Structural basis of thymidine-rich DNA recognition by Drosophila P75 PWWP domain.

Drosophila P75 (dP75), a homolog of the human LEDGF/p75, is crucial for oogenesis by recruiting the histone kinase Jil-1 to euchromatin and impeding H3K9me2 spreading. Like LEDGF, dP75 binds transcriptionally active chromatin, but its precise mechanism remains unclear. Here we show that its PWWP domain prefers binding to thymidine-rich DNA over GC-rich sequences.

Structural basis for the asymmetric binding of coactivator SRC1 to FXR-RXRα and allosteric communication within the complex.

Farnesoid X receptor (FXR) is a promising target for treatment of metabolic associated fatty liver disease (MAFLD). In this study, we employed an integrative approach to investigate the interaction between FXR-RXRα-DNA complex and the entire coactivator SRC1-NRID (nuclear receptor interaction domain). We constructed a multi-domain model of FXR-RXRα-DNA, highlighting the interface between FXR-DBD and LBD.

The correlation between proprotein convertase subtilisin/kexin type 9 and adiponectin in the progression from prediabetes to type 2 diabetes mellitus.

Data on the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) and adiponectin in prediabetes progression to type 2 diabetes mellitus (T2DM) remains inconclusive. Therefore, this study investigated the roles of PCSK9 and adiponectin in this process. This study included 1,528 participants with prediabetes and T2DM and conducted correlation analyses to investigate the relationship between PCSK9 and adiponectin levels, pancreatic beta-cell function, and insulin levels.

A real-world experience of efficacy and safety of belantamab mafodotin in relapsed refractory multiple myeloma.

While initial trials led to the accelerated approval of belantamab mafodotin, a BCMA-directed antibody-drug conjugate, confirmatory trials failed to establish benefit from this therapy for patients with relapsed refractory multiple myeloma (RRMM), eventually leading to its withdrawal from commercial use. With an imminent approval as an effective combination therapy, as seen in recent randomized trials, we report real-world clinical outcomes with belantamab mafodotin in 81 RRMM patients. With a median of 5 (range 2-15) prior lines of therapy, 92, 45, and 15% of the patients were triple-class refractory, penta-class refractory, and BCMA-refractory.

Mesenchymal stem cells alleviate idiopathic pneumonia syndrome by facilitating M2 polarization via CCL2/CCR2 axis and further inducing formation of regulatory CCR2 + CD4 + T cells.

Background: Our previous study revealed that mesenchymal stem cells (MSCs) can secrete large amounts of the chemokine CCL2 under inflammatory conditions and alleviate idiopathic pneumonia syndrome (IPS) by promoting regulatory CCR2 + CD4 + T-cell formation through the CCL2‒CCR2 axis. Given the abundance of macrophages in lung tissue, how these macrophages are regulated by MSC-based prophylaxis via IPS and their interactions with T cells in lung tissue during allo-HSCT are still not fully understood.

Methods: An IPS mouse model was established, and MSC-based prophylaxis was administered.

A Non-Invasive Approach for Facial Action Unit Extraction and Its Application in Pain Detection.

A significant challenge that hinders advancements in medical research is the sensitive and confidential nature of patient data in available datasets. In particular, sharing patients' facial images poses considerable privacy risks, especially with the rise of generative artificial intelligence (AI), which could misuse such data if accessed by unauthorized parties. However, facial expressions are a valuable source of information for doctors and researchers, which creates a need for methods to derive them without compromising patient privacy or safety by exposing identifiable facial images.

Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Identify Covalent TLCD1 Inhibitors.

Activity-based protein profiling (ABPP) of stereoisomerically defined sets of electrophilic compounds ('stereoprobes') offers a versatile way to discover covalent ligands for proteins in native biological systems. Here we report the synthesis and chemical proteomic characterization of stereoprobes bearing a P(V)-oxathiaphospholane (OTP) reactive group. ABPP experiments identified numerous proteins in human cancer cells that showed stereoselective reactivity with OTP stereoprobes, and we confirmed several of these liganding events with recombinant proteins.

Gut microbiota phospholipids regulate intestinal gene expression and can counteract the effects of antibiotic treatment.

The gut microbiome influences immune and metabolic homeostasis. Our research using non-obese diabetic (NOD) mice revealed that early-life antibiotic exposure remodels the gut microbiome affecting metabolism and accelerating type 1 diabetes (T1D) incidence, with cecal material transplant (CMT) mitigating the damage. Now examining murine intestinal lipidomic profiles, we identified 747 compounds.

Association of body roundness index with cardiovascular disease and all-cause mortality among Chinese adults.

Aims: To determine the impact of body roundness index (BRI) on the 10-year risk of cardiovascular disease (CVD) and all-cause mortality in Chinese adults.

Materials And Methods: We utilized data from a nationwide prospective cohort of 165 785 Chinese adults (aged ≥40 years, free of CVD and cancer at baseline), which was extracted from the China Cardiometabolic Disease and Cancer Cohort (4C). Cox regression and restricted cubic splines quantified BRI-outcome associations and identified optimal BRI cutoffs.

In vitro reconstitution of meiotic DNA double-strand-break formation.

The Spo11 complex catalyses the formation of DNA double-strand breaks (DSBs), initiating meiotic recombination-a process that is essential for fertility and genetic diversity. Although the function of Spo11 has been known for 27 years, previous efforts to reconstitute DSB formation in vitro have been unsuccessful. Here we biochemically characterize the mouse SPO11-TOP6BL protein complex, and show that this complex cleaves DNA and covalently attaches to the 5' terminus of DNA breaks in vitro.

High-quality genome of black wolfberry ( Murr.) provides insights into the genetics of anthocyanin biosynthesis regulation.

Black wolfberry ( Murr.) is an important plant for ecological preservation. In addition, its fruits are rich in anthocyanins and have important edible and medicinal value.

Efficiency of Early Sequential Laser Treatment for Facial Linear Scars in Cross-Sectional Regions.

Background: Long linear scars in cross-sectional regions can adversely affect facial aesthetics and functionality, leading to substantial psychological distress. Early intervention with carbon dioxide ablative fractional laser (CO-AFL) and 595-nm pulsed dye laser (PDL) has shown promise in mitigating post-surgical scarring. However, the effectiveness of this treatment for extensive facial scars across different areas remains unclear.

Carnosic acid reduces lipid content, enhances gut health, and modulates microbiota composition and metabolism in diet-induced obese mice.

Carnosic acid (CA) is a bioactive phenolic diterperne compound found in sage and rosemary. The present study investigated the beneficial effects of CA (50 and 100 mg per kg bw) in diet-induced obese mice and the underlying mechanisms of action. After the intervention, the physiology, lipid metabolism, and tissue morphology, as well as the inflammation, gut microbiota, and metabolomics in the colon were measured.

GPR180 reduces adiposity by inhibiting lipogenesis and fatty acid uptake in adipocytes.

In this study, we examined the effect of GPR180, a G protein-coupled receptor (GPCR) family member, on lipid metabolism of adipose tissue. We used adeno-associated virus overexpression of in subcutaneous adipose tissue, adipocyte-specific knockout mice and stromal vascular fraction (SVF) cells to explore the role and mechanism of GPR180 in lipid metabolism in adipocytes. Levels of mRNA in subcutaneous and epididymal adipose tissues were significantly reduced in mice fed high-fat diet (HFD).

Advances and insights into modeling extracellular electron transfer in anaerobic bioprocesses.

Extracellular electron transfer (EET) plays an important role in maintaining redox balance in both natural and engineered anaerobic microbial systems, driving key biochemical processes such as energy generation, bioremediation, and waste degradation. While EET has been characterized in a limited number of microbes and applied in anaerobic digestion and bioelectrochemical systems, further research is needed to explore its mechanism across a broader range of microbial species and anaerobic processes. This review highlights advanced modeling frameworks that provide deeper insights into EET mechanisms and dynamics, aiming to optimize research efforts and minimize time and resource expenditure.

DLAT is involved in ovarian cancer progression by modulating lipid metabolism through the JAK2/STAT5A/SREBP1 signaling pathway.

Background: Ovarian cancer (OC) remains a lethal gynecological malignancy with an alarming mortality rate, primarily attributed to delayed diagnosis and a lack of effective treatment modalities. Accumulated evidence highlights the pivotal role of reprogrammed lipid metabolism in fueling OC progression, however, the intricate underlying molecular mechanisms are not fully elucidated.

Methods: DLAT expression was assessed in OC tissues and cell lines by immunohistochemistry, western blot and qRT-PCR analysis.

A Novel Active Polyphase Filter Employing Frequency-Dependent Image Rejection Enhancement Technique.

In low intermediate frequency (low-IF) receivers, image interference rejection is one of the core tasks to be accomplished. Conventional active polyphase filters (APPFs) are unable to have a sufficient image rejection ratio (IRR) at high operating frequencies due to the degradation of the IRR by the amplitude and phase imbalances produced by the secondary pole. The proposed solution to the above problem is a frequency-dependent image rejection enhancement technique based on secondary pole compensation.

Disco-Interacting Protein 2 Homolog B CGG Repeat Expansion in Siblings with Neurodevelopmental Disability and Progressive Movement Disorder.

Background: Trinucleotide repeat expansions are an emerging class of genetic variants associated with various movement disorders. Unbiased genome-wide analyses can reveal novel genotype-phenotype associations and provide a diagnosis for patients and families.

Objective: The aim was to identify the genetic cause of a severe progressive movement disorder phenotype in 2 affected brothers.

Microneedle patch-involved local therapy synergized with immune checkpoint inhibitor for pre- and post-operative cancer treatment.

The metastasis and recurrence of cancer post-surgery remain the major reasons for treatment failures. Herein, a photo-immune nanoparticle decorating with M1 macrophage membrane (BD@LM) is designed based on the inflammatory environment after surgical resection. By loading photosensitizer black phosphorus quantum dots (BPQDs) and chemotherapeutics doxorubicin (DOX) in BD@LM nanoparticles, an effective chemophototherapy-mediated immunogenic cell death of tumor cells is triggered, subsequently leading to the maturation of dendritic cells for further immune cascade.

TiO-Modified Graphene Oxide Fillers Strengthen Acrylic Coated Samples Corrosion and Weathering Resistance on Q235 Steel.

As an exceptional 2D nanofiller, graphene oxide (GO) is extensively employed to amplify the protective properties of coatings. The dispersion of GO significantly influences the protective efficacy of the coatings. Here, a surface modification of GO through the integration of nanosized titanium dioxide (TiO) was employed, thereby facilitating the synthesis of an FGO-TiO nanoparticle characterized by a substantial interlayer spacing (0.

Exploring risk factors for all-cause hospital readmissions following chronic obstructive pulmonary disease exacerbation patients discharged on steroid tapers.

Background: Chronic obstructive pulmonary disease (COPD) exacerbations often lead to hospitalizations and subsequent readmissions. Steroid therapy is a common approach in managing COPD exacerbations, yet a considerable proportion of patients experience readmissions within a short timeframe, highlighting the persistent and complex nature of COPD exacerbations. The aim of this retrospective study is to investigate risk factors for all-cause hospital readmissions in COPD patients discharged on steroid tapers following exacerbations, emphasizing the need for personalized management strategies to reduce readmission rates.

Digital devices usage and neck and shoulder pain among college students: a cross-sectional study in China.

Neck and shoulder pain (NSP) is a common issue among college students, yet no studies have linked digital device usage to NSP prevalence in China. This cross-sectional survey aimed to explore this relationship among students in Shanghai. A total of 6,000 students were randomly selected, with 4,848 (80.

Impact of SARS-CoV-2 inactivated vaccine on symptoms following omicron variant breakthrough infection.

The SARS-CoV-2 Omicron variant and its sublineages continue to circulate widely. Clinical outcomes with this variant differ among individuals, primarily influenced by host immunity. Previous studies have explored the relationship between immune responses and severe diseases in infected or convalescent patients.

Pathogenetic mechanisms of muscle-specific ribosomes in dilated cardiomyopathy.

The heart employs a specialized ribosome in its muscle cells to translate genetic information into proteins, a fundamental adaptation with an elusive physiological role. Its significance is underscored by the discovery of neonatal patients suffering from often fatal heart failure caused by severe dilated cardiomyopathy when both copies of the gene are mutated. RPL3L is a muscle-specific paralog of the ubiquitous ribosomal protein L3 (RPL3), which makes the closest contact of any protein to the ribosome's RNA-based catalytic center.

Finite element analysis of stress distribution in cantilever resin-bonded zirconia fixed dental prosthesis and periodontal tissue with alveolar bone loss.

Purpose: To compare the stress distribution in loaded zirconia resin-bonded fixed dental prostheses (RBFDPs) and periodontal tissue using finite element analysis, considering reduced alveolar bone levels and the number of retainers.

Methods: A human skull was micro-CT scanned. Three framework designs were tested: a 2-unit RBFDP using the maxillary left central incisor (#21) as an abutment, another using a canine (#23), and a 3-unit RBFDP using both #21 and #23.