Deep Learning-Derived Quantitative Scores for Chronic Rhinosinusitis Assessment: Correlation With Quality of Life Outcomes.

Background: Computed tomography (CT) plays a crucial role in assessing chronic rhinosinusitis, but lacks objective quantifiable indicators.

Objective: This study aimed to use deep learning for automated sinus segmentation to generate distinct quantitative scores and explore their correlations with disease-specific quality of life.

Methods: From July 2021 to August 2022, 445 CT data were collected from 2 medical centers.

Papillary Renal Neoplasm With Reverse Polarity: CT and MR Imaging Characteristics in 26 Patients.

Rationale And Objectives: To improve the diagnostic recognition of papillary renal neoplasm with reverse polarity (PRNRP) through comprehensive analysis of computed tomography (CT) and magnetic resonance imaging (MRI) findings.

Materials And Methods: A retrospective multi-center study was conducted on patients with pathologically confirmed PRNRPs from 2019 to 2024, encompassing six institutions. Clinical and pathological data were meticulously documented.

Determining structures of RNA conformers using AFM and deep neural networks.

Much of the human genome is transcribed into RNAs, many of which contain structural elements that are important for their function. Such RNA molecules-including those that are structured and well-folded-are conformationally heterogeneous and flexible, which is a prerequisite for function, but this limits the applicability of methods such as NMR, crystallography and cryo-electron microscopy for structure elucidation. Moreover, owing to the lack of a large RNA structure database, and no clear correlation between sequence and structure, approaches such as AlphaFold for protein structure prediction do not apply to RNA.

Covalent DNA-Encoded Library Workflow Drives Discovery of SARS-CoV-2 Nonstructural Protein Inhibitors.

The COVID-19 pandemic, exacerbated by persistent viral mutations, underscored the urgent need for diverse inhibitors targeting multiple viral proteins. In this study, we utilized covalent DNA-encoded libraries to discover innovative triazine-based covalent inhibitors for the 3-chymotrypsin-like protease (3CL, Nsp5) and the papain-like protease (PL) domains of Nsp3, as well as novel non-nucleoside covalent inhibitors for the nonstructural protein 12 (Nsp12, RdRp). Optimization through molecular docking and medicinal chemistry led to the development of , a nonpeptide 3CL inhibitor with an IC of 0.

Discovery of ZLC491 as a Potent, Selective, and Orally Bioavailable CDK12/13 PROTAC Degrader.

Selective degradation of cyclin-dependent kinases 12 and 13 (CDK12/13) emerges as a new potential therapeutic approach for triple-negative breast cancer (TNBC) and other human cancers. While several proteolysis-targeting chimera (PROTAC) degraders of CDK12/13 were reported, none are orally bioavailable. Here, we report the discovery of as a potent, selective, and orally bioavailable CDK12/13 PROTAC degrader.

Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition.

Cyclin-dependent kinases 12/13 play pivotal roles in orchestrating transcription elongation, DNA damage response, and maintenance of genomic stability. Biallelic CDK12 loss has been documented in various malignancies. Here, we develop a selective CDK12/13 PROTAC degrader, YJ9069, which effectively inhibits proliferation in subsets of prostate cancer cells preferentially over benign immortalized cells.

Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection.

Background: Respiratory syncytial virus (RSV) is a leading cause of severe illness in infants, with no effective treatment. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection.

Methods: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial conducted in China, we enrolled participants 1 to 24 months of age who were hospitalized with RSV infection.

Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer.

Background: Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality.

Comprehensive proteogenomic characterization of rare kidney tumors.

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes.

CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation.

Background: Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown.

Methods: In vitro molecular and cellular biological analyses on genetically modified endothelial cells, in vivo vascular biological analyses on genetically engineered mouse models, and in silico systems biology and bioinformatics analyses on CD151-related events.

Results: Endothelial ablation of leads to pulmonary and cardiac inflammation, severe sepsis, and perilous COVID-19, and endothelial CD151 becomes downregulated in inflammation.

SUMOylation Fine-Tunes Endothelial HEY1 in the Regulation of Angiogenesis.

Background: Angiogenesis, which plays a critical role in embryonic development and tissue repair, is controlled by a set of angiogenic signaling pathways. As a TF (transcription factor) belonging to the basic helix-loop-helix family, HEY (hairy/enhancer of split related with YRPW motif)-1 (YRPW motif, abbreviation of 4 highly conserved amino acids in the motif) has been identified as a key player in developmental angiogenesis. However, the precise mechanisms underlying HEY1's actions in angiogenesis remain largely unknown.

Sex-Specific Early Retinal Dysfunction in Mutant TDP-43 Transgenic Mice.

Background: Increasing evidence has highlighted retinal impairments in neurodegenerative diseases. Dominant mutations in TAR DNA-binding protein 43 (TDP-43) cause amyotrophic lateral sclerosis (ALS), and the accumulation of TDP-43 in the cytoplasm is a pathological hallmark of ALS, frontotemporal dementia (FTD), and many other neurodegenerative diseases.

Objective: While homozygous transgenic mice expressing the disease-causing human TDP-43 M337V mutant (TDP-43M337V mice) experience premature death, hemizygous TDP-43M337V mice do not suffer sudden death, but they exhibit age-dependent motor-coordinative and cognitive deficits.

Leucine-rich repeat kinase 2 (LRRK2) inhibition upregulates microtubule-associated protein 1B to ameliorate lysosomal dysfunction and parkinsonism.

Mutations in 2 (encoding leucine-rich repeat kinase 2 protein, LRRK2) are the most common genetic risk factors for Parkinson's disease (PD), and increased LRRK2 kinase activity was observed in sporadic PD. Therefore, inhibition of LRRK2 has been tested as a disease-modifying therapeutic strategy using the LRRK2 mutant mice and sporadic PD. Here, we report a newly designed molecule, FL090, as a LRRK2 kinase inhibitor, verified in cell culture and animal models of PD.

A and B sites doped CaAlO: Phase component, energy band, color and photoluminescence tuning, color performance prediction and application for pigments.

The polyacrylamide gel method was used to fabricate the CaCoAlO, CaNiAlO, CaAlInO and CaAlWO (x = 0-0.5) pigments. The phase compositions, energy bands, color and photoluminescence properties of the pigments can be controlled by adjusting the type and content of doping ions.

Polarization-directed growth of spiral nanostructures by laser direct writing with vector beams.

Chirality is pivotal in nature which attracts wide research interests from all disciplines and creating chiral matter is one of the central themes for chemists and material scientists. Despite of significant efforts, a simple, cost-effective and general method that can produce different kinds of chiral metamaterials with high regularity and tailorability is still demanding but greatly missing. Here, we introduce polarization-directed growth of spiral nanostructures via vector beams, which is simple, tailorable and generally applicable to both plasmonic and dielectric materials.

Preclinical studies of a factor X activator and a phase 1 trial for hemophilia patients with inhibitors.

Background: Bleeding episodes in hemophiliacs with inhibitors are difficult to control. Staidson protein-0601 (STSP-0601), a specific factor (F)X activator purified from the venom of Daboia russelii siamensis, has been developed.

Objectives: We aimed to investigate the efficacy and safety of STSP-0601 in preclinical and clinical studies.

The Contribution of Genetic Risk and Lifestyle Factors in the Development of Adult-Onset Inflammatory Bowel Disease: A Prospective Cohort Study.

Introduction: The joint associations across genetic risk, modifiable lifestyle factors, and inflammatory bowel disease (IBD) remains unclear.

Methods: Genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) was estimated by polygenic risk scores and further categorized into high, intermediate, and low genetic risk categories. Weighted healthy lifestyle scores were constructed based on 5 common lifestyle factors and categorized into favorable (4 or 5 healthy lifestyle factors), intermediate (3 healthy lifestyle factors), and unfavorable (0-2 healthy lifestyle factors) groups.

Elevated Placental microRNA-155 Is a Biomarker of a Preeclamptic Subtype.

Background: Preeclampsia is a complicated syndrome with marked heterogeneity. The biomarker-based classification for this syndrome is more constructive to the targeted prevention and treatment of preeclampsia. It has been reported that preeclamptic patients had elevated microRNA-155 (miR-155) in placentas or circulation.

The Emerging Structural Pharmacology of ATP-Sensitive Potassium Channels.

ATP-sensitive potassium channels (K) are energy sensors that participate in a range of physiologic processes. These channels are also clinically validated drug targets. For decades, K inhibitors have been prescribed for diabetes and K activators have been used for the treatment of hypoglycemia, hypertension, and hair loss.

Association of Cardiovascular Health Score Trajectory With Incident Myocardial Infarction in Hypertensive Patients.

Background: The association between changes in cardiovascular health score (CHS) over time and myocardial infarction (MI) risk in hypertensive patients remains unclear.

Method: This was a prospective study comprising 17 374 hypertensive patients from the Kailuan study cohort who underwent 3 surveys and were identified to be free of MI, stroke, or cancer from 2006 to 2010. CHS consisted of 7 cardiovascular health metrics (plasma glucose, total cholesterol, blood pressure, smoking, body mass index, physical activity, salt intake), ranging from 0 (worst) to 13 (best) in the study.

Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13.

Selective degradation of the cyclin-dependent kinases 12 and 13 (CDK12/13) presents a novel therapeutic opportunity for triple-negative breast cancer (TNBC), but there is still a lack of dual CDK12/13 degraders. Here, we report the discovery of the first series of highly potent and selective dual CDK12/13 degraders by employing the proteolysis-targeting chimera (PROTAC) technology. The optimal compound effectively degraded CDK12 and CDK13 with DC values of 2.

T cell receptor β-chain-targeting chimeric antigen receptor T cells against T cell malignancies.

The success of chimeric antigen receptor (CAR) T cells in treating B cell malignancies comes at the price of eradicating normal B cells. Even though T cell malignancies are aggressive and treatment options are limited, similar strategies for T cell malignancies are constrained by the severe immune suppression arising from bystander T cell aplasia. Here, we show the selective killing of malignant T cells without affecting normal T cell-mediated immune responses in vitro and in a mouse model of disseminated leukemia.

MRI-based Texture Analysis of Infrapatellar Fat Pad to Predict Knee Osteoarthritis Incidence.

Background Infrapatellar fat pad (IPFP) quality has been implicated as a marker for predicting knee osteoarthritis (KOA); however, no valid quantification for subtle IPFP abnormalities has been established. Purpose To investigate whether MRI-based three-dimensional texture analysis of IPFP abnormalities could help predict incident radiographic KOA. Materials and Methods In this prospective nested case-control study, 690 participants whose knees were at risk for KOA were included from the Pivotal Osteoarthritis Initiative MRI Analyses incident osteoarthritis cohort.

Efficacy and Safety of Chinese Herbal Medicine Compared With Losartan for Mild Essential Hypertension: A Randomized, Multicenter, Double-Blind, Noninferiority Trial.

Background: Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)-a Chinese herbal formula-was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear.