Dispersion leading potential energy surface of N2·NbN12-: Anion photoelectron spectroscopy and theoretical studies.

In order to understand the dispersion interactions between molecules and to provide information about the potential energy surface of geometry evolutions, NbN12- and N2·NbN12- complexes were investigated by using photoelectron spectroscopy and ab initio calculations. The experimental adiabatic detachment energy (ADE) and vertical detachment energy (VDE) of NbN12- were both measured to be 2.129 ± 0.030 eV. The experimental ADE and VDE of N2·NbN12- were measured to be 2.17 ± 0.05 and 2.23 ± 0.05 eV, respectively, which are slightly higher than those of NbN12-. The structures of NbN12-/0 were confirmed to be hexacoordinated octahedrons. The investigation of N2·NbN12- structures shows that it is stable for N2 to bind to the face or vertex site of octahedron NbN12-; the face-side-on structure has the lowest energy. The calculations based on symmetry-adapted perturbation theory suggest that the dispersion term is predominant and leads to the stability of N2·NbN12- complexes.

Intraductal papillary mucinous neoplasm of the bile duct with choledochoduodenal fistula: a case report and literature review.

Background: Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is a neoplastic disease of the bile duct with papillary hyperplasia and mucus secretion, which originates from the duct epithelium and rarely complicates with fistula formation. Case Description: The patient was admitted to the hospital due to abdominal pain and yellow skin. Laboratory results showed alanine aminotransferase 299 U/L, total bilirubin 350 µmol/L, computerized tomography showed severe dilatation of common bile duct and extrahepatic bile duct. Magnetic resonance cholangiopancreatography showed the intra- and extrahepatic bile ducts were markedly dilated, and the signal of the bile ducts was uneven. Endoscope identified a large amount of mucus above the papilla that flowing out from the fistula. Further cholangiography through the fistula showed significant dilatation of the extrahepatic bile duct. SpyGlass examination showed a large amount of gelatinous mucus in the bile duct lumen and "fish-scaly or coral" changes in the mucosa of the right anterior branch bile duct, hepatic hilum as well as lower common bile duct. IPMN-B with choledochoduodenal fistula was diagnosed. The patient was then discharged with nasal biliary drainage and biliary stenting, oral antipyretic and hepatoprotective drugs. The patient's biliary obstruction and symptoms of infection improved with medical treatment but recured. Unfortunately, the patient died 10 months after his first visit. Conclusions: SpyGlass has advantages in identifying the nature and extent of lesions, providing important references for diagnosis and treatment. Endoscopic intervention relieves biliary obstruction to some extent in patients with high operative risk or reluctance to undergo surgery.

Antimicrobial Isochroman-Derived Atropo-diastereomeric Dimers from Penicillium steckii SCISO 41228.

A pair of unidentified atropisomeric dimers, penicisteckins G (1) and H (2), and twelve known compounds (3-16) were isolated from the marine coral-derived fungus Penicillium steckii SCISO41228. Their structures including the absolute configuration were determined by HR-ESI-MS, ECD, 1D-, and 2D-NMR spectra. Compounds 1 and 2 exhibited potent antibacterial activity against most pathogenic strains, especially for MASA and Micrococcus luteus, with MIC values of 4.0 µg·mL-1. In addition, compounds 2 and 3 exhibit potent antioxidant activity with IC50 values of 10.76 and 8.66 µg·mL-1, respectively.

Different FeS Concentrations for Encapsulating ZIF-67 Nanomaterials toward the Enhanced Oxidation Evolution Reaction.

Due to the slow kinetic nature of the oxygen evolution reaction (OER), the development of electrocatalysts with high efficiency, stability, and economy for oxygen production using metal-organic framework (MOF) materials is still a challenging research topic. In this work, we chose the different concentrations of FeS adsorption to encapsulate metal cobalt-based ZIF-67 MOF for preparing a series of electrocatalysts (ZIF1FeSx, x = 0.2, 0.5, 0.75, and 1), which were mainly explored for the electrocatalytic OER. Among them, ZIF1FeS0.5 has excellent electrocatalytic activity for OER, which can be driven by low overpotentials of 276 and 349 mV at 10 and 50 mA cm-2 current densities, and more than 92% of the initial overpotential can be maintained after 100 h of continuous OER at 10 mA cm-2 current density. This is mainly due to the electronic interactions between the cobalt-based MOF and the FeS, which shift the electronic state of the active metal center to a higher valence state for increasing the number of active sites and enhancing the efficiency of electron transfer to facilitate the OER course. This work may contribute to the design of effective catalysts for the OER during the electrolysis of alkaline solutions.

Expert Consensus on Big Data Collection of Skin and Appendage Disease Phenotypes in Chinese.

The collection of big data on skin and appendage phenotypes has revolutionized the field of personalized diagnosis and treatment by enabling the evaluation of individual characteristics and early detection of abnormalities. To establish a standardized system for collecting and measuring big data on phenotypes, a systematic categorization of measurement entries has been undertaken, accompanied by recommendations on measurement entries, environmental equipment requirements, and collection processes, tailored to the needs of different usage scenarios. Specific collection sites have also been recommended based on different index characteristics. A multi-center, multi-regional collaboration has been initiated to collect big date on phenotypes of healthy and diseased skin in the Chinese population. This data will be correlated with patient disease information, exploring the factors influencing skin phenotype, analyzing the phenotypic data features that can predict prognosis, and ultimately promoting the exploration of the pathophysiology and pathogenesis of skin diseases and therapeutic approaches. Non-invasive skin measurement robots are also in development. This consensus aims to provide a reference for the study of phenomics and the standardization of phenotypic measurements of skin and appendages in China.

Efficacy of Azvudine Therapy in Patients with Severe and Non-Severe COVID-19: A Propensity Score-Matched Analysis.

Objective: Azvudine is used to treat patients with the coronavirus disease 2019 (COVID-19). This study evaluated the clinical efficacy of azvudine in hospitalized patients with different severities of COVID-19 because few studies have described this in patients with severe and non-severe COVID-19. Methods: This retrospective study included hospitalized patients with COVID-19 in Guizhou Provincial People's Hospital between December 2022 and January 2023. Azvudine-treated patients and controls were matched for sex, age, and disease severity at admission. Laboratory results and outcomes, including all-cause mortality, invasive mechanical ventilation, intensive care unit admission, and hospital stay length, were evaluated. Stratified analysis was used to explore the difference in the efficacy of azvudine in severe and non-severe COVID-19 patients. Results: No significant differences in all-cause mortality were observed between the 303 azvudine recipients and 303 matched controls. However, azvudine-treated patients had shorter hospital stays (8.34±4.79 vs 9.17±6.25 days, P=0.046) and higher lymphocyte improvement rates (21.5% vs 13.9%, P=0.019), with a more pronounced effect in patients with non-severe COVID-19 (length of hospital stay, 8.07±4.35 vs 10.00±6.29 days, P=0.001; lymphocyte improvement rate, 23.8% vs 12.8%, P=0.015). Conclusion: Azvudine treatment shortens hospital stay length and increases the rate of lymphocyte count improvement in patients with non-severe COVID-19, suggesting that azvudine may be a treatment option for these patients.

Dynamic Graph Regularized Broad Learning With Marginal Fisher Representation for Noisy Data Classification.

Broad learning system (BLS) is an effective neural network requiring no deep architecture, however it is somehow fragile to noisy data. The previous robust broad models directly map features from the raw data, which inevitably learn useless or even harmful features for data representation when the inputs are corrupted by noise and outliers. To address this concern, a discriminative and robust network named as dynamic graph regularized broad learning (DGBL) with marginal fisher representation is proposed for noisy data classification. Different from the previous works, DGBL eliminates the effect of noise before the random feature mapping by the proposed robust and dynamic marginal fisher analysis (RDMFA) algorithm. The RDMFA is able to extract more robust and informative representations for classification from the latent clean data space with dynamically generated graphs. Furthermore, the dynamic graphs learned from RDMFA are incorporated as regularization terms into the objective of DGBL to enhance the discrimination capacity of the proposed network. Extensive quantitative and qualitative experiments conducted on numerous benchmark datasets demonstrate the superiority of the proposed model compared to several state-of-the-art methods.

A Multicenter Cohort Study on Ultrasound-based Deep Learning Nomogram for Predicting Post-Neoadjuvant Chemotherapy Axillary Lymph Node Status in Breast Cancer Patients.

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the capability of an ultrasound (US)-based deep learning (DL) nomogram for predicting axillary lymph node (ALN) status after neoadjuvant chemotherapy (NAC) in breast cancer patients and its potential to assist radiologists in diagnosis. METHODS: Two medical centers retrospectively recruited 535 node-positive breast cancer patients who had undergone NAC. Center 1 included 288 patients in the training cohort and 123 patients in the internal validation cohort, while center 2 enrolled 124 patients for the external validation cohort. Five DL models (ResNet 34, ResNet 50, VGG19, GoogLeNet, and DenseNet 121) were trained on pre- and post-NAC US images, and the best model was chosen. A US-based DL nomogram was constructed using DL predictive probabilities and clinicopathological characteristics. Furthermore, the performances of radiologists were compared with and without the assistance of the nomogram. RESULT: ResNet 50 performed best among all DL models, achieving areas under the curve (AUCs) of 0.837 and 0.850 in the internal and external validation cohorts, respectively. The US-based DL nomogram demonstrated strong predictive ability for ALN status post-NAC, with AUCs of 0.890 and 0.870 in the internal and external validation cohorts, respectively, outperforming both the clinical model and the DL model (p all < 0.05, except p = 0.19 for DL model in external validation cohort). Moreover, the nomogram significantly improved radiologists' diagnostic ability. CONCLUSION: The US-based DL nomogram is promising for predicting ALN status post-NAC and could assist radiologists for better diagnostic performance.

RNALocate v3.0: Advancing the Repository of RNA Subcellular Localization with Dynamic Analysis and Prediction.

Subcellular localization of RNA is a crucial mechanism for regulating diverse biological processes within cells. Dynamic RNA subcellular localizations are essential for maintaining cellular homeostasis; however, their distribution and changes during development and differentiation remain largely unexplored. To elucidate the dynamic patterns of RNA distribution within cells, we have upgraded RNALocate to version 3.0, a repository for RNA-subcellular localization (http://www.rnalocate.org/ or http://www.rna-society.org/rnalocate/). RNALocate v3.0 incorporates and analyzes RNA subcellular localization sequencing data from over 850 samples, with a specific focus on the dynamic changes in subcellular localizations under various conditions. The species coverage has also been expanded to encompass mammals, non-mammals, plants and microbes. Additionally, we provide an integrated prediction algorithm for the subcellular localization of seven RNA types across eleven subcellular compartments, utilizing convolutional neural networks (CNNs) and transformer models. Overall, RNALocate v3.0 contains a total of 1 844 013 RNA-localization entries covering 26 RNA types, 242 species and 177 subcellular localizations. It serves as a comprehensive and readily accessible data resource for RNA-subcellular localization, facilitating the elucidation of cellular function and disease pathogenesis.

Inhibition of Ubiquitin C-Terminal Hydrolase L1 Facilitates Cutaneous Wound Healing via Activating TGF-ß/Smad Signalling Pathway in Fibroblasts.

Ubiquitin C-terminal hydrolase L1 (UCHL1) plays vital roles in cell proliferation, angiogenesis, inflammation and oxidative stress. Nevertheless, it is unclear whether UCHL1 could regulate the biologic behaviour of cells and ultimately influences wound healing. We aim to illustrate the roles and the underlying mechanism of UCHL1 in cutaneous wound healing. Murine full-thickness excisional wound model was utilised to study the effects of UCHL1 on wound healing through topical administration of the UCHL1 inhibitor LDN57444, followed by assessment of wound areas and histological alterations. Subsequently, ethynyldeoxyuridine, scratch and transwell assays were performed to examine fibroblast migration and proliferation. The extracellular matrix (ECM)-related genes expression and transforming growth factor-ß (TGF-ß)/Smad signalling pathways activation were investigated by immuno-fluorescent staining, Western blots and quantitative reverse transcription polymerase chain reaction. We identified elevated UCHL1 expression in non-healing wound tissues. The UCHL1 expression displayed a dynamic change and reached a peak on Day-7 post-wounding during the healing process in mice. Cutaneous administration of LDN57444 promoted wound healing by facilitating collagen deposition, myofibroblast activation and angiogenesis. In vitro experiments demonstrated that UCHL1 concentration dependently inhibited migration, ECM synthesis and activation of human dermal fibroblasts, which was mechanistically related to downregulation of TGF-ß/Smad signalling. Furthermore, these effects could be reversed by TGF-ß inhibitor SB431542. Our findings reveal that UCHL1 is a negative regulator of cutaneous wound healing and considered as a novel prospective therapeutic target for effective wound healing.

The detrimental effect of rainforest conversion to rubber plantations on soil dissolved organic carbon and C: N stoichiometry, mediated by altered soil biogeochemistry.

Rainforest conversion into rubber (Hevea brasiliensis) plantations (RP) alters global carbon cycling and contributes to climate change. However, the impact of this widespread tropical land use change on various elements of the carbon cycle is poorly understood. Here, we aimed to investigate the impact of rainforest conversion into RP on soil-dissolved organic carbon (DOC), one of the most mobile organic matter (OM) in the terrestrial ecosystem that causes the transformation and migration of C. We also explored the underlying edaphic factors regulating soil DOC changes. Our study sites were rubber monoculture, mixed-rubber plantations (H. brasiliensis, Ficus langkokensis, and Actinodaphne henryi), and a reference rainforest. We found that soil DOC concentration was 150-200% higher in RP than in rainforests, with an unchanged pattern across the seasons (dry and rainy) and plantation type. These results were concomitant with degradation in main soil properties, markedly including lower pH, electrical conductivity, SOC, available nitrogen, available phosphorus, total nitrogen (TN), and total phosphorus (TP), following the RP establishment and explicitly having a significant negative correlation with DOC. Our fitted structure equation model (SEM) highlights that RP caused accelerated DOC production and a higher DOC/DN ratio by decreasing SOC (38.5%) and nutrients (TN and TP). Further, the SEM revealed a significant negative correlation between microbial biomass C (MBC) and N (MBN) and the DOC/DN ratio, implying limited microbial degradation of DOC under RP. This is further supported by our findings of 81.1% lower MBC per unit DOC and 37.1% lower MBN per unit DN under RP compared to rainforests, indicating poor transformation of DOC to microbial biomass under RP. Collectively, our findings suggest that RP with high nutrient demands and altered soil properties lead to increased leaching of DOC due to its limited utilization by microbes. These findings underscore the importance of robust and sustainable soil management (such as optimizing plant density and legume intercropping) in RP to improve soil health and minimize DOC leaching and its potential environmental consequences.

Shared Genetic Architecture and Causal Relationship between Serum 25-Hydroxyvitamin D and Bone Mineral Density.

BACKGROUND: Despite the well-established regulatory role of vitamin D in maintaining bone health, little is known about the shared genetics and causality of the association between serum 25-hydroxyvitamin D (25OHD) and bone mineral density (BMD). METHODS: Leveraging individual-level data from the UK Biobank (UKB) cohort and summary-level data from the genome-wide association studies (GWASs) conducted on European individuals for serum 25OHD (N = 417,580) and estimated heel BMD (eBMD, N = 426,824), we systematically elucidated the shared genetic architecture underlying serum 25OHD and eBMD through a comprehensive genome-wide cross-trait design. RESULTS: Despite a lack of global genetic correlation (rg = -0.001, P = 0.95), a significant local signal was discovered at 5p11-5q11.9. Two-sample Mendelian randomization (MR) indicated no causal association in the overall population (ß = 0.003, 95% CI = -0.04∼0.03, P = 0.93), while positive causal effects were observed in males (ß = 0.005, 95% CI = 0.00∼0.01, P = 0.03) and the elderly (ß = 0.009, 95% CI = 0.00∼0.02, P = 0.01) according to one-sample MR. A total of 49 pleiotropic SNPs, with 4 novel SNPs (rs1077151, rs79873740, rs12150353, and rs4760401), were identified, and a total of 95 gene-tissue pairs exhibited overlap, predominantly enriched in the nervous, digestive, exo-/endocrine and cardiovascular systems. Protein-protein interaction analysis identified RPS9 and RPL7A as hub genes. CONCLUSIONS: This study illuminates the potential health benefits of enhancing serum 25OHD levels to mitigate the risk of osteoporosis among males and the elderly. It also unveils a shared genetic basis between serum 25OHD and eBMD, offering valuable insights into the intricate biological pathways.

Superior metabolic improvement of polycystic ovary syndrome traits after GLP1-based multi-agonist therapy.

Polycystic ovary syndrome (PCOS) is a heterogeneous condition, defined by oligo-/anovulation, hyper-androgenism and/or polycystic ovaries. Metabolic complications are common in patients suffering PCOS, including obesity, insulin resistance and type-2 diabetes, which severely compromise the clinical course of affected women. Yet, therapeutic options remain mostly symptomatic and of limited efficacy for the metabolic and reproductive alterations of PCOS. We report here the hormonal, metabolic and gonadal responses to the glucagon-like peptide-1 (GLP1)-based multi-agonists, GLP1/Estrogen (GLP1/E), GLP1/gastric inhibitory peptide (GLP1/GIP) and GLP1/GIP/Glucagon, in two mouse PCOS models, with variable penetrance of metabolic and reproductive traits, and their comparison with metformin. Our data illustrate the superior efficacy of GLP1/E vs. other multi-agonists and metformin in the management of metabolic complications of PCOS; GLP1/E ameliorates also ovarian cyclicity in an ovulatory model of PCOS, without direct estrogenic uterotrophic effects. In keeping with GLP1-mediated brain targeting, quantitative proteomics reveals changes in common and distinct hypothalamic pathways in response to GLP1/E between the two PCOS models, as basis for differential efficiency. Altogether, our data set the basis for the use of GLP1-based multi-agonists, and particularly GLP1/E, in the personalized management of PCOS.

A Comparative Study of Traditional and Computer-aided Surgical Simulation Guides in Orthognathic Correction of Bimaxillary Protrusion.

OBJECTIVE: To compare the efficacy of traditional occlusal guides with computer-aided surgical simulation (CASS) guides in enhancing postoperative outcomes for patients with bimaxillary protrusion. METHODS: This retrospective study evaluated 34 patients undergoing anterior maxillary and mandibular subapical osteotomy at the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences. Fourteen patients were treated using traditional occlusal guides, whereas 20 patients were treated with CASS guides (median age 28.6 years, median follow-up 259 days). Pre and postoperative cephalometric indicators were measured using cephalometric software. Data analysis was conducted using SPSS 14.0, with significant differences determined at P < 0.05. RESULTS: All 34 patients experienced primary healing without complications. Follow-up indicated significant improvements in key cephalometric measurements in the CASS group compared with the traditional group, including mandibular position (SNB angle, P < 0.001), jaw relationship (ANB angle, P < 0.001), facial angle (FH-NPo, P = 0.002), and condyle-to-sella distance (Co-S, P = 0.024). The CASS group also showed better aesthetic outcomes, with significant reductions in overjet (P = 0.012), overbite (P = 0.001), and improved alignment of upper and lower incisors (U1-L1 angle, P = 0.031). CONCLUSION: CASS-guided surgery offers a superior alternative to traditional methods for treating bimaxillary protrusion, providing more precise and aesthetically pleasing results. This study highlights the significant advantages of using advanced digital simulation and 3-dimensional printing technologies in orthognathic surgery.

A multimodal zebrafish developmental atlas reveals the state-transition dynamics of late-vertebrate pluripotent axial progenitors.

Elucidating organismal developmental processes requires a comprehensive understanding of cellular lineages in the spatial, temporal, and molecular domains. In this study, we introduce Zebrahub, a dynamic atlas of zebrafish embryonic development that integrates single-cell sequencing time course data with lineage reconstructions facilitated by light-sheet microscopy. This atlas offers high-resolution and in-depth molecular insights into zebrafish development, achieved through the sequencing of individual embryos across ten developmental stages, complemented by reconstructions of cellular trajectories. Zebrahub also incorporates an interactive tool to navigate the complex cellular flows and lineages derived from light-sheet microscopy data, enabling in silico fate-mapping experiments. To demonstrate the versatility of our multimodal resource, we utilize Zebrahub to provide fresh insights into the pluripotency of neuro-mesodermal progenitors (NMPs) and the origins of a joint kidney-hemangioblast progenitor population.

Sinulariapeptide F, a new peptide from culture broth of marine-derived fungus Simplicillium sp. SCSIO 41222.

One new compound named sinulariapeptide F (1) together with one known butyrolactone (2) and seven known peptides (3-9) were isolated from the fungus Simplicillium sp. SCSIO 41222. Their structures and absolute configurations were established using HRESIMS, NMR spectroscopy (1H, 13C, HSQC, HMBC) and marfey's method. All of these compounds were assessed their inhibitory activity of acetylcholinesterase (AChE) and pancreatic lipase (PL). Compounds 4 and 6 were selected to test for the inhibitory activity against programmed cell death-1 (PD-1)/ programmed cell death-ligand 1 (PD-L1). The results indicated that compound 4 displayed potent inhibition activity against PD-1/ PD-L1 with an IC50 value of 0.656 µM. Furthermore, the docking analysis demonstrated the interactions between 4 and proteins, suggesting PD-L1 to be a probable target for compound 4.

Long-term efficacy and safety of stapokibart for moderate-to-severe atopic dermatitis: 52-week results from a phase 3 trial.

BACKGROUND: Management of moderate-to-severe atopic dermatitis (AD) needs long-term therapy. Stapokibart is a humanized monoclonal antibody targeting interleukin-4 receptor α subunit (IL-4Rα), a shared receptor for IL-4 and IL-13 which are key pathogenic drivers of AD. In a pivotal phase 3 trial (NCT05265923), significant higher proportions of adult AD patients receiving stapokibart than placebo achieved ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75; 66.9% vs. 25.8%) and Investigator's Global Assessment (IGA) score of 0/1 with ≥2-point reduction (44.2% vs. 16.1%) at Week 16. Herein, we report long-term (52 weeks) efficacy and safety of stapokibart from this trial. METHODS: After 16-week double-blind treatment completed, patients in both stapokibart and placebo groups entered a 36-week maintenance treatment period and received stapokibart 300 mg every 2 weeks. Concomitant use of topical medications for AD was permitted throughout the maintenance period. RESULTS: Of 476 patients entering maintenance period, 430 completed the treatment. At Week 52, EASI-75 was achieved in 92.5% of patients continuing stapokibart and 88.7% of those switching from placebo to stapokibart, respectively; an IGA score of 0 or 1 with a ≥2-point reduction was achieved in 67.3% and 64.2% of patients, respectively; a ≥4-point reduction in weekly average of daily Peak Pruritus Numerical Rating Scale (PP-NRS) was achieved in 67.3% and 60.5% of patients, respectively. Over the 52-week treatment period, 88.1% of patients reported treatment-emergent adverse events, most were mild or moderate. CONCLUSION: Long-term treatment with stapokibart demonstrated a sustained efficacy and favorable safety profile in adults with moderate-to-severe AD.