Astragaloside IV Reduces Lung Epithelial Cell Pyroptosis via TXNIP-NLRP3-GSDMD pathway.

This study aimed to investigate the detrimental impact of cigarettes on lung cells and the potential effects of astragaloside IV on lung epithelial cell oxidative stress and pyroptosis. The research utilized cigarette smoke extract (CSE) to stimulate lung epithelial cells BEAS-2B, assessed cytotoxicity using the CCK-8 method, and measured changes in reactive oxygen species (ROS) and mitochondrial membrane potential with a probe method. Additionally, Seahorse XF24 was employed to analyze the impact of CSE on mitochondria in lung epithelial cells.

Rapid, Multiplexed, and Enzyme-Free Nucleic Acid Detection Using Programmable Aptamer-Based RNA Switches.

Rapid, simple, and low-cost diagnostic technologies are crucial tools for combatting infectious disease. We describe a class of aptamer-based RNA switches or aptaswitches that recognize target nucleic acid molecules and initiate folding of a reporter aptamer. Aptaswitches can detect virtually any sequence and provide an intense fluorescent readout without intervening enzymes, generating signals in as little as 5 minutes and enabling detection by eye with minimal equipment.

High affinity and low PARP-trapping benzimidazole derivatives as a potential warhead for PARP1 degraders.

PARPi have been explored and applied in the treatment of various cancers with remarkable efficacy, especially BRCA1/2 mutated ovarian, breast, prostate, and pancreatic cancers. However, PARPi renders inevitable drug resistance and showed high toxicity because of PARP-Trapping with long-term clinic tracking. To overcome the drug resistance and the high toxicity of PARPi, many novel methods have been developed including PROTACs.

Comprehensive Identification of the β-Amylase (BAM) Gene Family in Response to Cold Stress in White Clover.

White clover ( L.) is an allopolyploid plant and an excellent perennial legume forage. However, white clover is subjected to various stresses during its growth, with cold stress being one of the major limiting factors affecting its growth and development.

sp. nov., an obligately chemolithoautotrophic, hydrogen-oxidizing bacterium isolated from coastal marine sediments.

A novel mesophilic, chemolithoautotrophic, hydrogen-oxidizing bacterium, designated strain ST1-3, was isolated from mud sediment samples collected from mangroves in Jiulong River estuary. The cells were Gram-stain-negative, non-motile and rod-shaped. The temperature, pH and salinity ranges for growth of strain ST1-3 were 4-45 °C (optimum, 35 °C), pH 5.

Evidence for RA-dependent meiosis onset in a turtle embryo.

Meiotic entry is one of the earliest sex determination events of the germ cell in higher vertebrates. Although advances in meiosis onset have been achieved in mammals, birds and fish, how this process functions in reptiles is largely unknown. In this study, we present the molecular analysis of meiosis onset and the role of retinoic acid (RA) in this process in the red-eared slider turtle.

Huangkui capsule attenuates diabetic kidney disease through the induction of mitophagy mediated by STING1/PINK1 signaling in tubular cells.

Background: Mitochondria is critic to tubulopathy, especially in diabetic kidney disease (DKD). Huangkui capsule (HKC; a new ethanol extract from the dried corolla of Abelmoschus manihot) has significant clinical effect on DKD. Previous studies have shown that HKC protects kidney by regulating mitochondrial function, but its mechanism is still unclear.

Rapid and Multiplexed Nucleic Acid Detection using Programmable Aptamer-Based RNA Switches.

Rapid, simple, and low-cost diagnostic technologies are crucial tools for combatting infectious disease. Here, we describe a class of aptamer-based RNA switches called aptaswitches that recognize specific target nucleic acid molecules and respond by initiating folding of a reporter aptamer. Aptaswitches can detect virtually any sequence and provide a fast and intense fluorescent readout, generating signals in as little as 5 minutes and enabling detection by eye with minimal equipment.

Loss- and gain-of-function analyses reveal the essential role of Cyp19a1 in ovarian determination of the red-eared slider turtle.

Estrogen signaling exerts a decisive role in female sex determination and differentiation in chicken and fish. Aromatase encoded by Cyp19a1 is the key enzyme that catalyzes the conversion of androgen to estrogen. Correlative analyses implicate the potential involvement of aromatase in reptilian sexual development, however, the direct genetic evidence is lacking.

Design, synthesis, and evaluation of 1H-benzo[d]imidazole-4-carboxamide PARP-1 inhibitors using different saturated nitrogen-contained heterocycle as linker group.

Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors have been successfully applied in the clinical treatment of various cancer. Side effects and drug resistant cases were reported, and more effective PARP-1 inhibitors were required. However, studies on the AD site of PARP-1 inhibitors are currently incomplete.

Antibacterial and β-amyloid precursor protein-cleaving enzyme 1 inhibitory polyketides from the fungus .

One new prenylated benzenoid, (±)-chevalieric acid (), and four new anthraquinone derivatives, (10,12)-, (10,12)-, (10,12)-, and (10,12)-chevalierone (-), together with ten previously described compounds (-), were isolated from the fungus (L. Mangin) Thom and Church. The structures of new compounds were elucidated by extensive 1D and 2D nuclear magnetic resonance (NMR), and HRESIMS spectroscopic analysis.

Infection-activated lipopeptide nanotherapeutics with adaptable geometrical morphology for in vivo bacterial ablation.

The nonselective membrane disruption of antimicrobial peptides (AMPs) helps in combating the antibacterial resistance. But their overall positive charges lead to undesirable hemolysis and toxicity toward normal living cells, as well as the rapid clearance from blood circulation. In consequence, developing smart AMPs to optimize the antimicrobial outcomes is highly urgent.

Foxl2 is required for the initiation of the female pathway in a temperature-dependent sex determination system in Trachemys scripta.

KDM6B-mediated epigenetic modification of the testicular regulator Dmrt1 has previously been identified as the primary switch of the male pathway in a temperature-dependent sex-determination (TSD) system; however, the molecular network of the female pathway has not yet been established. Here, we have functionally characterized for the first time an upstream regulator of the female pathway, the forkhead transcription factor FOXL2, in Trachemys scripta, a turtle species with a TSD system. FOXL2 exhibited temperature-dependent female-specific expression patterns before the onset of gonadal differentiation and was preferentially localized in ovarian somatic cells.

Infection prevention and control risk factors in health workers infected with SARS-CoV-2 in Jordan: A case control study.

Background: Despite under-reporting, health workers (HWs) accounted for 2 to 30% of the reported COVID-19 cases worldwide. In line with data from other countries, Jordan recorded multiple case surges among HWs.

Methods: Based on the standardized WHO UNITY case-control study protocol on assessing risk factors for SARS-CoV-2 infection in HWs, HWs with confirmed COVID-19 were recruited as cases from eight hospitals in Jordan.

Design to Implementation Study for Development and Patient Validation of Paper-Based Toehold Switch Diagnostics.

Access to low-burden molecular diagnostics that can be deployed into the community for testing is increasingly important and has meaningful wider implications for the well-being of societies and economic stability. Recent years have seen several new isothermal diagnostic modalities emerge to meet the need for rapid, low-cost molecular diagnostics. We have contributed to this effort through the development and patient validation of toehold switch-based diagnostics, including diagnostics for the mosquito-borne Zika and chikungunya viruses, which provided performance comparable to gold-standard reverse transcription-quantitative polymerase chain reaction (RT-qPCR) based assays.

WHO's support for COVID-19 research and knowledge management in the Eastern Mediterranean Region.

Health research, innovation and knowledge management remain major priorities of the WHO's response to the COVID-19 pandemic. WHO's Eastern Mediterranean Regional Office (EMRO) supports priority research initiatives that address gaps in current knowledge regarding the COVID-19 pandemic. Through a specific call for proposals, 122 research proposals were received and reviewed in 2020, of which 17 were recommended for funding from eight countries.

Computational Design of RNA Toehold-Mediated Translation Activators.

Translation activators are an important class of riboregulators that respond to nucleic acid signals by activating gene expression. Toehold switches and single-nucleotide-specific programmable riboregulators (SNIPRs) are two types of translation activators that can detect nearly any nucleic acid sequence using interactions initiated by single-stranded domains known as toeholds. Toehold switches operate with high dynamic range, orthogonality, and programmability, making them capable of detecting a variety of pathogens in paper-based cell-free diagnostic assays.

PM2.5-Induced Programmed Myocardial Cell Death via mPTP Opening Results in Deteriorated Cardiac Function in HFpEF Mice.

PM2.5 exposure can induce or exacerbate heart failure and is associated with an increased risk of heart failure hospitalization and mortality; however, the underlying mechanisms remain unclear. This study focuses on the potential mechanisms underlying PM2.

Novel sarbecovirus bispecific neutralizing antibodies with exceptional breadth and potency against currently circulating SARS-CoV-2 variants and sarbecoviruses.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern, including Alpha (B.1.1.

Recent Progress in the Research on Benzimidazole PARP-1 Inhibitors.

Poly (ADP-ribose) polymerase-1 (PARP-1) is a multifunctional protein that plays an important role in DNA repair and genome integrity. PARP-1 inhibitors can be used as effective drugs not only to treat BRCA-1/2 deficient cancers because of the synthetic lethality effect but also to treat non- BRCA1/2 deficient tumours because of the effect of PARP capture. Therefore, PARP inhibitors have become a focus of compelling research.

Multi-arm RNA junctions encoding molecular logic unconstrained by input sequence for versatile cell-free diagnostics.

Applications of RNA-based molecular logic have been hampered by sequence constraints imposed on the input and output of the circuits. Here we show that the sequence constraints can be substantially reduced by appropriately encoded multi-arm junctions of single-stranded RNA structures. To conditionally activate RNA translation, we integrated multi-arm junctions, self-assembled upstream of a regulated gene and designed to unfold sequentially in response to different RNA inputs, with motifs of loop-initiated RNA activators that function independently of the sequence of the input RNAs and that reduce interference with the output gene.