Developing the new diagnostic model by integrating bioinformatics and machine learning for osteoarthritis.

Background: Osteoarthritis (OA) is a common cause of disability among the elderly, profoundly affecting quality of life. This study aims to leverage bioinformatics and machine learning to develop an artificial neural network (ANN) model for diagnosing OA, providing new avenues for early diagnosis and treatment.

Methods: From the Gene Expression Omnibus (GEO) database, we first obtained OA synovial tissue microarray datasets.

Development of a Frailty Prediction Model Among Older Adults in China: A Cross-Sectional Analysis Using the Chinese Longitudinal Healthy Longevity Survey.

Aims: To identify the risk factors associated with frailty among older adults in China and develop a predictive model for assessing their frailty risk.

Design: Secondary cross-sectional analysis.

Methods: The 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) provided data for this study.

Sarcopenia is associated with new-onset acute biliary infection within 1 year in patients with hepatitis B virus-related decompensated cirrhosis.

Backgrounds: Malnutrition and sarcopenia are prevalent complications in cirrhosis. The relationship between sarcopenia and biliary infection in cirrhotic patients is not well understood. Our study aims to clarify this association.

Ultrasound Guided Local Delivery of Bioorthogonal PDL1 Degrader for Enhanced Immunotherapy.

Immunotherapy involving PDL1 degradation holds great potential in anti-tumor treatment. Optimal design of PDL1 degraders and subsequent efficient delivery into tumors are essential for expected efficacy, especially when abnormal tumor vasculature is considered. Herein, a nanodroplet-based novel drug delivery platform termed as NDs (nanodroplet-based therapeutics) for ultrasound targeted delivery of PDL1 degrader is designed.

TLR2 Activation as a Marker of Severe COVID-19 and a Potential Therapeutic Target.

SARS-CoV-2-induced COVID-19 has been a serious public health problem, resulting in millions of lives lost over the previous three years. Although the direct infection caused by virus invasion is important for the pathobiology of COVID-19, the hyperinflammatory response and tissue injury are major contributors in critically ill patients. As a host sensor, toll-like receptor 2 (TLR2) recognizes multiple pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), producing various inflammatory cytokines and inflammatory cell death signals, which are central to the inflammatory pathology observed in COVID-19.

Revealing the mechanism of natural product-induced immunogenic cell death: opening a new chapter in tumor immunotherapy.

This review underscores the role of natural products in inducing immunogenic cell death (ICD) as a key strategy in tumor immunotherapy. It reveals that natural products can activate ICD through multiple pathways-apoptosis, autophagy, pyroptosis, and necroptosis-leading to the release of danger-associated molecular patterns (DAMPs), dendritic cell activation, and improved antigen presentation, which together stimulate a potent anti-tumor immune response. The study also demonstrates the enhanced therapeutic potential of combining natural products with immune checkpoint inhibitors.

From ROS scavenging to boosted osseointegration: cerium-containing mesoporous bioactive glass nanoparticles functionalized implants in diabetes.

Excessive production of reactive oxygen species (ROS) around titanium implants under diabetic conditions causes persistent inflammation, leading to poor osseointegration and even implant failure. Surface modification is an effective way to promote ROS clearance, alleviate inflammation, and stimulate bone formation. In this study, a multifunctional coating is fabricated by introducing cerium (Ce)-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) onto the titanium surface via an electrophoretic deposition method.

The seventh blind test of crystal structure prediction: structure generation methods.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern.

Pickle water ameliorates castor oil-induced diarrhea in mice by regulating the homeostasis of the gut microbiota and intestinal mucosal barrier.

Introduction: Diarrhea is a common clinical condition that can potentially be fatal. Current treatment options often have side effects, such as constipation and vomiting, and there remains a need for more effective therapies. Pickled vegetables, a famous traditional food in China, have been suggested in clinical studies to alleviate diarrhea in children, particularly through the use of pickle water (PW).

Serial evaluation of liver enzyme activities in dogs with pulmonary coccidioidomycosis administered fluconazole.

Pulmonary coccidioidomycosis is a relatively common fungal disorder in dogs that have lived in or traveled to endemic regions and fluconazole is a common antifungal treatment. Liver enzymopathy can occur with fluconazole administration, but the frequency of occurrence nor potentially associative factors have been explored in dogs with pulmonary coccidioidomycosis. Therefore, our objectives were to describe the occurrence and magnitude of liver enzyme activity (LEA) elevation in dogs with pulmonary coccidioidomycosis during treatment with fluconazole and identify variables associated with liver enzymopathy.

Boosting of Redox-Active Polyimide Porous Organic Polymers with Multi-Walled Carbon Nanotubes towards Pseudocapacitive Energy Storage.

Redox-active porous organic polymers (POPs) demonstrate significant potential in supercapacitors. However, their intrinsic low electrical conductivity and stacking tendencies often lead to low utilization rates of redox-active sites within their structural units. Herein, polyimide POPs (donated as PMTA) are synthesized in situ on multi-walled carbon nanotubes (MWCNTs) from tetramino-benzoquinone (TABQ) and 1,4,5,8-naphthalene tetracarboxylic dianhydride (PMDA) monomers.

Hfq-binding small RNA PqsS regulates Pseudomonas aeruginosa pqs quorum sensing system and virulence.

Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P.

Ultrasound targeted microbubble destruction assisted exosomal delivery of siHmox1 effectively inhibits doxorubicin-induced cardiomyocyte ferroptosis.

Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-regulation of Hmox1, as knockdown of Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery of siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed by ultrasound microbubble targeted destruction (UTMD) in the heart region.

Compressible Hollow Microlasers in Organoids for High-Throughput and Real-Time Mechanical Screening.

Mechanical stress within organoids is a pivotal indicator in disease modeling and pharmacokinetics, yet current tools lack the ability to rapidly and dynamically screen these mechanics. Here, we introduce biocompatible and compressible hollow microlasers that realize all-optical assessment of cellular stress within organoids. The laser spectroscopy yields identification of cellular deformation at the nanometer scale, corresponding to tens of pascals stress sensitivity.

Anisotropic SmFeV Bulk Magnets with Enhanced Coercivity via Ball Milling Process.

Anisotropic bulk magnets of ThMn-type SmFeV with a high coercivity () were successfully fabricated. Powders with varying particle sizes were prepared using the ball milling process, where the particle size was controlled with milling time. A decrease in occurred in the heat-treated bulk pressed from large-sized powders, while heavy oxidation excessively occurred in small powders, leading to the decomposition of the SmFeV (1-12) phase.

Physician Associate/Assistant Program Medical Directors Are Important Advocates for the Physician Associate/Assistant Profession: Results From a National Pilot Study.

Introduction: This pilot study aimed to evaluate whether and how physician associate/assistant (PA) program medical directors play a role in advocating on behalf of PAs and what factors correlate with this.

Methods: The study used a mixed-methods grounded theory approach and was deemed institutional review board exempt. After literature review, a survey was developed and piloted by study personnel and faculty to affirm validity.

Single-cell laser emitting cytometry for label-free nucleolus fingerprinting.

The nucleolus, a recognized biomolecular condensate, serves as the hub for ribosome biogenesis within the cell nucleus. Its quantity and morphology are discernible indicators of cellular functional states. However, precise identification and quantification of nucleoli remain challenging without specific labeling, particularly for suspended cells, tissue-level analysis and high-throughput applications.

PDCD4 triggers α-synuclein accumulation and motor deficits via co-suppressing TFE3 and TFEB translation in a model of Parkinson's disease.

TFE3 and TFEB, as the master regulators of lysosome biogenesis and autophagy, are well characterized to enhance the synaptic protein α-synuclein degradation in protecting against Parkinson's disease (PD) and their levels are significantly decreased in the brain of PD patients. However, how TFE3 and TFEB are regulated during PD pathogenesis remains largely vague. Herein, we identified that programmed cell death 4 (PDCD4) promoted pathologic α-synuclein accumulation to facilitate PD development via suppressing both TFE3 and TFEB translation.

Gamma-type immunoglobulin enhances phagocytosis of amyloid-beta fibrils by microglia.

The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer's disease. Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system, though the mechanisms are unclear. Here, we found that gamma-type immunoglobulin, a product originating from peripheral blood B cells, localized in the brain parenchyma of multiple mouse models with amyloid pathology, and was enriched on microglia but not on other brain cell types.

IL-23 Priming Enhances the Neuroprotective Effects of MSC-Derived Exosomes in Treating Retinal Degeneration.

Purpose: Neuroinflammation is a characteristic feature of neurodegenerative diseases. Mesenchymal stem cell-derived exosomes (MSC-exo) have shown neuroprotective effects through immunoregulation, but the therapeutic efficacy remains unsatisfactory. This study aims to enhance the neuroprotective capacity of MSC-exo through IL-23 priming for treating retinal degeneration in mice.