Discovery of Orally Potent Small-Molecule CD73 Inhibitor for Cancer Immunotherapy.

CD73, an emerging immune checkpoint, plays a pivotal role in the adenosine (ADO) metabolic pathway by catalyzing the conversion of AMP to ADO. This process has been shown to inhibit the functions of T cells and natural killer (NK) cells, thereby exacerbating the immunosuppressive effects within the tumor microenvironment. These findings underscore the critical role of CD73 in modulating immune cell function and represent a promising therapeutic target for cancer treatment.

Temporal trends, disease burden and attributable risk factors of stomach and colorectal cancers among 31 countries and territories in Western Pacific region, 20002021.

Objective: This study aimed to describe the updated disease burden and temporal trends of stomach cancer (SC) and colorectal cancer (CRC), and to explore potential influence factors of the two cancers in the Western Pacific region (WPR).

Methods: Estimates of incidence, deaths, and disability-adjusted life years (DALYs) for SC and CRC were obtained from the Global Burden of Disease Study 2021. Trends in age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) were assessed.

The Role of N6-Methyladenosine in Mitochondrial Dysfunction and Pathology.

Mitochondria are indispensable in cells and play crucial roles in maintaining cellular homeostasis, energy production, and regulating cell death. Mitochondrial dysfunction has various manifestations, causing different diseases by affecting the diverse functions of mitochondria in the body. Previous studies have mainly focused on mitochondrial-related diseases caused by nuclear gene mutations or mitochondrial gene mutations, or mitochondrial dysfunction resulting from epigenetic regulation, such as DNA and histone modification.

Disparities in the incidence, mortality and disability-adjusted life years of 33 early-onset cancer groups globally, 2012-2021: a systematic analysis.

Background: The global cancer burden is rising, with early-onset cancers becoming more prevalent. We aimed to investigate the burden, trend and population disparity in 33 early-onset cancers from 2012 to 2021.

Methods: Annual incidence, death, and disability-adjusted life years (DALY) numbers and rates for early-onset (15-49 years) cancer groups were calculated from Global Burden of Diseases (GBD) 2021 dataset, covering 2012-2021 across global, five SDI groupings, and 204 countries and territories.

Mpox vaccination hesitancy, previous immunisation coverage, and vaccination readiness in the African region: a multinational survey.

Background: Vaccination hesitancy poses a serious threat to mpox vaccination programs. Historically, vaccine uptake in the African region has been low, and this trend may impact future vaccination efforts. Our aim was to investigate the relationships between mpox vaccination hesitancy, immunisation coverage for other vaccines, and vaccination readiness among African adults.

Network Pharmacology Suggests Mechanisms for Therapeutic Effects of on Avian Gout.

Avian gout (AG) is detrimental to the survival and production performance of poultry and effective drugs are lacking. has shown clinical efficacy against arthritis and may have potential value in AG prevention and treatment. In the present study, the components and targets of and AG-related targets were identified using relevant databases.

Whole-exome sequencing association study reveals genetic effects on tumor microenvironment components in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) presents a substantial clinical challenge due to the limited understanding of its genetic underpinnings. Here we conduct the largest scale whole-exome sequencing association study of NPC to date, encompassing 6,969 NPC cases and 7,100 controls. We unveil 3 germline genetic variants linked to NPC susceptibility: a common rs2276868 in RPL14, a rare rs5361 in SELE, and a common rs1050462 in HLA-B.

Global, regional, and national burden of dengue infection in children and adolescents: an analysis of the Global Burden of Disease Study 2021.

Background: Dengue remains a global threat to public health, however, its disease burden among children and adolescents has always been poorly quantified. Therefore, we aimed to systematically estimate the global, regional, and national burden and temporal trends of dengue infection in children and adolescents from 1990 to 2021.

Methods: Data on the number and rate of incidence and disability-adjusted life-years (DALYs) of dengue infection among children and adolescents under 20 years were obtained from the Global Burden of Disease Study (GBD) 2021.

Small Molecule Compound DHPA Screened by Computer-Aided Drug Design and Molecular Dynamics Simulation Inhibits Neuroblastoma Cell Proliferation by Targeting TrkB.

Neuroblastoma (NB) is a rare and malignant pediatric solid tumor. Due to its heterogeneity, it poses significant challenges for treatment, resulting in a high mortality rate. This study aimed to identify new therapeutic drugs by modeling the TrkB receptor from PDB 4AT5 and conducting virtual screening of compounds from the YaTCM database (containing 47,696 compounds derived from 6220 Traditional Chinese Medicines).

Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.

Cell death is of great significance in maintaining tissue homeostasis and bodily functions. With considerable research coming to the fore, it has been found that programmed cell death presents in multiple modalities in the body, which is not only limited to apoptosis, but also can be divided into autophagy, pyroptosis, ferroptosis, mitotic catastrophe, entosis, netosis, and other ways. Different forms of programmed cell death have disparate or analogous characteristics with each other, and their occurrence is accompanied by multiple signal transduction and the role of a myriad of regulatory factors.

Interaction between economic status and healthy lifestyle in long COVID among Chinese older population: a cross-sectional study.

Objectives: To estimate the interaction between economic status (ES) and healthy lifestyle in long COVID among Chinese older people infected with SARS-CoV-2.

Design: A cross-sectional study based on the Peking University Health Cohort in Anning, Yunnan.

Setting: All primary health institutions in Anning, Yunnan Province, China, from April to May 2023.

Amino Turbo Chirality and Its Asymmetric Control.

A series of new targets containing 3 chiral elements of central, orientational, and turbo chirality have been designed and synthesized asymmetrically. The absolute configurations and conformations of these types of chirality were concurrently controlled by using chiral sulfonimine auxiliary and unambiguously determined by x-ray diffraction analysis. These targets include alpha unnatural amino acid derivatives, which may play an important role for drug design, discovery, and development.

Burden and trends of infectious disease mortality attributed to air pollution, unsafe water, sanitation, and hygiene, and non-optimal temperature globally and in different socio-demographic index regions.

Background: Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019.

Methods: This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures.

Global, regional and national trends and impacts of natural floods, 1990-2022.

Objective: To assess global, regional and national trends in the impact of floods from 1990 to 2022 and determine factors influencing flood-related deaths.

Methods: We used data on flood disasters from the International Disaster Database for 1990-2022 from 168 countries. We calculated the annual percentage change to estimate trends in the rates of people affected and killed by floods by study period, World Health Organization (WHO) region, country income level and flood type.

C(sp)-C(sp) Lever-Based Targets of Orientational Chirality: Design and Asymmetric Synthesis.

In this study, the design and asymmetric synthesis of a series of chiral targets of orientational chirality were conducted by taking advantage of -sulfinylimine-assisted nucleophilic addition and modified Sonogashira catalytic coupling systems. Orientational isomers were controlled completely using alkynyl/alkynyl levers [C(sp)-C(sp) axis] with absolute configuration assignment determined by X-ray structural analysis. The key structural element of the resulting orientational chirality is uniquely characterized by remote through-space blocking.

Discovery of highly potent PARP7 inhibitors for cancer immunotherapy.

PARP7 has been proven to play an important role in immunity. Substantial upregulation of PARP7 is observed in numerous cancerous cell types, consequently resulting in the inhibition of type Ⅰ interferon signaling pathways. Therefore, inhibiting the activity of PARP7 can enhance type Ⅰ interferon signaling to exert an anti-tumor immune response.

TRPC4 aggravates hypoxic pulmonary hypertension by promoting pulmonary endothelial cell apoptosis.

Pulmonary hypertension (PH) is a devastating disease that lacks effective treatment options and is characterized by severe pulmonary vascular remodeling. Pulmonary arterial endothelial cell (PAEC) dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension. Canonical transient receptor potential (TRPC) channels, a family of Ca-permeable channels, play an important role in various diseases.

Design and Asymmetric Control of Orientational Chirality by Using the Combination of C(sp)-C(sp) Levers and Achiral N-Protecting Group.

New chiral targets of orientational chirality have been designed and asymmetrically synthesized by taking advantage of N-sulfinyl imine-directed nucleophilic addition/oxidation, Suzuki-Miyaura, and Sonogashira cross-coupling reactions. Orientation of single isomers has been selectively controlled by using aryl/alkynyl levers [C(sp)-C(sp) axis] and tBuSO- protecting group on nitrogen as proven by X-ray diffraction analysis. The key structural characteristic of resulting orientational products is shown by remote through-space blocking manner.

LiNAC100 contributes to linalool biosynthesis by directly regulating LiLiS in Lilium 'Siberia'.

The transcription factor LiNAC100 has a novel function of regulating floral fragrance by directly regulating linalool synthase gene LiLiS. Lilium 'Siberia', an Oriental hybrid, is renowned as both a cut flower and garden plant, prized for its color and fragrance. The fragrance comprises volatile organic compounds (VOCs), primarily monoterpenes found in the plant.

Association of temperature and precipitation with malaria incidence in 57 countries and territories from 2000 to 2019: A worldwide observational study.

Background: The transmission of malaria is known to be affected by climatic factors. However, existing studies on the impact of temperature and precipitation on malaria incidence offer no clear-cut conclusions, and there is a lack of research on a global scale. We aimed to estimate the association of temperature and precipitation with malaria incidence globally from 2000 to 2019.

Discovery of Highly Potent Small-Molecule PD-1/PD-L1 Inhibitors with a Novel Scaffold for Cancer Immunotherapy.

Inhibition of the PD-1/PD-L1 interaction through small-molecule inhibitors is a promising therapeutic approach in cancer immunotherapy. Herein, we utilized as the lead compound to develop a series of novel PD-1/PD-L1 small-molecule inhibitors with a naphthyridin scaffold. Among these compounds, displayed the most potent inhibitory activity for the PD-1/PD-L1 interaction (IC = 15.

Advanced strategies in high-throughput droplet screening for enzyme engineering.

Enzymes, as biocatalysts, play a cumulatively important role in environmental purification and industrial production of chemicals and pharmaceuticals. However, natural enzymes are limited by their physiological properties in practice, which need to be modified driven by requirements. Screening and isolating certain enzyme variants or ideal industrial strains with high yielding of target product enzymes is one of the main directions of enzyme engineering research.