Blockade of metastasis by targeting circulating tumor cells with platelet encapsuled oncolytic adenovirus.

Host immune elimination largely limits the application of oncolytic viruses in clinics. Here, we rationally design a bioactive platelet-based oncolytic adenovirus delivery system. Upon loading adenoviruses, platelets are transformed to a pro-endocytosis status, which facilitates their internalization by circulating tumor cells (CTCs).

Difference in the inhibitory mechanism against TMPRSS2 between camostat and nafamostat: implications for drug design.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), first identified in late 2019 as the causative agent of the COVID-19 pandemic, has triggered a global public health crisis. Transmembrane protease serine 2 (TMPRSS2) is one of the key host factors mediating SARS-CoV-2 infection and invasion. The inhibitors against TMPRSS2 emerge as a promising therapeutic strategy for COVID-19 and other potential viral infections.

High sensitivity detection of Hepatitis B virus RNA based on 3D-DNA nanomachine and protein nanopore sensing.

Serum Hepatitis B virus (HBV) RNA serves as a non-invasive biomarker for monitoring chronic hepatitis B and guiding treatment decisions. However, current diagnostic tests relying on Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) require centralized facilities and tedious operational steps, and there is currently no standardized HBV RNA detection method. Herein, we describe the rapid amplification-free detection of HBV RNA in clinical serum samples via a nanopore sensing method.

Discovery of Highly Selective and Potent Macrocyclic JAK2 Inhibitors for the Treatment of MPNs.

The development of selective JAK2 inhibitors represents a promising therapeutic strategy for MPNs. Building upon the foundation of our first-generation JAK2 inhibitor, we employed macrocyclization-driven structural optimization to address its off-target limitations. This strategy yielded a novel class of macrocyclic JAK2 inhibitors, with compound emerging as a standout candidate through systematic SAR studies.

Dietary sugar intervention: A promising approach for cancer therapy.

Cancer constitutes a significant global health challenge, with altered metabolism being a hallmark feature of cancer cells. Diet can directly modulate systemic metabolite levels, thereby exerting both direct and indirect influences on tumor progression. The primary mechanisms include: (1) directly altering signaling pathways related to tumor cell proliferation or apoptosis, (2) indirectly affecting tumor progression by modulating nutrient availability or immune cell function in the tumor microenvironment, and (3) influencing tumor development through changes in gut microbiota composition or metabolic activity.

PA28γ promotes the malignant progression of tumor by elevating mitochondrial function via C1QBP.

Proteasome activator 28γ (PA28γ) plays a critical role in malignant progression of various tumors, however, its role and regulation are not well understood. Here, using oral squamous cell carcinoma (OSCC) as the main research model, and combining co-immunoprecipitation (Co-IP), proximity ligation assays (PLA), AlphaFold 3-based molecular docking, and truncation constructs, we discovered that PA28γ interacted with complement 1q binding protein (C1QBP). This interaction is dependent on the C1QBP N-terminus (aa 1-167) rather than the known functional domain.

Pectin Metabolism Influences Phloem Architecture and Flowering Time in Arabidopsis Thaliana.

Cell wall matrices undergo continuous remodeling during plant growth and development. The methyl- and de-methyl-esterification of pectic homogalacturonan dynamically influence the physicochemical and mechanical properties of cell walls, and consequently regulate organ morphogenesis. Phloem plays a crucial role in the transport of photoassimilates and other organic molecules from source to sink tissues, and the walls of phloem cells are rich in pectins.

Transcriptome-wide decoding the roles of aberrant splicing in melanoma MAPK-targeted resistance evolution.

Drug resistance critically limits the long-term efficacy of MAPK-targeted therapy in melanoma. While resistance mechanisms at genetic, epigenetic, and transcriptional scales are well-documented, post-transcriptional splicing regulation remains poorly understood. By analyzing patient-matched pre-treatment and resistant melanoma biopsies, we uncover widespread alternative splicing alterations during therapy resistance.

Thyroid function and viability after larynx-trachea-thyroid allotransplantation: a case series.

Introduction: Larynx-trachea-thyroid allotransplantation is a multi-organ cluster transplant that involves both solid organs and the thyroid gland. Thyroid dysfunction is frequently reported after an organ transplant. However, there are few reports neither about the thyroid function after laryngeal allotransplantation nor about the feasibility of thyroid allotransplantation.

Discovery of Novel KuE PSMA PET Tracers through Structure Fine-Tuning and Direct Photocatalyzed F-Deoxyfluorination.

Prostate-specific membrane antigen (PSMA) PET imaging has been recognized as an effective modality for early and accurate prostate cancer (PCa) diagnosis. While the F-labeled PSMA tracer was initially approved for clinical use, the structure-activity relationship (SAR) has been underexplored due to limited accessibility of the tracers. Herein, we designed and synthesized a group of PSMA PET tracers through structure-based meticulous optimization for potential interactions at the amphipathic S1 site.

Discovery of degrader for FLT3, GSPT1 and IKZF1/3 proteins merging PROTAC and molecular glue targeting FLT3-ITD mutant acute myeloid leukemia.

Fms-like tyrosine kinase 3 (FLT3) is a type III receptor tyrosine kinase expressed in hematopoietic progenitor cells and in most AML cell lines. Pharmacological inhibition of FLT3 enzymatic function is now a well-established strategy for the treatment of patients with these malignancies. Herein, we report the discovery and characterization of a FLT3 degrader A2.

Design, synthesis, and evaluation of 1,3,4-oxadiazole-based EGFR inhibitors.

The epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase (RTK) family, serves as a validated and significant therapeutic target in various cancers. EGFR inhibitors have substantially improved the treatment outcomes for patients with EGFR-positive tumors. The EGFR mutation has emerged as a leading cause of clinically acquired resistance to both first- and second-generation EGFR inhibitors.

AdipoRon attenuates steatosis, inflammation and fibrosis in murine diet-induced NASH via inhibiting ER stress.

Aim: The rising global prevalence of obesity has accelerated the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), with nonalcoholic steatohepatitis (NASH) representing its progressive and life-threatening phenotype. Despite its clinical urgency, no pharmacotherapy is currently approved for NASH. AdipoRon, an orally active adiponectin receptor agonist, exhibits dual regulatory effects on glucose/lipid homeostasis alongside anti-inflammatory and antioxidant properties.

Challenges and opportunities for the diverse substrates of SPOP E3 ubiquitin ligase in cancer.

The Speckle-type POZ protein (SPOP), a substrate adaptor of the cullin-RING E3 ligase complex, mediates both the degradation and non-degradative ubiquitination of substrates, which are crucial for regulating various biological functions and cellular processes. Dysregulation of SPOP-mediated ubiquitination has been implicated in several cancers. Emerging evidence suggests that SPOP functions as a double-edged sword: acting as a tumor suppressor in prostate cancer (PCa), hepatocellular carcinoma (HCC), and colorectal cancer (CRC), while potentially serving as an oncoprotein in kidney cancer (KC).

NRF2 modulates WNT signaling pathway to enhance photodynamic therapy resistance in oral leukoplakia.

Oral leukoplakia (OLK) is a common potentially malignant oral disorder with high risk of malignant transformation. While photodynamic therapy (PDT) offers a minimally invasive treatment for OLK, some patients show resistance to PDT and the mechanisms remain unclear. This study aims to identify key regulatory pathways driving PDT resistance in OLK.

A cisplatin prodrug-based self-assembling ozone delivery nanosystem sensitizes radiotherapy in triple-negative breast cancer.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production.

Irradiation-induced increase in nuclear p62 levels contributes to chromosomal fragmentation and chromothripsis.

Chromosomal instability (CIN) is a hallmark of cancer, closely associated with tumor evolution, metastasis, immune evasion, and resistance to treatment. CIN is driven by persistent chromosome missegregation, resulting in abnormal chromosomal copy numbers and promoting tumor progression through mitotic errors, faulty chromosome segregation, and the formation of micronuclei or chromosome bridges. Previous studies have demonstrated that p62 localizes to micronuclei, where it interacts with mitochondria, enhancing reactive oxygen species-mediated cysteine oxidation and promoting p62 homo-oligomerization.

The E3 ligase TRIM21 promotes progression of pancreatic ductal adenocarcinoma by down-regulating TAp63α and derepressing .

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor and frequently has mutations in the transcription factor p53. TAp63α is a member of the p53 protein family that is generally tumor suppressive in various other p53-mutant or p53-deficient cancers. Here, we found that TAp63α inhibited cell proliferation, epithelial-mesenchymal transition (EMT), and migration in several p53-mutant PDAC cell lines.

Synthesis of polysubstituted cyclobutanes through a photoredox strain-release/[3,3]-rearrangement cascade.

Small saturated carbocycles, such as cyclobutanes, with elevated three-dimensionality and rich C centers are privileged scaffolds in naturally occurring molecules and drug discovery. It remains highly desirable and challenging to develop modular and straightforward strategies to craft densely substituted cyclobutanes. Herein, a photoredox-catalyzed radical strain-release/[3,3]-rearrangement cascade (SRRC) strategy for efficient synthesis of polysubstituted cyclobutanes is disclosed.

Ultrasensitive clinical identification of hepatitis B surface antigen (HBsAg) by CRISPR-assisted nanopore sensing.

Hepatitis B virus (HBV) infection is a major global health issue. The underdiagnosis of HBV contributes to the increasing mortality from hepatitis B-related complications. Hepatitis B surface antigen is a biomarker guiding the clinical management of chronic hepatitis B, and its disappearance from the blood is a key sign of functional cure.

Incidence, prevalence, and burden of type 2 diabetes in China: Trend and projection from 1990 to 2050.

Background: The epidemiological pattern and disease burden of type 2 diabetes have been shifting in China over the past decades. This analysis described the epidemiological transition of type 2 diabetes in the past three decades and projected the trend in the future three decades in China.

Methods: Age-, sex-, and year-specific incidence, prevalence, death, and disability-adjusted life years (DALYs) for people with 15 years or older and diabetes or high fasting glucose in China and related countries from 1990 to 2021 were obtained from the Global Burden of Disease.

Evaluation of anti-leukemic activity and underlying mechanisms of the novel GSPT1 degrader AB138 in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a relapsing and drug-resistant hematologic malignancy. We report AB138, a novel molecular glue degrader that recruits G1-to-S phase transition protein 1 (GSPT1) to cereblon (CRBN). In AML cell lines, AB138 induces rapid, sustained GSPT1 degradation.

Laparoscopic hepatectomy and near-infrared fluorescence based on the concept of "biliary territory" in the treatment of hepatolithiasis: a propensity score-matched study with videos.

Background: Hepatolithiasis, a common condition in East Asia, often requires surgical treatment. The aim of this study was to evaluate the safety and efficacy of near-infrared fluorescence (NIF)-guided laparoscopic hepatectomy (LH) using the 'biliary territory' concept for hepatolithiasis.

Methods: This retrospective study included 97 patients who had undergone LH for hepatolithiasis between June 2018 and November 2022.