An Automatic Deep-Radiomics Framework for Prostate Cancer Diagnosis and Stratification in Patients with Serum Prostate-Specific Antigen of 4.0-10.0 ng/mL: A Multicenter Retrospective Study.

Rationale And Objectives: To develop an automatic deep-radiomics framework that diagnoses and stratifies prostate cancer in patients with prostate-specific antigen (PSA) levels between 4 and 10 ng/mL.

Materials And Methods: A total of 1124 patients with histological results and PSA levels between 4 and 10 ng/mL were enrolled from one public dataset and two local institutions. An nnUNet was trained for prostate masks, and a feature extraction module identified suspicious lesion masks.

Roseburia intestinalis-derived butyrate alleviates neuropathic pain.

Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles.

Kartogenin-Loaded Exosomes Derived From Bone Marrow Mesenchymal Stem Cells Enhance Chondrogenesis and Expedite Tendon Enthesis Healing in a Rat Model of Rotator Cuff Injury.

Background: The insufficient regeneration of fibrocartilage at the tendon enthesis is the primary cause of retearing after surgical reattachment of the rotator cuff. Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSC-Exos) and kartogenin (KGN) have been demonstrated to induce fibrocartilage formation. Loading drugs into exosomes may lead to a synergistic effect, significantly enhancing the inherent activity of both components.

Clinical Benefit from Docetaxel +/- Ramucirumab Is Not Associated with Mutation Status in Metastatic Non-Small-Cell Lung Cancer Patients Who Progressed on Platinum Doublets and Immunotherapy.

Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population.

Biomarker Changes during 20 Years Preceding Alzheimer's Disease.

Background: Biomarker changes that occur in the period between normal cognition and the diagnosis of sporadic Alzheimer's disease have not been extensively investigated in longitudinal studies.

Methods: We conducted a multicenter, nested case-control study of Alzheimer's disease biomarkers in cognitively normal participants who were enrolled in the China Cognition and Aging Study from January 2000 through December 2020. A subgroup of these participants underwent testing of cerebrospinal fluid (CSF), cognitive assessments, and brain imaging at 2-year-to-3-year intervals.

Light controls mesophyll-specific post-transcriptional splicing of photoregulatory genes by AtPRMT5.

Light plays a central role in plant growth and development, providing an energy source and governing various aspects of plant morphology. Previous study showed that many polyadenylated full-length RNA molecules within the nucleus contain unspliced introns (post-transcriptionally spliced introns, PTS introns), which may play a role in rapidly responding to changes in environmental signals. However, the mechanism underlying post-transcriptional regulation during initial light exposure of young, etiolated seedlings remains elusive.

ZBTB20 Regulates SERCA2a Activity and Myocardial Contractility Through Phospholamban.

Background: Intracellular Ca cycling determines myocardial contraction and relaxation in response to physiological demands. SERCA2a (sarcoplasmic/endoplasmic reticulum Ca-ATPase 2a) is responsible for the sequestration of cytosolic Ca into intracellular stores during cardiac relaxation, and its activity is reversibly inhibited by PLN (phospholamban). However, the regulatory hierarchy of SERCA2a activity remains unclear.

Preoperative Prediction of Perineural Invasion in Oesophageal Squamous Cell Carcinoma Based on CT Radiomics Nomogram: A Multicenter Study.

Rationale And Objectives: To investigate the value of computed tomography (CT) radiomics nomogram in the preoperative prediction of perineural invasion (PNI) in oesophageal squamous cell carcinoma (ESCC) through a multicenter study.

Materials And Methods: We retrospectively collected postoperative pathological data of 360 ESCC patients with definite PNI status (131 PNI-positive and 229 PNI-negative) from two centres. Radiomic features were extracted from the arterial-phase CT images, and the least absolute shrinkage and selection operator and logistic regression algorithm were used to screen valuable features for identifying the PNI status and calculating the radiomics score (Rad-score).

Resolvin E1/ChemR23 Protects Against Hypertension and Vascular Remodeling in Angiotensin II-Induced Hypertensive Mice.

Background: Inflammation plays a critical role in the development of hypertension and vascular remodeling. Resolvin E1 (RvE1), as one of the specialized proresolving lipid mediators, promotes inflammation resolution by binding with a G protein-coupled receptor, ChemR23 (chemerin receptor 23). However, whether RvE1/ChemR23 regulates hypertension and vascular remodeling is unknown.

Surface-immobilized cross-linked cationic polyelectrolyte enables CO reduction with metal cation-free acidic electrolyte.

Electrochemical CO reduction in acidic electrolytes is a promising strategy to achieve high utilization efficiency of CO. Although alkali cations in acidic electrolytes play a vital role in suppressing hydrogen evolution and promoting CO reduction, they also cause precipitation of bicarbonate on the gas diffusion electrode (GDE), flooding of electrolyte through the GDE, and drift of the electrolyte pH. In this work, we realize the electroreduction of CO in a metal cation-free acidic electrolyte by covering the catalyst with cross-linked poly-diallyldimethylammonium chloride.

DNA-encoded chemical libraries yield non-covalent and non-peptidic SARS-CoV-2 main protease inhibitors.

The development of SARS-CoV-2 main protease (M) inhibitors for the treatment of COVID-19 has mostly benefitted from X-ray structures and preexisting knowledge of inhibitors; however, an efficient method to generate M inhibitors, which circumvents such information would be advantageous. As an alternative approach, we show here that DNA-encoded chemistry technology (DEC-Tec) can be used to discover inhibitors of M. An affinity selection of a 4-billion-membered DNA-encoded chemical library (DECL) using M as bait produces novel non-covalent and non-peptide-based small molecule inhibitors of M with low nanomolar K values.

Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer.

The role of combination chemotherapy with immune checkpoint inhibitors (ICI) (ICI-chemo) over ICI monotherapy (ICI-mono) in non-small cell lung cancer (NSCLC) remains underexplored. In this retrospective study of 1133 NSCLC patients, treatment with ICI-mono vs ICI-chemo associate with higher rates of early progression, but similar long-term progression-free and overall survival. Sequential vs concurrent ICI and chemotherapy have similar long-term survival, suggesting no synergism from combination therapy.

Blood Pressure Levels, Cardiovascular Events, and Renal Outcomes in Chronic Kidney Disease Without Antihypertensive Therapy: A Nationwide Population-Based Cohort Study.

Background: High blood pressure (BP) is highly prevalent in patients with chronic kidney disease. However, the thresholds to initiate BP-lowering treatment in this population are unclear. We aimed to examine the associations between BP levels and clinical outcomes and provide evidence on potential thresholds to initiate BP-lowering therapy in people with chronic kidney disease.

GPX2 Gene Affects Feed Efficiency of Pigs by Inhibiting Fat Deposition and Promoting Muscle Development.

GPX2 has been recognized as a potential candidate gene for feed efficiency in pigs. This article aimed to elucidate polymorphism of GPX2 associated with feed efficiency and its related molecular mechanism. In this study, seven single nucleotide polymorphisms (SNP) of GPX2 were found among 383 Duroc pigs.

Generation of a humanized afucosylated BAFF-R antibody with broad activity against human B-cell malignancies.

B-cell activating factor receptor (BAFF-R) is a mature B-cell survival receptor, which is highly expressed in a wide variety of B-cell malignancies but with minimal expression in immature B cells. These properties make BAFF-R an attractive target for therapy of B-cell lymphomas. We generated a novel humanized anti BAFF-R monoclonal antibody (mAb) with high specificity and potent in vitro and in vivo activity against B-cell lymphomas and leukemias.

Genetic deconvolution of fetal and maternal cell-free DNA in maternal plasma enables next-generation non-invasive prenatal screening.

Current non-invasive prenatal screening (NIPS) analyzes circulating fetal cell-free DNA (cfDNA) in maternal peripheral blood for selected aneuploidies or microdeletion/duplication syndromes. Many genetic disorders are refractory to NIPS largely because the maternal genetic material constitutes most of the total cfDNA present in the maternal plasma, which hinders the detection of fetus-specific genetic variants. Here, we developed an innovative sequencing method, termed coordinative allele-aware target enrichment sequencing (COATE-seq), followed by multidimensional genomic analyses of sequencing read depth, allelic fraction, and linked single nucleotide polymorphisms, to accurately separate the fetal genome from the maternal background.

An anti-CTLA-4 heavy chain-only antibody with enhanced T depletion shows excellent preclinical efficacy and safety profile.

The value of anti-CTLA-4 antibodies in cancer therapy is well established. However, the broad application of currently available anti-CTLA-4 therapeutic antibodies is hampered by their narrow therapeutic index. It is therefore challenging and attractive to develop the next generation of anti-CTLA-4 therapeutics with improved safety and efficacy.

Dynamic trafficking patterns of IL-17-producing γδ T cells are linked to the recurrence of skin inflammation in psoriasis-like dermatitis.

Background: Psoriasis recurrence is a clinically challenging issue. However, the underlying mechanisms haven't been fully understood.

Methods: RNAseq analysis from affected skin of psoriatic patients treated with topical glucocorticoid (GC) with different outcomes was performed.