Identification of high-functioning autism spectrum disorders based on gray-white matter functional network connectivity.

In the field of autism spectrum disorder (ASD), research on functional connectivity between gray matter and white matter remains under-researched. To address this gap, this study innovatively introduced a nested cross-validation method that integrates gray-white matter functional connectivity with an F-Score algorithm. This method calculates the correlation based on signals extracted from functional magnetic resonance imaging data using gray matter and white matter brain region templates. After applying the method to a New York University Langone Medical Center dataset consisting of 55 individuals with high-functioning ASD and 52 healthy subjects, we achieved a classification accuracy of 72.94%. This study found abnormal functional connectivity, primarily involving the left anterior prefrontal cortex and right superior corona radiata, left retrosplenial cortex and left superior corona radiata, as well as the left ventral anterior cingulate cortex and body of corpus callosum. Besides, we discovered that these abnormal connections are closely related to social impairment and restrictive and repetitive behaviors in ASD. In conclusion, this study provides a gray-white matter functional connectivity perspective for the diagnosis and understanding of ASD.

Effect of Different Dietary Iron Contents on Liver Transcriptome Characteristics in Wujin Pigs.

Iron is an important trace element that affects the growth and development of animals and regulates oxygen transport, hematopoiesis, and hypoxia adaptations. Wujin pig has unique hypoxic adaptability and iron homeostasis; however, the specific regulatory mechanisms have rarely been reported. This study randomly divided 18 healthy Wujin piglets into three groups: the control group, supplemented with 100 mg/kg iron (as iron glycinate); the low-iron group, no iron supplementation; and the high-iron group, supplemented with 200 mg/kg iron (as iron glycinate). The pre-feeding period was 5 days, and the formal period was 30 days. Serum was collected from empty stomachs before slaughter and at slaughter to detect changes in the serum iron metabolism parameters. Gene expression in the liver was analyzed via transcriptome analysis to determine the effects of low- and high-iron diets on transcriptome levels. Correlation analysis was performed for apparent serum parameters, and transcriptome sequencing was performed using weighted gene co-expression network analysis to reveal the key pathways underlying hypoxia regulation and iron metabolism. The main results are as follows. (1) Except for the hypoxia-inducible factor 1 (HIF-1) content (between the low- and high-iron groups), significant differences were not observed among the serum iron metabolic parameters. The serum HIF-1 content of the low-iron group was significantly higher than that of the high-iron group (p < 0.05). (2) Sequencing analysis of the liver transcriptome revealed 155 differentially expressed genes (DEGs) between the low-iron and control groups, 229 DEGs between the high-iron and control groups, and 279 DEGs between the low- and high-iron groups. Bioinformatics analysis showed that the HIF-1 and transforming growth factor-beta (TGF-ß) signaling pathways were the key pathways for hypoxia regulation and iron metabolism. Four genes were selected for qPCR validation, and the results were consistent with the transcriptome sequencing data. In summary, the serum iron metabolism parameter results showed that under the influence of low- and high-iron diets, Wujin piglets maintain a steady state of physiological and biochemical indices via complex metabolic regulation of the body, which reflects their stress resistance and adaptability. The transcriptome results revealed the effects of low-iron and high-iron diets on the gene expression level in the liver and showed that the HIF-1 and TGF-ß signaling pathways were key for regulating hypoxia adaptability and iron metabolism homeostasis under low-iron and high-iron diets. Moreover, HIF-1α and HEPC were the key genes. The findings provide a theoretical foundation for exploring the regulatory pathways and characteristics of iron metabolism in Wujin pigs.

Surface Reconstruction of High-Voltage LiNi0.5Mn1.5O4 Cathode via the Sculpture Method toward Enhanced Stability.

High-voltage LiNi0.5Mn1.5O4 (LNMO) cathodes suffer from severe capacity degradation during long-term cycling due the manganese dissolution and their high operating voltage (∼4.95 V), which pose serious challenges at the surface or interface. Moreover, both traditional ion-doping and passivation layer coating are difficult to apply consistently to LNMO cathode because of their complicated procedures, especially in large-scale production. To address these issues, a strategy employing HNO3/H2O2 leaching in synergy with a sintering process at a mid-temperature of 700 °C was used to achieve selective surface reconstruction. An optimal ratio of reactants was applied to balance the capacity and the cyclic stability of the LNMO cathode. The optimized valence composition of Mn on the material surface mitigates the occurrence of Jahn-Teller distortion, accompanied by a reasonable ratio of ordered and disordered phases and the concentration of oxygen vacancies after sintering, which improves the interface behavior between the electrode and electrolyte. This method delivers a high reversible capacity of 116.5 mAh g-1 after 200 cycles at 0.5 C (1 C = 147 mAh g-1) with a capacity retention of 91.30% and 110 mAh g-1 with a remarkably high capacity retention of 86.85% after 500 cycles at 2 C. This balanced approach, utilizing the protective effects of oxidation (O22-) and the erosive action of acid (H+), is proposed to achieve regional surface reconstruction of advanced LNMO cathode. This opens up a strategy for improving oxide-based cathode materials with low cost and mass production capability, especially favoring high consistency.

HSDF: Hybrid Sign and Distance Field for Neural Representation of Surfaces with Arbitrary Topologies.

Neural implicit function based on signed distance field (SDF) has achieved impressive progress in reconstructing 3D models with high fidelity. However, such approaches can only represent closed surfaces. Recent works based on unsigned distance function (UDF) are proposed to handle both watertight and single-layered open surfaces. Nonetheless, as UDF is signless, its direct output is limited to the point cloud, which imposes an additional challenge on extracting high-quality meshes from discrete points. To address this challenge, we present a novel neural implicit representation coded HSDF, which is a hybrid of signed and unsigned distance fields. In particular, HSDF is able to represent arbitrary topologies containing both closed and open surfaces while being compatible with existing iso-surface extraction techniques for easy field-to-mesh conversion. In addition to predicting a UDF, we propose to learn an additional sign field. Unlike traditional SDF, HSDF is able to locate the surface of interest before level surface extraction by generating surface points following NDF [1]. We are then able to obtain open surfaces via an adaptive meshing approach that only instantiates regions containing surfaces into a polygon mesh. HSDF benefits downstream tasks like neural rendering, as it enables the rendering of back-faces of open surfaces. We also propose HSDF-Net, a dedicated learning framework that factorizes the learning of HSDF into two easier sub-problems. Experiments and evaluations show that HSDF outperforms the state-of-the-art techniques both qualitatively and quantitatively on some of the used datasets.

FAT1 as a tumor mutation burden specific gene affects the immunotherapy effect in head and neck squamous cell cancer.

BACKGROUND: Response to immunotherapy is the main challenge of head and neck squamous cancer (HNSCC) treatment. Previous studies have indicated that tumor mutational burden (TMB) is associated with prognosis, but it is not always a precise index. Hence, investigating specific genetic mutations and tumor microenvironment (TME) changes in TMB-high patients is essential for precision therapy of HNSCC. METHODS: A total of 33 HNSCC patients were enrolled in this study. We calculated the TMB score based on next-generation sequencing (NGS) sequencing and grouped these patients based on TMB score. Then, we examined the immune microenvironment of HNSCC using assessments of the bulk transcriptome and the single-cell RNA sequence (scRNA-seq) focusing on the molecular nature of TMB and mutations in HNSCC from our cohort. The association of the mutation pattern and TMB was analyzed in The Cancer Genome Atlas (TCGA) and validated by our cohort. RESULTS: 33 HNSCC patients were divided into three groups (TMB-low, -medium, and -high) based on TMB score. In the result of 520-gene panel sequencing data, we found that FAT1 and LRP1B mutations were highly prevalent in TMB-high patients. FAT1 mutations are associated with resistance to immunotherapy in HNSCC patients. This involves many metabolism-related pathways like RERE, AIRE, HOMER1, etc. In the scRNA-seq data, regulatory T cells (Tregs), monocytes, and DCs were found mainly enriched in TMB-high samples. CONCLUSION: Our analysis unraveled the FAT1 gene as an assistant predictor when we use TMB as a biomarker of drug resistance in HNSCC. Tregs, monocytes, and dendritic cells (DCs) were found mainly enriched in TMB-high samples.

Osteoking prevents bone loss and enhances osteoblastic bone formation by modulating the AGEs/IGF-1/ß-catenin/OPG pathway in type 2 diabetic db/db mice.

Type 2 diabetic osteoporosis (T2DOP) is a skeletal metabolic syndrome characterized by impaired bone remodeling due to type 2 diabetes mellitus, and there are drawbacks in the present treatment. Osteoking (OK) is widely used for treating fractures and femoral head necrosis. However, OK is seldom reported in the field of T2DOP, and its role and mechanism of action need to be elucidated. Consequently, this study investigated whether OK improves bone remodeling and the mechanisms of diabetes-induced injury. We used db/db mice as a T2DOP model and stimulated MC3T3-E1 cells (osteoblast cell line) with high glucose (HG, 50 mM) and advanced glycation end products (AGEs, 100 µg/mL), respectively. The effect of OK on T2DOP was assessed using a combined 3-point mechanical bending test, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay. The effect of OK on enhancing MC3T3-E1 cell differentiation and mineralization under HG and AGEs conditions was assessed by an alkaline phosphatase activity assay and alizarin red S staining. The AGEs/insulin-like growth factor-1(IGF-1)/ß-catenin/osteoprotegerin (OPG) pathway-associated protein levels were assayed by western blot analysis and immunohistochemical staining. We found that OK reduced hyperglycemia, attenuated bone damage, repaired bone remodeling, increased tibial and femoral IGF-1, ß-catenin, and OPG expression, and decreased receptor activator of nuclear kappa B ligand and receptor activator of nuclear kappa B expression in db/db mice. Moreover, OK promoted the differentiation and mineralization of MC3T3-E1 cells under HG and AGEs conditions, respectively, and regulated the levels of AGEs/IGF-1/ß-catenin/OPG pathway-associated proteins. In conclusion, our results suggest that OK may lower blood glucose, alleviate bone damage, and attenuate T2DOP, in part through activation of the AGEs/IGF-1/ß-catenin/OPG pathway.

Enhancing Dengue Virus Production and Immunogenicity with Celcradle™ Bioreactor: A Comparative Study with Traditional Cell Culture Methods.

The dengue virus, the primary cause of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, is the most widespread mosquito-borne virus worldwide. In recent decades, the prevalence of dengue fever has increased markedly, presenting substantial public health challenges. Consequently, the development of an efficacious vaccine against dengue remains a critical goal for mitigating its spread. Our research utilized Celcradle™, an innovative tidal bioreactor optimized for high-density cell cultures, to grow Vero cells for dengue virus production. By maintaining optimal pH levels (7.0 to 7.4) and glucose concentrations (1.5 g/L to 3.5 g/L) during the proliferation of cells and viruses, we achieved a peak Vero cell count of approximately 2.46 × 109, nearly ten times the initial count. The use of Celcradle™ substantially decreased the time required for cell yield and virus production compared to conventional Petri dish methods. Moreover, our evaluation of the immunogenicity of the Celcradle™-produced inactivated DENV4 through immunization of mice revealed that sera from these mice demonstrated cross-reactivity with DENV4 cultured in Petri dishes and showed elevated antibody titers compared to those from mice immunized with virus from Petri dishes. These results indicate that the dengue virus cultivated using the Celcradle™ system exhibited enhanced immunogenicity relative to that produced in traditional methods. In conclusion, our study highlights the potential of the Celcradle™ bioreactor for large-scale production of inactivated dengue virus vaccines, offering significant promise for reducing the global impact of dengue virus infections and accelerating the development of effective vaccination strategies.

Ganoderma lucidum Polysaccharides Ameliorate Acetaminophen-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Apoptosis along the Nrf2 Pathway.

The excessive employment of acetaminophen (APAP) is capable of generating oxidative stress and apoptosis, which ultimately result in acute liver injury (ALI). Ganoderma lucidum polysaccharides (GLPs) exhibit hepatoprotective activity, yet the protective impact and potential mechanism of GLPs in relation to APAP-induced ALI remain ambiguous. The intention of this research was to scrutinize the effect of GLPs on APAP-induced ALI and to shed light on their potential mechanism. The results demonstrated that GLPs were capable of notably alleviating the oxidative stress triggered by APAP, as shown through a significant drop in the liver index, the activities of serum ALT and AST, and the amounts of ROS and MDA in liver tissue, along with an increase in the levels of SOD, GSH, and GSH-Px. Within these, the hepatoprotective activity at the high dose was the most conspicuous, and its therapeutic efficacy surpassed that of the positive drug (bifendate). The results of histopathological staining (HE) and apoptosis staining (TUNEL) indicated that GLPs could remarkably inhibit the necrosis of hepatocytes, the permeation of inflammatory cells, and the occurrence of apoptosis induced by APAP. Moreover, Western blot analysis manifested that GLPs enhanced the manifestation of Nrf2 and its subsequent HO-1, GCLC, and NQO1 proteins within the Nrf2 pathway. The results of qPCR also indicated that GLPs augmented the expression of antioxidant genes Nrf2, HO-1, GCLC, and NQO1. The results reveal that GLPs are able to set off the Nrf2 signaling path and attenuate ALI-related oxidative stress and apoptosis, which is a potential natural medicine for the therapy of APAP-induced liver injury.

[Anatomical study of the limited osteotomy suture button fixation Latarjet procedure with coracoacromial ligament preservation].

Objective: To investigate the morphological characteristics of the glenohumeral joint (including the glenoid and coracoid) in the Chinese population and determine the feasibility of designing coracoid osteotomy based on the preoperative glenoid defect arc length by constructing glenoid defect models and simulating suture button fixation Latarjet procedure. Methods: Twelve shoulder joint specimens from 6 adult cadavers donated voluntarily were harvested. First, whether the coracoacromial ligament and conjoint tendon connected was anatomically observed and their intersection point was identified. The vertical distance from the intersection point to the coracoid, the maximum allowable osteotomy length starting from the intersection point, and the maximum osteotomy angle were measured. Next, the anteroinferior glenoid defect models of different degrees were randomly constructed. The arc length and area of the glenoid defect were measured. Based on the arc length of the glenoid defect of the model, the size of coracoid oblique osteotomy was designed and the actual length and angle of the coracoid osteotomy were measured. A limited osteotomy suture button fixation Latarjet procedure with the coracoacromial ligament and pectoralis minor preservation was performed and the position of coracoid block was observed. Results: All shoulder joint specimens exhibited crossing fibers between the coracoacromial ligament and the conjoint tendon. The vertical distance from the tip of the coracoid to the coracoid return point was 24.8-32.2 mm (mean, 28.5 mm). The maximum allowable osteotomy length starting from the intersection point was 26.7-36.9 mm (mean, 32.0 mm). The maximum osteotomy angle was 58.8°-71.9° (mean, 63.5°). Based on the anteroinferior glenoid defect model, the arc length of the glenoid defect was 22.6-29.4 mm (mean, 26.0 mm); the ratio of glenoid defect was 20.8%-26.2% (mean, 23.7%). Based on the coracoid block, the length of the coracoid osteotomy was 23.5-31.4 mm (mean, 26.4 mm); the osteotomy angle was 51.3°-69.2° (mean, 57.1°). There was no significant difference between the arc length of the glenoid defect and the length of the coracoid osteotomy ( P>0.05). After simulating the suture button fixation Latarjet procedure, the highest points of the coracoid block (suture loop fixation position) in all models located below the optimal center point, with the bone block concentrated in the anteroinferior glenoid defect position. Conclusion: The size of the coracoid is generally sufficient to meet the needs of repairing larger glenoid defects. The oblique osteotomy with preserving the coracoacromial ligament may potentially replace the traditional Latarjet osteotomy method.

Neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective cohort study.

BACKGROUND: Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC. MATERIALS AND METHODS: Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. Disease-free survival (DFS) and overall survival (OS) rate were assessed. RESULTS: Our analysis involved 104 patients who received NACI. Notably, the pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1-2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%) and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive score (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3% versus 64.0%, respectively. CONCLUSIONS: The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.

Fluorescence molecular tomography based on an online maximum a posteriori estimation algorithm.

Fluorescence molecular tomography (FMT) is a non-invasive, radiation-free, and highly sensitive optical molecular imaging technique for early tumor detection. However, inadequate measurement information along with significant scattering of near-infrared light within the tissue leads to high ill-posedness in the inverse problem of FMT. To improve the quality and efficiency of FMT reconstruction, we build a reconstruction model based on log-sum regularization and introduce an online maximum a posteriori estimation (OPE) algorithm to solve the non-convex optimization problem. The OPE algorithm approximates a stationary point by evaluating the gradient of the objective function at each iteration, and its notable strength lies in the remarkable speed of convergence. The results of simulations and experiments demonstrate that the OPE algorithm ensures good reconstruction quality and exhibits outstanding performance in terms of reconstruction efficiency.

Heme Oxygenase-1 Gene (GT)n Polymorphism Linked to Deep White Matter Hyperintensities, Not Periventricular Hyperintensities.

BACKGROUND: Oxidative stress plays a principal role in the pathogenesis of white matter hyperintensities (WMHs). The induction of heme oxygenase-1 (HO-1) gene in the brain represents 1 of the pivotal mechanisms to counteract the noxious effects of reactive oxygen species, and the transcriptional modulation of HO-1 induction depends on the length of a GT-repeat (GT)n in the promoter region. We investigated whether the HO-1 gene (GT)n polymorphism is associated with the risk of WMHs. METHODS AND RESULTS: A total of 849 subjects from the memory clinic were consecutively enrolled, and the HO-1 (GT)n genotype was determined. WMHs were assessed with the Fazekas scale and further divided into periventricular WMHs and deep WMHs (DWMHs). Allelic HO-1 (GT)n polymorphisms were classified as short (≤24 (GT)n), median (25≤[GT]n<31), or long (31≤[GT]n). Multivariate logistic regression analysis was used to evaluate the effect of the HO-1 (GT)n variants on WMHs. The number of repetitions of the HO-1 gene (GT)n ranged from 15 to 39 with a bimodal distribution at lengths 23 and 30. The proportion of S/S genotypes was higher for moderate/severe DWMHs than none/mild DWMHs (22.22% versus 12.44%; P=0.001), but the association for periventricular WMHs was not statistically significant. Logistic regression suggested that the S/S genotype was significantly associated with moderate/severe DWMHs (S/S versus non-S/S: odds ratio, 2.001 [95% CI, 1.323-3.027]; P<0.001). The HO-1 gene (GT)n S/S genotype and aging synergistically contributed to the progression of DWMHs (relative excess risk attributable to interaction, 6.032 [95% CI, 0.149-11.915]). CONCLUSIONS: Short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from DWMHs, but not periventricular WMHs. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100045869.

MRI-based deep learning and radiomics for prediction of occult cervical lymph node metastasis and prognosis in early-stage oral and oropharyngeal squamous cell carcinoma: a diagnostic study.

INTRODUCTION: The incidence of occult cervical lymph node metastases (OCLNM) is reported to be 20-30% in early-stage oral cancer and oropharyngeal cancer. There is a lack of an accurate diagnostic method to predict occult lymph node metastasis and to help surgeons make precise treatment decisions. AIM: To construct and evaluate a preoperative diagnostic method to predict OCLNM in early-stage oral and oropharyngeal squamous cell carcinoma (OC and OP SCC) based on deep learning features (DLFs) and radiomics features. METHODS: A total of 319 patients diagnosed with early-stage OC or OP SCC were retrospectively enrolled and divided into training, test and external validation sets. Traditional radiomics features and DLFs were extracted from their MRI images. The least absolute shrinkage and selection operator (LASSO) analysis was employed to identify the most valuable features. Prediction models for OCLNM were developed using radiomics features and DLFs. The effectiveness of the models and their clinical applicability were evaluated using the area under the curve (AUC), decision curve analysis (DCA), and survival analysis. RESULTS: Seventeen prediction models were constructed. The Resnet50 deep learning (DL) model based on the combination of radiomics and DL features achieves the optimal performance, with AUC values of 0.928 (95% CI: 0.881-0.975), 0.878 (95% CI: 0.766-0.990), 0.796 (95% CI: 0.666-0.927), and 0.834 (95% CI: 0.721-0.947) in the training, test, external validation set1, and external validation set2, respectively. Moreover, the Resnet50 model has great prediction value of prognosis in patients with early-stage OC and OP SCC. CONCLUSION: The proposed MRI-based Resnet50 DL model demonstrated high capability in diagnosis of OCLNM and prognosis prediction in the early-stage OC and OP SCC. The Resnet50 model could help refine the clinical diagnosis and treatment of the early-stage OC and OP SCC.

Applying Red Mud in Cadmium Contamination Remediation: A Scoping Review.

Red mud is an industrial solid waste rarely utilized and often disposed of in landfills, resulting in resource waste and environmental pollution. However, due to its high pH and abundance of iron and aluminum oxides and hydroxides, red mud has excellent adsorption properties which can effectively remove heavy metals through ion exchange, adsorption, and precipitation. Therefore, red mud is a valuable resource rather than a waste byproduct. In recent years, red mud has been increasingly studied for its potential in wastewater treatment and soil improvement. Red mud can effectively reduce the migration and impact of heavy metals in soils and water bodies. This paper reviews the research results from using red mud to mitigate cadmium pollution in water bodies and soils, discusses the environmental risks of red mud, and proposes key research directions for the future management of red mud in cadmium-contaminated environments.

Combined miRNA and mRNA sequencing reveals the defensive strategies of resistant YHY15 rice against differentially virulent brown planthoppers.

Introduction: The brown planthopper (BPH) poses a significant threat to rice production in Asia. The use of resistant rice varieties has been effective in managing this pest. However, the adaptability of BPH to resistant rice varieties has led to the emergence of virulent populations, such as biotype Y BPH. YHY15 rice, which carries the BPH resistance gene Bph15, exhibits notable resistance to biotype 1 BPH but is susceptible to biotype Y BPH. Limited information exists regarding how resistant rice plants defend against BPH populations with varying levels of virulence. Methods: In this study, we integrated miRNA and mRNA expression profiling analyses to study the differential responses of YHY15 rice to both avirulent (biotype 1) and virulent (biotype Y) BPH. Results: YHY15 rice demonstrated a rapid response to biotype Y BPH infestation, with significant transcriptional changes occurring within 6 hours. The biotype Y-responsive genes were notably enriched in photosynthetic processes. Accordingly, biotype Y BPH infestation induced more intense transcriptional responses, affecting miRNA expression, defenserelated metabolic pathways, phytohormone signaling, and multiple transcription factors. Additionally, callose deposition was enhanced in biotype Y BPH-infested rice seedlings. Discussion: These findings provide comprehensive insights into the defense mechanisms of resistant rice plants against virulent BPH, and may potentially guide the development of insect-resistant rice varieties.

Access Polyarylbipyrazoles via Palladium-Catalysis and Visible-Light-Driven C(sp3)-P(V) Cleavage Relay Strategy.

An unprecedented palladium-catalyzed and visible-light-driven relay reaction of allenylphosphine oxide with in situ generated nitrile imines is presented for the direct synthesis of highly valuable polyarylbipyrazole skeletons. This one-pot strategy involves double 1,3-dipolar cycloaddition and C(sp3)-P(V) bond cleavage under photocatalyst-free and mild reaction conditions. The approach features simple operation, a high step economy, and a broad substrate scope, affording the corresponding products in moderate to excellent yields.

First Report of Paramyrothecium breviseta Causing Target Spot on Amorphophallus muelleri in Yunnan, China.

Amorphophallus muelleri is an Araceae plant with perennial tuber, widely used in food, pharmaceutical and chemical industry due to its richness in glucomannan. In April 2022, an outbreak of a target spot on A. muelleri plantlets was observed in a nursery in Ruili, Yunnan, China. The leafstalks of the diseased plantlets in the nursery turned brown and decayed (Fig.1 A-B), then gradually some water-soaked spots on the true leaves developed along the veins (Fig.1 A). Subquencely, the spots on the true leaves turned dark green to white-grayish in the center, which formed light to dark brown concentric rings with a target-like appearance surrounded by a yellow halo (Fig.1 C). When the temperature was 20-34℃ and the relatively humidity was 25-80%, dark-green to black sporodochia with white hypha appeared on the lower and upper leaf surfaces. Finally, 5-8% of the plants surveyed on 800 m2 of one-year-old plantlets in the nursery showed the symptoms and some plants with infected leafstalks would be death. Similar symptoms were also observed on about 10% of the transplanted plants surveyed on 12000 m2 (1.2 ha) of two-year-old plantlets in the field. Five diseased leaves from five distinct plantlets in the nursery were collected for pathogen isolation. Leaf pieces(5 x 5 mm) were cut from the edge of necrotic lesions, and surface-sterilized with 2.5% sodium hypochlorite for 1 min, 75% ethanol for 30 s, then rinsed 5 times by sterilized distilled water, finally put the leaf pieces on sterilized filter paper for 3-5 minutes to dry them and transferred onto potato dextrose agar (PDA) in petri dishes at 25℃ for three days. Five pure cultures identical to colony and conidial characteristics were isolated from five individual plants. The representative pure culture (M1) was grayish-white and circular colonies were 7.50 cm in diamter after 15 days at 25℃, with dark green concentric rings of sporodochia, the dorsal view of the colonies were yellowish. Conidia were aseptate, smooth, cylindrical, 5.00-6.25 (5.71) x 1.25-1.67 (1.63) µm (n = 20) rounded at both ends. A spore suspension (1 x 106 spores/ml) was prepared by harvesting spores from 15-day-old cultures grown in the dark at 25℃, then a thirty-ml of spore suspension was sprayed on the healthy leaves of 10 two-year-old plantlets. Thirty-ml of sterile water was sprayed on the healthy leaves of another 10 seedlings and used as the control. All seedlings were placed in a nursery at 20 to 34℃ and a relative humidity of 25 to 80%. Similar symptoms (Fig.1 D-F) to those observed in the nursery and field developed on all the 10 seedlings inoculated with M1 after two days, but not on the control leaves. The pathogenicity tests were repeated for three times. Fungal cultures reisolated from the infected leaves were identical to the original colonies and conidia, completing Koch's postulates. The internal transcribed spacer (ITS, primers ITS1 and ITS4) region of ribosomal DNA (OQ553785), calmodulin (cmdA, primers CAL-228F and CAL2Rd)(OQ559103), RNA polymerase II second largest subunit (rpb2, primers RPB2-5F2 and RPB2-7cR) (OQ559104) and ß-tubulin (tub2, primers Bt2a and Bt2b) (OQ559105) of M1 had 100%, 98.52%, 98.98% and 98.98% identity with the sequences of Paramyrothecium breviseta CBS544.75 (KU846289 for ITS, KU846262 for cmdA, KU846351 for rpb2, and KU846406 for tub2), respectively. In the phylogenic tree based on ITS, cmdA, rpb2 and tub2 gene sequences, the pure culture M1 clustered with P. breviseta CBS544.75, SDBR-CMU387, DRL4 and DRL3, which has been reported as the pathogen of leaf spot of Coffea arabica in China, C. canephora in China and Thailand (Wu et al. 2021; Withee et al. 2022). Molecular and morphological observations showed the pure culture M1 were P. breviseta (Withee et al. 2022), in addition the disease was named as target spot dueing to the typical target symptom on the leaves. To our knowledge, this is the first report of P. breviseta on A. muelleri from Yunnan, China, as well as worldwide. This disease can caused serious economic losses of A. muelleri dueing to that it can result 5-8% death of the plants in the nursery.

Enhancement of SARS-CoV-2 mRNA Vaccine Efficacy through the Application of TMSB10 UTR for Superior Antigen Presentation and Immune Activation.

The development of effective vaccines against SARS-CoV-2 remains a critical challenge amidst the ongoing global pandemic. This study introduces a novel approach to enhancing mRNA vaccine efficacy by leveraging the untranslated region (UTR) of TMSB10, a gene identified for its significant mRNA abundance in antigen-presenting cells. Utilizing the GEO database, we identified TMSB10 among nine genes, with the highest mRNA abundance in dendritic cell subtypes. Subsequent experiments revealed that TMSB10's UTR significantly enhances the expression of a reporter gene in both antigen-presenting and 293T cells, surpassing other candidates and a previously optimized natural UTR. A comparative analysis demonstrated that TMSB10 UTR not only facilitated a higher reporter gene expression in vitro but also showed marked superiority in vivo, leading to enhanced specific humoral and cellular immune responses against the SARS-CoV-2 Delta variant RBD antigen. Specifically, vaccines incorporating TMSB10 UTR induced significantly higher levels of specific IgG antibodies and promoted a robust T-cell immune response, characterized by the increased secretion of IFN-γ and IL-4 and the proliferation of CD4+ and CD8+ T cells. These findings underscore the potential of TMSB10 UTR as a strategic component in mRNA vaccine design, offering a promising avenue to bolster vaccine-induced immunity against SARS-CoV-2 and, potentially, other pathogens.

Rapamycin facilitates healing of the tendon-bone interface in an aging rat model of chronic rotator cuff injury.

BACKGROUND: Tendon-bone interface (TBI) healing in chronic rotator cuff injury (CRCI) in older individuals is a common clinical challenge due to cellular senescence, as well as decreased tissue repair and regeneration. Many studies have demonstrated the antiaging, improved tissue repair, and bone regeneration properties of rapamycin (RPM) in multiple age-related diseases. This study aimed to explore the effects of RPM on TBI healing after CRCI in an aging rat model. METHODS: A CRCI model was established in 60 Sprague-Dawley rats (24 months old). Rats were then randomly allocated into the control, 0.1 µg RPM, and 1 µg RPM groups. At 4 and 8 weeks postreconstructive surgery, the supraspinatus tendon-humerus complexes were harvested for biomechanical, microimaging, histological, and immunohistochemical evaluations. RESULTS: Biomechanical testing results demonstrated that the failure load, ultimate strength, and stiffness of the 2 RPM groups were significantly higher than those of the control group at 4 and 8 weeks postoperatively. Microradiographically, both RPM groups had significantly higher values of bone mineral density and the ratio of trabecular bone volume to total volume than controls at each time point. Moreover, the RPM groups had higher histological scores and showed better regenerated TBI, characterized by better organizational tissue, more fibrocartilage cells, and more bone formation. Immunohistochemical evaluations showed that RUNX2-, SOX9-, and SCX-positive cells were significantly more in the 2 RPM groups than in the controls at each time point. CONCLUSIONS: RPM may effectively enhance CRCI healing after reconstruction by facilitating osteogenesis, tenogenesis, and fibrocartilage reformation at the TBI, as well as improving biomechanical properties.

Robust reactive oxygen species modulator hitchhiking yeast microcapsules for colitis alleviation by trilogically intestinal microenvironment renovation.

Ulcerative colitis (UC) is characterized by chronic inflammatory processes of the intestinal tract of unknown origin. Current treatments lack understanding on how to effectively alleviate oxidative stress, relieve inflammation, as well as modulate gut microbiota for maintaining intestinal homeostasis synchronously. In this study, a novel drug delivery system based on a metal polyphenol network (MPN) was constructed via metal coordination between epigallocatechin gallate (EGCG) and Fe3+. Curcumin (Cur), an active polyphenolic compound, with distinguished anti-inflammatory activity was assembled and encapsulated into MPN to generate Cur-MPN. The obtained Cur-MPN could serve as a robust reactive oxygen species modulator by efficiently scavenging superoxide radical (O2•-) as well as hydroxyl radical (·OH). By hitchhiking yeast microcapsule (YM), Cur-MPN was then encapsulated into YM to obtain CM@YM. Our findings demonstrated that CM@YM was able to protect Cur-MPN to withstand the harsh gastrointestinal environment and enhance the targeting and retention abilities of the inflamed colon. When administered orally, CM@YM could alleviate DSS-induced colitis with protective and therapeutic effects by scavenging ROS, reducing pro-inflammatory cytokines, and regulating the polarization of macrophages to M1, thus restoring barrier function and maintaining intestinal homeostasis. Importantly, CM@YM also modulated the gut microbiome to a favorable state by improving bacterial diversity and transforming the compositional structure to an anti-inflammatory phenotype as well as increasing the content of short-chain fatty acids (SCFA) (such as acetic acid, propionic acid, and butyric acid). Collectively, with excellent biocompatibility, our findings indicate that synergistically regulating intestinal microenvironment will be a promising approach for UC.