Evaluation of Double Self-Immolative Linker-Based Antibody-Drug Conjugate FDA022-BB05 with Enhanced Therapeutic Potential.

Typical antibody-drug conjugates (ADCs) with valine-alanine linkage, often conjugated with the amino group in payloads, face challenges when interacting with hydroxyl group-containing payloads. Herein, we introduced a transformative Val-Ala-based double self-immolative linker-payload platform, reshaping ADCs by optimizing hydroxyl group-containing payload integration. Utilizing this platform, was successfully conjugated with the hydroxyl group-containing payload DXd using trastuzumab (FDA022) as the monoclonal antibody (mAb).

Differential miR-195-5p and its potential role during the development of carotid artery stenosis.

Objectives: Carotid artery stenosis (CAS) is a leading cause of cerebral ischemic events (CIE). Timely detection and risk assessment can aid in managing CAS patients and improving their prognosis. The aim of the current study is to identify a new biomarker for CAS and to further investigate the impact of miR-195-5p on cellular processes in vascular smooth muscle cells (VSMCs).

Internal iliac artery ligation as a damage control method in hemodynamically unstable pelvic fractures: A systematic review of the literature.

Purpose: Internal iliac artery ligation (IIAL) has been used as a damage control procedure to treat hemodynamically unstable pelvic fracture for many years. However, there is ongoing debate regarding the effectiveness and safety of this hemostatic method. Therefore, we performed a systematic literature review to assess the efficacy and safety of IIAL for pelvic fracture hemostasis.

A randomized controlled trial investigating the impact of a single flash cupping session on patients with chronic lower back pain using multichannel surface electromyographic assessment.

Background: Chronic lower back pain (CLBP) is one of the most common disorders worldwide. Flash cupping has the ability to relieve CLBP; nevertheless, its impact on CLBP and the likely mechanism of action have not been studied.

Objective: The goal of this study was to assess the impact of a single, brief cupping session on CLBP and low back muscle activity using multichannel surface electromyography (sEMG).

Synthesis and biological evaluation of novel quaternary ammonium antibody drug conjugates based on camptothecin derivatives.

Antibody drug conjugates (ADCs) have emerged as a highly promising class of cancer therapeutics, comprising antibodies, effector molecules, and linkers. Among them, DS-8201a with DXd as the effector molecule, has shown remarkable anti-tumor efficacy against solid tumors, sparking a surge of interest in ADCs with camptothecin derivatives as ADC effector molecules. In this study, we introduced and successfully constructed quaternary ammonium ADCs utilizing camptothecin derivatives WL-14 and CPTS-1 for the first time.

Cross-species investigation into the requirement of XPA for nucleotide excision repair.

After reconstitution of nucleotide excision repair (excision repair) with XPA, RPA, XPC, TFIIH, XPF-ERCC1 and XPG, it was concluded that these six factors are the minimal essential components of the excision repair machinery. All six factors are highly conserved across diverse organisms spanning yeast to humans, yet no identifiable homolog of the XPA gene exists in many eukaryotes including green plants. Nevertheless, excision repair is reported to be robust in the XPA-lacking organism, Arabidopsis thaliana, which raises a fundamental question of whether excision repair could occur without XPA in other organisms.

In vitro DNA repair genomics using XR-seq with and mammalian cell-free extracts.

The XR-seq (eXcision Repair-sequencing) method has been extensively used to map nucleotide excision repair genome-wide in organisms ranging from to yeast, , Arabidopsis, mice, and humans. The basic feature of the method is to capture the excised oligomers carrying DNA damage, sequence them, and align their sequences to the genome. We wished to perform XR-seq in vitro with cell-free extract supplemented with a damaged DNA substrate so as to have greater flexibility in investigating factors that affect nucleotide excision repair in the cellular context [M.

Increasing positive rate of IgG against hepatitis E virus with steady IgM positivity and clinical incidence: A retrospective seroprevalence time series analysis of HEV from 2012 to 2021 in Chongqing, China.

China is an epidemic area of hepatitis E, and the serum prevalence data is very important for formulating prevention and control strategies. However, almost all related research in the past decade are cross-sectional studies. In this study, we analyzed the serological data from 2012 to 2021 in Chongqing for 10 consecutive years.

Acalculous cholecystitis is a common extrahepatic manifestation of hepatitis E and suggests a more serious condition.

Background: This study aimed to understand the incidence and clinical significance of acalculous cholecystitis in patients with acute hepatitis E (HE).

Patients And Methods: A single center enrolled 114 patients with acute HE. All patients underwent imaging of the gallbladder, and patients with gallstones and cholecystectomy were excluded.

Analysis of mammalian circadian clock protein complexes over a circadian cycle.

Circadian rhythmicity is maintained by a set of core clock proteins including the transcriptional activators CLOCK and BMAL1, and the repressors PER (PER1, PER2, and PER3), CRY (CRY1 and CRY2), and CK1δ. In mice, peak expression of the repressors in the early morning reduces CLOCK- and BMAL1-mediated transcription/translation of the repressors themselves. By late afternoon the repressors are largely depleted by degradation, and thereby their expression is reactivated in a cycle repeated every 24 h.

Systematic Evaluation of the Efficacy of Acupuncture Associated with Physical and Mental Intervention when Treating Idiopathic Tinnitus and the Improvement of Tinnitus Symptoms.

Objective: To systematically evaluate the efficacy of acupuncture associated with physical and mental intervention when treating idiopathic tinnitus and the improvement of tinnitus symptoms, so as to supply evidence-based medicine for its popularization and adoption.

Methods: PubMed, EMBASE, ScienceDirect, Cochrane Library, China knowledge Network Database (CNKI), China VIP Database, Wanfang Database, and China Biomedical Literature Database (CBM) online database were searched for the controlled trial of acupuncture associated with physical and mental intervention when treating idiopathic tinnitus. The retrieval time limit is from January 2010 to March 2022.

Nucleotide excision repair removes thymidine analog 5-ethynyl-2'-deoxyuridine from the mammalian genome.

Nucleotide excision repair is the principal mechanism for removing bulky DNA adducts from the mammalian genome, including those induced by environmental carcinogens such as UV radiation, and anticancer drugs such as cisplatin. Surprisingly, we found that the widely used thymidine analog EdU is a substrate for excision repair when incorporated into the DNA of replicating cells. A number of thymidine analogs were tested, and only EdU was a substrate for excision repair.

CSB-independent, XPC-dependent transcription-coupled repair in .

has been extensively used as a model system to study ionizing radiation and chemical-induced mutagenesis, double-strand break repair, and recombination. However, there are only limited studies on nucleotide excision repair in this important model organism. An early study reported that lacks the transcription-coupled repair (TCR) form of nucleotide excision repair.

The Durability of Recycled Fine Aggregate Concrete: A Review.

With the rapid development of urbanization, many new buildings are erected, and old ones are demolished and/or recycled. Thus, the reuse of building materials and improvements in reuse efficiency have become hot research topics. In recent years, scholars around the world have worked on improving recycle aggregates in concrete and broadening the scope of applications of recycled concrete.

Quantification of Ceramsite Granules in Lightweight Concrete Panels through an Image Analysis Technique.

Ceramsite particles are an important component of lightweight ceramsite concrete wall panels, and the density of the aggregate is much lower than the density of the slurry. It is generally accepted that there are inhomogeneities in the distribution of ceramsite particles in wall panels. Ceramsite concrete wallboard material is a research hotspot in the field of fabricated building materials at home and abroad; however, there is no effective way to quantify their inhomogeneity.

High myosin binding protein H expression predicts poor prognosis in glioma patients.

Glioma is the most common and fatal primary brain tumor in humans. Myosin binding protein H (MYBPH), which was first identified as an important myofibrillar constituent of vertebrate skeletal and cardiac muscles, reduces cell motility and metastasis. However, its role in gliomas remains unclear.

Seeking transnational social protection during a global pandemic: The case of Chinese immigrants in the United States.

Drawing on in-depth interviews with Chinese immigrants in the U.S. during the COVID-19 pandemic, this article examines the construction of immigrants' transnational social safety net and its gaps as the pandemic struck their home and host societies successively.

Circadian clock, carcinogenesis, chronochemotherapy connections.

The circadian clock controls the expression of nearly 50% of protein coding genes in mice and most likely in humans as well. Therefore, disruption of the circadian clock is presumed to have serious pathological effects including cancer. However, epidemiological studies on individuals with circadian disruption because of night shift or rotating shift work have produced contradictory data not conducive to scientific consensus as to whether circadian disruption increases the incidence of breast, ovarian, prostate, or colorectal cancers.

Ectopic Overexpression of PPARγ2 in the Heart Determines Differences in Hypertrophic Cardiomyopathy After Treatment With Different Thiazolidinediones in a Mouse Model of Diabetes.

The clinical controversy of rosiglitazone as a hypoglycemic agent is potentially associated with heart failure, mainly due to its potent activation of peroxisome proliferator-activated receptor γ (PPARγ). PPARγ partial agonists showed superior pharmacological profiles to rosiglitazone. This study compared differences in cardiac morphology and function of the PPARγ partial agonist CMHX008 with rosiglitazone.

Electroacupuncture and Transcutaneous Electrical Nerve Stimulation Induced Sensations in Bell's Palsy Patients: A Quantitative Current Intensity Analysis.

Background: The intensity of electrical acupoint stimulation such as electroacupuncture (EA) and transcutaneous electrical nerve stimulation (TENS) is regulated by the observation of skin shivering or the participant's comfort response. However, the specific intensity and spatial scope following EA or TENS stimulation are unclear.

Objective: This study aimed to test the stimulatory current intensities of lower and upper sensation thresholds in TENS- and EA-based treatment of Bell's palsy patients.

Comparison of Facial Muscle Activation Patterns Between Healthy and Bell's Palsy Subjects Using High-Density Surface Electromyography.

Facial muscle activities are essential for the appearance and communication of human beings. Therefore, exploring the activation patterns of facial muscles can help understand facial neuromuscular disorders such as Bell's palsy. Given the irregular shape of the facial muscles as well as their different locations, it should be difficult to detect the activities of whole facial muscles with a few electrodes.

Molecular mechanism of the repressive phase of the mammalian circadian clock.

The mammalian circadian clock consists of a transcription-translation feedback loop (TTFL) composed of CLOCK-BMAL1 transcriptional activators and CRY-PER transcriptional repressors. Previous work showed that CRY inhibits CLOCK-BMAL1-activated transcription by a "blocking"-type mechanism and that CRY-PER inhibits CLOCK-BMAL1 by a "displacement"-type mechanism. While the mechanism of CRY-mediated repression was explained by both in vitro and in vivo experiments, the CRY-PER-mediated repression in vivo seemed in conflict with the in vitro data demonstrating PER removes CRY from the CLOCK-BMAL1-E-box complex.

Circadian regulation of c-MYC in mice.

The circadian clock is a global regulatory mechanism that controls the expression of 50 to 80% of transcripts in mammals. Some of the genes controlled by the circadian clock are oncogenes or tumor suppressors. Among these has been the focus of several studies which have investigated the effect of clock genes and proteins on transcription and MYC protein stability.

Improving Care for Elders Who Prefer Informal Spaces to Age-Separated Institutions and Health Care Settings.

Background And Objectives: Despite advantages of urban areas (such as walkability, public transportation, nearby shopping, and health care services), challenges remain for elders aging in place to access care. The changing demographics of older adults, with higher rates of divorce, singlehood, and childlessness, often living alone and far from family, necessitate new strategies to support health and well-being.

Research Design And Methods: Drawing on 5 years of ethnographic fieldwork and 25 interviews with elders in New York City, this study presents empirical insights into older adults' use of "third places" close to home, in conjunction with more formal settings.