.

Moderate hypothermia protects increased neuronal autophagy via activation of extracellular signal-regulated kinase signaling pathway in a rat model of early brain injury in subarachnoid hemorrhage.

Moderate hypothermia (MH) used as treatment for neurological diseases has a protective effect; however, its mechanism remains unclear. Neuronal autophagy is a fundamental pathological process of early brain injury in subarachnoid hemorrhage (SAH). We found that moderate activation of autophagy can reduce nerve cells damage. In this study, We found that MH can moderately increase the level of autophagy in nerve cells and improve the neurological function in rats. This type of autophagy activation is dependent on extracellular signal-regulated kinase (ERK) signaling pathways. The level of neuronal autophagy was down-regulated significantly by using U0126, an ERK signaling pathway inhibitor. In summary, these results suggest that MH can moderately activate neuronal autophagy through ERK signaling pathway, reduce nerve cell death, and produce neuroprotective effects.

[Influence on the expression of RHOA and ROCK-II after global cerebral ischemia-reperfusion in hippocampus by shenxiong huayu capsule].

OBJECTIVE: To investigate the effect of Shenxiong Huayu capsule on the expression of hippocampal CA1 recombinant protein A (small GTP binding protein A, RHOA) and ROCK-2 (RHO associated protein kinase-2, ROCK-II). METHODS: Clean SD male rats (n=96), divided into three groups with 32 rats for each group, gavage was applied 7 days before modeling until the morning of the day to put to death. The groups included the normal control group (normal saline), global cerebral ischemia model group (normal saline) and Shenxiong Huayu capsule+global cerebral ischemia group (Shenxiong Huayu capsule 0.048 g/kg, was dissolved in 0.5 mL double distilled water, once a day, orally 0.3 mL/100 g). Modified Pulsinelli four-vessel occlusion model was constructed in global cerebral ischemia model and Shenxiong Huayu treatment groups and at 1, 3, 7, 14 d after successful modeling, water maze learning test was applied to evaluate the memory abilities of different groups, histopathological changes in HE staining, expression and protein content of RHOA and ROCK-II in immunohistochemical staining and Western blot was observed. RESULTS: At each time point, escape latency in model group was prolonged (P<0.05) when compared with that in normal control group, and that in Shenxiong Huayu was shorter (P<0.05) than that of model group, but still longer (P<0.05) than that of normal control group. HE staining showed that, compared with the normal group, model hippocampal CA1 reduced gradually from 1 d to 14 d; an increased survival neurons (P<0.05) in Shenxiong Huayu treatment group at each time points was observed, but still less than that in normal group (P<0.05); immunohistochemistry and Western blot analysis demonstrated that the expression of RHOA and ROCK-II in normal control group was not obvious, in model group was decreased after an initial increasing, and that in Shenxiong Huayu treatment group was lower than that of model group (P<0.05), but still higher than that in normal group (P<0.05). CONCLUSION: Shenxiong Huayu capsule improve neuronal damage induced by global ischemia, decreased the expression of hippocampal CA1 region of RHOA and ROCK-II.

Effects of body mass index and body fat percentage on gestational complications and outcomes.

AIM: The aim of this study was to investigate the correlation between body mass index (BMI), body fat percentage (BFP) and gestational outcomes. MATERIAL AND METHODS: Maternal- and infant-related data of gestation and gestational outcomes of 411 pregnant women were retrospectively analyzed. BMI was used to classify the women as obese, overweight, or normal. BFP was measured by the segmental multi-frequency bioelectrical impedance method. The mothers' blood lipid profiles were assessed by automated chemical analysis. Logistic regression analysis was performed to determine the correlation of BMI and BFP with gestational complications. RESULTS: The rates of gestational diabetes and hypertension were significantly different between mothers who were obese (33.3%, 52.6%), overweight (10.3%, 32.2%) and normal (8.7%, 14.9%) (P < 0.001). The Apgar score at 1 min and intensive care unit admissions rate at birth were significantly different between infants born to obese (6.14 ± 0.80, 14.0%), overweight (6.64 ± 1.10, 8.9%) and normal (7.20 ± 0.78, 1.9%) mothers (P < 0.01). The Apgar score at 5 min and the birthweights were not significantly different between these three groups (P > 0.05). Additionally, the levels of serum total cholesterol (mmol/L), total triglycerides (mmol/L), and leptin (ng/mL) were significantly higher in obese (5.87 ± 2.26, 2.04 ± 1.65, 24.79 ± 18.38) and overweight (5.29 ± 1.85, 1.74 ± 1.05, 20.79 ± 15.19) women, compared to normal women (4.89 ± 1.05, 1.45 ± 0.77, 13.35 ± 6.51) (P < 0.05). Furthermore, BFP was more strongly correlated to gestational diabetes (rs = 0.57 vs 0.68) and hypertension (rs = 0.31 vs 0.43) than BMI. CONCLUSIONS: Obesity and overweight are associated with increased adverse maternal and neonatal complications. BFP is a more accurate predictor of gestational outcomes than BMI.

[Effect of shenxiong huayu capsule on cerebral ischemia/reperfusion injury and the expression of GAP43 in hippocampal CA1 of rats].

OBJECTIVE: To explore the effect of Shenxiong Huayu Capsule (SHC) on the cerebral ischemia-reperfusion (IR) injury and the expression of growth associated protein 43 (GAP43) after total cerebral IR in the hippocampal CA1 region of rats. METHODS: Totally 100 male adult SD rats were randomly divided into five groups, i.e., the control group, the model group, the group A (by taking SHC once daily), the group B (by taking SHC twice daily), and the group C (by taking SHC thrice daily), 20 in each group. The total IR model was prepared by improved Pulsinelli's 4-vessel occlusion method. Morphological changes of the hippocampal CA1 region were observed by HE staining at day 1, 3, 7, and 14. The expression of GAP43 in the hippocampal CA1 region was detected using immunohistochemical assay at day 1, 3, 7, and 14. Meanwhile, the behavioral score was determined. The expression of GAP43 in the hippocampal CA1 region was detected using Western blot at day 14. RESULTS: Compared with the control group, the expression of GAP43 increased in the model group, the behavioral score was elevated, degenerated neurons increased, and survival neurons decreased in the model group (all P < 0.05). Compared with the model group, the expression of GAP-43 increased (with the most significant difference seen in the group C, P < 0.01), the behavioral score significantly decreased, degenerated neurons decreased, and survival neurons increased in each HSC group (all P < 0.05). Survival neurons obviously increased at day 14, of which, most number of survival neurons and highest contents of GAP43 protein could be seen in the group C, showing statistical difference when compared with those of the group A and the group B (P < 0.01). CONCLUSION: SHC had protective effect on total cerebral IR in the hippocampal CA1, which might be associated with increased expression of GAP43.

Herbicide Safeners: From Molecular Structure Design to Safener Activity.

Herbicide safeners, highly effective antidotes, find widespread application in fields for alleviating the phytotoxicity of herbicides to crops. Designing new herbicide safeners remains a notable issue in pesticide research. This review focuses on discussing and summarizing the structure-activity relationships, molecular structures, physicochemical properties, and molecular docking of herbicide safeners in order to explore how different structures affect the safener activities of target compounds. It also provides insights into the application prospects of computer-aided drug design for designing and synthesizing new safeners in the future.

Non-coding RNAs and leaf senescence: Small molecules with important roles.

Non-coding RNAs (ncRNAs) are a special class of functional RNA molecules that are not translated into proteins. ncRNAs have emerged as pivotal regulators of diverse developmental processes in plants. Recent investigations have revealed the association of ncRNAs with the regulation of leaf senescence, a complex and tightly regulated developmental process. However, a comprehensive review of the involvement of ncRNAs in the regulation of leaf senescence is still lacking. This manuscript aims to summarize the molecular mechanisms underlying ncRNAs-mediated leaf senescence and the potential applications of ncRNAs to manipulate the onset and progression of leaf senescence. Various classes of ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are discussed in terms of their regulatory mechanisms in leaf senescence. Furthermore, we explore the interactions between ncRNA and the key regulators of senescence, including transcription factors as well as core components in phytohormone signaling pathways. We also discuss the possible challenges and approaches related to ncRNA-mediated leaf senescence. This review contributes to a further understanding of the intricate regulatory network involving ncRNAs in leaf senescence.

The Mediating Effect of Coping Style in the Relationship Between Sleep Quality and Perceived Cognitive Impairment Among Breast Cancer Patients: A Cross-sectional Study.

BACKGROUND: Perceived cognitive impairment is a significant symptom experienced by breast cancer patients and may be affected by sleep quality. Coping styles have potential relevancies with both sleep quality and perceived cognitive impairment. However, the empirical evidence supporting their association among breast cancer patients is limited. OBJECTIVE: This study explored the associations between sleep quality, coping styles, and perceived cognitive impairment and tested the mediating role of coping styles in breast cancer patients. METHODS: A total of 294 breast cancer patients were included in this cross-sectional study. Patients were assessed using the Pittsburgh Sleep Index Scale, the Simplified Coping Styles Questionnaire, and the Functional Assessment of Cancer Therapy-Cognitive Functioning (Version 3) Scale. The data were analyzed using SPSS and Process macros. RESULTS: The direct effect of sleep quality on reported cognitive impairment was significant (ß = -0.245, P < .001). Furthermore, sleep quality was found to have a significant indirect effect on perceived cognitive impairment through positive coping style (ß = -0.026, P < .05) and negative coping style (ß = -0.131, P < .05). CONCLUSIONS: Our research suggests that sleep quality has both a direct effect on perceived cognitive impairment and an indirect effect through positive and negative coping styles in breast cancer patients. Moreover, negative coping style had a more pronounced mediating effect than positive coping style. IMPLICATIONS FOR PRACTICE: Clinical medical staff could reduce the perceived cognitive impairment of breast cancer patients by improving their sleep quality and encouraging them to adopt a more positive coping style.

Incidence of Cytomegalovirus Infection After Repeat Keratoplasty and Associated Rate of Graft Failure.

INTRODUCTION: The aim of this work was to compare the prognosis and characteristics of patients with Cytomegalovirus (CMV) infection (CMV+) with those of patients without virus infection (Virus-) undergoing repeat keratoplasty. METHODS: This prospective propensity score-matched cohort study enrolled patients who underwent repeat keratoplasty for graft failure at the Peking University Third Hospital between January 2016 and May 2022. Patients with prior viral keratitis before the first keratoplasty were excluded. The primary outcome measure was the graft failure rate. The secondary outcome measures included the anterior segment characteristics, intraocular pressure (IOP), and endothelial cell density. RESULTS: Ninety-four matched patient pairs were included. The graft failure rate in the CMV+ group (71%) was higher than that in the Virus- group (29%) (P < 0.001). CMV infection in the cornea increased the risk of repeat graft failure and shortened the median survival time (hazard ratio, 3.876; 95% confidence intervals, 2.554-5.884; P < 0.001). The characteristics of graft failure included exacerbation of ocular surface inflammation, neovascularization, and opacification. Epithelial defects, high IOP, and endothelial decompensation were observed at an increased frequency in the CMV+ group (all P < 0.005). Recurrent CMV infection presented as early endothelial infection in the CMV+ group. Recurrence of CMV infection was confined to the graft endothelium without involving the stroma and epithelium post-repeat endothelial keratoplasty. CONCLUSIONS: CMV infection post-keratoplasty leads to persistent endothelial damage and graft opacification and significantly increases the risk of repeat graft failure. Localized recurrence of CMV infection in the endothelial grafts underscores the importance of monitoring and treatment. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1800014684.

Identification of ATM Mutation as a Potential Prognostic Biomarker for Immune Checkpoint Inhibitors Therapy.

BACKGROUND: Ataxia telangiectasia mutated (ATM), an apical DNA damage response gene, is a commonly mutated gene in tumors, and its mutation could strengthen tumor immunogenicity and alter the expression of PD-L1, which potentially contributes to immune checkpoint inhibitors (ICIs) therapy. METHODS: The characteristics of ATM mutation and its relationship with the ICIs-treated clinical prognosis have been analyzed comprehensively in this paper. The overall frequency of ATM mutations has been found to be 4% (554/10953) in the cancer genome atlas (TCGA) cohort. RESULTS: Both the TMB and MSI levels in patients with ATM mutations were significantly higher than those in patients without mutations (P < 0.0001). The median TMB was positively correlated with the frequency of ATM mutations (r = 0.54, P = 0.003). In the TCGA cohort, patients with ATM mutations had better clinical benefits in terms of overall survival (OS, hazard ratio (HR) = 0.736, 95% CI = 0.623 - 0.869), progression-free survival (PFS, HR = 0.761, 95% CI = 0.652 - 0.889), and disease-free survival (DFS, HR = 0.686, 95% CI = 0.512 - 0.919)] than patients without ATM mutations. Subsequently, the verification results showed ATM mutations to be significantly correlated with longer OS in ICIs-treated patients (HR = 0.710, 95% CI = 0.544 - 0.928). Further exploration indicated ATM mutation to be significantly associated with regulated anti-tumor immunity (P < 0.05). CONCLUSION: Our findings highlight the value of ATM mutation as a promising biomarker to predict ICIs therapy in multiple tumors.

Leaf Senescence Database v5.0: A Comprehensive Repository for Facilitating Plant Senescence Research.

Through an extensive literature survey, we have upgraded the Leaf Senescence Database (LSD v5.0; https://ngdc.cncb.ac.cn/lsd/), a curated repository of comprehensive senescence-associated genes (SAGs) and their corresponding mutants. Since its inception in 2010, LSD undergoes frequent updates to encompass the latest advances in leaf senescence research and its current version comprises a high-quality collection of 31,740 SAGs and 1,209 mutants from 148 species, which were manually searched based on robust experimental evidence and further categorized according to their functions in leaf senescence. Furthermore, LSD was greatly enriched with comprehensive annotations for the SAGs through meticulous curation using both manual and computational methods. In addition, it was equipped with user-friendly web interfaces that facilitate text queries, BLAST searches, and convenient download of SAG sequences for localized analysis. Users can effortlessly navigate the database to access a plethora of information, including literature references, mutants, phenotypes, multi-omics data, miRNA interactions, homologs in other plants, and cross-links to various databases. Taken together, the upgraded version of LSD stands as the most comprehensive and informative plant senescence-related database to date, incorporating the largest collection of SAGs and thus bearing great utility for a wide range of studies related to plant senescence.

Janus Membrane with Intrafibrillarly Strontium-Apatite-Mineralized Collagen for Guided Bone Regeneration.

Commercial collagen membranes face difficulty in guided bone regeneration (GBR) due to the absence of hierarchical structural design, effective interface management, and diverse bioactivity. Herein, a Janus membrane called SrJM is developed that consists of a porous collagen face to enhance osteogenic function and a dense face to maintain barrier function. Specifically, biomimetic intrafibrillar mineralization of collagen with strontium apatite is realized by liquid precursors of amorphous strontium phosphate. Polycaprolactone methacryloyl is further integrated on one side of the collagen as a dense face, which endows SrJM with mechanical support and a prolonged lifespan. In vitro experiments demonstrate that the dense face of SrJM acts as a strong barrier against fibroblasts, while the porous face significantly promotes cell adhesion and osteogenic differentiation through activation of calcium-sensitive receptor/integrin/Wnt signaling pathways. Meanwhile, SrJM effectively enhances osteogenesis and angiogenesis by recruiting stem cells and modulating osteoimmune response, thus creating an ideal microenvironment for bone regeneration. In vivo studies verify that the bone defect region guided by SrJM is completely repaired by newly formed vascularized bone. Overall, the outstanding performance of SrJM supports its ongoing development as a multifunctional GBR membrane, and this study provides a versatile strategy of fabricating collagen-based biomaterials for hard tissue regeneration.