A novel antibody-KSP inhibitor conjugate improves KSP inhibitor efficacy in vitro and in vivo.

Many clinical trials of kinesin spindle protein (KSP) inhibitors have failed due to issues such as high toxicity and a short circulation half-life in vivo. To address the limitations of current KSP inhibitors and thus broad its use in antitumor therapy, this study applied antibody-drug conjugate (ADC) technology to the KSP inhibitor SB-743921, which was coupled with the HER2-specific antibody trastuzumab using a cathepsin B-dependent valine-alanine (Val-Ala, VA) dipeptide-type linker to generate H2-921. Ex vivo and in vivo analyses of H2-921 showed an increased half-life of SB-743921 and prolonged contact time with tumor cells.

Evaluation of deproteinised bovine bone matrix combined with absorbable biofilm for the preservation of extraction sites of mandibular impacted wisdom teeth.

Background: Bone defects and deep periodontal pockets often exist distal to the second molar after mandibular third molar extraction, seriously threatening the periodontal health of the second molar.

Objective: To evaluate the effect of socket preservation with bone substitute materials on alveolar bone resorption and prevention of the distal periodontal defect of the adjacent tooth after mandibular impacted third molar extraction compared with natural healing.

Methods: Ninety-nine patients with mandibular impacted teeth, treated in our hospital from January 2018 to December 2020, were randomly divided into the control and experimental groups.

Prenatal diagnosis of tuberous sclerosis complex: Echocardiography, cranial magnetic resonance, and genetic testing of 40 cases with fetal cardiac tumors.

Objective: To explore the relationship between Tuberous sclerosis complex (TSC) and cardiac tumors at our institution over the past five years and to evaluate the value of imaging technologies and genetic testing in the prenatal diagnosis of TSC.

Methods: Fetal echocardiography (FE) was performed in the whole population between 2016 and 2020. Fetuses detected with cardiac tumor(s) were included.

Lightweight Football Motion Recognition and Intensity Analysis Using Low-Cost Wearable Sensors.

In recent years, machine learning has been utilized in health informatics and sports science. There is a great demand and development potential for combining the Internet of Things (IoT) and artificial intelligence (AI) to be applied to football sports. The conventional teaching and training methods of football sports have limited collection and mining of real raw data using wearable devices, and lack human motion capture and gesture recognition based on sports science theories.

Immediate and long-term changes in infectious diseases in China at the "First-level-response", "Normalized-control" and "Dynamic-COVID-zero" stages from 2020 to 2022: a multistage interrupted-time-series-analysis.

Background: From January 2020 to December 2022, China implemented "First-level-response", "Normalized-control" and "Dynamic-COVID-zero" to block the COVID-19 epidemic; however, the immediate and long-term impact of three strategies on other infectious diseases and the difference in their impact is currently unknown. We aim to provide a more comprehensive understanding of the impact of non-pharmacological interventions (NPIs) on infectious diseases in China.

Methods: We collected data on the monthly case count of infectious diseases in China from January 2015 to July 2022.

Two-center validation of Pilot Tone Based Cardiac Triggering of a Comprehensive Cardiovascular Magnetic Resonance Examination.

Background: The electrocardiogram (ECG) signal is prone to distortions from gradient and radiofrequency interference and the magnetohydrodynamic effect during cardiovascular magnetic resonance imaging (CMR). Although Pilot Tone Cardiac (PTC) triggering has the potential to overcome these limitations, effectiveness across various CMR techniques has yet to be established.

Purpose: To evaluate the performance of PTC triggering in a comprehensive CMR exam.

The Seasonal Divergence in the Weakening Relationship between Interannual Temperature Changes and Northern Boreal Vegetation Activity.

The response of boreal vegetation to global warming has shown a weakening trend over the last three decades. However, in previous studies, models of vegetation activity responses to temperature change have often only considered changes in the mean daily temperature (T), with the diurnal temperature range (DTR) being neglected. The goal of this study was to evaluate the temporal trends of the relationships between two temperature factors (T and DTR) and the vegetation activity across the boreal regions on both annual and seasonal timescales, by simultaneously employing satellite and climate datasets.

Regulation of the CB1R/AMPK/PGC-1α signaling pathway in mitochondria of mouse hearts and cardiomyocytes with chronic intermittent hypoxia.

Purpose: This study evaluated the effects of chronic intermittent hypoxia (CIH) at different times on the mitochondria of mouse hearts and H9C2 cardiomyocytes to determine the role of the cannabinoid receptor 1 (CB1R)/adenosine 5'-monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) signaling pathway.

Methods: Animal and cellular CIH models were prepared in an intermittent hypoxia chamber at different times. The cardiac function of mice was determined, and heart tissue and ultrastructural changes were observed.

Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer.

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC).

Effectiveness of traditional Chinese medicine formulas combined with acupuncture in the treatment of ovulation dysfunction infertility: A systematic review and meta-analysis.

Background: To evaluate the efficacy and safety of traditional Chinese medicine formulas combined with acupuncture for the treatment of ovulation dysfunction infertility (ODI).

Methods: From January 1, 2018 to March 12, 2023, 7 electronic databases, PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, Wanfang Database, and CBM, were systematically searched to identify eligible randomized controlled trial studies.

Results: Meta analysis showed that traditional Chinese medicine combined with acupuncture can more effectively improve sex hormone levels compared to Western medicine alone, including follicle stimulating hormone (FSH) in older patients (standardized mean difference [SMD]: 3.

Fabrication of Antibacterial Sponge Microneedles for Sampling Skin Interstitial Fluid.

Microneedles (MNs) have recently garnered extensive interest concerning direct interstitial fluid (ISF) extraction or their integration into medical devices for continuous biomarker monitoring, owing to their advantages of painlessness, minimal invasiveness, and ease of use. However, micropores created by MN insertion may provide pathways for bacterial infiltration into the skin, causing local or systemic infection, especially with long-term in situ monitoring. To address this, we developed a novel antibacterial sponge MNs (SMNs@PDA-AgNPs) by depositing silver nanoparticles (AgNPs) on polydopamine (PDA)-coated SMNs.

Genome Sequence and Evaluation of Safety and Probiotic Potential of LPJZ-658.

This study aims to systematically evaluate the safety of a novel LPJZ-658 explored on whole-genome sequence analysis, safety, and probiotic properties assessment. Whole genome sequencing results demonstrated that LPJZ-658 consists of 3.26 Mbp with a GC content of 44.

Effects of LPJZ-658 Supplementation on the Production, Meat Quality, Intestinal Morphology, and Cecal Microbiota of Broilers Chickens.

This study aimed to investigate the effects of LPJZ-658 on the production, meat quality, intestinal morphology, and cecal microbiota of broilers. White-feathered broilers (1 day old, n = 600) were randomly assigned to two groups and raised for six weeks. The individuals in the LPJZ-658 group were supplemented with 2.

Repeatability and comparison of 2D and 4D flow MRI measurement of intracranial blood flow and pulsatility in healthy individuals and patients with cerebral small vessel disease.

Introduction: While 2D phase-contrast MRI is often used to examine intracranial vessels in neurovascular disease contexts, the ability of 4D flow to assess many vessels at once makes it an attractive alternative. We aimed to assess the repeatability, reliability, and conformity of 2D and 4D flow across intracranial vessels.

Methods: Using correlation analyses and paired -tests, test-retest repeatability, intra-rater reliability, and inter-method conformity for measurements of pulsatility index (PI) and mean flow were assessed in the arteries and veins of 11 healthy volunteers.

Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates.

Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines.

The tumor microbiome as a predictor of outcomes in patients with metastatic melanoma treated with immune checkpoint inhibitors.

Emerging evidence supports the important role of the tumor microbiome in oncogenesis, cancer immune phenotype, cancer progression, and treatment outcomes in many malignancies. In this study, we investigated the metastatic melanoma tumor microbiome and potential roles in association with clinical outcomes, such as survival, in patients with metastatic disease treated with immune checkpoint inhibitors (ICIs). Baseline tumor samples were collected from 71 patients with metastatic melanoma before treatment with ICIs.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-β and inflammatory cytokines.

Gut microbiota metabolite TMAO promoted lipid deposition and fibrosis process via KRT17 in fatty liver cells in vitro.

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide but still lacks specific treatment modalities. The gut microbiota and its metabolites have been shown to be intimately involved in NAFLD development, participating in and regulating disease progression. Trimethylamine N-oxide (TMAO), a metabolite highly dependent on the gut microbiota, has been shown to play deleterious regulatory roles in cardiovascular disease, but the relationship between it and NAFLD lacks validation from basic experiments.

Mitochondrial energy metabolism is downregulated in repeated implantation failure patients related to alteration of PGC-1α acetylation level.

Herein we aimed at exploring mitochondrial energy metabolism status in patients with repeated implantation failure (RIF) and whether key regulatory factor PGC-1α of energy metabolism is involved in the decidualization of endometrial stromal cells. Mitochondrial oxidative phosphorylation level and ATP synthesis were compared in primary endometrial stromal cells from RIF and control group. At the same time, as one of key transcription regulators of mitochondrial energy metabolism, the expression level and acetylation level of PGC-1α were compared with two groups.

Could an amorphous binder Co phase improve the mechanical properties of WC-Co? A study of molecular dynamics simulation.

The trade-off effect between strength and fracture toughness typically observed in composites is challenging for the design and development of novel materials. An amorphous state can impede the trade-off effect of strength and fracture toughness, improving the mechanical properties of composites. Choosing the typical tungsten carbide-cobalt (WC-Co) cemented carbides as examples, where the amorphous binder phase was found, the impact of binder phase Co on the mechanical properties was further investigated by molecular dynamics (MD) simulations.

Macrophage in liver Fibrosis: Identities and mechanisms.

Liver fibrosis is a chronic disease characterized by the deposition of extracellular matrix and continuous loss of tissues that perform liver functions. Macrophages are crucial modulators of innate immunity and play important roles in liver fibrogenesis. Macrophages comprise heterogeneous subpopulations that exhibit different cellular functions.