Acceptor Elongation Boosted Intersystem Crossing Affords Efficient NIR Type-I and AIE-Active Photosensitizers for Targeting Ferroptosis-Based Cancer Therapy.

Photosensitizers (PSs) featuring type I reactive oxygen species (ROS) generation and aggregation-induced emission (AIE) activity offer a promising solution to achieve non-invasive and precise theranostics. However, the reported AIE luminogens (AIEgens) with both AIE characteristic and strong type-I ROS generation are still scarce and the structure-property relationship is still unclear. Herein, an innovative acceptor elongation boosted intersystem crossing (AEBIC) design strategy has been proposed to endow the AIEgen strong type-I ROS producibility.

Gas-propelled anti-hair follicle aging microneedle patch for the treatment of androgenetic alopecia.

Existing treatments for androgenetic alopecia (AGA) are unsatisfactory, owing to the two major reasons: (1) Oxidative stress and vascularization deficiency in the perifollicular microenvironment provoke the premature senescence of hair follicles, limiting the transformation of hair growth cycle from the telogen to the anagen phase; (2) The amount of drug delivered to the perifollicular region located in the deep dermis is very limited for passive drug delivery systems. Herein, we developed a gas-propelled microneedle patch integrated with ferrum-chelated puerarin/quercetin nanoparticles (PQFN) to increase drug accumulation in hair follicles and reshape the perifollicular microenvironment for improved hair-regenerating effects. PQFN can rejuvenate testosterone (Tes)-induced senescence of dermal papilla cells by scavenging ROS, restoring mitochondrial function, regulating signaling pathways related to hair regeneration, and upregulating hair growth-promoting genes.

Dynamic culturing of large cell-loaded PCL/gelatin methacryloyl scaffolds for bone critical size defect repair.

Due to the limited ability to self-repair, the regeneration of bone critical-sized defects (CSD) is a significant challenge. Bone tissue engineering scaffolds are considered promising candidates for CSD repair, but low cell infiltration efficiency and a lack of nutrients greatly restrict bone regeneration abilities. Herein, we developed a dynamic culturing of large biomimetic bone scaffolds, PCL/GelMA@cells that combining 3D printed polycaprolactone (PCL) multi-channel cylinder with gelatin methacryloyl (GelMA) encapsulated with bone marrow mesenchymal stem cells (BMSCs) and rat aortic endothelial cells (RAECs).

IgA class switching enhances neutralizing potency against SARS-CoV-2 by increased antibody hinge flexibility.

IgA antibodies are critical components of the mucosal immune barrier, providing essential first-line defense against viral infections. In this study, we investigated the impact of antibody class switching on neutralization efficacy by engineering recombinant antibodies of different isotypes (IgA1, IgG1) with identical variable regions from SARS-CoV-2 convalescent patients. A potent, broad-spectrum neutralizing monoclonal antibody CAV-C65 exhibited a ten-fold increase in neutralization potency upon switching from IgG1 to IgA1 monomer.

The dual function of autophagy in doxorubicin-induced cardiotoxicity: Mechanism and natural products.

Doxorubicin (DOX) is an anthracycline antitumor drug discovered in 1969, which can care for leukemia, breast cancer, lymphoma, and sarcoma. However, cardiotoxicity induced by DOX seriously limits its clinical value. The etiopathogenesis and therapeutic strategies are not unified.

IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.

Background: It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC).

Methods: In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone.

Sinensetin attenuates LPS-induced acute pulmonary inflammation in mice and RAW264.7 cells by modulating NF-κB p65-mediated immune resistance and STAT3-mediated tissue resilience.

Acute pulmonary inflammation is a severe lower respiratory tract infection. Sinensetin (SIN), a polymethoxyflavone with strong anti-inflammatory properties, is known to ameliorate LPS-induced acute inflammatory lung injury, but its molecular mechanisms are not fully understood. This study aimed to provide insight into the pharmacological mechanisms of SIN in attenuating acute pulmonary inflammation.

Lipidomic characterization of polar and non-polar lipids in egg yolk and their anti-inflammatory and analgesic activities in zebrafish.

In this study, a technique that combines supercritical fluid extraction with ethanol extraction was employed to effectively fractionate egg yolk extracts into non-polar and polar lipids. By utilizing feature based molecular networking (FBMN) and MS-DIAL database search, 35 glycerolipids were identified in the supercritical extract (SE), and 70 glycerophospholipids in the ethanol extract (EE). Following the identification of lipids, a heatmap was generated using R software to visualize the abundance of lipids across both fractions.

NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression.

Pancreatic cancer liver metastasis is an important factor leading to dismal prognoses. The details of adaptive immune remodeling in liver metastasis, especially the role of neutrophils, remain elusive. Here, combined single-cell sequencing with spatial transcriptomics results revealed that liver metastases exhibit more aggressive transcriptional characteristics and higher levels of immunosuppression compared with the primary tumor.

Effects of Yin and Yang supplement on reproductive performance, antioxidant and immunity of dairy goats.

This study aims to explore the effects of Yin and Yang Double Supplement Compound Chinese Medicine Preparations (YYSBFF) on the reproductive performance, antioxidant levels, and immunity of dairy goats. For the experiment, 36 Alps milk goats were selected and randomly divided into an experimental group and a control group, with 18 goats in each group. The ewes in the experimental group were fed with YYSBFF for 14 d prior to breeding and farrowing.

Review of osteokines in spinal cord injury: potential biomarkers during rehabilitation.

After spinal cord injury (SCI), mechanical unloading, denervation, as well as negative changes in blood supply, inflammation state, and hormone levels produce significant negative effects on bone density, leading to a high prevalence of osteoporosis after SCI. It has been recently discovered that skeletal bone also has endocrine functions. Osteokines, secreted from bone tissue, could play multiple roles in regulating bone density, muscle mass, glucose metabolism, and functions of the central nervous system-changes in the osteokine levels after SCI have been detected.

Early attainment of 20-hydroxyecdysone threshold shapes mosquito sexual dimorphism in developmental timing.

In holometabolous insects, critical weight (CW) attainment triggers pupation and metamorphosis, but its mechanism remains unclear in non-model organisms like mosquitoes. Here, we investigate the role of 20-hydroxyecdysone (20E) in CW assessment and pupation timing in Aedes albopictus and Ae. aegypti, vectors of arboviruses including dengue and Zika.

CDK14 regulates the development and repair of lung.

Cyclin-dependent kinases (CDK) 14 regulates cell cycle, tumor expansion by influencing the downstream targets of the canonical Wnt signaling pathway. However, the function of CDK14 during organ development and regeneration has not been investigated in genetically-modified animals. Here, we found that genetic ablation of Cdk14 influenced pulmonary vascular endothelial cells and alveolar epithelial cells during mice embryonic development as well as repair of lung after bleomycin or lipopolysaccharide induced injury.

CK2α-mediated phosphorylation of DUB3 promotes YAP1 stability and oncogenic functions.

The aberrant upregulation of Yes-associated protein 1 (YAP1) in a variety of solid cancers contributes to tumor progression and poor clinical outcomes, rendering it an appealing therapeutic target. However, effective therapies to directly target YAP1 remain challenging. In this study, we perform a high-throughput screening and identify Casein kinase II (CK2) as an uncharacterized upstream regulator of YAP1 turnover in cancer cells of ovarian cancer and several other cancer types.

Discovery and characterization of a new β-glucosidase from Wolfiporia cocos through RNA sequencing and heterologous expression in Escherichia coli.

De novo RNA-sequencing of Wolfiporia cocos mycelia cultured with filter paper composed of cellulose as the sole carbon source revealed a total of five expressed β-glucosidase genes. Among these, the β-glucosidase named Wcbg1B-1, which is composed of 539 amino acid residues and belongs to the GH1 family, had the highest mRNA abundance, accounting for 65 % of the total mRNA of the five expressed β-glucosidases. The recombinant Wcbg1B-1 was successfully expressed in Escherichia coli, with an optimal pH of 6.

Prediction of OCT contours of short-term response to anti-VEGF treatment for diabetic macular edema using generative adversarial networks.

Diabetic macular edema (DME) stands as a leading cause for vision loss among the working-age population. Anti-vascular endothelial growth factor (VEGF) agents are currently recognized as the first-line treatment. However, a significant portion of patients remain insensitive to anti-VEGF, resulting in sustained visual impairment.

THSWD upregulates the LTF/AMPK/mTOR/Becn1 axis and promotes lysosomal autophagy in hepatocellular carcinoma cells by regulating gut flora and metabolic reprogramming.

THSWD has the effect of reducing inflammation, improving microcirculation, and regulating immune status in patients with hepatocellular carcinoma. Regardless of its clear therapeutic effect, the underlying mechanism of action against hepatocellular carcinoma is not clear. To identify critical gut microbiota and its associated metabolites related to THSWD inhibition against hepatocellular carcinoma progression, we assessed the microbe-dependent anti-hepatocellular carcinoma effects of THSWD through 16 s rRNA gene sequencing, fecal microbial transplantation and antibiotic treatment.

Protocol for genetic analysis of population-scale ultra-low-depth sequencing data.

Non-invasive prenatal testing (NIPT) not only enables the detection of chromosomal anomalies in fetuses but also generates vast amounts of ultra-low-depth sequencing data, which can be leveraged for population genomic studies. Here, we present a protocol designed for massive ultra-low-depth sequencing datasets. We detail the steps for data processing, quality control, and genotype imputation, followed by genome-wide association study (GWAS) and post-GWAS analyses.

From chaos to order: optimizing fecal microbiota transplantation for enhanced immune checkpoint inhibitors efficacy.

The integration of fecal microbiota transplantation (FMT) with immune checkpoint inhibitors (ICIs) presents a promising approach for enhancing cancer treatment efficacy and overcoming therapeutic resistance. This review critically examines the controversial effects of FMT on ICIs outcomes and elucidates the underlying mechanisms. We investigate how FMT modulates gut microbiota composition, microbial metabolite profiles, and the tumor microenvironment, thereby influencing ICIs effectiveness.

Stochastic galvanic vestibular stimulation improves kinetic performance in adolescent idiopathic scoliosis during obstacle negotiation.

Vestibular dysfunction has been reported as a potential cause in adolescent idiopathic scoliosis (AIS). However, it remained unclear how stochastic galvanic vestibular stimulation (GVS) affected kinetic performance of patients with AIS. This study aimed to investigate the effect of stochastic GVS on ground reaction forces (GRF) measures during obstacle negotiation among patients with AIS.

Associations between anthropogenic heat emissions and serum lipids among adults in northeastern China.

Few epidemiological studies have investigated associations between anthropogenic heat emissions (AE) and serum lipids. We recruited 15,477 adults from 33 communities in northeastern China in 2009. We estimated AE flux by using data on energy consumption and socio-economic statistics covering building, transportation, industry, and human metabolism.

Individualized PEEP titration by lung compliance during one-lung ventilation: a meta-analysis.

Background: Despite the physiological advantages of positive end-expiratory pressure (PEEP), its optimal utilization during one-lung ventilation (OLV) remains uncertain. We aimed to investigate whether individualized PEEP titration by lung compliance is associated with a reduced risk of postoperative pulmonary complications during OLV.

Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials until April 1, 2024, to identify published randomized controlled trials that compared individualized PEEP titration by lung compliance with fixed PEEP during OLV.

Proteome-wide mendelian randomization identifies causal plasma proteins in interstitial lung disease.

Interstitial lung disease (ILD) has shown limited treatment advancements, with minimal exploration of circulating protein biomarkers causally linked to ILD and its subtypes beyond idiopathic pulmonary fibrosis (IPF). In this study, we aimed to identify potential drug targets and circulating protein biomarkers for ILD and its subtypes. We utilized the most recent large-scale plasma protein quantitative trait loci (pQTL) data detected from the antibody-based method and ILD and its subtypes' GWAS data from the updated FinnGen database for Mendelian randomization analysis.

Regulation of enzymatic lipid peroxidation in osteoblasts protects against postmenopausal osteoporosis.

Oxidative stress plays a critical role in postmenopausal osteoporosis, yet its impact on osteoblasts remains underexplored, limiting therapeutic advances. Our study identifies phospholipid peroxidation in osteoblasts as a key feature of postmenopausal osteoporosis. Estrogen regulates the transcription of glutathione peroxidase 4 (GPX4), an enzyme crucial for reducing phospholipid peroxides in osteoblasts.

TGR5 attenuates DOCA-salt hypertension through regulating histone H3K4 methylation of ENaC in the kidney.

Epithelial sodium channel (ENaC), located in the collecting duct principal cells of the kidney, is responsible for the reabsorption of sodium and plays a critical role in the regulation of extracellular fluid volume and consequently blood pressure. The G protein-coupled bile acid receptor (TGR5) is a membrane receptor mediating effects of bile acid and is implicated in kidney diseases. The current study aims to investigate whether TGR5 activation in the kidney regulated ENaC expression and potential mechanism.