Network Pharmacology, Experimental Validation Explored Kakkalide to Ameliorate Endothelial Cell Dysfunction and Inflammatory Response.

Background: Sepsis continues to represent a significant challenge due to its detrimental effects and high mortality rate. The protection of endothelial function and the attenuation of the excessive inflammatory response are pivotal in the reduction of mortality risk. is the flower of var.

Chromosome-level genome assembly of the caddisfly Stenopsyche angustata (Insecta: Trichoptera).

Stenopsyche angustata, a species within the diverse order Trichoptera, is widely distributed across freshwater environments and exhibits unique ecological traits that make it an ideal subject for studying adaptive evolution. In this study, we employed Illumina second-generation sequencing, PacBio third-generation sequencing, along with high-throughput chromosome conformation capture (Hi-C) technologies to generate raw sequencing data and construct chromosome-level genome assemblies of S. angustata.

A Bifunctional Anti-PD-1/TGF-β Fusion Antibody Restores Antitumour Immunity and Remodels the Tumour Microenvironment.

Although PD-1/PD-L1 inhibitors have transformed cancer immunotherapy, a substantial proportion of patients derive no clinical benefit due to resistance driven by the tumour microenvironment (TME). Transforming growth factor-β (TGF-β) is a key immunosuppressive cytokine implicated in this resistance. Several bifunctional antibodies that co-target PD-1 and TGF-β signalling have entered clinical trials and shown encouraging efficacy, but the mechanistic basis of their synergy is not fully understood.

Per- and Polyfluoroalkyl Substances (PFASs) in Market Meats from Guangzhou, China: Age-Specific Dietary Exposure and Threshold Exceedance Risks.

Per- and polyfluoroalkyl substances (PFASs), known for their environmental persistence and adverse health effects, pose an elevated risk to vulnerable populations through dietary exposure. Yet, there is limited research on PFAS concentrations in market basket meats and offal from Guangzhou, China. We examined the distribution of 16 PFAS in 166 market basket samples (beef, pork, and offal (pork liver)) from Guangzhou.

Clinical significance and prognostic value of SIRT1 genetic variants in sepsis: a multicenter hospital-based case-control study.

Background: SIRT1 exerts pivotal roles in the pathogenesis of sepsis. However, the clinical relevance of SIRT1 genetic variants in the onset and progression of sepsis remains poorly understood. This multicenter hospital-based case-control study, for the first time, explored the potential genetic association of SIRT1 genetic variants with sepsis, as well as their impact on sepsis-associated inflammation.

Biomimetic mineralization guided protein-based multifunctional bio-separators realizing dendrites free and high-performance lithium‑sulfur batteries.

Lithium‑sulfur batteries (LSB) are considered promising energy storage systems owing to their high theoretical energy density and abundant sulfur resources. However, issues such as lithium polysulfide (LiPSs) shuttle, uneven Li transport, and lithium dendrite growth severely limit their practical deployment. Herein, a biomimetic mineralization (BM) strategy was employed to fabricate a multifunctional separator by integrating Zeolite imidazolate frameworks-8 (ZIF-8) nanocrystals with β-sheet silk fibroin (β-SF) membranes.

Comparison of Deep Learning Models for Objective Auditory Brainstem Response Detection: A Multicenter Validation Study.

Auditory brainstem response (ABR) interpretation in clinical practice often relies on visual inspection by audiologists, which is prone to inter-practitioner variability. While deep learning (DL) algorithms have shown promise in objectifying ABR detection in controlled settings, their applicability to real-world clinical data is hindered by small datasets and insufficient heterogeneity. This study evaluates the generalizability of nine DL models for ABR detection using large, multicenter datasets.

Trio Whole Exome Sequencing in Chinese Childhood-Onset Lupus Reveals Novel Candidate Genes.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease in which rare and common gene variants contribute to pathogenesis. Severe sporadic disease in children is often explained by "de novo" variants that can be uncovered by trio sequencing.

Methods: Whole-exome sequencing was performed in 50 Chinese trios with childhood-onset SLE (cSLE).

Efficacy and influencing factors of immunosuppressive therapy for pure red cell aplasia: meta-analysis and systematic review.

Acquired pure red cell aplasia (aPRCA) is a rare hematological syndrome characterized by anemia and a significant reduction in erythroid progenitor cells. Immunosuppressive therapy (IST), including Corticosteroids (CS), Cyclosporine (CsA), and cyclophosphamide (CYC), is the primary treatment. However, variations in clinical efficacy and limited comparative studies have created uncertainty in therapeutic choices.

Suppression of Liver Fibrogenesis with Photothermal Sorafenib Nanovesicles via Selectively Inhibiting Glycolysis and Amplification of Active HSCs.

As the major driving factor of hepatic fibrosis, the activated hepatic stellate cells (aHSCs) rely on active glycolysis to support their aberrant proliferation and secretion of the extracellular matrix. Sorafenib (Sor) can combat liver fibrosis by suppressing HIF-1α and glycolysis, but its poor solubility, rapid metabolism, and low bioavailability restrict such a clinical application. Here, Sor was loaded onto polydopamine nanoparticles and then encapsulated by a retinoid-decorated red blood cell membrane, yielding HSC-targeted Sor nanovesicles (PDA/Sor@RMV-VA) with a high Sor-loading capacity and photothermally controlled drug release for antifibrotic treatment.

Inhibition of HSC proliferation and hepatic fibrogenesis with Erythrocyte membrane coated Doxorubicin/Black phosphorus nanosheets.

Rapid proliferation underlies the abnormal expansion of activated hepatic stellate cells (aHSCs) and thereby contributes to the development and progression of liver fibrosis, so inhibition of HSC proliferation serves as a good antifibrotic strategy. As a potent topoisomerase II inhibitor, doxorubicin (DOX), an antineoplastic drug, exhibits a significant antifibrotic activity in vitro via retarding the growth of aHSCs and reversing their myofibroblastic phenotype, but its severe hepatotoxicity, cardiotoxicity, and renal toxicity limit its wide clinical application. Therefore, enhancing the specificity and efficacy of DOX in targeting aHSCs to improve its therapeutic index and minimize its adverse effects has become a key point for the success of DOX in antifibrotic treatment.

RECK as a Potential Crucial Molecule for the Targeted Treatment of Sepsis.

Reversion inducing cysteine rich protein with kazal motifs (RECK), a Kazal motif-containing protein, regulates pro-inflammatory cytokines production, migration of inflammatory cells, vascular endothelial growth factor (VEGF) and Wnt pathways and plays critical roles in septic inflammatory storms and vascular endothelial dysfunction. Recently, RECK has been defined as the negative regulator of adisintegrin and metalloproteinases (ADAMs) and matrix metalloproteinases (MMPs), which are both membrane "molecular scissors" and aggravate the poor prognosis of sepsis. To better understand the roles of RECK and the related mechanisms, we make here a systematic and in-depth review of RECK.

Protein-Guided Biomimetic Calcification Constructing 3D Nitrogen-Rich Core-Shell Structures Realizing High-Performance Lithium-Sulfur Batteries.

Biomimetic calcification is a micro-crystallization process that mimics the natural biomineralization process, where biomacromolecules regulate the formation of inorganic minerals. In this study, it is presented that a protein-assisted biomimetic calcification method for the in situ synthesis of nitrogen-doped metal-organic framework (MOF) materials. A series of unique core-shell structures are created by utilizing proteins as templates and guiding agents in the nucleation step, creating ideal conditions for shell growth.

Morphological Characteristics, Mitochondrial Genome, and Evolutionary Insights Into a New Sea Squirt From the Beibu Gulf.

A new species of the genus Microcosmus was described in this study based on specimens collected from the coast of Xilian Town, Xuwen County, Zhanjiang, Guangdong Province, China. The morphological and molecular characteristics of this new species, sp. z YZ-2024 (YZ-2024), distinguish it from other sea squirts.

Colon-targeted engineered postbiotics nanoparticles alleviate osteoporosis through the gut-bone axis.

The potential for mitigating intestinal inflammation through the gut-bone axis in the treatment of osteoporosis is significant. While various gut-derived postbiotics or bacterial metabolites have been created as dietary supplements to prevent or reverse bone loss, their efficacy and safety still need improvement. Herein, a colon-targeted drug delivery system is developed using surface engineering of polyvinyl butyrate nanoparticles by shellac resin to achieve sustained release of postbiotics butyric acid at the colorectal site.

Targeting hyperactive mitochondria in activated HSCs and inhibition of liver fibrogenesis in mice using sorafenib complex micelles.

Liver fibrosis is a pathological condition marked by the excessive buildup of extracellular matrix primarily resulting from the transformation of quiescent hepatic stellate cells (HSCs) to myofibroblastic (MF) phenotype and their resultant over-expansion. Activated HSCs completely rely on their hyperactive mitochondria to supply the energy and biomass for their rapid proliferation and collagen secretion, so an intervention targeting their mitochondria can effectively restrict their pathological amplification and contribution to liver fibrosis. Here we tried sorafenib, a drug that plays anticancer roles by inducing the disruption and loss of mitochondrial functions, to reach an antifibrotic goal.

Immune defense adaptation of Strauchbufo raddei population in heavy metal polluted area: Insights from developmental and environmental perspectives.

The adjustment of immune defense mechanisms is a crucial aspect of biological adaptation to stressful environments. Amphibians, with their unique metamorphic process, experience distinct life stages and exhibit diverse immune defense components. While previous studies have focused on specific immune changes during particular life stages under stress, this research addresses a critical gap by exploring the adaptive immune defense strategies of Strauchbufo raddei in heavy metal-polluted environments.

Structure-Guided Conformational Restriction Leading to High-Affinity, Selective, and Cell-Active Tetrahydroisoquinoline-Based Noncovalent Keap1-Nrf2 Inhibitors.

Inhibition of the protein-protein interaction between Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2) has been recognized as an attractive approach for treating oxidative stress-related diseases. Here, we present a new series of noncovalent Keap1-Nrf2 inhibitors developed by a conformational restriction strategy of our fluorenone-based compounds previously identified by fragment-based drug discovery. The design was guided by X-ray cocrystal structures, and the subsequent optimization process aimed at improving affinity, cellular activity, and metabolic stability.

Pregnancy-related intracranial venous sinus thrombosis secondary to cryptococcal meningoencephalitis: a case report and literature review.

Background: Cerebral venous sinus thrombosis (CVST), a serious cerebrovascular and neurological emergency, is common in pregnant individuals and accounts for approximately 0.5-1.0% of all cerebrovascular diseases.

Benefits and costs: Understanding the influence of heavy metal pollution on environmental adaptability in Strauchbufo raddei tadpoles through an energy budget perspective.

Understanding the impact of environmental pollution on organismal energy budgets is crucial for predicting adaptive responses and potential maladaptation to stressors. However, the regulatory mechanism governing the trade-off between energy intake and consumption remains largely unknown, particularly considering the diverse adaptations influenced by exposure history in realistic field conditions. In the present study, we conducted a simulated field reciprocal transplant experiment to compare the energy budget strategies of Strauchbufo raddei tadpoles exposed to heavy metal.

Allogeneic haematopoietic stem cell transplantation might overcome the poor prognosis of adolescents and adult patients with T-lineage acute lymphoblastic leukaemia and CDKN2 deletion.

This study delves into the clinical implications of cyclin-dependent kinase inhibitor 2 (CDKN2) deletion in adult T-lineage acute lymphoblastic leukemia (T-ALL). Among 241 patients included in this study, 57 had CDKN2 deletion and 184 had CDKN2 wild-type (WT), and 165 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 76 did not undergo allo-HSCT. CDKN2 deletion correlated with higher white blood cell count, more high-risk diseases, and complex karyotype.

Monogenic lupus: insights into disease pathogenesis and therapeutic opportunities.

Purpose Of Review: This review aims to provide an overview of the genes and molecular pathways involved in monogenic lupus, the implications for genome diagnosis, and the potential therapies targeting these molecular mechanisms.

Recent Findings: To date, more than 30 genes have been identified as contributors to monogenic lupus. These genes are primarily related to complement deficiency, activation of the type I interferon (IFN) pathway, disruption of B-cell and T-cell tolerance and metabolic pathways, which reveal the multifaceted nature of systemic lupus erythematosus (SLE) pathogenesis.

The enzymes of serine synthesis pathway in cancer metastasis.

Metastasis, the major cause of cancer mortality, requires cancer cells to reprogram their metabolism to adapt to and thrive in different environments, thereby leaving metastatic cells metabolic characteristics different from their parental cells. Mounting research has revealed that the de novo serine synthesis pathway (SSP), a glycolytic branching pathway that consumes glucose carbons for serine makeup and α-ketoglutarate generation and thus supports the proliferation, survival, and motility of cancer cells, is one such reprogrammed metabolic pathway. During different metastatic cascades, the SSP enzyme proteins or their enzymatic activity are both dynamically altered; manipulating their expression or catalytic activity could effectively prevent the progression of cancer metastasis; and the SSP enzymatic proteins could even conduce to metastasis via their nonenzymatic functions.

GP60 and SPARC as albumin receptors: key targeted sites for the delivery of antitumor drugs.

Albumin is derived from human or animal blood, and its ability to bind to a large number of endogenous or exogenous biomolecules makes it an ideal drug carrier. As a result, albumin-based drug delivery systems are increasingly being studied. With these in mind, detailed studies of the transport mechanism of albumin-based drug carriers are particularly important.

The transcription factor ZEB2 drives the formation of age-associated B cells.

Age-associated B cells (ABCs) accumulate during infection, aging, and autoimmunity, contributing to lupus pathogenesis. In this study, we screened for transcription factors driving ABC formation and found that zinc finger E-box binding homeobox 2 (ZEB2) is required for human and mouse ABC differentiation in vitro. ABCs are reduced in haploinsufficient individuals and in mice lacking in B cells.