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Abstract The calcium-binding protein S100A9 has emerged as a pivotal biomolecular actor in oncology, implicated in numerous malignancies. This comprehensive bioinformatics study transcends traditional boundaries, investigating the prognostic and therapeutic potential of S100A9 across diverse neoplastic entities. Leveraging a wide array of bioinformatics tools and publicly available cancer genomics databases, such as TCGA, we systematically examined the S100A9 gene. Our approach included differential expression analysis, mutational burden assessment, protein interaction networks, and survival analysis. This robust computational framework provided a high-resolution view of S100A9’s role in cancer biology. The study meticulously explored S100A9’s oncogenic facets, incorporating comprehensive analyses of its relationship with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and immune cell infiltration across various tumor types. This study presents a panoramic view of S100A9 expression across a spectrum of human cancers, revealing a heterogeneous expression landscape. Elevated S100A9 expression was detected in malignancies such as BLCA (Bladder Urothelial Carcinoma), CESC (Cervical squamous cell carcinoma and endocervical adenocarcinoma), COAD (Colon adenocarcinoma), ESCA (Esophageal carcinoma), and GBM (Glioblastoma multiforme), while reduced expression was noted in BRCA (Breast invasive carcinoma), HNSC (Head and Neck squamous cell carcinoma), and KICH (Kidney Chromophobe). This disparate expression pattern suggests that S100A9’s role in cancer biology is multifaceted and context-dependent. Prognostically, S100A9 expression correlates variably with patient outcomes across different cancer types. Furthermore, its expression is intricately associated with TMB and MSI in nine cancer types. Detailed examination of six selected tumors—BRCA, CESC, KIRC (Kidney renal clear cell carcinoma), LUSC (Lung squamous cell carcinoma), SKCM (Skin Cutaneous Melanoma); STAD (Stomach adenocarcinoma)—revealed a negative correlation of S100A9 expression with the infiltration of most immune cells, but a positive correlation with neutrophils, M1 macrophages, and activated NK cells, highlighting the complex interplay between S100A9 and the tumor immune environment. This bioinformatics synthesis posits S100A9 as a significant player in cancer progression, offering valuable prognostic insights. The data underscore the utility of S100A9 as a prognostic biomarker and its potential as a therapeutic target. The therapeutic implications are profound, suggesting that modulation of S100A9 activity could significantly impact cancer management strategies.

Abstract The lack of a simple design strategy to obtain ideal conjugated polymers (CPs) with high absorbance and fluorescence (FL) in the near-infrared-II (NIR-II; 1000–1700 nm) region still hampers the success of NIR-II light-triggered phototheranostics. Herein, novel phototheranostic nanoparticles (PPN-NO NPs) were successfully prepared by coloading a cationic NIR-II CPs (PBC-co-PBF-NMe3) and a NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto a 1:1 mixture of DSPE-PEG5000 and dimyristoylphosphatidylcholine (DMPC) for NIR-II FL and NIR-II photoacoustic (PA) imaging-guided low-temperature NIR-II photothermal therapy (PTT) and gas combination therapy for cancer treatment. A precise NIR-II FL dually enhanced design tactic was proposed herein by integrating flexible nonconjugated segments (C6) into the CPs backbone and incorporating quaternary ammonium salt cationic units into the CPs side chain, which considerably increased the radiative decay pathway, resulting in desirable NIR-II FL intensity and balanced NIR-II absorption and NIR PTT properties. The phototheranostic PPN-NO NPs exhibited distinguished NIR-II FL and PA imaging performance in tumor-bearing mice models. Furthermore, the low-temperature photothermal effect of PPN-NO NPs could initiate NO release upon 980 nm laser irradiation, efficiently suppressing tumor growth owing to the combination of low-temperature NIR-II PTT and NO gas therapy in vitro and in vivo. Graphical Abstract

Abstract Background Previous research has revealed a negative association between social support and procrastination. However, few studies have investigated the mechanism underlying this relationship among vocational college students. Objective Based on the social cognitive theory, this study was intended to investigate the multiple mediating effects of self-efficacy and resilience on the relationship between social support and procrastination among vocational college students. Methods This study employed a cross-sectional design involving a sample of 1,379 students from a vocational college in China. Data were collected using the General Procrastination Scale, the Multidimensional Scale of Perceived Social Support, the General Self-Efficacy Scale, and the Resilience Scale-14. The PROCESS macro for SPSS was used to examine the multiple mediation model. Results Our findings indicate significant negative correlations between social support, self-efficacy, resilience, and procrastination. The multiple mediation analysis showed that social support did not have a significant direct impact on procrastination. Instead, the relationship between social support and procrastination was fully mediated by self-efficacy (indirect effect: -0.017; 95% CI: -0.032, -0.004) and resilience (indirect effect: -0.047; 95% CI: -0.072, -0.025), and sequentially mediated by both factors (indirect effect: -0.013; 95% CI: -0.020, -0.007). Conclusions The results emphasise the importance of enhancing self-efficacy and resilience in initiatives aimed at preventing and intervening in case of procrastination among vocational college students. Additionally, strengthening social support may also be crucial to preventing or reducing procrastination among this population.

Abstract College students represent a burgeoning force in mass entrepreneurship, underscoring the critical need to nurture their entrepreneurial endeavors. This study adopts a quantitative method, surveying 33,660 Chinese college students engaged in entrepreneurial activities. It examines the impact of various entrepreneurial policies and regional entrepreneurship spirit on these students’ decision-making processes. The findings reveal a positive correlation between entrepreneurial policies and entrepreneurial decision-making among college students, with regional entrepreneurship spirit serving as a mediator. Gender influences the relationship between regional entrepreneurship spirit and entrepreneurial decision-making, primarily moderating the effects of supply-based and environmentally-oriented policies. Entrepreneurship must be deeply integrated within China’s unique social networks and informal institutional frameworks. The moderating influence of gender also highlights differing policy impacts among various student groups. This research contributes to the enhancement and understanding of the policy support mechanism’s effect on college students and underscores the necessity for precise implementation of entrepreneurship policies tailored to college students.

In this study, the cloud macro-physical characteristics in Xiangyang of Hubei Province are statistically analyzed from the aspects of cloud occurrence frequency, number of cloud layers, and cloud base height by using the observation data of ceilometer from 2019 to 2021. The results are as follows. (1) The cloud coverage in Xiangyang is relatively high throughout the year, with an average cloud occurrence frequency of 61.3% in the three years. The frequency of cloud occurrence shows a seasonal variation of higher in summer but lower in winter, and a diurnal variation of higher level during nighttime but lower during daytime. (2) The cloud layer is dominated by single-layer clouds (78.3%), especially in winter (80.1%). In the multi-layer cloud system, two-layer clouds account for the largest proportion (18.5%). The occurrence frequency of multi-layer clouds decreases with the increase in the number of cloud layers, and it is usually high in summer but low in winter, which is mainly related to the relatively sufficient water vapor in summer and the strong convection caused by high temperatures. (3) For clouds with a cloud base height below 1.0 km, the occurrence frequency is 26% in January and 40% in July, indicating that the cloud distribution is relatively dispersed in January but relatively concentrated in July. However, for clouds with a cloud base height between 1.0 and 3.5 km, the occurrence frequency is 57% in January and 24% in July, that is, the cloud distribution is relatively concentrated in January, while relatively dispersed in July. (4) Convective precipitation clouds mainly occur from June to August, accounting for 83.3% of all convective precipitation clouds, and the probability of convective precipitation around the evening is the highest. In terms of cloud base height distribution, the average cloud base height of convective precipitation clouds is lower than that of all precipitation clouds, with a large occurrence frequency of low clouds.

Abstract Photothermal immunotherapy is regarded as the ideal cancer therapeutic modality to against malignant solid tumors; however, its therapeutic benefits are often modest and require improvement. In this study, a thermoresponsive nanoparticle (BTN@LND) composed of a photothermal agent (PTA) and pyroptosis inducer (lonidamine) were developed to enhance immunotherapy applications. Specifically, our “two-step” donor engineering strategy produced the strong NIR-II-absorbing organic small-molecule PTA (BTN) that exhibited high NIR-II photothermal performance (ε1064 = 1.51 × 104 M−1 cm−1, η = 75.8%), and this facilitates the diagnosis and treatment of deep tumor tissue. Moreover, the fabricated thermally responsive lipid nanoplatform based on BTN efficiently delivered lonidamine to the tumor site and achieved spatiotemporal release triggered by the NIR-II photothermal effect. In vitro and in vivo experiments demonstrated that the NIR-II photothermal therapy (PTT)-mediated on-demand release of cargo effectively faciliated tumor cell pyroptosis, thereby intensifying the immunogenic cell death (ICD) process to promote antitumor immunotherapy. As a result, this intelligent component bearing photothermal and chemotherapy can maximally suppress the growth of tumors, thus providing a promising approach for pyroptosis/NIR-II PTT synergistic therapy against tumors. Graphical Abstract

Abstract Continuous immunosuppression has been widely used in xenografts into non-human primate brains. However, how immune responses change after transplantation in host brains under continuous immunosuppressive administration and whether immunosuppression can be withdrawn to mitigate side effects remain unclear. Human induced neural stem/progenitor cells (iNPCs) have shown long-term survival and efficient neuronal differentiation in primate brains. Here, we evaluate the immune responses in primate brains triggered by human grafts. The results show that the immune responses, including the evident activation of microglia and the strong infiltration of lymphocytes (both T- and B-cells), are caused by xenografts at 4 months post transplantation (p.t.), but significantly reduced at 8 months p.t. under continuous administration of immunosuppressant Cyclosporin A. However, early immunosuppressant withdrawal at 5 months p.t. results in severe immune responses at 10 months p.t. These results suggest that continuous long-term immunosuppression is required for suppressing immune responses to xenografts in primate brains.

The transitory emergence of myeloid-derived suppressor cells (MDSCs) in infants is important for the homeostasis of the immune system in early life. The composition and functional heterogeneity of MDSCs in newborns remain elusive, hampering the understanding of the importance of MDSCs in neonates. In this study, we unraveled the maturation trajectory of polymorphonuclear (PMN)-MDSCs from the peripheral blood of human newborns by performing single-cell RNA sequencing. Results indicated that neonatal PMN-MDSCs differentiated from self-renewal progenitors, antimicrobial PMN-MDSCs, and immunosuppressive PMN-MDSCs to late PMN-MDSCs with reduced antimicrobial capacity. We also established a simple framework to distinguish these distinct stages by CD177 and CXCR2. Importantly, preterm newborns displayed a reduced abundance of classical PMN-MDSCs but increased late PMN-MDSCs, consistent with their higher susceptibility to infections and inflammation. Furthermore, newborn PMN-MDSCs were distinct from those from cancer patients, which displayed minimum expression of genes about antimicrobial capacity. This study indicates that the heterogeneity of PMN-MDSCs is associated with the maturity of human newborns.

Chinese Baijiu has always been preferred by the majority of alcoholic drink lovers with its rich aroma. With the popularity of drinking culture and mental health, low-alcohol Baijiu has achieved increasing attention. This paper innovatively adopts the coalescence method of separating emulsion to solve the turbidity problem in the process of degrading Baijiu. Firstly, the characteristics of feasible materials for turbidity removal via coalescence were explored. Three materials with different pore size, chemical composition, and wetting behavior, namely polyether sulfone (PES), glass fiber (GF) and polyvinylidene fluoride (PVDF), were characterized. Secondly, the emulsion structure and composition of the diluted Chinese Baijiu were analyzed. Finally, the selected porous materials were conducted to separate the precipitates in the degraded Baijiu for a clear Baijiu. The results found that both PVDF with excellent affinity to esters under alcohol solution and PES with small pore size exhibited efficient turbidity removal efficiency. Furthermore, the effect of pore size ranging from 0.1 to 5 μm of the PVDF coalescing material on the turbidity removal was investigated. However, the small pore size resulted in great pressure drop and followed the screening mechanism which contributed to high energy consumption and membrane fouling issue. The large pore size PVDF materials with average pore size of 1.6–4.0 μm achieved high flux of 5.30 × 104 L/(m2·h) with 90∼100% turbidity removal for 39% alcohol content-Baijiu via coalescence. The quality after coalescence removal of turbid was good indicating the coalescence removal method is a Chinese Baijiu turbidity removal potential technology.

Abstract Hail, a highly destructive weather phenomenon, necessitates critical identification and forecasting for the protection of human lives and properties. The identification and forecasting of hail are vital for ensuring human safety and safeguarding assets. This research proposes a deep learning algorithm named Dual Attention Module EfficientNet (DAM-EfficientNet), based on EfficientNet, for detecting hail weather conditions. DAM-EfficientNet was evaluated using FY-4A satellite imagery and real hail fall records, achieving an accuracy of 98.53% in hail detection, a 97.92% probability of detection, a false alarm rate of 2.08%, and a critical success index of 95.92%. DAM-EfficientNet outperforms existing deep learning models in terms of accuracy and detection capability, with fewer parameters and computational needs. The results validate DAM-EfficientNet’s effectiveness and superior performance in hail weather detection. Case studies indicate that the model can accurately forecast potential hail-affected areas and times. Overall, the DAM-EfficientNet model proves to be effective in identifying hail weather, offering robust support for weather disaster alerts and prevention. It holds promise for further enhancements and broader application across more data sources and meteorological parameters, thereby increasing the precision and timeliness of hail forecasting to combat hail disasters and boost public safety.

Abstract The inner ear is the hub where hair cells (HCs) transduce sound, gravity, and head acceleration stimuli to the brain. Hearing and balance rely on mechanosensation, the fastest sensory signals transmitted to the brain. The mechanoelectrical transducer (MET) channel is the entryway for the sound-balance-brain interface, but the channel-complex composition is not entirely known. Here, we report that the mouse utilizes Piezo1 (Pz1) and Piezo2 (Pz2) isoforms as MET-complex components. The Pz channels, expressed in HC stereocilia, and cell lines are co-localized and co-assembled with MET complex partners. Mice expressing non-functional Pz1 and Pz2 at the ROSA26 locus have impaired auditory and vestibular traits that can only be explained if the Pzs are integral to the MET complex. We suggest that Pz subunits constitute part of the MET complex and that interactions with other MET complex components yield functional MET units to generate HC MET currents.

The discovery of novel botanical pesticides as a preferred alternative to synthetic pesticides is regarded as an environmentally friendly strategy, yet it remains a great challenge due to limited insights into the synthesis and accumulation of active ingredient intermediates. Herein, we demonstrate the use of gold nanoparticle (AuNP)-assisted laser desorption/ionization mass spectrometry imaging (LDI-MSI) for the tissue-specific distribution and spatiotemporal accumulation effect of rotenone and active ingredient intermediates in its biosynthetic pathway within the roots of Derris elliptica. The MSI results revealed that rotenone was mainly concentrated in the epidermis, cortex, and xylem in the first two years and began to accumulate in the phloem since the 3rd year. Meanwhile, the rotenone contents increased in the epidermis, cortex, and xylem in the 4th year and finally decreased in the 5th year. The ultra-performance liquid chromatography (UPLC) results revealed that there was a significant difference in rotenone content between the root and non-root bark (p < 0.05) except for the 1st year. It reached its maximum value at 9.71% in the root bark in the 4th year and 7.98% in the non-root bark in the 1st year, which was in accordance with the MSI results. Additionally, the active ingredient intermediates in the Hydroxylation/Methylation and Rotenoid Phases of the biosynthetic pathway of rotenone were concentrated in the root region. Taken together, the collective results provide the scientific guidance for the scientific cultivation of D. elliptica and the efficient extraction of botanical pesticides.

Background: Diesel exhaust particles (DEPs), a predominant component of ambient particulate matter (PM), are classified as ultrafine particles with the capacity to penetrate the cerebral blood-brain barrier (BBB). This penetration is implicated in the pathogenesis of central nervous system (CNS) disorders. The integrity of the BBB is inextricably linked to cerebrovascular homeostasis and the development of neurodegenerative disease, highlighting the importance of studying the effects and mechanisms of DEPs on BBB function damage. Methods and results: Utilizing mouse cerebral microvascular endothelial cells (bEnd.3 cells) as an in vitro model of the BBB, we explored the detrimental effects of DEPs exposure on BBB permeability and integrity, with particular focus on inflammation, cell apoptosis, and miRNA expression profiles. Our findings revealed that exposure to DEPs at varying concentrations for 48 h resulted in the inhibition of bEND.3 cell proliferation, induction of cell apoptosis, and an upregulation in the secretion of inflammatory cytokines/chemokines and adhesion molecules. The BBB integrity was further compromised, as evidenced by a decrease in trans-epithelial electrical resistance(TEER), a reduction in cytoskeletal F-actin, , and diminished tight junction (TJ) protein expression. Microarray analysis revealed that 23 miRNAs were upregulated and 11 were downregulated in response to a 50 μg/mL DEPs treatment, with miR-466d-3p being notably differentially expressed. Wnt3 was identified as a target of miR-466d-3p, with the Wnt signaling pathway being significantly enriched. We validated that miR-466d-3p expression was downregulated, and the protein expression levels of Wnt/β-catenin and Wnt/PCP signaling components were elevated. The modulation of the Wnt signaling pathway by miR-466d-3p was demonstrated by the transfection of miR-466d-3p mimic, which resulted in a downregulation of Wnt3 and β-catenin protein expression, and the mRNA level of Daam1, as well as an enhancement of TJ proteins ZO-1 and Claudin-5 expression. Conclusions: Our study further confirmed that DEPs can induce the disruption of BBB integrity through inflammatory processes. We identified alterations in the expression profile of microRNAs (miRNAs) in endothelial cells, with miR-466d-3p emerging as a key regulator of tight junction (TJ) proteins, essential for maintaining BBB integrity. Additionally, our findings primarily demonstrated that the Wnt/ β-catenin and Wnt/PCP signaling pathway can be activated by DEPs and are regulated by miR-466d-3p. Under the combined effects of Wnt/PCP and inflammation, there is an ultimate increase in BBB hyperpermeability. Methods and results: Employing mouse cerebral microvascular endothelial cells (bEnd.3 cells) as an in vitro model of the BBB, we investigated the adverse effects of DEPs exposure on BBB permeability and integrity, with particular focus on inflammation, cell apoptosis, and miRNA expression profiles. Our findings revealed that exposure to DEPs at varying concentrations for 48 h resulted in the inhibition of bEND.3 cell proliferation, induction of cell apoptosis, and an increase in the release of inflammatory cytokines/chemokines and adhesion molecules. The BBB integrity was further compromised, as evidenced by a decrease in trans-epithelial electrical resistance(TEER), a reduction in cytoskeletal F-actin, loss of intercellular junctional organization, and diminished tight junction (TJ) protein expression. Microarray analysis disclosed that 23 miRNAs were upregulated and 11 were downregulated in bEND.3 cells treated with 50 μg/mL DEPs compared to the controls. In particular, miR-466d-3p was identified as a significantly differentially expressed miRNA. Wnt3 was predicted to be a target of miR-466d-3p, and the Wnt signaling pathway was identified as one of the most significantly enriched pathways. We validated that miR-466d-3p expression was downregulated, and the protein expression levels of Wnt/β-catenin and Wnt/PCP signaling components were elevated. The modulation of the Wnt signaling pathway by miR-466d-3p was demonstrated by the transfection of miR-466d-3p mimic, which resulted in a downregulation of Wnt3 and β-catenin protein expression, and the mRNA level of Daam1, as well as an enhancement of TJ proteins ZO-1 and Claudin-5 expression. Conclusions: Our study further confirmed that DEPs can induce the disruption of BBB integrity by inflammation. We identified changes in the expression profile of microRNAs (miRNAs) in endothelial cells, with miR-466d-3p emerging as a regulator of tight junction (TJ) proteins, which are critical for maintaining BBB integrity. Additionally, our findings primarily demonstrated that the Wnt/ β-catenin and Wnt/PCP signaling pathway can be activated by DEPs and is regulated by miR-466d-3p, and under the combined effects of Wnt/PCP and inflammation ultimately led to hyperpermeability BBB.

AbstractThe Weishan Lake serves as a crucial reservoir and regulating lake in the Eastern Route of the South-to-North Water Diversion Project and the ecological health of its lake ecosystem directly impacts the water quality for water diversion. Diatoms are particularly sensitive to changes in water environments, and the composition of diatom communities serves as a significant indicator of the health of aquatic ecosystems. To understand the composition of diatom communities in Weishan Lake and their relationship with environmental factors, thereby providing scientific grounds for the protection of the lake’s ecological environment, surface sediment diatoms, water samples, and sediments were collected and analyzed. The study revealed that there are 64 species from 19 genera of diatoms in Weishan Lake, predominantly comprising epiphytic and planktonic species. Dominant species include Fragilaria brevistriata, Achnanthes minutissima, and Stephanodiscus parvus, indicating an overall meso-eutrophic status. According to the diatom composition and biodiversity index, the diatom community was divided into three combination zones. Redundancy analysis (RDA) results indicated that the water environmental factors influencing the composition and distribution of diatom communities in Weishan Lake are TP, TOC, DO, NO2−–N, and Ca2+, collectively explaining 35.60% of the variation in diatom community composition. Due to the influence of agricultural and industrial wastewater runoff, domestic sewage discharge, and cage aquaculture, Weishan Lake is in a mesotrophic eutrophication state. Therefore, it is recommended that strict control over inappropriate human activities in the lake area be implemented in the future to ensure the safety of water quality for water diversion.

IntroductionAdverse life events constitute primary risk factors for major depressive disorder (MDD), influencing brain function and structure. Adolescents, with their brains undergoing continuous development, are particularly susceptible to enduring impacts of adverse events.MethodsWe investigated differences and correlations among childhood trauma, negative life events, and alterations of brain function in adolescents with first-episode MDD. The study included 23 patients with MDD and 19 healthy controls, aged 10–19 years. All participants underwent resting-state functional magnetic resonance imaging and were assessed using the beck depression inventory, childhood trauma questionnaire, and adolescent self-rating life events checklist.ResultsCompared with healthy controls, participants with first-episode MDD were more likely to have experienced emotional abuse, physical neglect, interpersonal relationship problems, and learning stress (all p’ < 0.05). These adverse life events were significantly correlated with alterations in brain functions (all p < 0.05).DiscussionThis study contributes novel evidence on the underlying process between adverse life events, brain function, and depression, emphasizing the significant neurophysiological impact of environmental factors.

IntroductionAn easily accessible and cost-free machine learning model based on prior probabilities of vascular aging enables an application to pinpoint high-risk populations before physical checks and optimize healthcare investment.MethodsA dataset containing questionnaire responses and physical measurement parameters from 77,134 adults was extracted from the electronic records of the Health Management Center at the Third Xiangya Hospital. The least absolute shrinkage and selection operator and recursive feature elimination-Lightweight Gradient Elevator were employed to select features from a pool of potential covariates. The participants were randomly divided into training (70%) and test cohorts (30%). Four machine learning algorithms were applied to build the screening models for elevated arterial stiffness (EAS), and the performance of models was evaluated by calculating the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy.ResultsFourteen easily accessible features were selected to construct the model, including “systolic blood pressure” (SBP), “age,” “waist circumference,” “history of hypertension,” “sex,” “exercise,” “awareness of normal blood pressure,” “eat fruit,” “work intensity,” “drink milk,” “eat bean products,” “smoking,” “alcohol consumption,” and “Irritableness.” The extreme gradient boosting (XGBoost) model outperformed the other three models, achieving AUC values of 0.8722 and 0.8710 in the training and test sets, respectively. The most important five features are SBP, age, waist, history of hypertension, and sex.ConclusionThe XGBoost model ideally assesses the prior probability of the current EAS in the general population. The integration of the model into primary care facilities has the potential to lower medical expenses and enhance the management of arterial aging.

Background: Patients with leukemia rely on social and family support. This study aimed to explore the knowledge, attitude, and practice (KAP) toward leukemia among family members of patients with leukemia and the general population in southeast China. Methods: A cross-sectional study was conducted in September 2022 in southeast China (Anhui Province). The KAP scores and demographic data were assessed by questionnaire and analyzed by multivariable logistic regression and structural equation modeling. Results: A total of 760 valid questionnaires were collected, including 117 (15.39%) answered by family members of patients with leukemia. The mean knowledge (8.30 ± 2.79 vs. 8.72 ± 2.56, P = 0.103), attitude (52.17 ± 5.52 vs. 52.27 ± 5.53, P = 0.862), and practice (8.06 ± 2.00 vs. 8.18 ± 2.05, P = 0.547) scores were comparable among family members and the general population. Higher knowledge scores [OR = 1.18 (1.10, 1.27), P

Abstract Background Trans- inferior alveolar nerve (IAN) implantation technique was wildly used while the potential appropriate angle range in which the residual alveolar bone can bear the stress without absorption are currently unclear. This study aimed to evaluate the stress distribution pattern of the interface between bone and implant by finite element analysis (FEA) to determine the appropriate range of the implant tilt angle. Methods Cone beam computed tomography (CBCT) images of 120 patients with missing mandibular second molars and vertical bone height

Accurate precipitation estimates over space and time are critically important, particularly in data-scarce areas, for effective hydrological modeling and efficient regional water resources management. Gridded precipitation datasets are the preeminent alternative in such areas. However, gridded precipitation datasets contain different kinds of uncertainties owing to the retrieval algorithms used in their development. In this study, five precipitation datasets (Tropical Rainfall Measuring Mission (TRMM), Climate Prediction Centre (CPC), APHRODITE, Climate Hazards Group Infra-Red Precipitation with Station data (CHIRPS), and PERSIANN) were evaluated, and an ensemble of daily precipitation datasets from 2001 to 2017 at a resolution of 0.05 degree was created based on three ensemble approaches (Bayesian model ensemble, relative bias-based ensemble, and correlation-based ensemble) over the Upper Indus basin. To improve the accuracy of the ensemble dataset, a linear bias correction technique is applied with respect to gauging precipitation. The accuracy of the bias-corrected ensemble dataset was evaluated using statistical and novelty categorical measures. A reasonable agreement was found between the ensemble and gauge precipitation (Pearson correlation 0.83–0.89 and relative bias 1–8.7 mm/month), while large biases were noted in five precipitation datasets (1.7–53.9 mm/month). The study suggests that utilizing ensemble approaches to gridded precipitation can significantly enhance the accuracy of the estimates compared to relying on a single precipitation dataset. HIGHLIGHTS The study developed bias-corrected precipitation estimates using three ensemble approaches.; The new relative bias-based ensemble approach estimates are slightly better than the existing ensemble approaches used in this study.; A nonlinear precipitation increase/decrease trend is found with altitude.; The direct use of gridded precipitation is not recommended due to the large biases present in each precipitation dataset.;

Abstract Understanding of the molecular drivers of lineage diversification and tissue patterning during primary germ layer development requires in-depth knowledge of the dynamic molecular trajectories of cell lineages across a series of developmental stages of gastrulation. Through computational modeling, we constructed at single-cell resolution, a spatio-temporal transcriptome of cell populations in the germ-layers of gastrula-stage mouse embryos. This molecular atlas enables the inference of molecular network activity underpinning the specification and differentiation of the germ-layer tissue lineages. Heterogeneity analysis of cellular composition at defined positions in the epiblast revealed progressive diversification of cell types. The single-cell transcriptome revealed an enhanced BMP signaling activity in the right-side mesoderm of late-gastrulation embryo. Perturbation of asymmetric BMP signaling activity at late gastrulation led to randomization of left-right molecular asymmetry in the lateral mesoderm of early-somite-stage embryo. These findings indicate the asymmetric BMP activity during gastrulation may be critical for the symmetry breaking process.

Depsides and depsidones have attracted attention for biosynthetic studies due to their broad biological activities and structural diversity. Previous structure‒activity relationships indicated that triple halogenated depsidones display the best anti-pathogenic activity. However, the gene cluster and the tailoring steps responsible for halogenated depsidone nornidulin (3) remain enigmatic. In this study, we disclosed the complete biosynthetic pathway of the halogenated depsidone through in vivo gene disruption, heterologous expression and in vitro biochemical experiments. We demonstrated an unusual depside skeleton biosynthesis process mediated by both highly-reducing polyketide synthase and non-reducing polyketide synthase, which is distinct from the common depside skeleton biosynthesis. This skeleton was subsequently modified by two in-cluster enzymes DepG and DepF for the ether bond formation and decarboxylation, respectively. In addition, the decarboxylase DepF exhibited substrate promiscuity for different scaffold substrates. Finally, and interestingly, we discovered a halogenase encoded remotely from the biosynthetic gene cluster, which catalyzes triple-halogenation to produce the active end product nornidulin (3). These discoveries provide new insights for further understanding the biosynthesis of depsidones and their derivatives.

Background: Thymic neuroendocrine tumors (Th-NETs) are rare and aggressive, with a scarcity of research on predicting patient prognosis. Our study aimed to assess the impact of prognostic markers and temozolomide (TMZ)-based chemotherapy on survival in Th-NETs. Methods: We retrospectively reviewed the medical records of patients diagnosed with Th-NETs between 2013 and 2023 at our institution. We collected clinicopathological data, including tumor pathological grading, staging, serum concentrations of neuron-specific enolase (NSE) and pro-gastrin-releasing peptide, levels of inflammatory factors, and expression of oxygen 6-methylguanine-DNA methyltransferase (MGMT). Treatment details (such as surgery and chemotherapy) and survival outcomes were also documented. Results: A total of 32 patients were included in our study after excluding those without complete available information. The median progression-free survival (PFS) was 12.5 months (95%CI, 8–16 months) for 19 patients who received TMZ-based chemotherapy. Twenty-one patients underwent surgery as the primary treatment, demonstrating a median disease-free survival (DFS) of 51.0 months. The inflammatory factor neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic indicator of DFS in postoperative patients and PFS in TMZ-treated patients. The overall 3-, 5-, and 10-year survival rates were 86.6%, 69.5%, and 33.8%, respectively. Ki67 level exceeding 10% (p = 0.048) and absence of surgical resection (p = 0.003) were significantly associated with worse overall survival (OS). Conclusion: Surgical treatment was currently the primary method for treating Th-NETs, and postoperative adjuvant therapy was an essential consideration for specific patient cohorts. Despite widespread positive MGMT expression, TMZ-based chemotherapy showed promise. Some potential prognostic biomarkers such as NLR and NSE need more attention.

The degradation of urban ecology, particularly in metropolitan areas distinguished by dense populations and impervious surfaces, presents a worldwide challenge linked to swift urban expansion. Despite extensive documentation of urbanization’s impact on broad regions or specific urban ecosystems over defined time periods, there remains a scarcity of studies investigating the spatiotemporal dynamics of landscape pattern (LP) changes in specific ecosystems at small-to-medium scales within inland megacities as a response to urbanization. Therefore, this work focused on the Bailuwan Wetland Park (BWP) in Chengdu, an inland megacity in southwestern China. Employing satellite imagery data from selected years spanning the previous decade (2010–2021, encompassing 2010, 2012, 2015, 2018, and 2021), this investigation delved into the influences of urbanization on the LP over various time-frames and across different land use/land cover (LULC) types. Our study revealed that urbanization has a significant impact on the patch-/landscape-level characteristics, including the class area (CA), number of patches (NP), patch density (PD), percentage of landscape (PLAND), aggregation index (AI), contagion index (CONTAG), largest patch index (LPI), landscape shape index (LSI), fractal dimension index (FRAC_MN), Shannon’s diversity (SHDI), and evenness index (SHEI). Over the period from 2010 to 2021, NP and PD experienced notable increases, while landscape shape (LSI/FRAC_MN) exhibited greater complexity and fragmentation (PLAND) intensified. Further, landscape heterogeneity (AI/CONTAG) and diversity (SHDI/SHEI) decreased. Particularly significant was the conversion of 52 ha of agricultural land to vegetation, resulting in heightened complexity and fragmentation in vegetation patterns. Additionally, the CA of lakes and rivers decreased following the establishment of the park, while the CA and NP of bare land presented significant increases. These findings suggest that rapid urbanization significantly influences the spatial–temporal dynamics of wetland landscape patterns. Consequently, it is imperative for society to prioritize the restoration and protection of urban constructed wetlands.

β-Glucan is the main component of the cell wall of pathogen-associated molecular patterns (PAMPs) including various yeast, fungi, or certain bacteria. Previous reports demonstrated that β-glucan was widely investigated as a potent immunomodulators to stimulate innate and adaptive immune responses, which indicated that it could be recommended as an effective adjuvant in immunotherapy. However, the detailed effects of β-glucan on neonatal immunity are still largely unknown. Here, we found that β-glucan did not affect the frequencies and numbers of myeloid cells in the spleen and bone marrow from neonates. Functional assay revealed that β-glucan from neonates compromised the immunosuppressive function of immature myeloid cells, which were myeloid-derived suppressor cells (MDSCs). Flow cytometry or gene expression analysis revealed that β-glucan-derived polymorphonuclear (PMN)-MDSCs produced lower level of reactive oxygen species (ROS) and arginase-1 (Arg1) in neonatal mice. Furthermore, β-glucan administration significantly decreased the frequency and ROS level of PMN-MDSCs in vitro. These observations suggest that β-glucan facilitates the maturation of myeloid cells in early life, which may contribute to its beneficial effects against immune disorders later in life.

Abstract Background Colorectal cancer (CRC), known as prevalent cancer, has risen to be the leading cause of cancer‐related death. Engineered exosomes had attracted much attention since they acted as carriers to deliver small molecule drugs, therapeutic nucleic acids, and polypeptides to treat a series of cancers. Methods and Results Here, we found that the PKH‐26 labeled exosomes, which were derived from the CRC cells, could be efficiently absorbed by SW1116 cells and had an abundant fluorescence distribution in tumors, compared with the exosomes derived from mesenchymal stem cells (MSC) and HepG2 cells. This Research demonstrated that engineered CRC‐exosomes loaded with functional miR‐1270 (Exo‐miR‐1270) enriched in miR‐1270 strongly inhibited the proliferation by CCK‐8 and EdU assays, migration by wound‐healing and transwell assays, and promoted the apoptosis for CRC cells through flow cytometry. MiR‐1270 overexpression delivered by CRC exosomes contributed to inhibiting the tumor growth potential of CRC in vivo and increasing the overall survival of the mice. Moreover, the safety evaluation results showed that CRC‐exosomes loaded with functional miR‐1270‐mimics had no toxicity for other organs by histopathological analysis and no influence on the vital chemistry and hematology parameters for mice in vivo safety evaluation. Conclusion These results indicate that Exo‐miR‐1270 can effectively treat CRC tumors by intravenous administration. Our work provided a foundation that the homologous tumor‐derived exosomes mediated miRNA delivery for the treatment of CRC.

BackgroundHearing loss can exacerbate cognitive decline; therefore, exploring the mechanisms through which hearing loss affects cognitive function is crucial. The current study aimed to investigate the impact of hearing loss on cognitive function and the mediating role played by self-rated health and depressive anxiety symptoms.MethodsUsing stratified whole-group random sampling, the study employed a cross-sectional design and included 624 participants aged ≥65 years from three communities in Urumqi, China. Cognitive function was assessed using the Mini-Mental State Examination. Hearing function and self-rated health were determined by self-report. The 15-item Geriatric Depression Scale and the 7-item Generalized Anxiety Disorder Scale were used to assess depressive anxiety symptoms. Serial mediation analysis was performed using AMOS 26.0.ResultsHearing loss can not only negatively affect cognitive function in older adults directly (direct effect = −0.106; SE = 0.045; 95% confidence interval (CI): −0.201 to −0.016), but also indirectly affect the relationship between hearing loss and cognitive function through self-rated health and depressive anxiety symptoms. The results of the serial mediation analysis showed that the total indirect effect of self-rated health and depressive anxiety symptoms was −0.115 (95% CI: −0.168 to −0.070), and the total effect of the model was −0.221 (95% CI: −0.307 to −0.132), with the total indirect effect accounting for 52.04% of the total effect of the model.ConclusionOur study discovered that there is a partial mediation of the relationship between hearing loss and cognitive function by self-rated health and depressive anxiety symptoms. It is suggested that by enhancing self-rated health and ensuring good mental health, the decline in cognitive function among older adults with hearing loss can be delayed.

ABSTRACT The emerging infectious agent Elizabethkingia meningoseptica is associated with life-threatening infections in immunocompromised individuals. However, there are limited data on its geographic distribution, phylogenetic evolution, pathogenesis, and transmission. In this study, we comprehensively analyze and compare the genomic features, evolutionary history, emergence date, and transmission networks of global E. meningoseptica. Geographical distribution reveals the presence of the emerging bacteria in Asia, Europe, and North America, three continents with similar latitudes. Phylogenetic analyses show no relationship between the strain’s evolutionary history and its location, origin, or source, despite the presence of genetic diversity. Analysis of the emergence timeline suggests that America is the most likely source of E. meningoseptica with the common ancestor of this pathogen dating back 90 years. Putative transmission networks indicate that E. meningoseptica bacteria can spread within the same hospital and even across borders. Minor variations in resistance genotypes and virulence genes are observed, supporting existing evidence of inherent resistance and pathogenicity in E. meningoseptica. Additionally, minocycline and doxycycline demonstrate potent antimicrobial activity against this pathogen, making them promising candidates for treating E. meningoseptica infections. Our research highlights the potential for severe nosocomial outbreaks caused by E. meningoseptica with horizontal transmission occurring between countries worldwide. To prevent future outbreak infections, increased genomic surveillance of global E. meningoseptica populations is necessary. IMPORTANCE Elizabethkingia meningoseptica is an emerging infectious agent associated with life-threatening infections in immunocompromised individuals. However, there are limited data available on the genomic features of E. meningoseptica. This study aims to characterize the geographical distribution, phylogenetic evolution, pathogenesis, and transmission of this bacterium. A systematic analysis of the E. meningoseptica genome revealed that a common ancestor of this bacterium existed 90 years ago. The evolutionary history showed no significant relationship with the sample source, origin, or region, despite the presence of genetic diversity. Whole genome sequencing data also demonstrated that E. meningoseptica bacteria possess inherent resistance and pathogenicity, enabling them to spread within the same hospital and even across borders. This study highlights the potential for E. meningoseptica to cause severe nosocomial outbreaks and horizontal transmission between countries worldwide. The available evidence is crucial for the development of evidence-based public health policies to prevent global outbreaks caused by emerging pathogens.

The variation of pore structure due to freeze-thaw (F-T) plays a vital role in revealing the thaw settlement mechanism of soils. In this study, remolded saturated clay specimens experienced unidirectional freezing and natural thawing in an open or closed system (i.e., with or without water supply). X-ray computed tomography (CT) and mercury intrusion porosimetry (MIP) were conducted to analyze pore structural characteristics, including macropores, mesopores, and micropores, along the temperature gradient direction before and after F-T. The longitudinal pore binary images, obtained by processing CT images, were used to assess the changes in porosity, pore shape, and orientation of macropores and mesopores due to F-T. The results indicate that the total longitudinal-sectional porosity and macropore percentage increased, whereas the mesopore percentage decreased. F-T considerably influenced the shape and orientation of macropores but had minimal effects on mesopores. The most significant changes occurred in the unfrozen zone due to F-T in an open system but near the final freezing front in a closed system. Additionally, Micropore porosity, diameter, and thermal fractal dimension were analyzed based on MIP data. The results showed that micropore porosity and diameter decreased, with significant changes occurring in the unfrozen zone of the open and closed systems. The micropore porosity and diameter decreased more in the unfrozen zone and near the final freezing front after F-T in a closed system, whereas a smaller decrease occurred in the frozen zone. The thermal fractal dimension value increases after F-T, indicating that the micropore structure became complex. In general, the multiscale pore analysis demonstrated that pore structure, including macropores, mesopores, and micropores, is significantly affected by F-T in the open system compared to the closed system.

AbstractInduction of oral tolerance by vaccination with type 1 diabetes mellitus (T1DM)-associated autoantigens exhibits great potential in preventing and treating this autoimmune disease. However, antigen degradation in the gastrointestinal tract (GIT) limits the delivery efficiency of oral antigens. Previously, bacterium-like particles (BLPs) have been used to deliver a single-chain insulin (SCI-59) analog (BLPs-SCI-59) or the intracellular domain of insulinoma-associated protein 2 (IA-2ic) (BLPs-IA-2ic). Both monovalent BLPs vaccines can suppress T1DM in NOD mice by stimulating the corresponding antigen-specific oral tolerance, respectively. Here, we constructed two bivalent BLPs vaccines which simultaneously deliver SCI-59 and IA-2ic (Bivalent vaccine-mix or Bivalent vaccine-SA), and evaluated whether there is an additive beneficial effect on tolerance induction and suppression of T1DM by treatment with BLPs-delivered bi-autoantigens. Compared to the monovalent BLPs vaccines, oral administration of the Bivalent vaccine-mix could significantly reduce morbidity and mortality in T1DM. Treatment with the bivalent BLPs vaccines (especially Bivalent vaccine-mix) endowed the mice with a stronger ability to regulate blood glucose and protect the integrity and function of pancreatic islets than the monovalent BLPs vaccines treatment. This additive effect of BLPs-delivered bi-autoantigens on T1DM prevention may be related to that SCI-59- and IA-2-specific Th2-like immune responses could be induced, which was more beneficial for the correction of Th1/Th2 imbalance. In addition, more CD4+CD25+Foxp3+ regulatory T cells (Tregs) were induced by treatment with the bivalent BLPs vaccines than did the monovalent BLPs vaccines. Therefore, multiple autoantigens delivered by BLPs maybe a promising strategy to prevent T1DM by efficiently inducing antigen-specific immune tolerance.

Abstract Salvia is widely used as medicine, food, and ornamental plants all over the world, with three main distribution centers, the Central and western Asia/Mediterranean (CAM), the East Aisa (EA), and the Central and South America (CASA). Along with its large number of species and world-wide distribution, Salvia is paraphyletic with multiple diversity. Chloroplast genomes (CPs) are useful tools for analyzing the phylogeny of plants at lower taxonomic levels. In this study, we reported chloroplast genomes of five species of Salvia and performed phylogenetic analysis with current available CPs of Salvia. Repeated sequence analysis and comparative analysis of Salvia CPs were also performed with representative species from different distribution centers. The results showed that the genetic characters of the CPs are related to the geographic distribution of plants. Species from CAM diverged first to form a separate group, followed by species from EA, and finally species from CASA. Larger variations of CPs were observed in species from CAM, whereas more deficient sequences and less repeated sequences in the CPs were observed in species from CASA. These results provide valuable information on the development and utilization of the worldwide genetic resources of Salvia.

The identification of projected changes in temperature caused by global warming at a fine-scale spatial resolution is of great importance for the high-altitude glacier and snow covered Upper Indus Basin. This study used a multimodel ensemble mean bias-correction technique which uses the ensemble empirical mode decomposition method to correct the bias of ensemble mean of seven CMIP6 GCMs outputs with reference to the European Centre for Medium-Range Weather Forecasts Reanalysis 5 (ERA5). The bias-corrected data have a nonlinear trend of seven GCMs but interannual variance and mean climate of ERA5 dataset. The dataset spans from 1985 to 2100 for historical and future climate scenarios (SSP126, SSP245, SSP370, and SSP585) at daily time intervals with a 1 km grid resolution. The result of different scenarios indicates that the increase in maximum (Tmax) and minimum temperature (Tmin) ranging from 1.5 to 5.4 °C and 1.8 to 6.8 °C from 2015 to 2100, respectively. Similarly, elevation-dependent warming is identified in Tmin from 1.7 to 7.0 °C at elevations

Abstract Background Immunosuppressive medication reduces the immunogenicity of the coronavirus disease 2019 (COVID‐19) vaccines in patients with rheumatic and musculoskeletal diseases (RMDs). However, the underlying mechanism remains unclear. The primary aim of our study was to dissect the impact of immunosuppressive medication on cellular and humoral immune responses in RMD patients receiving the inactivated COVID‐19 vaccine. Methods A total of 28 RMD patients and five healthy controls (HCs) receiving two doses of the inactivated COVID‐19 vaccine (Sinovac‐CoronaVac) were prospectively enrolled. Blood samples were collected before the primary vaccination (Week 0) and one week after the second vaccination (Week 5). Neutralizing antibody (nAb) titers and autoantibody titers were measured by a pseudovirus‐based neutralization assay and enzyme‐linked immunosorbent assay, respectively. CD4+ T‐cell and CD19+ B‐cell subsets and serum cytokines were analyzed by flow cytometry. Results The inactivated COVID‐19 vaccine was immunogenic in RMD patients and HCs after the second vaccination, but the nAb titers were lower in RMD patients than those in HCs. Only patients with systemic lupus erythematosus (SLE) had notably increased nAb titers. Remarkably, IgG+CD27+, IgG+IgG1+, and IgG+IgG1− B cells were reduced, whereas IgG−IgG1+ B cells, and total IgA and IgG titers were markedly increased. However, Tfh cell and Tfr cell subsets and cytokines produced by Tfh cells were not increased. The flare rate was low in RMD patients with comparable autoantibody titers, unchanged CD4+ T cell subsets and serum pro‐inflammatory cytokines (interleukin [IL]‐6, IL‐17, interferon‐γ, and tumor necrosis factor‐α) after the second vaccination. Conclusions Immunosuppressive therapy decreased the immunogenicity of the vaccine and maintained a low flare rate by selectively modulating B cell but not CD4+ T cell responses in RMD patients receiving the inactivated COVID‐19 vaccine. Optimization of the treatment regimen might ensure a durable and robust COVID‐19 vaccination response.

Abstract T-LAK-originated protein kinase (TOPK), a dual specificity serine/threonine kinase, is up-regulated and related to poor prognosis in many types of cancers. Y-box binding protein 1 (YB1) is a DNA/RNA binding protein and serves important roles in multiple cellular processes. Here, we reported that TOPK and YB1 were both highly expressed in esophageal cancer (EC) and correlated with poor prognosis. TOPK knockout effectively suppressed EC cell proliferation and these effects were reversible by rescuing YB1 expression. Notably, TOPK phosphorylated YB1 at Thr 89 (T89) and Ser 209 (S209) amino acid residues, then the phosphorylated YB1 bound with the promoter of the eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) to activate its transcription. Consequently, the AKT/mTOR signal pathway was activated by up-regulated eEF1A1 protein. Importantly, TOPK inhibitor HI-TOPK-032 suppressed the EC cell proliferation and tumor growth by TOPK/YB1/eEF1A1 signal pathway in vitro and in vivo. Taken together, our study reveals that TOPK and YB1 are essential for the growth of EC, and TOPK inhibitors may be applied to retard cell proliferation in EC. This study highlights the promising therapeutic potential of TOPK as a target for treatment of EC.

Ammopiptanthus, a unique evergreen broadleaf shrub endemic to the desert regions of Northwest China, exhibits a remarkable capacity for aeolian erosion control and dune stabilization. Attributed to its robust tolerance in terms of xerotolerance, halophytic adaptations, extreme thermotolerance, resistance to biotic and abiotic degradation and its defensive strategies against herbivory, Ammopiptanthus has emerged as an exemplary model organism for the study of plant resilience to diverse environmental stressors. Current research on Ammopiptanthus is scattered, lacking a systematic review, which poses a disadvantage for subsequent in-depth studies and the effective conservation of this endangered resource. In recent years, natural Ammopiptanthus communities have been severely disrupted, and the species’ natural range is rapidly shrinking. Here, this review summarizes the signaling pathways in the Ammopiptanthus response to biotic stress (especially the early signaling events), as well as the research advances in the resistance interactions between biotic and abiotic stresses. Then, the synergistic effects of multiple environmental pressures on Ammopiptanthus could be established, which may provide guidance for further studies on the resistance mechanism of Ammopiptanthus and be beneficial to its natural community protection and reconstruction.

Submillimeter wave radiometers are promising remote sensing tools for sounding ice cloud parameters. The Ice Cloud Imager (ICI) aboard the second generation of the EUMETSAT Polar System (EPS−SG) is the first operational submillimeter wave radiometer used for ice cloud remote sensing. Ice clouds simultaneously contain three species of ice hydrometeors—ice, snow, and graupel—the physical distributions and submillimeter wave radiation characteristics of which differ. Therefore, jointly retrieving the mass parameters of the three ice hydrometeors from submillimeter brightness temperatures is very challenging. In this paper, we propose a multiple species of ice hydrometeor parameters retrieval algorithm based on convolutional neural networks (CNNs) that can jointly retrieve the total content and vertical profiles of ice, snow, and graupel particles from submillimeter brightness temperatures. The training dataset is generated by a numerical weather prediction (NWP) model and a submillimeter wave radiative transfer (RT) model. In this study, an end to end ICI simulation experiment involving forward modeling of the brightness temperature and retrieval of ice cloud parameters was conducted to verify the effectiveness of the proposed CNN retrieval algorithm. Compared with the classical Unet, the average relative errors of the improved RCNN–ResUnet are reduced by 11%, 25%, and 18% in GWP, IWP, and SWP retrieval, respectively. Compared with Bayesian Monte Carlo integration algorithm, the average relative error of the total content retrieved by RCNN–ResUnet is reduced by 71%. Compared with BP neural network algorithm, the average relative error of the vertical profiles retrieved by RCNN–ResUnet is reduced by 69%. In addition, this algorithm was applied to actual Advanced Technology Microwave Sounder (ATMS) 183 GHz observed brightness temperatures to retrieve graupel particle parameters with a relative error in the total content of less than 25% and a relative error in the profile of less than 35%. The results show that the proposed CNN algorithm can be applied to future space borne submillimeter wave radiometers to jointly retrieve mass parameters of ice, snow, and graupel.

In this paper, the large time behavior of globally smooth solutions of the Cauchy problem for the three dimensional Euler-Poisson system of compressible fluids coupled to a magnetic field is studied. We prove that the smooth solutions (near a given constant equilibrium state) of the problem converge asymptotically to a stationary solution exponentially fast as t goes to ∞.

Abstract Stacking of monolayer 2D transition metal dichalcogenides (TMDs) into van der Waals heterostructures can enable the formation of interlayer excitons (IXs) with long lifetimes and permanent out‐of‐plane electric dipoles, allowing them to propagate over long distances. While early studies on TMD heterobilayrs show efficient electrical control of excitonic transport of IXs by creating different energy potentials, the electrically controllable exciton states and associated spatial migration remain elusive. Here, an electrical control of exciton diffusion through the change of exciton states between charged IXs (CIXs) and charged intralayer excitons is reported. The repulsive dipolar interaction of IXs accounts for the growing exciton cloud size and increasing diffusion length in the power‐dependent PL study. More importantly, the electrically tunable spatial exciton distribution is demonstrated by switching the exciton states, which shows a 1.5‐fold change in diffusion length and an order of magnitude increase in lifetime from charged intralayer excitons to CIXs. The electrical control of exciton states and the relevant diffusion dynamics provide another knob to study the interplay between propagation and many‐body interactions for the development of excitonic devices.

Mitochondrial dysfunction is one of the key features of acute kidney injury (AKI) and associated fibrosis. Leucine-rich repeat kinase 2 (LRRK2) is highly expressed in kidneys and regulates mitochondrial homeostasis. How it functions in AKI is unclear. Herein we reported that LRRK2 was dramatically downregulated in AKI kidneys. Lrrk2−/− mice exhibited less severity of AKI when compared to wild-type counterparts with less mitochondrial fragmentation and decreased reactive oxygen species (ROS) production in proximal renal tubular cells (PTCs) due to mitofusin 2 (MFN2) accumulation. Overexpression of LRRK2 in human PTC cell lines promoted LRRK2-MKK4/JNK-dependent phosphorylation of MFN2Ser27 and subsequently ubiquitination-mediated MFN2 degradation, which in turn exaggerated mitochondrial damage upon ischemia/reperfusion (I/R) mimicry treatment. Lrrk2 deficiency also alleviated AKI-to-chronic kidney disease (CKD) transition with less fibrosis. In vivo pretreatment of LRRK2 inhibitors attenuated the severity of AKI as well as CKD, potentiating LRRK2 as a novel target to alleviate AKI and fibrosis.

ObjectiveAquaporin-4 (AQP4) antibody-seropositive optic neuritis (AQP4-ON) is one of the most common types of optic neuritis in China. However, the association between AQP4-ON and vision-related quality of life (QoL) and depression remains poorly understood.MethodsIn this cross-sectional study, 57 patients with optic neuritis were evaluated for their vision-related QoL using a Chinese version of the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) and assessed for depressive symptoms using a Chinese version of the Beck Depression Inventory-II (BDI-II). Data regarding participants’ age, sex, visual acuity, and the number of recurrence events were gathered. Linear regression analysis was employed to investigate the relationships between AQP4-ON and vision-related QoL, as well as depression.ResultsOf the 57 included patients, 28 were AQP4-ON, and 29 were idiopathic optic neuritis (ION). AQP4-ON demonstrated a significant correlation with a decreased VFQ-25 composite score (Mean difference, −11.65 [95% CI, −21.61 to −1.69]; p = 0.023) and an increased BDI-II score (Mean difference, 6.48 [95% CI, 0.25 to 12.71]; p = 0.042) when compared to ION. The BDI-II score was correlated with the VFQ-25 composite score (Spearman ρ = −0.469; p

Background: Traffic-related air pollution (TRAP) is a risk factor for cognitive function, whereas healthy lifestyles are associated with better cognition. We aimed to examine their joint effects on cognition among the Chinese elderly. Methods: The data from the Chinese Longitudinal Healthy Longevity Survey was used. Participants’ cognitive performance was assessed by the Chinese version of the mini-mental state examination. Residential proximity to major roadways was obtained through self-report and categorized into five categories: > 300 m, 201–300 m, 101–200 m, 50–100 m, and 300 m from major roadways and adopting a healthy lifestyle had a significantly decreased risk of cognitive impairment. Stratified analysis indicated that the associations between TRAP and cognitive impairment were more pronounced among participants adopting an unhealthy lifestyle compared to the participants adopting a healthy lifestyle. Conclusions: TRAP may impair cognitive function, and its detrimental impacts may be lessened by healthy lifestyles.

In order to identify volatile oil synthesis related genes in Illicium verum, transcriptome sequencing and assembly annotation were carried out on the leaves of the superior clone Guijiao 69 and common variety Zhen 01, two varieties with significant difference in volatile oil content. Then GO and KEGG pathways analyses of differentially expressed genes (DEGs) were performed. The results were as follows: (1) A total of 84 182 Unigenes were obtained after transcripts assembly, and 59 161 Unigenes were annotated in NR, NT, Swissprot, KEGG, KOG, GO, and Pfam databases. A total of 30 572 DEGs were obtained after filtering the low abundance genes, and 15 025 up-regulated and 15 547 down-regulated genes were identified in Guijiao 69 compared to the common variety Zhen 01. (2) GO classification results showed that 20 287 DEGs were annotated. In addition, 21 600 DEGs were involved in 133 KEGG pathways. Among them, genes encoding the key enzymes related to volatile oil synthesis such as linalool synthase, myrcene synthase, geranyl geranyl pyrophosphate synthase, cinnamoyl CoA reductase, caffeic acid 3-O-methyltransferase and cinnamyl alcohol dehydrogenase were differentially expressed and enriched in monoterpene biosynthesis pathway, terpene skeleton biosynthesis pathway and phenylpropanoid biosynthesis pathway. (3) Transcription factor analysis showed that the DEGs were distributed in 31 transcription factor families, of which MYB family had the most Unigenes. In this study, transcriptome sequencing was performed to analyze the DEGs superior clones and common varieties of I. verum as well as their related functions and pathways. The candidate genes obtained provide the references for further exploring the synthesis mechanism of characteristic components of volatile oil and molecular breeding of I. verum.

A fast and efficient recognition method of transgenic lines will greatly improve detection efficiency and reduce cost. In this study, we successfully identified the transgenic soybean plants by the color. We isolated a GmW1 gene encoding a flavonoid 3′5′-hydroxylase from a soybean cultivar ZH42 (purple flower). We found that purple flowers occurred in the overexpression lines in the Jack and Williams 82 backgrounds (white flower). All plants with purple flowers were positive, and this trait seems stably inherited in the offspring. We have also obtained the editing plants, which were classified into three types according to the different flower colors appeared. We analyzed the phenotype and the homozygous types of the T1 mutants. We also found that a correspondence between flower color and stem color. This study provides a visible color reporter on soybean transformation. It can be quickly and early to identify the transgenic soybean plants by stem color of seedlings, which substantially reduces the amount of labor and cost.

Sleep benefits the restoration of energy metabolism and thereby supports neuronal plasticity and cognitive behaviors. Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes. The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation (CSD). We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex (PrL). We then assessed cerebral functional connectivity (FC) using resting-state functional MRI, neuron/astrocyte metabolism using a metabolic kinetics analysis; dendritic spine densities using sparse-labeling; and miniature excitatory postsynaptic currents (mEPSCs) and action potential (AP) firing rates using whole-cell patch-clamp recordings. In addition, we evaluated cognition via a comprehensive set of behavioral tests. Compared with controls, Sirt6 was significantly decreased (P < 0.05) in the PrL after CSD, accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus, piriform cortex, motor cortex, somatosensory cortex, olfactory tubercle, insular cortex, and cerebellum. Sirt6 overexpression reversed CSD-induced cognitive impairment and reduced FC. Our analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4 and GABA2 synthesis, which could be fully restored via forced Sirt6 expression. Furthermore, Sirt6 overexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons. These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network, neuronal glucose metabolism, and glutamatergic neurotransmission. Thus, Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.

Ti3SiC2/Al2O3 composites have attracted attention due to their excellent mechanical and electromagnetic properties, but the high temperatures (≥ 1400 ℃) required for the densification of aluminum oxide (Al2O3) leads to the decomposition of Ti3SiC2. To address this issue, Ti3(SixAl1−x)C2/Al2O3 (x represents the Si content) composites were synthesized for the first time via hot-pressing (HP) sintering and current-assisted sintering (CAS) of mixed Ti3AlC2 and silicon monoxide (SiO) powders at 1300 and 1200 ℃, respectively. Both approaches produced composites with x values greater than 0.9, indicating that the compositions of the prepared composites were similar to those of Ti3SiC2/Al2O3 composites. The synthetic mechanism involved substitution and continuous interdiffusion of Al and Si atoms. The composite prepared by CAS at 1200 ℃ was compacted, whereas the composite prepared by HP had a low density. The low-temperature densification mechanism is attributed to the combined effects of amorphous SiO, liquid Al, and the high heating rates for CAS. The flexural strength and hardness of the composite prepared by CAS were also comparable to those of compacted Ti3SiC2/Al2O3 composites.

Abstract Objectives Immunoglobulin-G4-related disease (IgG4-RD) is a distinct systemic autoimmune-mediated disease manifesting as chronic inflammation and tissue fibrosis. Since the role of DNA methylation in the pathogenesis of IgG4-RD is still unclear, we conduct this study to investigate epigenetic modifications in IgG4-RD. Methods A genome-wide DNA methylation study was conducted with B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients and matched controls by using the Illumina HumanMethylation 850K BeadChip. We further performed pyrosequencing and immunohistochemistry assays to validate the methylation status of some targets of interest. Results We identified differentially methylated CpG sites including 44 hypomethylated and 166 hypermethylated differentially methylated probes (DMPs) in B cells and 260 hypomethylated and 112 hypermethylated DMPs in CD4+ T cells from 10 IgG4-RD patients compared with 10 healthy controls. We also identified 36945 hypomethylated and 78380 hypermethylated DMPs in salivary gland tissues of 4 IgG4-RD patients compared with 4 controls. DPM2 (cg21181453), IQCK (cg10266221), and ABCC13 (cg05699681, cg04985582) were hypermethylated and MBP (cg18455083) was hypomethylated in B cells, CD4+ T cells, and salivary gland tissues of IgG4-RD patients. We also observed the hypomethylated HLA-DQB2 in CD4+ T cells from IgG4-RD patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DMPs in salivary gland tissues of IgG4-RD patients revealed enrichment of pathways involved in the regulation of immune cell responses and fibrosis. Conclusion This is the first DNA methylation study in peripheral B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients. Our findings highlighted the role of epigenetic modification of DNA methylation and identified several genes and pathways possibly involved in IgG4-RD pathogenesis.

Abstract Background Somatic embryogenesis (SE) was recognized as an important tool for plants to propagate. However, our knowledge about the proteins involved in early SE including the callus dedifferentiation is still limited, especially in the economic woody tree – Eucalyptus. Results We used the data-independent acquisition mass-spectrometry to study the different proteome profiles of early SE of two Eucalyptus species—E. camaldulensis (high regeneratively potential) and E. grandis x urophylla (low regenerative potential). Initially, 35,207 peptides and 7,077 proteins were identified in the stem and tissue-culture induced callus of the two Eucalyptus species. MSstat identified 2,078 and 2,807 differentially expressed proteins (DEPs) in early SE of E. camaldulensis and E. grandis x urophylla, respectively. They shared 760 upregulated and 420 downregulated proteins, including 4 transcription factors, 31 ribosomal proteins, 1 histone, 3 zinc finger proteins (ZFPs), 16 glutathione transferases, 10 glucosyltransferases, ARF19, WOX8 and PIN1. These proteins might be involved in the early SE of Eucalyptus. By combining the miRNA and RNA-Seq results, some miRNA ~ gene/protein regulatory networks were identified in early SE of Eucalyptus, such as miR160 ~ TPP2, miR164 ~ UXS2, miR169 ~ COX11 and miR535 ~ Eucgr.E01067. Further, we found SERK, WRKY, ZFP and ABC transporter might be related with high SE potential. Conclusions Overall, our study identified proteins involved in the early SE and related to the high regeneration potential of Eucalyptus. It greatly enhanced our understanding of the early SE and the SE capacity of Eucalyptus.

BBIBP-CorV exerts efficient protection against SARS-CoV-2 infection. However, waning vaccine-induced humoral immune responses after two-dose vaccination have significantly undermined durable immuno-protection. In this study, we have demonstrated that although anti-spike (S) antibody responses in BBIBP-CorV vaccinees exhibited three serotypes after 6 months, including de novo sero-negative, sero-positive, and sero-decay features, S-specific interferon-γ release as well as Th1 cytokine production in CD4+ and CD8+ T cells were comparable, especially in vaccinees without detectable neutralizing antibodies. Notably, regardless of dramatic increases in humoral immunity after booster vaccination, T cell responses targeting S protein from either wild type or Omicron remained stable before and after booster vaccination in all three serotype vaccinees. No severe cases were observed even in the sero-decay group during the Omicron epidemic in Shanghai. Our results thus illustrate that unlike fluctuating humoral responses, viral-specific T cell responses are extremely stable after booster vaccination. Sustained T cell responses might be dedicated to the rapid restoration of antibody responses after booster vaccination.

Antigen-specific immune tolerance, which possesses great potential in preventing or curing type 1 diabetes mellitus (T1DM), can be induced by oral vaccination with T1DM-related autoantigens. However, direct administration of autoantigens via oral route exhibits a low tolerance-inducing effect as a result of the digestion of protein antigens in the gastrointestinal tract (GIT) and therefore, a large dosage of autoantigens may be needed. In this study, bacterium-like particles (BLPs) made from food-grade lactic acid bacteria were used to deliver the intracellular domain of the insulinoma-associated protein 2 (IA-2ic). For this purpose, BLPs-IA-2ic vaccine in which IA-2ic bound to the surface of BLPs was constructed. BLPs enhanced the stability of the delivered IA-2ic based on the stability analysis in vitro. Oral administration of BLPs-IA-2ic significantly reduced T1DM incidence in NOD mice. The mice fed BLPs-IA-2ic exhibited a significant reduction in insulitis and preserved the ability to secrete insulin. Immunologic analysis showed that oral vaccination with BLPs-IA-2ic induced antigen-specific T cell tolerance. The results revealed that the successful induction of immune tolerance was dependent on the immune deviation (in favor of T helper 2 responses) and CD4+CD25+FoxP3+ regulatory T cells. Hence, oral vaccination with BLPs-IA-2ic shows potential for application in preventing T1DM.