Using Pharmacokinetic and Pharmacodynamic Analysis to Optimize the Dosing Regimens of Fanastomig (EMB-02) in Patients With Advanced Solid Tumors.

Fanastomig (also known as EMB-02) is a bispecific antibody targeting programmed cell death protein-1(PD-1) and lymphocyte activation gene-3 (LAG-3), developed for the treatment of advanced solid tumors. A first-in-human (FIH) Phase I study (NCT04618393) evaluated safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and clinical efficacy of Fanastomig in patients with advanced solid tumors. To determine the recommended Phase II dose (RP2D), population pharmacokinetics (PopPK), and exposure and response analysis (E-R) were conducted.

The Bromodomain and Extraterminal Protein Inhibitor Apabetalone Ameliorates Kidney Injury in Diabetes by Regulating Cholesterol Accumulation and Modulating the Gut Microbiota.

Introduction: A US Food and Drug Administration-approved new bromodomain (BRD) and extraterminal (BET) bromine domain antagonist called apabetalone, which targets BRD4, has been shown to increase prebeta-1 high-density lipoprotein (HDL) particles, enhance apolipoprotein A-I in both humans and animals, and restore angiogenesis in experimental diabetes. Its action is not however fully known mechanistically. The objective of our research was to investigate the impact of apabetalone on renal damage linked to diabetic kidney disease (DKD).

The low-temperature dissolution characteristics of water in coal-based hydrocarbon fuels and its molecular dynamics simulation.

Context: As a substitute for traditional petroleum derived jet fuels, water in coal-based hydrocarbon fuels may precipitate into ice at low temperatures, leading to fuel system failures and endangering flight safety. This study employed Karl Fischer titration in conjunction with an optimized combination of an oil moisture detector to jointly measure the water solubility of coal-based hydrocarbon fuels at room temperature. The coefficient correction was performed on the oil moisture detector, and the water solubility curves of coal-based hydrocarbon fuels 233 to 313 K were finally measured and compared with other literature results.

Research on detection methods of related substances and degradation products of the antitumor drug selpercatinib.

Background: Selpercatinib, a selective RET kinase inhibitor, is approved for treating various cancers with RET gene mutations such as RET-rearranged thyroid cancer and non-small cell lung cancer. The presence of process-related and degradation impurities in its active pharmaceutical ingredient (API) can significantly affect its safety and effectiveness. However, research on detecting these impurities is limited.

N6-methyladenosine regulates metabolic remodeling in kidney aging through transcriptional regulator GLIS1.

Background: Age-related kidney impairment, characterized by tubular epithelial cell senescence and renal fibrosis, poses a significant global public health threat. Although N6-methyladenosine (m6A) methylation is implicated in various pathological processes, its regulatory mechanism in kidney aging remains unclear.

Methods: An m6A-mRNA epitranscriptomic microarray was performed to identify genes with abnormal m6A modifications in aged human kidney tissues.

Immature PIT1-lineage Pituitary Neuroendocrine Tumors/Adenomas, a Morphologically Unique Pituitary Neuroendocrine Tumors/Adenomas Commonly With Cytologic Atypia Features and a Predilection for Aggressive Clinical Potential.

Immature PIT1-lineage pituitary neuroendocrine tumors (PitNETs)/adenomas (Immature PIT1-lineage tumors) are a rare and underrecognized subtype of PitNETs that exhibits distinct cytologic atypia features and aggressive clinical potential. This study characterizes the clinical, radiological, histologic, and immunohistochemical features of 15 immature PIT1-lineage tumors identified from 1084 PitNETs patients over 5 years. Our cohort of 6 males and 9 females had a median age of 37.

Chromatographic analysis of ponatinib and its impurities: method development, validation, and identification of new degradation product.

Background: Ponatinib, a third-generation tyrosine kinase inhibitor, is employed in the management of adult chronic myeloid leukemia. Nevertheless, the presence of process impurities and degradation impurities linked to ponatinib may potentially influence its effectiveness and safety. Therefore, the objective of this research was to establish a robust liquid chromatography method and systematically validate it for the detection of substances related to ponatinib.

improves drought tolerance and increases fiber yield in cotton.

Drought poses a significant challenge to global crop productivity, necessitating innovative approaches to bolster plant resilience. Leveraging transgenic technology to bolster drought tolerance in crops emerges as a promising strategy for addressing the demands of a rapidly growing global populace. AtZAT10/STZ1, a C2H2-type zinc finger protein transcription factor has shown to significantly improve Arabidopsis' tolerance to various abiotic stresses.

Development and validation of a novel high-performance liquid chromatography (HPLC) method for the detection of related substances of pralsetinib, a new anti-lung cancer drug.

Background: Pralsetinib, a targeted inhibitor of the RET enzyme, plays a critical role in the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by RET gene fusion mutations following platinum-based chemotherapy. Nevertheless, impurities resulting from the manufacturing and degradation of pralsetinib have the potential to impact its therapeutic effectiveness and safety profile.

Methods: To address this issue, a liquid chromatography method was developed and validated for the specific identification of pralsetinib and its related impurities.

M6A RNA Methylation-Mediated TUG1 Stability Maintains Mitochondrial Homeostasis during Kidney Aging by Epigenetically Regulating PGC1-α Expression.

Aging is a significant risk factor for the increased incidence of acute kidney injury and chronic kidney disease, posing significant challenges to global public health. The role of N6-methyladenosine (m6A) in the development of chronic kidney disease has been reported, but the regulatory mechanism of m6A in kidney aging remains unclear. In this study, we identified a long noncoding RNA (lncRNA), called taurine up-regulated 1 (TUG1), which exhibited a significantly decreased level of m6A modification in human aged kidney through the m6A-lncRNA epitranscriptome microarray.

Using exploratory pharmacokinetic and pharmacodynamic analyses to predict the probability of flu-like symptoms in healthy volunteers and patients with chronic hepatitis B treated with the toll-like receptor 7 agonist ruzotolimod.

Ruzotolimod (Toll-like receptor 7 (TLR7) agonist, RG7854) is an oral, small molecule immuno-modulator activating the TLR 7 and is being evaluated in patients with CHB. As with other TLR7 agonists, the study drug-related adverse events of flu-like symptoms have been reported in some participants during phase I studies with ruzotolimod. An exploratory analysis of the relationship between pharmacokinetic (PK)/pharmacodynamic (PD) and flu-like symptoms was performed in participants from two phase I studies including both healthy volunteers and NUC-suppressed CHB patients who received either single or multiple ascending doses of orally administered ruzotolimod.

Double S-scheme CuSe/twinned-CdZnS homo-heterojunctions with surface plasmon effects for efficient photocatalytic H evolution.

The enhancement of charge separation and utilization efficiency in both the bulk phase and interface of semiconductor photocatalysts, as well as the expansion of light absorption range, are crucial research topics in the field of photocatalysis. To address this issue, twinned CdZn5S (T-CZS) homojunctions consisting of wurtzite CdZnS (WZ-CZS) and zinc blende CdZnS (ZB-CZS) were synthesized via a hydrothermal method to facilitate the bulk-phase charge separation. Meanwhile, CuSe with localized surface plasmon resonance effect (LSPR) generated by Cu vacancies was also obtained through a hydrothermal process.

Association of dietary live microbe intake with diabetic kidney disease in patients with type 2 diabetes mellitus in US adults: a cross-sectional study of NHANES 1999-2018.

Aims: Several studies have reported dietary microorganisms' beneficial effects on human health. We aimed to detect the potential association between dietary live microbe intake and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) through a cross-sectional analysis of the National Health and Nutrition Examination Survey from 1999 to 2018.

Methods: According to the Sanders classification system of dietary live microbes, the study participants were divided into three groups: low, medium, and high live microbe groups.

Clinical application of combination [C]C-methionine and [N]N-ammonia PET/CT in recurrent functional pituitary adenomas with negative MRI or [F]F-FDG PET/CT.

Background: We assessed the value of positron emission tomography/computed tomography (PET/CT) with [N]N-ammonia ([N]N-NH3) and [C]C-methionine ([C]C-MET) for the evaluation and management of recurrent secreting pituitary adenoma, which could not be detected by magnetic resonance imaging (MRI) or fluorine-18 fluorodeoxyglucose ([F]F-FDG) PET.

Methods: Nine consecutive patients with biochemical and clinical evidence of active recurrent tumor not detected by MRI and [F]F-FDG PET were enrolled in this study. All of the patients underwent [N]N-NH3 and [C]C-MET PET/CT, after which the pattern of tracer uptake was studied, the tumor position was located, and a clinical decision was made.

Endophytic fungus Penicillium steckii DF33 promoted tanshinones biosynthesis in Salvia miltiorrhiza by regulating the expression of CYP450 genes.

Salvia miltiorrhiza, a prominent traditional Chinese medicinal resource, has been extensively employed in the management of cardiovascular and cerebrovascular ailments. Ensuring the consistency of S. miltiorrhiza raw materials revolves around the imperative task of maintaining stable tanshinones content and composition.

Correlation between tumor invasion and somatostatin receptor subtypes in acromegaly.

Objective: The low expression of somatostatin receptor (SSTR) subtypes in somatotropinoma is associated with a poor response to somatostatin analogs (SSAs). However, the correlation between SSTRs and tumor invasion has not yet been clarified. Therefore, the authors aimed to investigate the relationship between SSTRs and tumor invasion, as well as the correlation between tumor invasiveness and pharmacological response to SSAs.

The relevance of the non-invasive biomarkers lncRNA GAS5/miR-21 ceRNA regulatory network in the early identification of diabetes and diabetic nephropathy.

Background: To investigate the diagnostic value of serum lncRNA growth arrest-specific transcript 5 (lncRNA GAS5) and microRNA-21 (miR-21) in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), and elucidate their roles in the pathogenesis.

Methods: A microarray technology was used asses lncRNA GAS5 and miR-21 expression profiles in non-anticoagulant blood from 44 patients including T2DM without DN group (DM), T2DM with DN group (DN), and healthy controls group (N), followed by real-time PCR validation. Logistic regression and receiver operating characteristic (ROC) curves were applied to evaluate the clinical indicators among normal, T2DM, and DN patients.

Permeameter and solenoid measurements of Epstein strips of electrical steels.

The dc and ac flux density vs magnetic field B(H) loops of Epstein electrical strips are measured in an IEC type-A permeameter with a high-quality electrical strip wound double yokes of inside length l0 = 0.2 m and inside height h0 = 0.1 m and in a long solenoid.

Senescence-related gene c-Myc affects bladder cancer cell senescence by interacting with HSP90B1 to regulate cisplatin sensitivity.

Patients with advanced bladder cancer gradually become less sensitive to chemotherapeutic agents, leading to tumor recurrence. Initiating the senescence program in solid tumors may be an important means of improving short-term drug sensitivity. The important role of c-Myc in bladder cancer cell senescence was determined using bioinformatics methods.

Study on the Hydroconversion Law of Coal-Based Heavy Fractions with Different Catalyst Contents Based on an Improved Separation Method.

Heavy fractions (e.g., asphaltene and resin) can easily be subjected to physical aggregation and chemical coking reaction through molecular force in the process of lightweight processing and use of coal tar (CT), such that the normal processing and use can be affected.

Using 2-dimensional hand photographs to predict postoperative biochemical remission in acromegaly patients: a transfer learning approach.

Background: The primary treatment goals in acromegaly patients are complete surgical removal of underlying pituitary tumors and biochemical remission. One of the challenges in developing countries is the difficulty in monitoring postoperative biochemical levels in acromegaly patients, particularly those who live in remote areas or regions with limited medical resources.

Methods: In an attempt to overcome the abovementioned challenges, we conducted a retrospective study and established a mobile and low-cost method to predict biochemical remission in acromegaly patients after surgery, the efficacy of which was assessed retrospectively using the China Acromegaly Patient Association (CAPA) database.

Feasibility analysis of ACTH adenoma model in USP8-/- mice.

Introduction: Patients with adrenocorticotropic hormone (ACTH)-secreting pituitary tumours (35% to 60%) present with somatic mutations in the USP8 gene. USP8 mutations lead to enhanced deubiquitination of the epidermal growth factor receptor (EGFR) and result in an imbalance in EGFR signalling, accompanied by excessive activation of ACTH production and cell growth. USP8 emerged as a novel and exciting candidate gene for Cushing's disease.

YY1-induced upregulation of LncRNA-ARAP1-AS2 and ARAP1 promotes diabetic kidney fibrosis aberrant glycolysis associated with EGFR/PKM2/HIF-1α pathway.

Dimeric pyruvate kinase (PK) M2 (PKM2) plays an important role in promoting the accumulation of hypoxia-inducible factor (HIF)-1α, mediating aberrant glycolysis and inducing fibrosis in diabetic kidney disease (DKD). The aim of this work was to dissect a novel regulatory mechanism of Yin and Yang 1 (YY1) on lncRNA-ARAP1-AS2/ARAP1 to regulate EGFR/PKM2/HIF-1α pathway and glycolysis in DKD. We used adeno-associated virus (AAV)-ARAP1 shRNA to knocked down ARAP1 in diabetic mice and overexpressed or knocked down YY1, ARAP1-AS2 and ARAP1 expression in human glomerular mesangial cells.

[Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review].

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch.