Loss of Fbxo45 in AT2 cells leads to insufficient histone supply and initiates lung adenocarcinoma.

Dysregulation of histone supply is implicated in various cancers, including lung adenocarcinoma (LUAD), although the underlying mechanisms remain poorly understood. Here, we demonstrate that knockout of Fbxo45 in mouse alveolar epithelial type 2 (AT2) cells leads to spontaneous LUAD. Our findings reveal that FBXO45 is a novel cell-cycle-regulated protein that is degraded upon phosphorylation by CDK1 during the S/G2 phase.

Modified Mucosal Advancement Flap Combined With De-Epithelialized Mucosal Flap for Labia Minora Hypertrophy.

Background: This study aimed to explore a novel and effective modified technique for the improvement in labia minora hypertrophy.

Methods: From January 2020 to December 2022, 25 patients with labia minora hypertrophy underwent surgical treatment using a modified mucosal advancement flap combined with a de-epithelialized mucosal flap for labia minora reduction. Postoperative follow-up ranged from 3 to 12 months.

A clinically feasible algorithm for the parallel detection of glioma-associated copy number variation markers based on shallow whole genome sequencing.

Molecular features are incorporated into the integrated diagnostic system for adult diffuse gliomas. Of these, copy number variation (CNV) markers, including both arm-level (1p/19q codeletion, +7/-10 signature) and gene-level (EGFR gene amplification, CDKN2A/B homozygous deletion) changes, have revolutionized the diagnostic paradigm by updating the subtyping and grading schemes. Shallow whole genome sequencing (sWGS) has been widely used for CNV detection due to its cost-effectiveness and versatility.

A Rhein-Based Derivative Targets .

The rise in antibiotic-resistant bacteria highlights the need for novel antimicrobial agents. This study presents the design and synthesis of a series of rhein (RH)-derived compounds with improved antimicrobial properties. The lead compound, RH, exhibited a potent antibacterial activity against () isolates, with minimum inhibitory concentrations (MICs) ranging from 8 to 16 μg/mL.

N6-methyladenosine-driven miR-143/145-KLF4 circuit orchestrates the phenotypic switch of pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is characterized by vascular remodeling predominantly driven by a phenotypic switching in pulmonary artery smooth muscle cells (PASMCs). However, the underlying mechanisms for this phenotypic alteration remain incompletely understood. Here, we identified that RNA methyltransferase METTL3 is significantly elevated in the lungs of hypoxic PH (HPH) mice and rats, as well as in the pulmonary arteries (PAs) of HPH rats.

Coumarin Glycosides Reverse Enterococci-Facilitated Enteric Infections.

Commensal enterococci with pathogenic potential often facilitate the growth of diverse pathogens, thereby exacerbating infections. However, there are few effective therapeutic strategies to prevent and intervene in enterococci-mediated polymicrobial infections. Here, we find that enterococci at high density drive the expansion and pathogenicity of enteric serotype Typhimurium (.

Nuclear transport of phosphorylated LanCL2 promotes invadopodia formation and tumor progression of glioblastoma by activating STAT3/Cortactin signaling.

Introduction: Our previous study showed that the abscisic acid receptor lanthionine synthetase C-like 2 (LanCL2) is a significant prognostic factor for overall survival in young glioblastoma patients. However, the role of LanCL2 in glioblastoma remains unclear yet.

Objectives: This study aims to investigate the role of LanCL2 in regulating in-vitro cell invasion and in-vivo tumor progression of glioblastoma and its underlying mechanism.

The Relationship between Muscle Ultrasound Parameters and Diabetic Peripheral Neuropathy among Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background: Muscle dysfunction is an early complication of diabetic peripheral neuropathy (DPN). As a convenient and low-cost tool, muscle ultrasound has been used to assess muscle quality and muscle mass. However, the relationship between different muscle ultrasound parameters and DPN is unclear.

Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids.

Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown.

USP7 reduces the level of nuclear DICER, impairing DNA damage response and promoting cancer progression.

Endoribonuclease DICER is an RNase III enzyme that mainly processes microRNAs in the cytoplasm but also participates in nuclear functions such as chromatin remodelling, epigenetic modification and DNA damage repair. The expression of nuclear DICER is low in most human cancers, suggesting a tight regulation mechanism that is not well understood. Here, we found that ubiquitin carboxyl-terminal hydrolase 7 (USP7), a deubiquitinase, bounded to DICER and reduced its nuclear protein level by promoting its ubiquitination and degradation through MDM2, a newly identified E3 ubiquitin-protein ligase for DICER.

USP2 promotes tumor immune evasion via deubiquitination and stabilization of PD-L1.

The abnormal upregulation of programmed death ligand-1 (PD-L1) on tumor cells impedes T-cell mediated cytotoxicity through PD-1 engagement, and further exploring the mechanisms regulation of PD-L1 in cancers may enhance the clinical efficacy of PD-L1 blockade. Here, using single-guide RNAs (sgRNAs) screening system, we identify ubiquitin-specific processing protease 2 (USP2) as a novel regulator of PD-L1 stabilization for tumor immune evasion. USP2 directly interacts with and increases PD-L1 abundance in colorectal and prostate cancer cells.

Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes.

Background: The activation of lymphatic vessel function is the crux to resolving atherosclerosis (AS), a chronic inflammatory disease. Rapamycin (RAPA) recently has attracted considerable attention as a potent drug to induce atherosclerotic plaque attenuation. The objective of this work was to develop a ligand-decorated, RAPA-loaded liposome for lymphatic-targeted delivery of drugs to improve abnormal lymphatic structure and function, resulting in highly effective regression of atherosclerotic plaques.

Histopathological auxiliary system for brain tumour (HAS-Bt) based on weakly supervised learning using a WHO CNS5-style pipeline.

Purpose: Classification and grading of central nervous system (CNS) tumours play a critical role in the clinic. When WHO CNS5 simplifies the histopathology diagnosis and places greater emphasis on molecular pathology, artificial intelligence (AI) has been widely used to meet the increased need for an automatic histopathology scheme that could liberate pathologists from laborious work. This study was to explore the diagnosis scope and practicality of AI.

Reconstruction of Concha-Type Microtia Using a Delayed Postauricular Skin Flap.

Summary: Understanding how to remove and retain the relatively large residual auricle is important in concha-type microtia reconstruction. The authors present a method for concha-type microtia reconstruction using a delayed postauricular skin flap. A total of 40 patients with concha-type microtia who underwent ear reconstruction using a delayed postauricular skin flap were retrospectively examined.

Grading criteria for venous invasion in thoracic esophageal squamous cell carcinoma.

Background: Venous invasion (VI) is an adverse prognostic indicator in esophageal squamous cell carcinoma. However, grading criteria for venous invasion in thoracic esophageal squamous cell carcinoma (ESCC) have not been established.

Methods: We enrolled 598 thoracic ESCC patients from 2005 to 2017.

Efficacy of pulsed dye laser combined with fractional CO laser in the treatment of pediatric burn scars.

Objective: The present study aimed to investigate the efficacy and safety of pulsed dye laser (PDL) combined with fractional CO laser in the treatment of burn scars in pediatric patients.

Methods: The present retrospective study enrolled 60 pediatric patients with burn scars from July 2017 to June 2021. In the 4-month treatment period, all patients received PDL treatment every 1 month and received fractional CO laser treatment every 3 months.

Raddeanin A Enhances Mitochondrial DNA-cGAS/STING Axis-Mediated Antitumor Immunity by Targeting Transactive Responsive DNA-Binding Protein 43.

Immune checkpoint therapies (ICT) have achieved unprecedented efficacy in multiple cancer treatments, but are still limited by low clinical response rates. Identification of immunogenic cell death (ICD)-inducing drugs that can induce tumor cell immunogenicity and reprogram the tumor microenvironment is an attractive approach to enhance antitumor immunity. In the present study, Raddeanin A (RA), an oleanane class triterpenoid saponin isolated from Anemone raddeana Regel, is uncovered as a potent ICD inducer through an ICD reporter assay combined with a T cell activation assay.

Landscape Aesthetic Value of Waterfront Green Space Based on Space-Psychology-Behavior Dimension: A Case Study along Qiantang River (Hangzhou Section).

As an important part of urban green infrastructure, the landscape effect of the urban waterfront green space varies, and sometimes, the green space with an excellent landscape aesthetic value fails to serve the needs of most citizens. This seriously affects the construction of a green ecological civilization and the implementation of the concept of "common prosperity" in China. Based on multi-source data, this study took the Qiantang River Basin as an example, selected 12 representative waterfront green spaces along the river as the research objects, and used qualitative and quantitative analysis methods to determine the landscape aesthetic value of the research area from the different dimensions of space, psychology, and physiology.

Apoptotic effects of phenols from the twigs and leaves of Garcinia nujiangensis.

In order to find potential agents for treating cancer disease in naturally occurring compounds, we conducted a systematic phytochemical investigation on the endemic species of Garcinia nujiangensis. Three new biphenyl derivatives (1-3) and one new polycyclic polyprenylated benzophenone (4), together with four known benzophenone analogues (5-8), have been isolated from the CHCl extract of the twigs and leaves of G. nujiangensis.

Quercetin 7-rhamnoside protects against alpha-naphthylisothiocyanate (ANIT)-induced in cholestatic hepatitis rats by improving biliary excretion and inhibiting inflammatory responses.

To explore the pharmacological effects and molecular mechanism of quercetin 7-rhamnoside (Q7R) in the treatment of cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT). ANIT-induced cholestatic hepatitis rat model was used to investigate the hepatoprotective effects of three different doses of Q7R (1.25 mg/kg; 2.

Novel Small-Molecule PD-L1 Inhibitor Induces PD-L1 Internalization and Optimizes the Immune Microenvironment.

Blocking the PD-1/PD-L1 interaction has become an important strategy for tumor therapy, which has shown outstanding therapeutic effects in clinical settings. However, unsatisfactory response rates and immune-related adverse effects limit the use of anti-PD1/PD-L1 antibodies. Here, we report the discovery and identification of , an innovative small-molecule inhibitor of PD-L1.

Novel phthalimides regulating PD-1/PD-L1 interaction as potential immunotherapy agents.

Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1) have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy. Despite the inherent advantages of small-molecule inhibitors over antibodies, the discovery of small-molecule inhibitors has fallen behind that of antibody drugs. Based on docking studies between small molecule inhibitor and PD-L1 protein, changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein, which was not reported before.

A 7.6-nW 1-kS/s 10-Bit SAR ADC for Biomedical Applications.

This paper presents a 10-bit successive approximation register analog-to-digital converter with energy-efficient low-complexity switching scheme, automatic ON/OFF comparator and automatic ON/OFF SAR logic for biomedical applications. The energy-efficient switching scheme achieves an average digital-to-analog converter switching energy of 63.56 , achieving a reduction of 95.

A 100 KS/s 8-10-Bit Resolution-Reconfigurable SAR ADC for Biosensor Applications.

A DAC switching scheme that combines energy efficiency and resolution reconfigurability is proposed. Compared with the conventional switching scheme, the proposed scheme achieves 93.8%, 96.