Industry Perspective on First-in-Human and Clinical Pharmacology Strategies to Support Clinical Development of T-Cell Engaging Bispecific Antibodies for Cancer Therapy.

T-cell-engaging bispecific antibodies (TCEs) that target tumor antigens and T cells have shown great promise in treating cancer, particularly in hematological indications. The clinical development of TCEs often involves a lengthy first-in-human (FIH) trial with many dose-escalation cohorts leading up to an early proof of concept (POC), enabling either a no-go decision or dose selection for further clinical development. Multiple factors related to the target, product, disease, and patient population influence the efficacy and safety of TCEs.

An Investigation of the Correlation Between Retinal Nerve Fiber Layer Thickness with Blood Biochemical Indices and Cognitive Dysfunction in Patients with Type 2 Diabetes Mellitus.

Objective: The study aimed to explore the correlation between retinal nerve fiber layer thickness (RNFLT) with blood biochemical indicators and cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM) and the possible mechanism, thereby providing more theoretical basis for the occurrence and prevention of diabetes related complications.

Methods: Eighty T2DM patients treated in our hospital from March 2022 to September 2022 were selected as the study subjects, and the clinical data of the patients were retrospectively analyzed. All patients underwent fundus fluorescein angiography (FFA) to analyze the changes in retinal blood vessels.

Comparison of dose selection based on target engagement versus inhibition of receptor-ligand interaction for checkpoint inhibitors.

Immune checkpoint inhibitors block the interaction between a receptor on one cell and its ligand on another cell, thus preventing the transduction of an immunosuppressive signal. While inhibition of the receptor-ligand interaction is key to the pharmacological activity of these drugs, it can be technically challenging to measure these intercellular interactions directly. Instead, target engagement (or receptor occupancy) is commonly measured, but may not always be an accurate predictor of receptor-ligand inhibition, and can be misleading when used to inform clinical dose projections for this class of drugs.

Spherical Silver Nanoparticles Located on Reduced Graphene Oxide Nanocomposites as Sensitive Electrochemical Sensors for Detection of L-Cysteine.

A new, simple, and effective one-step reduction method was applied to prepare a nanocomposite with spherical polycrystalline silver nanoparticles attached to the surface of reduced graphene oxide (Ag@rGO) at room temperature. Equipment such as X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR) was used to characterize the morphology and composition of the Ag@rGO nanocomposite. A novel electrochemical sensor for detecting L-cysteine was proposed based on fixing Ag@rGO onto a glassy carbon electrode.

Mitigating bisphenol A-induced apoptosis in KGN cells: the therapeutic role of 1,25-dihydroxyvitamin D through upregulation of PGC-1α expression and inhibition of the mitochondrial cytochrome c pathway.

Purpose: This study investigated the potential of 1,25-dihydroxyvitamin D (1,25(OH)VD) to mitigate bisphenol A (BPA)-induced apoptosis in human ovarian granulosa KGN cells with the aim of establishing a theoretical foundation for understanding of how vitamin D improved ovarian function in patients with polycystic ovary syndrome (PCOS).

Methods: The impact of varying concentrations of BPA and 1,25(OH)VD on KGN cell viability was elucidated. It was established that BPA-induced apoptosis in KGN cells.

Association Between the Water Distribution in the Human Body and 25-Hydroxyvitamin D Among the Type 2 Diabetes Mellitus Population: A Possible Pathway Between Vitamin D and Diabetic Nephropathy.

Purpose: To explore the association between the water distribution in the human body and 25-hydroxyvitamin D among patients with type 2 diabetes mellitus (T2DM), and to analyze whether water distribution is a mediator between vitamin D and T2DM complications.

Patients And Methods: In total, 533 T2DM inpatients were included from August 1, 2016 to April 1, 2023. Water distribution indicators, whether from the whole body, arms, trunk, or legs, were measured to calculate the association with vitamin D using linear regression analysis.

Long noncoding RNA lncPostn links TGF-β and p53 signaling pathways to transcriptional regulation of cardiac fibrosis.

Cardiac fibroblasts are essential for the homeostasis of the extracellular matrix, whose remodeling in many cardiovascular diseases leads to fibrosis. Long noncoding RNAs (lncRNAs) are associated with cardiac pathologies, but their functions in cardiac fibroblasts and contributions to cardiac fibrosis remain unclear. Here, we aimed to identify fibroblast-enriched lncRNAs essential in myocardial infarction (MI)-induced fibrosis and explore the molecular mechanisms responsible for their functions.

Landscape of molecular crosstalk between SARS-CoV-2 infection and cardiovascular diseases: emphasis on mitochondrial dysfunction and immune-inflammation.

Background: SARS-CoV-2, the pathogen of COVID-19, is a worldwide threat to human health and causes a long-term burden on the cardiovascular system. Individuals with pre-existing cardiovascular diseases are at higher risk for SARS-CoV-2 infection and tend to have a worse prognosis. However, the relevance and pathogenic mechanisms between COVID-19 and cardiovascular diseases are not yet completely comprehended.

Association between serum lipoprotein(a) and mildly reduced eGFR: a cross-sectional study.

Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD) and aortic stenosis. However, the data on the relationship between Lp(a) and mildly reduced estimated glomerular filtration rate (eGFR) has been disputed. This study was conducted to assess the relationship between Lp(a) concentrations and mildly reduced eGFR in healthy subjects.

MiR-210 promotes bone formation in ovariectomized rats by regulating osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells through downregulation of EPHA2.

Purpose: In osteoporosis, the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) is disrupted. The osteogenic differentiation of bone marrow MSCs (BMSCs) is important for improving osteoporosis. The aim of this study was to explore the role and molecular mechanism of miR-210 in the balance of osteogenic/adipogenic differentiation of BMSCs in postmenopausal osteoporosis.

Cultivation of Spirulina platensis for nutrient removal from piggery wastewater.

The discharge of livestock wastewater without appropriate treatment causes severe harm to the environment and human health. In the pursuit of finding solutions to this problem, the cultivation of microalgae as feedstock for biodiesel and animal feed additive using livestock wastewater coupled with the removal of nutrients from wastewater has become a hot research topic. In this study, the cultivation of Spirulina platensis using piggery wastewater for the production of biomass and the removal of nutrients were studied.

Effects of dulaglutide combined with insulin degludec on glucose fluctuations and appetite in type 2 diabetes.

Introduction: The aim of this study was to describe appetite and glucose fluctuation in type 2 diabetes mellitus patients initiating treatment with dulaglutide combined with insulin degludec.

Methods: This retrospective study of patients identified adults starting treatment with once-weekly (QW) dulaglutide combined with insulin degludec (experimental group) or insulin degludec alone (control group). Patients were followed for up to 6 months from treatment initiation.

Machine learning models for prediction of invasion Klebsiella pneumoniae liver abscess syndrome in diabetes mellitus: a singled centered retrospective study.

Objective: This study aimed to develop and validate a machine learning algorithm-based model for predicting invasive Klebsiella pneumoniae liver abscess syndrome(IKPLAS) in diabetes mellitus and compare the performance of different models.

Methods: The clinical signs and data on the admission of 213 diabetic patients with Klebsiella pneumoniae liver abscesses were collected as variables. The optimal feature variables were screened out, and then Artificial Neural Network, Support Vector Machine, Logistic Regression, Random Forest, K-Nearest Neighbor, Decision Tree, and XGBoost models were established.

1,25-Dihydroxyvitamin D inhibits hepatic diacyglycerol accumulation and ameliorates metabolic dysfunction in polycystic ovary syndrome rat models.

We aimed to evaluate the influence of 1,25-dihydroxyvitamin D (1,25(OH)D) on metabolic dysfunction and elucidate its underlying mechanism using a rat model of polycystic ovary syndrome (PCOS). Twenty-four Sprague-Dawley rats were randomly divided into four groups: control group (CON, 2 ml/kg of oral 0.5% CMC), 1,25VD group (oral 0.

Structural characteristics and thermal performances of lauric-myristic-palmitic acid introduced into modified water hyacinth porous biochar for thermal energy storage.

Water hyacinth (WH) was used to prepare biochar for phase change energy storage field to realize encapsulation and enhance thermal conductivity of phase change materials (PCMs) in this work. The maximum specific surface area of modified water hyacinth biochar (MWB) obtained by lyophilization and carbonization at 900 °C was 479.966 m/g.

Characterizing sources and ozone formations of summertime volatile organic compounds observed in a medium-sized city in Yangtze River Delta region.

Volatile organic compounds (VOCs) emitted from various sources into atmosphere could cause serious O pollution in urban areas. Although characterizations of ambient VOCs have been extensively studied in megacities, they are scarcely investigated in medium/small-sized cities, which could present different pollution characterizations due to the factors like emission sources and populations. Herein, field campaigns were conducted concurrently at six sites in a medium-sized city of Yangtze River Delta region to determine ambient levels, O formations and source contributions of summertime VOCs.

Quantitative colorimetric sensing of heavy metal ions via analyte-promoted growth of Au nanoparticles with timer or smartphone readout.

This work describes two new colorimetric nanosensors for label-free, equipment-free quantitative detection of nanomolar copper (II) (Cu) and mercury (II) (Hg) ions. Both are based on the analyte-promoted growth of Au nanoparticles (AuNPs) from the reduction of chloroauric acid by 4-morpholineethanesulfonic acid. For the Cu nanosensor, the analyte can accelerate such a redox system to rapidly form a red solution containing dispersed, uniform, spherical AuNPs that is related to these particles' surface plasmon resonance property.

A bimetallic (Ni/Co) metal-organic framework with excellent oxidase-like activity for colorimetric sensing of ascorbic acid.

A novel nanozyme of bimetallic (Ni/Co) metal-organic framework (Ni/Co-MOF) was synthesized using a simultaneous precipitation and acid etching method with a zeolitic imidazolate framework ZIF-67 as the template. The as-synthesized Ni/Co-MOF catalyst presented a three-dimensional hollow nanocage structure and exhibited excellent intrinsic oxidase-like activity. It was demonstrated that Ni/Co-MOF could directly catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to produce a blue product (oxidized TMB, oxTMB) in the absence of HO.

Metabolically healthy obesity is associated with higher risk of both hyperfiltration and mildly reduced estimated glomerular filtration rate: the role of serum uric acid in a cross-sectional study.

Background: The impact of metabolically healthy obesity (MHO) on kidney dysfunction remains debatable. Moreover, few studies have focused on the early stages of kidney dysfunction indicated by hyperfiltration and mildly reduced eGFR. Thus, we aimed to investigate the association between the MHO and early kidney dysfunction, which is represented by hyperfiltration and mildly reduced estimated glomerular filtration rate (eGFR), and to further explore whether serum uric acid affects this association.

Mechanistic PK/PD modeling to address early-stage biotherapeutic dosing feasibility questions.

Early assessment of dosing requirements should be an integral part of developability assessments for a discovery program. If a very high dose is required to achieve the desired pharmacological effect, it may not be clinically feasible or commercially desirable to develop the biotherapeutic for the selected target unless extra measures are taken to develop a high concentration formulation or maximize yield during manufacturing. A quantitative understanding of the impact of target selection, biotherapeutic format, and optimal drug properties on potential dosing requirements to achieve efficacy can affect many early decisions.

1,25-Dihydroxyvitamin D3 alleviates hyperandrogen-induced ferroptosis in KGN cells.

Purpose: Hyperandrogenism, one of the most frequent causes of anovulation in women, increases the risk of metabolic disorders in patients with polycystic ovary syndrome (PCOS). Ferroptosis, characterized by iron-dependent lipid peroxidation, has provided new insight into the progression of PCOS. 1,25-dihydroxyvitamin D3 (1,25D3) may play a role in reproduction because its receptor, VDR, which contributes to the inhibition of oxidative stress, is primarily located in the nuclei of granulosa cells.