Design and Synthesis of Topoisomerases-Histone Deacetylase Dual Targeted Quinoline-Bridged Hydroxamates as Anticancer Agents.

The multifactorial nature of cancer requires treatment that involves simultaneous targeting of associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study that involves the simultaneous inhibition of human topoisomerases (hTopos) and histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features and catalytic sites of the cross-talk proteins, synthesized, and assessed for their anticancer potential.

Design, Synthesis, and Pharmacological Evaluation of Nonsteroidal Tricyclic Ligands as Modulators of GABA Receptors.

GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.

Targeted Theranostic Nanoprobes Assisted NIR-II Fluorescence Imaging-Guided Surgery Therapy for Alveolar Echinococcosis.

Alveolar echinococcosis (AE) is a serious parasitic infectious disease that is highly invasive and destructive to the liver and has a high mortality rate. However, currently, there is no effective targeted imaging and treatment method for the precise detection and therapy of AE. We proposed a new two-step targeting strategy (TSTS) for AE based on poly(lactic--glycolic acid) (PLGA).

Diabetes Endothelial Keratoplasty Study: Methods and Impact on the Use of Corneas From Donors With Diabetes for Descemet Membrane Endothelial Keratoplasty.

Purpose: Describe aims, methods, characteristics of donors, donor corneas and recipients, and potential impact of the Diabetes Endothelial Keratoplasty Study (DEKS).

Methods: The DEKS is a randomized, clinical trial to assess graft success and endothelial cell density (ECD) 1 year after Descemet membrane endothelial keratoplasty (DMEK) using corneas from donors with versus without diabetes in a 1:2 minimization assignment. Diabetes severity in the donor is assessed by medical history, postmortem HbA1c, and donor skin advanced glycation end-products and oxidation markers.

Inhalable Metal-Organic Frameworks: A Promising Delivery Platform for Pulmonary Diseases Treatment.

Inhalation delivery, offering a direct pathway for administering drugs to the lungs in the form of dry powders or aerosols, stands out as an optimal approach for the localized treatment of pulmonary diseases. However, the intricate anatomical architecture of the lung often poses challenges in maintaining effective drug concentrations within the lungs over extended periods. This highlights the pressing need to develop rational inhalable drug delivery systems that can improve treatment outcomes for respiratory diseases.

Novel Protective Role for Gut Microbiota-derived Metabolite PAGln in Doxorubicin-induced Cardiotoxicity.

Purpose: Doxorubicin (Dox) is a classic anthracycline chemotherapy drug with cause cumulative and dose-dependent cardiotoxicity. This study aimed to investigate the potential role and molecular mechanism of phenylacetylglutamine (PAGln), a novel gut microbiota metabolite, in Dox-induced cardiotoxicity (DIC).

Methods: DIC models were established in vivo and in vitro, and a series of experiments were performed to verify the cardioprotective effect of PAGln.

LCN2 blockade mitigating metabolic dysregulation and redefining appetite control in type 2 diabetes.

Unlabelled: LCN2 has an osteokine important for appetite regulation; in type 2 diabetes (T2D) it is not known whether appetite regulation mediated by LCN2 in the brain is altered. In this work, we focus on exploring the role of blocking LCN2 in metabolic health and appetite regulation within the central nervous system of mice with T2D.

Material And Methods: 4-week-old male C57BL/6 mice were used, divided into four experimental groups: intact, T2D, TD2/anti-LCN2, and T2D/IgG as isotype control.

Monounsaturated fatty acids from plant or animal sources and risk of type 2 diabetes in three large prospective cohorts of men and women.

Aims/hypothesis: Existing evidence on the relationship between intake of monounsaturated fatty acids (MUFAs) and type 2 diabetes is conflicting. Few studies have examined whether MUFAs from plant or animal sources (MUFA-Ps and MUFA-As, respectively) exhibit differential associations with type 2 diabetes. We examined associations of intakes of total MUFAs, MUFA-Ps and MUFA-As with type 2 diabetes risk.

De novo root regeneration from leaf explant: a mechanistic review of key factors behind cell fate transition.

De novo root regeneration (DNRR) involves activation of special cells after wounding, along with the converter cells, reactive oxygen species, ethylene, and jasmonic acid, also playing key roles. An updated DNRR model is presented here with gene regulatory networks. Root formation after tissue injury is a type of plant regeneration known as de novo root regeneration (DNRR).

Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling.

Diffuse-type tenosynovial giant cell tumor (dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects.

FSD1 inhibits glioblastoma diffuse infiltration through restriction of HDAC6-mediated microtubule deacetylation.

The infiltration of glioblastoma multiforme (GBM) is predominantly characterized by diffuse spread, contributing significantly to therapy resistance and recurrence of GBM. In this study, we reveal that microtubule deacetylation, mediated through the downregulation of fibronectin type III and SPRY domain-containing 1 (FSD1), plays a pivotal role in promoting GBM diffuse infiltration. FSD1 directly interacts with histone deacetylase 6 (HDAC6) at its second catalytic domain, thereby impeding its deacetylase activity on α-tubulin and preventing microtubule deacetylation and depolymerization.

Extracutaneous sporotrichosis.

SUMMARYSporotrichosis is a subacute-to-chronic infection endemic to tropical and subtropical regions. It usually involves subcutaneous tissue but can occasionally cause extracutaneous infections, especially in hyperendemic areas. Extracutaneous infections are classified based on the anatomic location of the lesion and the route of infection (primary or multifocal).

Effect of defects on ballistic transport in a bilayer SnS-based junction with Co intercalated electrodes.

This study theoretically investigates the defect-related electronic structure and transport properties in a device where a semiconductor bilayer SnS (BL-SnS) serves as the central scattering region and bilayer SnS with cobalt atom intercalation (Co-SnS) as the metallic electrodes. The Co-SnS/BL-SnS junction forms an ohmic contact, which is robust to defects. Low contact resistances of 52.

Lyme neuroborreliosis in Japan: Borrelia burgdorferi sensu lato as a cause of meningitis of previously undetermined etiology in hospitalized patients outside of the island of Hokkaido, 2010-2021.

Background And Purpose: Clinical manifestations of Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), include erythema migrans, Lyme neuroborreliosis (LNB), carditis, and arthritis. LB is a notifiable disease in Japan with <30 surveillance-reported LB cases annually, predominately from Hokkaido Prefecture. However, LB, including LNB, may be under-diagnosed in Japan since diagnostic tests are not readily available.

Regulating Intermediate Adsorption and Promoting Charge Transfer of CoCr-LDHs by Ce Doping for Enhancing Electrooxidation of 5-Hydroxymethylfurfural.

Electrochemical oxidation of 5-hydroxymethylfurfural (HMFOR) to generate high-value chemicals under mild conditions acts as an energy-saving and sustainable strategy. However, it is still challenging to develop electrocatalysts with high efficiency and good durability. Here, nickel foam (NF) supported CoCrCe(7.

Translational nanorobotics breaking through biological membranes.

In the dynamic realm of translational nanorobotics, the endeavor to develop nanorobots carrying therapeutics in rational applications necessitates a profound understanding of the biological landscape of the human body and its complexity. Within this landscape, biological membranes stand as critical barriers to the successful delivery of therapeutic cargo to the target site. Their crossing is not only a challenge for nanorobotics but also a pivotal criterion for the clinical success of therapeutic-carrying nanorobots.

Validation Status of Electronic Sphygmomanometers in China: A National Survey.

Background: Although the information on the validation status of electronic sphygmomanometer (ES) devices in use in health care institutions and households is much more clinically relevant than that of ES models available on the market, it remains insufficient.

Methods: A national survey was conducted across all administrative regions of mainland China to assess the validation status of ESs. Fifty-eight cities were selected with stratification by municipality, provincial capital, and other cities, and health care institutions and households in each city were chosen by convenience to identify ES devices in use according to the study protocol.

Simultaneous Copper and EDTA Ligands Recovery from Electroless Effluent with Metallic Copper and Formaldehyde.

The traditional treatment of toxic and refractory copper(II)-ethylenediaminetetraacetic acid chelate (Cu(II)-EDTA) in electroless effluents often generates hazardous waste and secondary nitrogen-containing pollutants without maximizing the resource recovery. This study demonstrates a facile strategy to simultaneously recover Cu and EDTA ligands from Cu(II)-EDTA electroless effluent with commercially available metallic Cu and formaldehyde. In this strategy, metallic Cu is used to activate formaldehyde, a prevalent yet often overlooked cocontaminant in Cu(II)-EDTA effluents, to produce highly reductive hydrogen radical (H), which in situ decomplex Cu(II)-EDTA, reduces the central Cu(II) into metallic Cu, and release EDTA ligand.

MEDIATOR15 destabilizes DELLA protein to promote gibberellin-mediated plant development.

Mediator, a transcriptional coactivator, regulates plant growth and development by interacting with various transcriptional regulators. MEDIATOR15 (MED15) is a subunit in the Mediator complex potentially involved in developmental control. To uncover molecular functions of Arabidopsis MED15 in development, we searched for its interactors.

The Role of Pyroptosis-Related Gene Signature and Immune Infiltration in Juvenile Dermatomyositis.

Objective: Juvenile dermatomyositis (JDM) is a complex autoimmune disease, and its pathogenesis remains poorly understood. Building upon previous research on the immunological and inflammatory aspects of JDM, this study aims to investigate the role of pyroptosis in the pathogenesis of JDM using a comprehensive bioinformatics approach.

Methods: Two microarray datasets (GSE3307 and GSE11971) were obtained from the Gene Expression Omnibus database, and a list of 62 pyroptosis-related genes was compiled.

Survival outcomes among periviable infants: a systematic review and meta-analysis comparing different income countries and time periods.

Background: Periviable infants are a highly vulnerable neonatal group, and their survival rates are considerably affected by patient-, caregiver-, and institution-level factors, exhibiting wide variability across different income countries and time periods. This study aims to systematically review the literature on the survival rates of periviable infants and compare rates among countries with varied income levels and across different time periods.

Methods: Comprehensive searches were conducted across MEDLINE, Embase, CENTRAL, and Web of Science.

Reductive stress-a common metabolic feature of obesity and cancer.

Reductive stress, characterized by rising level of NADH (nicotinamide adenine dinucleotide) for a status of NADH/NAD ratio elevation, has been reported in obesity and cancer. However, the mechanism and significance of reductive stress remain to be established in obesity. This perspective is prepared to address the issue with new insights published recently.

High‑intensity focused ultrasound thermal ablation boosts the efficacy of immune checkpoint inhibitors in advanced cancers with liver metastases: A single‑center retrospective cohort study.

High-intensity focused ultrasound thermal ablation (HIFU) is a novel non-invasive technique in the treatment of liver metastases (LIM) that allows focal destruction and is not affected by dose limits. This retrospective study aimed to explore the efficacy of HIFU in improving survival and the safety of the method in newly diagnosed patients with cancer with LIM who received first-line immune checkpoint inhibitor (ICI) therapy. Between January 2018 and December 2023, data from 438 newly diagnosed patients with cancer and LIM who were treated at Mianyang Central Hospital (Mianyang, China) were reviewed.

Mannose Promotes β-Amyloid Pathology by Regulating BACE1 Glycosylation in Alzheimer's Disease.

Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression.

Nanotherapy for Neural Retinal Regeneration.

Retinal diseases can severely impair vision and even lead to blindness, posing significant threats to both physical and mental health. Physical retinal regenerative therapies are poised to revolutionize the treatment of various disorders associated with blindness. However, these therapies must overcome the challenges posed by the protective inner and outer blood‒retinal barriers.