Phenotypic screening converges on CDK9 inhibition as a therapeutic strategy in translocation renal cell carcinoma.

Translocation renal cell carcinoma (tRCC) is an aggressive kidney cancer driven by gene fusions of the transcription factor. is essential in tRCC but dispensable in normal cells, presenting an attractive but pharmacologically challenging therapeutic target. We show that the basic helix-loop-helix (bHLH) domain of TFE3 is crucial for chromatin binding and transcriptional function.

Adenosarcoma of uterus characterized by differentiation of rhabdomyosarcoma and chondrosarcoma: A case report and review of literature.

Although Müllerian adenosarcoma of the uterus shows weak malignant potential, there are still some factors indicating a worse prognosis. An incontinuous pelvic pain with urinary frequency, urgency, and hypouricemia arose in a mid-70s woman who refused to acknowledge the history of Tamoxifen use. A huge mass in the pelvis was found simultaneously by palpation, B-ultrasonography, and computed tomography.

Glia maturation factor-β deficiency improves insulin resistance by promoting CARM1-mediated lipid turnover.

Insulin resistance (IR) is a major factor for obesity-associated type 2 diabetes. The molecular mechanisms of IR and its systemic control remain poorly understood, and pharmacological drugs to ameliorate IR are an unmet need. So finding new therapeutic targets and drugs is important.

Green Synthesis and Flexibilization Engineering of (ECMP)MnBr for Smart Textile-Integrated Luminescence.

0D hybrid manganese halides represent an emerging class of luminescent materials, yet their practical application has been hindered by the intrinsic trade-off between optical performance and mechanical flexibility. Here, a green synthesis of 0D (ECMP)MnBr crystal is reported, exhibiting unprecedented triple-mode emission (photoluminescence, X-ray scintillation, and mechanoluminescence) through rationally designed highly symmetric [MnBr] tetrahedra, achieving near-unity photoluminescence quantum yield (98.97%), record-low X-ray detection limit (15.

Targeting miR-337 mitigates disuse-induced bone loss.

Disuse-induced bone loss occurs in long-term bed-ridden patients and in astronauts during spaceflight. The underlying mechanisms are poorly understood. In a rodent model of disuse-induced bone loss (called hindlimb unloading (HU)), we observed that decreased numbers of leptin receptor (LepR) positive mesenchymal stem cells (MSCs) in adult bone marrow, contribute to bone loss.

Assessing coronary artery disease severity using the TyG index in patients with LDL-C < 2.6 mmol/l.

Background: Determining the triglyceride‒glucose (TyG) index’s relationship to coronary lesions in patients with low-density lipoprotein cholesterol (LDL-C) targes will inform precision management of cardiovascular disease.

Methods: This retrospective cohort included 821 enrolled patients with LDL-C levels < 2.6 mmol/L who underwent coronary angiography at the Department of Cardiology, Tianjin Medical University General Hospital from January 2016 to February 2024.

Fibroblast-Myofibroblast Transition in Osteoarthritis Progression: Current Insights.

Osteoarthritis (OA) is a multifactorial joint disease traditionally characterized by cartilage degradation, while growing evidence underscores the critical role of synovial fibrosis in driving disease progression. The synovium exhibits pathological remodeling in OA, primarily due to the phenotypic transition of fibroblast-like synoviocytes (FLSs) into myofibroblasts. This fibroblast-myofibroblast transition (FMT) results in excessive deposition of extracellular matrix (ECM) and increased tissue stiffness and contractility, collectively contributing to chronic inflammation and fibrotic stiffening of the joint capsule.

High-speed computation of high-quality light fluence distribution from low-photon Monte Carlo using a Fourier neural network.

Monte Carlo (MC) simulation is the gold standard for studying light propagation in biological tissues within the field of tissue optics. However, the high computational costs of MC simulation limit its broader use in practice. Although GPU-accelerated MC methods significantly enhance computational efficiency, the time required remains substantial under conditions of high-photon numbers and fine mesh due to limited computational resources.

Design and Synthesis of Indole-Containing Tetrahydrothiazolo[3,2-]pyrimidine Mesoionics against Hemipteran Pests.

Mesoionic insecticides have emerged as promising pest nAChR modulators devoid of cross-resistance with neonicotinoids, demonstrating exceptional efficacy against sap-feeding insects. Nevertheless, the tetrahydrothiazolo[3,2-]pyrimidine structure remains underexplored within this chemotype. Here, we report an indole-based scaffold hopping of tetrahydrothiazolo[3,2-]pyrimidine, which leads to the development of a series of novel mesoionics.

TfOH-Mediated Synthesis of Unsymmetrical Disulfides from Diethyl 2,2'-Disulfanediylbis(4-methyl-6-phenylpyrimidine-5-carboxylate).

A novel approach for the S-S bond exchange reaction of two symmetrical disulfides, promoted by TfOH under metal-free conditions at room temperature, has been developed. This protocol facilitates the efficient and effortless synthesis of a series of important unsymmetrical disulfides with yields of up to 93% and excellent functional group compatibility. The advantages of this strategy include straightforward operation, broad substrate scope, good functional group tolerance, high chemoselectivity, and the ability to operate under ambient conditions.

Combined Biologics and Exclusive Enteral Nutrition Promote Early Transmural Healing and Improve Long-Term Outcomes in Crohn's Disease: A Multicenter Retrospective Study.

Transmural healing (TH), a comprehensive therapeutic target in Crohn's disease (CD), is associated with reduced long-term complications. However, evidence on the role of exclusive enteral nutrition (EEN) in TH remains limited. This study aimed to evaluate the efficacy of biologics combined with 16-week EEN in achieving early TH and improving clinical outcomes.

Clinical outcome and influencing factors of differentiated thyroid cancer with biochemical incomplete response.

Purpose: The aim of our study was to investigate the clinical outcomes and predictive factors in patients with biochemical incomplete response (BIR) after initial radioiodine therapy (RAI).

Materials & Methods: This retrospective study enrolled 198 patients with BIR from two institutions and stratified them into a training cohort (Qingdao cohort, n = 144) and an external validation cohort (Beijing cohort, n = 54). The patients were classified as having incomplete response (IR) or non-IR disease at the final follow-up.

Clinical outcome and influencing factors of differentiated thyroid cancer patients with radioiodine-refractory lung metastasis.

Purpose: A subset of patients with differentiated thyroid cancer and lung metastases (DTC-LM) may progress to radioiodine-refractory (RAIR) disease, which is associated with a poor prognosis. This study aimed to investigate the clinical outcomes and potential risk factors associated with RAIR disease in DTC-LM patients.

Methods: 177 DTC-LM patients who underwent radioiodine (RAI) therapy at our center were retrospectively analyzed.

Unusual 131I Uptake in Talus May Reveal Distant Papillary Thyroid Cancer Metastasis With Anaplastic Transformation.

Talus metastasis is rarely observed on a 131I whole-body scan (WBS). We report a case of abnormal 131I uptake in the talus on the post-therapeutic WBS in a 54-year-old woman with papillary thyroid cancer (PTC). The patient received 2 courses of radioactive 131I therapy (RAIT) after the thyroid surgery.

Algorithms to minimize the effect of maternal contamination in non-invasive chromosome screening.

Research Question: Can algorithms be developed to assess maternal contamination in the embryo spent culture medium without parental samples and correct copy number variations (CNV)?

Design: An algorithm was developed to confirm the proportion of maternal contamination based on the mosaic ratios of X and Y chromosomes and an algorithm to correct copy number variation (CNV) in embryos with maternal contamination. Performance of algorithms was tested in 317 culture medium samples. A prospective clinical study was then conducted to validate the accuracy.

Analysis of HBV infection characteristics and OBI prevalence in pregnant women: a focus on HBcAb + alone or in combination with HBeAb + subgroups in Northwest China.

Background: Hepatitis B virus (HBV) infection is a major global health concern. Serological patterns such as "HBeAb + and HBcAb+" or "HBcAb + only" are typically markers, which may represent either resolved infection or potential occult HBV infection (OBI) with risk of vertical transmission. But OBI in these subgroups of pregnant women in Northwest China remains underreported.

Glycosylated quercetin/cisplatin combinational nanodrugs for enhanced oxidative therapy and chemotherapy.

Drug self-assembly technology holds great potential for drug delivery; however, its practical application is often hindered by poor dispersibility, instability, and suboptimal therapeutic efficacy in monotherapy. To address these limitations, we developed a co-assembly strategy based on glycosylation and coordination crosslinking. Lactobionic acid (LA)-modified quercetin (QC) derivatives were synthesized via phenylboronic acid ester bonds and further assembled with cisplatin (CDDP) through Pt-O coordination bonds, forming LA-QC@Pt/NPs.

Multimodal artificial intelligence for subepithelial lesion classification and characterization: a multicenter comparative study (with video).

Background: Subepithelial lesions (SELs) present significant diagnostic challenges in gastrointestinal endoscopy, particularly in differentiating malignant types, such as gastrointestinal stromal tumors (GISTs) and neuroendocrine tumors, from benign types like leiomyomas. Misdiagnosis can lead to unnecessary interventions or delayed treatment. To address this challenge, we developed ECMAI-WME, a parallel fusion deep learning model integrating white light endoscopy (WLE) and microprobe endoscopic ultrasonography (EUS), to improve SEL classification and lesion characterization.

ATF4 regulates PI3K/AKT signaling axis to promote angiogenesis after myocardial infarction.

Effective neovascularization is critical for tissue repair and the enhancement of cardiac function following myocardial infarction (MI). However, the hypoxic microenvironment post-MI significantly impedes neovascular formation. Although ATF4 has been implicated in heart failure and myocardial cell regeneration and repair, its role in angiogenesis remains unclear.

Innovative pyrido[1,2-a]pyrimidine-based cinnamic acid derivatives against Sogatella furcifera with better biosafety to pollinators.

Background: Sogatella furcifera, commonly known as white-backed planthopper, is a highly threatening migratory pest that feeds on rice and can transmit phytoviruses. Recently, mesoionic insecticides, exemplified by triflumezopyrim (TFM), have proven effective in managing such pests. Nevertheless, available data indicate that TFM remains highly toxic to ecologically important pollinators.

ZnS-SnS-NiCoS: a new breakthrough in quaternary sulfide composites for the oxygen evolution reaction.

A ZnS-SnS-NiCoS composite was fabricated on Ni foam by polymetallic compositing of NiS. The optimized catalyst exhibits outstanding OER performance with a low overpotential (149 mV at 10 mA cm) and Tafel slope (33.57 mV dec), offering a promising strategy for efficient water splitting and sustainable hydrogen production.

A mechano-resistance mechanism in skin adapts to terrestrial locomotion.

The transition from water to land required animals to evolve specialized paw skin to support body weight and enable locomotion. We identify an evolutionarily emerged mechanism in skin epithelial cells that adapts to this mechanical demand. We show that the Slurp1 gene, conserved across tetrapods, is specifically expressed in palmoplantar skin.