Development and optimization of a high-throughput LC-MS/MS method for the simultaneous determination of Exatecan and its Cathepsin B-sensitive prodrug, and ARV-825 in rat plasma: Application to pharmacokinetic study.

For most cancers, the combination of chemotherapy drugs is a promising approach. The combination of DNA damage agent Exatecan and proteolysis targeting chimera (PROTAC) agent ARV-825, which is a selective bromodomain-containing protein 4 degrader, can further improve efficacy through the DNA damage-repair mechanism. The Cathepsin B-sensitive prodrug with high albumin affinity of Exatecan (C14-VC-PAB-Exa) was introduced and co-encapsulated with ARV-825 into the nano-drug delivery system for improving the physicochemical properties of the two drugs.

Emerging prodrug and nano-drug delivery strategies for the detection and elimination of senescent tumor cells.

Tumor cellular senescence, characterized by reversible cell cycle arrest following anti-cancer therapies, presents a complex paradigm in oncology. Given that senescent tumor cells may promote angiogenesis, tumorigenesis, and metastasis, selective killing senescent cells (SCs)-a strategy termed senotherapy-has emerged as a promising approach to improve cancer treatment. However, the clinical implementation of senotherapy faces significant hurdles, including lack of precise methods for SCs identification and the potential for adverse effects associated with highly cytotoxic senolytic agents.

Integrated Transcriptomic and Targeted Metabolomic Analysis Reveals the Key Genes Involved in Triterpenoid Biosynthesis of .

is a traditional Chinese medicinal fungus, and ganoderma triterpenoids (GTs) are one of the main bioactive compounds. These compounds have various pharmacological functions, including anti-tumor, antioxidant, anti-inflammatory, liver-protective, and immune-regulating effects. However, the manner in which they accumulate, and their biosynthesis mechanisms remain unclear.

The role of phospholipid transfer protein in sepsis-associated acute kidney injury.

Background: Phospholipid transfer protein (PLTP), a glycoprotein widely expressed in the body, is primarily involved in plasma lipoprotein metabolism. Previous research has demonstrated that PLTP can exert anti-inflammatory effects and improve individual survival in patients with sepsis and endotoxemia by neutralizing LPS and facilitating LPS clearance. However, the role of PLTP in sepsis-associated acute kidney injury (SA-AKI) and the specific mechanism of its protective effects are unclear.

Electrochemical Synthesis of Quinazolines: N-H/C(sp)-H Coupling of -Carbonyl Anilines with Amino Acids and Amines.

A mild and efficient electrochemical protocol for the synthesis of quinazolines through N-H/C(sp)-H coupling of -carbonyl anilines with natural amino acids/amines has been developed. The products quinazolines can easily be isolated in moderate to excellent yields under external chemical oxidant-free conditions. Moreover, this reaction can be safely conducted on gram scale.

Comparative genomics reveals ample evidence to Ganoderma sinense cultivars for molecular identification and new FIP exploration.

The first dikaryotic genome of Ganoderma cultivar Zizhi S2 (56.76 Mb, 16,681 genes) has been sequenced recently. 98.

Effects of soil moisture and an AC-electric field on the phytoremediation of the Cd-contaminated soil.

Phytoremediation enhanced by electric field has been considered a green and low-cost technology for remediating heavy metal-contaminated soils. Soil moisture is a main environmental factor that affects Cd availability in the soil. However, the effects of soil moisture and AC-electric field on the remediation efficiency of willow ( spp.

Cost-effectiveness of different intervention strategies of HIV in Zhejiang, China.

Objective: Mass screening for HIV and preexposure prophylaxis (PrEP) may be effective measures for reducing the probability of HIV transmission. Our study aimed to determine the cost-effectiveness of preliminary screening in the general population, PrEP for HIV-negative spouses in serodiscordant couples, or both approaches in Zhejiang Province.

Design: From a policy-maker's perspective, a Markov model was constructed to compare four strategies over a 30-year horizon.

Computed tomography guided electromagnetic navigation system in percutaneous laser ablation for treating primary lung cancer: a case report.

Background: The majority of patients of lung cancer have already lost the chance of surgery at the time of diagnosis. Percutaneous local thermal ablation is a precise minimally invasive technique and a viable alternative to surgical treatment. Compared with radiofrequency ablation and microwave ablation, percutaneous laser ablation for the treatment of lung tumors is less commonly used and reported, especially for primary lung cancer.

[Construction of a risk predictive model of acute kidney injury based on urinary tissue inhibitor of metalloproteinase 2 and insulin-like growth factor-binding protein 7 and its early predictive value in critically ill patients].

Objective: To establish a risk predictive model nomogram of acute kidney injury (AKI) in critically ill patients by combining urinary tissue inhibitor of metalloproteinase 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7), and to verify the predictive value of the model.

Methods: A prospective observational study was conducted. The patients with acute respiratory failure or circulatory disorder admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from November 2017 to April 2020 were enrolled.

Emerging non-antibody‒drug conjugates (non-ADCs) therapeutics of toxins for cancer treatment.

The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins. In recent years, toxins have been widely used as warheads for antibody‒drug conjugates (ADCs) due to their efficient killing activity against various cancer cells. Although ADCs confer certain targeting properties to the toxins, low drug loading capacity, possible immunogenicity, and other drawbacks also limit the potential application of ADCs.

Electrochemical oxidative decarboxylative of α-oxocarboxylic acids towards the synthesis of quinazolines and quinazolinones.

A mild and environmentally electrochemical method for the synthesis of quinazolines and quinazolinones has been developed through anodic oxidation decarboxylative of α-oxocarboxylic acids. The present reaction was efficiently conducted by using simple and cheap NHI as the N-source and electrolyte in an undivided cell. The desired products, quinazolines and quinazolinones, were isolated in high yield under chemical oxidant free conditions.

Efficient Photoelectrochemical Hydrogen Generation Based on Core Size Effect of Heterostructured Quantum Dots.

Colloidal quantum dots (QDs) are shown to be effective as light-harvesting sensitizers of metal oxide semiconductor (MOS) photoelectrodes for photoelectrochemical (PEC) hydrogen (H) generation. The CdSe/CdS core/shell architecture is widely studied due to their tunable absorption range and band alignment via engineering the size of each composition, leading to efficient carrier separation/transfer with proper core/shell band types. However, until now the effect of core size on the PEC performance along with tailoring the core/shell band alignment is not well understood.

Polarization structured light 3D depth image sensor for scenes with reflective surfaces.

Highly reflective surfaces are notorious in the field of depth sensing and three-dimensional (3D) imaging because they can cause severe errors in perception of the depth. Despite recent progress in addressing this challenge, there are still no robust and error-free solutions. Here, we devise a polarization structured light 3D sensor for solving these problems, in which high-contrast-grating (HCG) vertical-cavity surface-emitting lasers (VCSELs) are used to exploit the polarization property.

Decarboxylative -Formylation of Amines with Glyoxylic Acid Promoted by HO.

A novel method for the synthesis of formamides through the decarboxylative -formylation of amines with glyoxylic acid has been developed. This transformation provides an efficient protocol for the synthesis of various formamides with moderate to excellent yields, and it can accommodate a wide range of functional groups under metal free and base free conditions. In addition, the large-scale experiments and high chemoselectivity have shown great potential application of this strategy.

HCC prediction models in chronic hepatitis B patients receiving entecavir or tenofovir: a systematic review and meta-analysis.

Background: Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk.

Methods: We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk.

Diagnostic Value of the Combination of Ultrasonographic Optic Nerve Sheath Diameter and Width of Crural Cistern with Respect to the Intracranial Pressure in Patients Treated with Decompressive Craniotomy.

Background: The monitoring of intracranial pressure (ICP) and detection of increased ICP are crucial because such increases may cause secondary brain injury and a poor prognosis. Although numerous ultrasound parameters, including optic nerve sheath diameter (ONSD), width of the crural cistern (WCC), and the flow velocities of the central retinal artery and middle cerebral artery, can be measured in patients after hemicraniectomy, researchers have yet to determine which of these is better for evaluating ICP. This study aimed to analyze the correlation between ICP and ultrasound parameters and investigate the best noninvasive estimator of ICP.

Age and Serum Creatinine Can Differentiate Wilson Disease Patients with Pseudonormal Ceruloplasmin.

Methods: We retrospectively screened individuals with serum Cp ≥ 140 mg/L from 1032 WD patients who were hospitalised for the first time. Logistic regression analyses were performed in a case-control study between the WD cohort and another liver disease cohort to explore the independent risk factors for WD diagnosis and establish a regression model to identify them. The follow-up medical records of the WD cohort were subjected to mixed-effects model analysis in a longitudinal study to discover factors associated with Cp normalisation.

Screening and mutation analysis of phenylalanine hydroxylase deficiency in newborns from Jiangxi province.

Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive disorder of amino acid metabolism and caused by mutations in the phenylalanine hydroxylase () gene. Without timely and appropriate dietary management, the disturbance of amino acid metabolism may impair cognitive development and neurophysiological function. Newborn screening (NBS) can aid the early diagnosis of PAHD, which can give accurate therapy to PAHD patients in time.

Changing incidence of hepatitis B and persistent infection risk in adults: a population-based follow-up study from 2011 in China.

Background: This study aimed to estimate hepatitis B incidence and chronicity risk in rural adults in China under the background of eliminating viral hepatitis.

Methods: Hepatitis B surface antigen (HBsAg) screening was conducted every 2 years in demonstration areas since 2011. Individuals with baseline HBsAg-negative were included.

A male-sterile mutant with necrosis-like dark spots on anthers was generated in cotton.

Although conventional hybrid breeding has paved the way for improving cotton production and other properties, it is undoubtedly time and labor consuming, while the cultivation of male sterile line can fix the problem. Here, we induced male sterile mutants by simultaneously editing three cotton () genes by CRISPR/Cas9. Notably, the genes are homologous to genes, which inhibit the production of middle layer and tapetum cells as well, leading to male sterility in cotton.