Nanosize Non-Viral Gene Therapy Reverses Senescence Reprograming Driven by PBRM1 Deficiency to Suppress iCCA Progression.

Polybromo-1 (PBRM1) serves as a crucial regulator of gene transcription in various tumors, including intrahepatic cholangiocarcinoma (iCCA). However, the exact role of PBRM1 in iCCA and the mechanism by which it regulates downstream target genes remain unclear. This research has revealed that PBRM1 is significantly downregulated in iCCA tissues, and this reduced expression is linked to aggressive clinicopathological features and a poor prognosis.

Analysis of the effect of ALA-PDT on macrophages in footpad model of mice infected with based on single-cell sequencing.

Chromoblastomycosis (CBM) is a chronic neglected fungal disease that causes serious damage to the physical and mental health of patients. 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has garnered significant attention in the recent era for the treatment of CBM and has exhibited promising effects in several clinical case reports. We established a mice footpad infection model with and analyzed the impact of PDT treatment on the immune response of macrophages using single-cell sequencing.

Breaking Anionic Solvation Barrier for Safe and Durable Potassium-ion Batteries Under Ultrahigh-Voltage Operation.

Ultrahigh-voltage potassium-ion batteries (PIBs) with cost competitiveness represent a viable route towards high energy battery systems. Nevertheless, rapid capacity decay with poor Coulombic efficiencies remains intractable, mainly attributed to interfacial instability from aggressive potassium metal anodes and cathodes. Additionally, high reactivity of K metal and flammable electrolytes pose severe safety hazards.

Selective G6PDH inactivation for Helicobacter pylori eradication with transformed polysulfide.

Alternative treatment for the highly prevalent Helicobacter pylori infection is imperative due to rising antibiotic resistance. We unexpectedly discovered that the anti-H. pylori component in garlic is hydrogen polysulfide (HS, n⩾2), not organic polysulfides.

Explainable machine learning framework for cataracts recognition using visual features.

Cataract is the leading ocular disease of blindness and visual impairment globally. Deep neural networks (DNNs) have achieved promising cataracts recognition performance based on anterior segment optical coherence tomography (AS-OCT) images; however, they have poor explanations, limiting their clinical applications. In contrast, visual features extracted from original AS-OCT images and their transform forms (e.

Lerociclib plus fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial.

Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safety of lerociclib in HR+/HER2- locally advanced or metastatic breast cancer patients, who had relapsed or progressed on prior endocrine therapy. A total of 275 patients were randomized at 1:1 ratio to receive lerociclib (137 patients, 150 mg twice daily) or placebo (138 patients) plus fulvestrant.

A "hand-held" polarimeter for on-site chiral drug measurement and chemical reaction monitoring.

A polarimeter is a common but critical instrument for measuring the optical rotation of chiral compounds, ranging from the pharmaceutical to chemical industry, or even employed in monitoring chemical reactions for research purposes. Developing a portable polarimeter helps to transfer the measurements from the laboratory to on-site detection. Herein, we design a new portable polarimeter with a "hand-held" scale.

Targeting MXD1 sensitises pancreatic cancer to trametinib.

Background: The resistance of pancreatic ductal adenocarcinoma (PDAC) to trametinib therapy limits its clinical use. However, the molecular mechanisms underlying trametinib resistance in PDAC remain unclear.

Objective: We aimed to illustrate the mechanisms of resistance to trametinib in PDAC and identify trametinib resistance-associated druggable targets, thus improving the treatment efficacy of trametinib-resistant PDAC.

Epilepsy therapy beyond neurons: unveiling astrocytes as cellular targets.

Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies.

Heterotopic ossification: Current developments and emerging potential therapies.

This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating.

Mechanistic Insights into Kaempferol's Therapeutic Effects on Postmenopausal Osteoporosis: A Proteomic and Experimental Validation in Ovariectomized Rats.

Background: Postmenopausal Osteoporosis (PMOP) is characterized by decreased bone mass and deterioration of bone microarchitecture, leading to increased fracture risk. Current treatments often have adverse effects, necessitating safer alternatives. Kaempferol, a flavonoid identified as a key active component of the traditional Chinese medicine Yishen Gushu formula, has shown promise in improving bone health, but its mechanisms in PMOP treatment remain unclear.

PEGylation Improves the Therapeutic Index of Dexamethasone To Treat Acute Respiratory Distress Syndrome with Obesity Background in Mouse.

With increasing prevalence globally, obesity presents unique challenges to the clinical management of other diseases. In the case of acute respiratory distress syndrome (ARDS), glucocorticoid therapy (e.g.

Utilization of structure-specific lignin extracted from coconut fiber via deep eutectic solvents to enhance the functional properties of PVA nanocomposite films.

This study utilized deep eutectic solvents (DES) based on choline chloride/lactic acid (ChCl/LA) to deconstruct coconut fibers. The effects of DES with different temperatures and molar ratios on the yield of lignin, recovery rate of residues, structural changes in lignin and solid residues, and saccharification efficiency were investigated. The results showed that acidic DES treatment effectively deconstructed the coconut fibers, resulting in a high lignin yield of 68.

Construction of a fusant bacterial strain simultaneously degrading atrazine and acetochlor and its application in soil bioremediation.

Application of herbicide-degrading bacteria is an effective strategy to remove herbicide in soil. However, the ability of bacteria to degrade a herbicide is often severely limited in the presence of other pesticide. In this study, the atrazine-degrading strain Klebsiella varicola FH-1 and acetochlor-degrading strain Bacillus Aryabhatti LY-4 were used as parent strains to construct the recombinant RH-92 strain through protoplast fusion technology.

Compound heterozygous mutations (p.L68R∗37 and p.T241N) lead to abnormal protein levels and structures in hereditary FVII deficiency.

Background: Congenital factor VII (FVII) deficiency is a genetic disorder characterized by decreased FVII activity, which sometimes leads to fatal bleeding. Numerous variants have been found in FVII deficiency, but mutations vary among patients. Each mutation deserves further exploration for each patient at risk of bleeding.

Rare and common genetic variants underlying the risk of Hirschsprung's disease.

Hirschsprung's disease (HSCR) is a congenital enteric neuropathic disorder characterized by high heritability (>80%) and polygenic inheritance (>20 genes). The previous genome-wide association studies (GWAS) identified several common variants associated with HSCR and demonstrated increased predictive performance for HSCR risk in Europeans using a genetic risk score, there remains a notable gap in knowledge regarding Chinese populations. We conducted whole exome sequencing in a HSCR case cohort in Chinese.

Prognostic Value of D-Dimer in Acute Type A Aortic Dissection and Intramural Hematoma: Observations from the Acute Aortic Syndrome Group of the Registry of Acute Non-Traumatic Chest Pain in China.

Background: Acute type A aortic dissection (AAD) and acute type A intramural hematoma (AIMH) are life-threatening conditions with high mortality rates, and prognostic indicators are critical for guiding urgent treatment decisions. We assessed the prognostic significance of admission D-dimer levels in patients with AAD and AIMH.

Methods And Results: The prospective, multicenter, observational study in China recruited participants from 2013 to 2019.

Small Molecular Oligopeptides Adorned with Tryptophan Residues as Potent Antitumor Agents: Design, Synthesis, Bioactivity Assay, Computational Prediction, and Experimental Validation.

Tryptophan participates in important life activities and is involved in various metabolic processes. The indole and aromatic binuclear ring structure in tryptophan can engage in diverse interactions, including π-π, π-alkyl, hydrogen bonding, cation-π, and CH-π interactions with other side chains and protein targets. These interactions offer extensive opportunities for drug development.

Characteristics of gut microbiota dysbiosis in patients with colorectal polyps.

This editorial, inspired by a recent study published in the , covers the research findings on microbiota changes in various diseases. In recurrent colorectal polyps, the abundances of , , and increase, while those of and decrease. This dysbiosis may promote the formation and recurrence of polyps.

Flavonoids of Diels et Gilg Against Acute Hepatic Injury by Blocking PI3K/AKT Signaling Pathway.

This study aims to investigate the mechanism of Diels et Gilg flavonoids (THF) on acute hepatic injury (AHI). First, high-performance liquid chromatography (HPLC) fingerprints were established to obtain the main chemical components of THF. According to the network pharmacology databases, collect active targets of AHI and potential targets.

Neurofibromatosis with diffuse intestinal ganglioneuromatosis: a case report.

Background: Neurofibromatosis type 1 (NF-1), a rare autosomal dominant disorder, arises from gene mutations affecting neurofibromin, a Ras GTPase regulator. These mutations activate Ras proteins, triggering clinical symptoms such as skin spots, epilepsy, pain, and tumors. Although gastrointestinal stromal tumors are well-known in NF-1, diffuse intestinal ganglioneuromatosis remains an extremely rare complication.

Effect of Laminectomy Methods on the Surgical Safety of Automatic Laminectomy Robot.

Background: The efficacy of laminectomy procedures is contingent on the method of resection. The objective of this study was to investigate the impact of different methods of resection on the surgical safety of automated laminectomy robots, an area that remains uncharted.

Methods: Lamina resection surgeries using both drilling and layer-by-layer methods, are performed on ovine spinal samples.

High-security physical layer encryption scheme for dual-mode index modulation-aided OFDM in magnetic induction communication.

A high security physical layer encryption scheme for dual-mode orthogonal frequency division multiplexing with index modulation (DM-OFDM-IM) in magnetic induction communication is proposed. The scheme utilizes DM-OFDM-IM, where subcarriers within each subblock are divided into two groups, each modulated by distinct signal constellations. DM-OFDM-IM leverages the sequential information from the modulated constellation to transmit extra information, leading to a substantial enhancement in spectral efficiency.

A Phase-Transition-Free Sodium Vanadium Phosphate Cathode via Medium-Entropy Engineering for Superior Sodium Ion Batteries.

NaV(PO), based on multi-electron reactions between V/V/V, is a promising cathode material for SIBs. However, its practical application is hampered by the inferior conductivity, large barrier of V/V, and stepwise phase transition. Herein, these issues are addressed by constructing a medium-entropy material (NaVTiAlCrMnNi(PO), ME-NVP) with strong ME─O bond and highly occupied Na2 sites.