MMFuncPhos: A Multi-Modal Learning Framework for Identifying Functional Phosphorylation Sites and Their Regulatory Types.

Protein phosphorylation plays a crucial role in regulating a wide range of biological processes, and its dysregulation is strongly linked to various diseases. While many phosphorylation sites have been identified so far, their functionality and regulatory effects are largely unknown. Here, a deep learning model MMFuncPhos, based on a multi-modal deep learning framework, is developed to predict functional phosphorylation sites.

Optimal Timing and Approaches for First Tangential Excision in Patients with ≥70% TBSA Burns: Insights from a Retrospective Cohort of a Mass Casualty Incident.

Objective: We aim to determine the optimal timing and approaches for first tangential excision of severely burned patients ≥70% total body surface area (TBSA).

Background: Early tangential excision is the gold-standard surgical therapy for full-thickness burns. However, there are debates about its optimal timing and approaches for severely burned patients ≥70%TBSA.

New insights into constitutive neutrophil death.

Neutrophils undergo rapid aging and death known as constitutive or spontaneous death. Constitutive neutrophil death (CND) contributes to neutrophil homeostasis and inflammation resolution. CND has long been considered to be apoptotic until our findings reveal that it was a heterogeneous combination of diverse death.

A broadly neutralizing antibody against the SARS-CoV-2 Omicron sub-variants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5.

The global spread of Severe Acute Respiratory Syndrome Coronavirus 2. (SARS-CoV-2) and its variant strains, including Alpha, Beta, Gamma, Delta, and now Omicron, pose a significant challenge. With the constant evolution of the virus, Omicron and its subtypes BA.

Identification of Novel and Rare GNAS Mutations in Craniofacial Fibrous Dysplasia.

Background: Fibrous dysplasia (FD), caused by activating mutations of GNAS, is a skeletal disorder with considerable clinicopathological heterogeneity. Although prevalent mutations such as R201C and R201H dominate in FD, a limited number of rare mutations, including R201S, R201G, and Q227L, have been documented. The scarcity of information concerning these uncommon mutations motivates our investigation, seeking to enhance comprehension of this less-explored subgroup within FD.

BRD4-targeted photodegradation nanoplatform for light activatable melanoma therapy.

The targeted protein degradation (TPD) strategy modulates tumor growth pathways by degrading proteins of interest (POIs) and has reshaped anti-tumor drug research and development. Recently, the emergence of photodegradation-targeting chimeras (PDTACs) and laser irradiation at specific sites enables precise spatiotemporal controllability of TPD. Capitalizing on the advances of PDTACs, herein, we report a nanoplatform for efficiently delivering PDTAC molecule for photodegradation of bromodomain-containing protein 4 (BRD4) proteins, the key activators of oncogenic transcription.

Possible linking and treatment between Parkinson's disease and inflammatory bowel disease: a study of Mendelian randomization based on gut-brain axis.

Background: Mounting evidence suggests that Parkinson's disease (PD) and inflammatory bowel disease (IBD) are closely associated and becoming global health burdens. However, the causal relationships and common pathogeneses between them are uncertain. Furthermore, they are uncurable.

Public awareness, attitudes, and motivation toward biobanks: a survey of China.

Background: Biobanks are vital for advancing medical research, and public participation is a crucial determinant of their success. This study uses a survey to assess the awareness, attitudes, and motivation of the public in China with regard to participating in biobanks.

Methods: We conducted an online survey that yielded 616 responses from participants with diverse demographic backgrounds.

Clinical implications of longitudinally assessed uric acid in heart failure.

Background And Aims: Numerous studies have evaluated the association between baseline uric acid (UA) and heart failure (HF) outcomes. The impact of longitudinal UA on HF survival remains unknown. We aim to investigate the association between different parameterizations of longitudinal UA measurements and survival outcomes in HF patients.

NVP-AUY922 relieves radiation-induced intestinal injury via regulating EPHX1.

As a common side effect of radiotherapy, radiation-induced intestinal injury (RIII) greatly affects the prognosis of patients and the efficacy of radiotherapy. Current therapeutic strategies for RIII are still very limited. Thus, the identification of effective radioprotective agents is of great importance.

Discovery of potent antiosteoporotic cyclic depsipeptides with an unusual nitrile hydroxy acid from Microascus croci.

Two cyclic octadepsipeptides, microascusins A and B (1 and 2), were identified from the marine sponge-associated Microascus croci IMB19-064 co-cultivated with Escherichia coli. Their structures and conformations in solution were determined by comprehensive spectroscopic data analysis. The absolute configurations of amino and hydroxy acids were determined by the advanced Marfey's and O-Marfey's methods, respectively, as well as chiral-phase HPLC analysis.

Molecular Stratification of Light-Chain Cardiac Amyloidosis With F-Florbetapir and Ga-FAPI-04 for Enhanced Prognostic Precision.

Background: Cardiac involvement in amyloid light chain (AL) amyloidosis significantly influences prognosis, necessitating timely diagnosis and meticulous risk stratification.

Objectives: This prospective study aimed to delineate the molecular phenotypes of AL cardiac amyloidosis (AL-CA) by characterizing fibro-amyloid deposition using F-florbetapir and gallium-68-labeled fibroblast activation protein inhibitor-04 (Ga-FAPI-04) positron emission tomography (PET)/computed tomography (CT) imaging. The authors also proposed a novel molecular stratification methodology for prognosis.

Disrupted mitochondrial morphology and function exacerbate inflammation in elderly-onset ulcerative colitis.

Background: The characteristics of ulcerative colitis (UC) in the elderly are quite different from the young population. Mitochondrial injury is a key mechanism regulating both aging and inflammation. This study aims to reveal the role of mitochondrial damage in the pathogenesis of adult- and elderly-onset UC.

Gut microbial-derived phenylacetylglutamine accelerates host cellular senescence.

Gut microbiota plays a crucial role in the host health in the aging process. However, the mechanisms for how gut microbiota triggers cellular senescence and the consequent impact on human aging remain enigmatic. Here we show that phenylacetylglutamine (PAGln), a metabolite linked to gut microbiota, drives host cellular senescence.

Bioorthogonal strategy-triggered In situ co-activation of aggregation-induced emission photosensitizers and chemotherapeutic prodrugs for boosting synergistic chemo-photodynamic-immunotherapy.

In situ activation of prodrugs or photosensitizers is a promising strategy for specifically killing tumor cells while avoiding toxic side effects. Herein, we originally develop a bioorthogonally activatable prodrug and pro-photosensitizer system to synchronously yield an aggregation-induced emission (AIE) photosensitizer and a chemotherapeutic drug for synergistic chemo-photodynamic-immunotherapy of tumors. By employing molecular engineering strategy, we rationally design a family of tetrazine-functionalized tetraphenylene-based photosensitizers, one of which (named TzPS5) exhibits a high turn-on ratio, a NIR emission, a typical AIE character, and an excellent ROS generation efficiency upon bioorthogonal-activation.

A Dual-Targeting Biomimetic Nanoplatform Integrates SDT/CDT/Gas Therapy to Boost Synergistic Ferroptosis for Orthotopic Hepatocellular Carcinoma Therapy.

The development of efficient therapeutic strategies to promote ferroptotic cell death offers significant potential for hepatocellular carcinoma (HCC) treatment. Herein, this study presents an HCC-targeted nanoplatform that integrates bimetallic FeMoO nanoparticles with CO-releasing molecules, and further camouflaged with SP94 peptide-modified macrophage membrane for enhanced ferroptosis-driven multi-modal therapy of HCC. Leveraging the multi-enzyme activities of the multivalent metallic elements, the nanoplatform not only decomposes HO to generate oxygen and alleviate tumor hypoxia but also depletes glutathione to inactivate glutathione peroxides 4, which amplify sonodynamic therapy and ferroptotic tumor death under ultrasound (US) irradiation.

Tubulointerstitial nephritis antigen-like 1 promotes the progression of liver fibrosis after HCV eradication with direct-acting antivirals.

Although therapies based on direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus (HCV) in patients, there is still a high risk of liver fibrosis even after a sustained virological response. Therefore, it is of great clinical importance to understand the mechanism of potential factors that promote liver fibrosis after virological cure by treatment with DAAs. Here, we found that tubulointerstitial nephritis antigen-like 1 (TINAGL1) is significantly increased in HCV-infected hepatocytes and in the liver of patients with liver fibrosis, and that higher TINAGL1 expression persists in HCV-eradicated hepatocytes after treatment with DAAs.

How Accurately Does Bone Mineral Density Predict Bone Strength? A Clinical Observational Study of Osteoporosis Vertebral Compression Fractures in Postmenopausal Women.

Objectives: Dual energy x-ray absorptiometry (DXA) provides incomplete information about bone strength. There are few data on the relationship between osteoporosis-related examinations and bone strength. The objective of the present study was to determine which osteoporosis-related examinations best predicted trabecular bone strength, and to enhance a formula for predicting bone strength on the basis of bone density examination.

Augmented immunogenicity of the HPV16 DNA vaccine via dual adjuvant approach: integration of CpG ODN into plasmid backbone and co-administration with IL-28B gene adjuvant.

Therapeutic human papillomavirus (HPV) DNA vaccine is an attractive option to control existed HPV infection and related lesions. The two early viral oncoproteins, E6 and E7, are continuously expressed in most HPV-related pre- and cancerous cells, and are ideal targets for therapeutic vaccines. We have previously developed an HPV 16 DNA vaccine encoding a modified E7/HSP70 (mE7/HSP70) fusion protein, which demonstrated significant antitumor effects in murine models.

A Bibliometric Review of Software Tools in Plastic Surgery: How They Benefit Surgeons and Improve Practice from 2004 to 2024.

Background: Bibliometric analyses of software applications in plastic surgery are relatively limited. This study aims to address this gap by summarizing current research trends and providing insights that may guide future developments in this field.

Methods: Data were retrieved from the Web of Science Core Collection.

SEE: A Method for Predicting the Dynamics of Chromatin Conformation Based on Single-Cell Gene Expression.

The dynamics of chromatin conformation involve continuous and reversible changes within the nucleus of a cell, which participate in regulating processes such as gene expression, DNA replication, and damage repair. Here, SEE is introduced, an artificial intelligence (AI) method that utilizes autoencoder and transformer techniques to analyze chromatin dynamics using single-cell RNA sequencing data and a limited number of single-cell Hi-C maps. SEE is employed to investigate chromatin dynamics across different scales, enabling the detection of (i) rearrangements in topologically associating domains (TADs), and (ii) oscillations in chromatin interactions at gene loci.

Metabolomic and transcriptomic analyses revealed potential mechanisms of Anchusa italica Retz. in alleviating cerebral ischemia-reperfusion injury via Wnt/β-catenin pathway modulation.

Anchusa italica Retz. (AIR), a traditional herbal remedy, is commonly applied in managing heart and brain disorders. However, its specific function and mechanism in acute cerebral ischemia-reperfusion injury (CIRI) are not fully understood.

Early differentiation of committed erythroid cells defined by miR-144/451 expression.

Before committing to an erythroid cell lineage, hematopoietic stem cells differentiate along a myeloid cell pathway to generate megakaryocyte-erythroid biopotential progenitor cells in bone marrow. Recent studies suggest that erythroid progenitors (EryPs) could be generated at the level of common myeloid progenitors (CMPs). However, due to a lack of suitable markers, little is known about the early differentiation of these committed EryP cells during CMP development.

Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip.

The development of the mammalian neocortex is precisely regulated by temporal gene expression, yet the temporal regulatory mechanisms of cortical neurogenesis, particularly how radial glial cells (RGCs) sequentially generate deep to superficial neurons, remain unclear. Here, the hnRNP family member Syncrip (hnRNP Q) is identified as a key modulator of superficial neuronal differentiation in neocortical neurogenesis. Syncrip knockout in RGCs disrupts differentiation and abnormal neuronal localization, ultimately resulting in superficial cortical layer defects as well as learning and memory impairments in mice.