How NINJ1 mediates plasma membrane rupture and why NINJ2 cannot.

Ninjurin-1 (NINJ1) is an active executioner of plasma membrane rupture (PMR), a process previously thought to be a passive osmotic lysis event in lytic cell death. Ninjurin-2 (NINJ2) is a close paralog of NINJ1 but cannot mediate PMR. Using cryogenic electron microscopy (cryo-EM), we show that NINJ1 and NINJ2 both assemble into linear filaments that are hydrophobic on one side but hydrophilic on the other.

C-Labdane diterpenoid alkaloids bearing a rare skeleton with anti-inflammatory and anti-oxidant activities from Forsythia suspensa.

Two undescribed C-Labdane diterpenoid alkaloids, named forsylinfenines A and B (1-2), attributable to a rare 4,4,10,13-tetramethyl-1(2),3(4),5(10),6(7)-octahydrobenzo[f]quinolin skeleton, along with three known β-carboline-type alkaloids (3-5), were isolated. The chemical structures including absolute configurations of two undescribed compounds were established by means of integrated spectroscopic techniques and electronic circular dichroism (ECD) calculations. In addition, a plausible biosynthetic pathway for the formation of compounds 1 and 2 was proposed.

Alstoscholarisine L, a novel caged monoterpenoid indole alkaloid with antifungal activity from Alstonia scholaris.

Alstoscholarisine L is an architecturally complex monoterpenoid indole alkaloid with a unique ring fusion pattern, isolated from the leaves of Alstonia scholaris. The 6/5/5/6/6/6-membered rings contain two lactonic rings and one aminal carbon and possess seven contiguous aligned stereocenters, three of which are quaternary. Its structure was elucidated by extensive spectroscopic data analyses, quantum chemical computations, and single-crystal X-ray diffraction.

Hyaluronic acid regulated facile synthesis of size-tunable multifunctional nanomedicine for effective cancer therapy.

The complex and heterogeneous nature of cancer necessitates the development of innovative multifunctional nanomedicines (MN). Hyaluronic acid (HA) is a functional carbohydrate polysaccharide that is widely used in various biomedical fields. In this study, we employed HA as a stabilizer and regulator for the synthesis of a size-tunable nanomedicine comprising ferric ions, doxorubicin, and epigallocatechin gallate (EGCG), referred to as HDE-MN, for cancer therapy.

Patellar tendon lateral deviation angle: a new computed tomography scan measurement for evaluation of patellar instability.

Background: The tibial tuberosity-trochlear groove (TT-TG) distance is an important reference for the evaluation of patellar instability. However, measurement of the TT-TG distance has disadvantages with relatively low reproducibility. This study aimed to investigate the reliability of patellar tendon lateral deviation angle (PTLD-A) measured on a single computed tomography (CT) slice and the clinical significance for predicting patellar instability.

A nonlinear creep model of hard structural planes.

Hard structural planes mainly exist in rock slopes and their creep characteristics largely determine slope stability. Traditional models have some shortcomings in describing the creep characteristics of hard structural planes, such as poor adaptability and unclear physical meaning of parameters. In order to overcome these shortcomings, based on the creep failure mechanism of hard structural planes, an element combination model is adopted in the study.

Loss of Notch dimerization perturbs intestinal homeostasis by a mechanism involving HDAC activity.

A tri-protein complex containing NICD, RBPj and MAML1 binds DNA as monomer or as cooperative dimers to regulate transcription. Mice expressing Notch dimerization-deficient alleles (NDD) of Notch1 and Notch2 are sensitized to environmental insults but otherwise develop and age normally. Transcriptomic analysis of colonic spheroids uncovered no evidence of dimer-dependent target gene miss-regulation, confirmed impaired stem cell maintenance in-vitro, and discovered an elevated signature of epithelial innate immune response to symbionts, a likely underlying cause for heightened sensitivity in NDD mice.

Does the establishment of civilized cities promote urban inclusive development?--Quasi-natural experiment based on the selection of "National Civilized City".

Taking the selection of "National Civilized City" as a quasi-natural experiment and basing on the research samples of 272 prefecture level and above cities in China from 2003 to 2020, this paper explores the impact of the establishment of civilized cities on urban inclusive development and its mechanism by using the time-varying DID model. The findings are as follows: firstly, the establishment of civilized cities has significantly promoted the urban inclusive development, and then parallel trend test, placebo test and other robustness tests verify the reliability of the research conclusions. Secondly, in regions with larger population, stronger financial strength and belonging to the Excellent Tourism City, the establishment of civilized cities has a more obvious role in promoting urban inclusiveness.

Global trends and regional differences in the burden of HIV/AIDS attributed to intimate partner violence among females in 204 countries and territories, 1999-2019: An analysis of the global burden of disease study.

Objective: This study aimed to analyze the temporal and spatial trends in the burden of HIV/AIDS related to intimate partner violence (IPV) on global, regional, and country scales among females.

Method: Data were from the 2019 Global Burden of Disease (GBD) Study. We assessed the global disability-adjusted life years (DALYs; per 100,000 population) and death of HIV/AIDS attributable to IPV by age and geographical location.

A systematic review and meta-analysis comparing the short-term efficacy of the KangDuo surgical robot with the da Vinci robotic system in radical prostatectomy.

To determine the efficacy and adverse consequences between KangDuo and Da Vincii surgical robotic systems in facilitating radical prostatectomy. All the papers, that were included in the current analysis, were identified with PubMed, Embase, and the Cochrane Library through October 1, 2024. To make the comparison easier, only the English-language articles have been used for the analysis and only those focusing on comparing the use of the KangDuo and da Vinci robotic systems in radical prostatectomy were used.

Cytoskeleton dysfunction of motor neuron in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by deletions or mutations of survival of motor neuron 1 (SMN1) gene. To date, the mechanism of selective cell death of motor neurons as a hallmark of SMA is still unclear. The severity of SMA is dependent on the amount of survival motor neuron (SMN) protein, which is an essential and ubiquitously expressed protein involved in various cellular processes including regulation of cytoskeletal dynamics.

Predicting and optimizing pure electric vehicle road noise via a locality-sensitive hashing transformer and interval analysis.

Pure electric vehicles (PEVs) lack engine noise; thus, the overall noise level within vehicle cabins are reduced. However, due to the absence of engine noise, previously overlooked noise sources are accentuated and detrimentally affect interior noise quality. Road noise is a predominant PEV noise source and significantly contributes to middle- and low-frequency interior noise levels.

The rice microRNA159-SPOROCYTELESS EAR2 module regulates starch biosynthesis during pollen development and maintains male fertility.

Starch is an indispensable energy reserve for pollen and failure of starch biosynthesis in pollen leads to male sterility in flowering crops. Nonetheless, the regulatory mechanisms underlying starch biosynthesis in rice (Oryza sativa) pollen remain unclear. Here, we identified a target of the microRNA OsmiR159, SPOROCYTELESS ETHYLENE-RESPONSIVE ELEMENT BINDING FACTOR-ASSOCIATED AMPHIPHILIC-REPRESSION 2 (OsSPEAR2).

Microbial Synthesis of Nucleosides: Advances and Prospects.

Nucleosides and its derivatives are essential chemicals with extensive applications in the food, agricultural, and pharmaceutical industries. Chemical synthesis of these compounds often faces problems such as harsh reaction conditions and environmental pollution, whereas microbial synthesis provides a promising and sustainable alternative. This review discusses recent advances in the biosynthesis of nucleosides and their derivatives.

Identification and Correlation Analysis of Ferroptosis-Related Genes in Three Brain Regions of Patients with Schizophrenia.

Background: Schizophrenia (SZ) is a severe mental disorder that is marked by hallucinations and cognitive impairments. Ferroptosis is a type of cell death that is associated with iron and lipid peroxidation; it may play a role in SZ etiology. The present study aimed to explore the correlations between ferroptosis-related genes and SZ in three brain regions.

Elucidating Microstructural Alterations in Neurodevelopmental Disorders: Application of Advanced Diffusion-Weighted Imaging in Children With Rasopathies.

Neurodevelopmental disorders (NDDs) can severely impact functioning yet effective treatments are limited. Greater insight into the neurobiology underlying NDDs is critical to the development of successful treatments. Using a genetics-first approach, we investigated the potential of advanced diffusion-weighted imaging (DWI) techniques to characterize the neural microstructure unique to neurofibromatosis type 1 (NF1) and Noonan syndrome (NS).

A real-world disproportionality analysis of colchicine: data mining of the public version of FDA Adverse Event Reporting System.

Background: Colchicine is widely used for gout and familial Mediterranean fever (FMF) and has cardiovascular benefits. However, it is linked to various adverse drug reactions (ADRs). This study aimed to analyze colchicine-related ADRs using FAERS data for safer clinical use.

A nomogram to predict the risk of insulin resistance in Chinese women with polycystic ovary syndrome.

Background: Insulin resistance (IR) is considered a major driver of the pathophysiology of polycystic ovary syndrome (PCOS), mediating the progression of hyperandrogenism and metabolic and reproductive dysfunction in patients with PCOS. Early detection of the risk of concurrent IR is essential for women with PCOS. To address this need, this study developed a predictive nomogram for assessing the risk of IR in women with PCOS, aiming to provide a tool for risk stratification and assist in clinical decision-making.

Higher expression of mir-31-5p is associated with reduced risk of head and neck keloid recurrence following surgical resection.

Objective: In this study, we aimed to evaluate mir-31-5p as a prognostic biomarker of keloid disease (KD) recurrence using a retrospective, treatment naïve, surgical cohort of head and neck KD cases from Henry Ford Health.

Methods: Using a tissue microarray, mir-31-5p expression was measured with miRNAscope, and mir-31-5p cell positivity was determined with QuPath. Logistic regression was used to test the association between mir-31-5p positive cells and KD recurrence at 1 year.

Transcranial direct current stimulation alleviates the pain severity in people suffering from knee osteoarthritis: a systematic review and meta-analysis.

Considerable research has shown the benefits of transcranial direct current stimulation (tDCS) for the alleviation of pain associated with knee osteoarthritis (KOA). Still, a large variance in study protocols and observations across publications exists. We here thus completed a systematic review and meta-analysis to comprehensively and quantitatively characterize the effects of tDCS on KOA-related pain.

Prognostic significance of elevated expression levels of protein phosphatase 1 regulatory subunit 3G in thyroid carcinoma.

The prognosis of the poorly differentiated subtype of thyroid carcinoma (THCA) is less favorable due to its aggressive nature, which also increases the likelihood of metastasis to distant organs. The present study aimed to assess the potential application of protein phosphatase 1 regulatory subunit 3G (PPP1R3G) as a molecular biomarker for early identification and prognosis prediction in THCA. The Cancer Genome Atlas (TCGA) database was used to identify genes associated with prognosis and differentially expressed genes in THCA.

IKBKE regulates renal cell carcinoma progression and sunitinib resistance through the RRM2-AKT pathway.

Tyrosine kinase inhibitors (TKIs), such as sunitinib, have emerged as promising agents in renal cell carcinoma (RCC) treatment, particularly in patients at advanced/metastatic clinical stages. However, acquired resistance to sunitinib is common following prolonged clinical treatment in RCC. Increasing evidence has demonstrated a strong correlation between inhibitor of nuclear factor kappa B kinase subunit epsilon (IKBKE) and cancer progression as well as drug resistance.

The depletion of gut microbiome impairs the beneficial effect of Gui-Shen-Wan in restoring mice ovarian function and associated protein expression of ovarian tissues.

Introduction: Traditional Chinese Medicine (TCM), specifically Gui-Shen-Wan, has shown promise in restoring ovarian function among reproductive-age women who had impaired ovarian functions, yet the underlying mechanisms remain elusive. Recent studies highlight the pivotal role of the gut microbiome (GM) in mediating the therapeutic effects of TCM. However, it is unclear whether the GM contributes to Gui-Shen-Wan's therapeutic restoration of ovarian functions.