Projections of urban land exposure to drought and flood in China.

With global warming, the risk of human exposure to extreme climates increases, profoundly impacting sustainable development. Using rapidly developing China as an example, this study estimates the exposure of urban land to drought and flood based on historical and future climate and land data. The results show that the area of urban land exposed to drought in China generally decreases in the future.

Harnessing native-cryptic plasmids for stable overexpression of heterologous genes in Clostridium butyricum DSM 10702 for industrial and medical applications.

Clostridium butyricum has emerged as a promising candidate for both industrial and medical biotechnologies, underscoring the key pursuit of stable gene overexpression in engineering C. butyricum. Unlike antibiotic-selective vectors, native-cryptic plasmids can be utilized for antibiotic-free expression systems in bacteria but have not been effectively exploited in C.

Small extracellular vesicle CA1 as a promising diagnostic biomarker for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC), a malignant cancer originating from the epithelial cells of the nasopharynx, presents diagnostic challenges with current methods such as plasma Epstein-Barr virus (EBV) DNA testing showing limited efficacy. This study focused on identifying small extracellular vesicle (sEV) proteins as potential noninvasive biomarkers to enhance NPC diagnostic accuracy. We isolated sEVs from plasma and utilized 4D label-free proteomics to identify differentially expressed proteins (DEPs) among healthy controls (NC = 10), early-stage NPC (E-NPC = 10), and late-stage NPC (L-NPC = 10).

Recommendations for nutritional supplements for dry eye disease: current advances.

Dry eye disease (DED) represents a prevalent ocular surface disease. The development of effective nutritional management strategies for DED is crucial due to its association with various factors such as inflammation, oxidative stress, deficiencies in polyunsaturated fatty acids (PUFAs), imbalanced PUFA ratios, and vitamin insufficiencies. Extensive research has explored the impact of oral nutritional supplements, varying in composition and dosage, on the symptoms of DED.

Interferon-induced transmembrane protein-1 competitively blocks Ephrin receptor A2-mediated Epstein-Barr virus entry into epithelial cells.

Epstein-Barr virus (EBV) can infect both B cells and epithelial cells (ECs), causing diseases such as mononucleosis and cancer. It enters ECs via Ephrin receptor A2 (EphA2). The function of interferon-induced transmembrane protein-1 (IFITM1) in EBV infection of ECs remains elusive.

Short macrocyclic peptides in sponge genomes.

Sponges (Porifera) contain many peptide-specialized metabolites with potent biological activities and significant roles in shaping marine ecology. It is well established that symbiotic bacteria produce bioactive "sponge" peptides, both on the ribosome (RiPPs) and nonribosomally. Here, we demonstrate that sponges themselves also produce many bioactive macrocyclic peptides, such as phakellistatins and related proline-rich macrocyclic peptides (PRMPs).

Promising Diagnostic and Therapeutic Approaches Based on VHHs for Cancer Management.

The discovery of the distinctive structure of heavy chain-only antibodies in species belonging to the Camelidae family has elicited significant interest in their variable antigen binding domain (VHH) and gained attention for various applications, such as cancer diagnosis and treatment. This article presents an overview of the characteristics, advantages, and disadvantages of VHHs as compared to conventional antibodies, and their usage in diverse applications. The singular properties of VHHs are explained, and several strategies that can augment their utility are outlined.

An Autocatalytic Peptide Cyclase Improves Fidelity and Yield of Circular Peptides In Vivo and In Vitro.

Peptide cyclization improves conformational rigidity, providing favorable pharmacological properties, such as proteolytic resistance, target specificity, and membrane permeability. Thus, many synthetic and biosynthetic peptide circularization strategies have been developed. PatG and related natural macrocyclases process diverse peptide sequences, generating millions of cyclic derivatives.

The role of ROS-pyroptosis in PM induced air-blood barrier destruction.

Fine particulate matter (PM) has attracted increasing attention due to its health-threatening effects. Although numerous studies have investigated the impact of PM on lung injuries, the specific mechanisms underlying the damage to the air-blood barrier after exposure to PM remain unclear. In this study, we established an in vitro co-culture system using lung epithelial cells and capillary endothelial cells.

EBV-Associated Hub Genes as Potential Biomarkers for Predicting the Prognosis of Nasopharyngeal Carcinoma.

This study aimed to develop a model using Epstein-Barr virus (EBV)-associated hub genes in order to predict the prognosis of nasopharyngeal carcinoma (NPC). Differential expression analysis, univariate regression analysis, and machine learning were performed in three microarray datasets (GSE2371, GSE12452, and GSE102349) collected from the GEO database. Three hundred and sixty-six EBV-DEGs were identified, 25 of which were found to be significantly associated with NPC prognosis.

A truncated DNA aptamer with high selectivity for estrogen receptor-positive breast cancer cells.

The estrogen receptor-positive (ER+) breast cancers constitute more than 50 % of breast cancers, seriously threatening the health of women. Unfortunately, the detection and targeted therapy of ER+ breast cancers remain a challenge. Here, a novel nucleic acid aptamer S1-4 was developed to specifically target ER+ breast cancer MCF-7 cells by using Cell-SELEX and nucleic acid truncation strategies.

Conjugating 4β-NH-(5-Aminoindazole)-podophyllotoxin and Galectin-1-Targeted Aptamer for Synergistic Chemo-Immunotherapy of Hepatocellular Carcinoma.

By conjugating a chemotherapeutic candidate drug 4β-NH-(5-aminoindazole)-podophyllotoxin (βIZP) and an immunosuppressive protein galectin-1 targeted aptamer AP74, a chemo-immunotherapy molecule (AP74-βIZP) is developed against liver cancer. AP74-βIZP can target galectin-1 and enrich the tumor microenvironment to improve the tumor inhibition ratio by 6.3%, higher than that of βIZP in a HepG2 xenograft model.

AgeMTPT, a Catalyst for Peptide N-Terminal Modification.

A key goal of synthetic biology is to enable designed modification of peptides and proteins, both in vivo and in vitro. N- and C-Terminal modification enzymes are crucial in this regard, but there are a few enzymatic options to protect peptide termini. AgeMTPT protects the N-terminus of short peptides with isoprene and the C-terminus as a methyl ester, but its substrate scope is unknown, limiting its application.

N-glycosylation of CD82 at Asn157 is required for suppressing migration and invasion by reversing EMT via Wnt/β-catenin pathway in colon cancer.

CD82, a tetraspanin superfamily member, has been identified to be glycosylated at three specific residues (Asn129, Asn157, and Asn198). However, CD82 post-translational modification and its effect on colorectal cancer (CRC) metastasis remain unclear. Here, we constructed various deficient mutants of CD82 N-glycosylation in SW620 cells and demonstrated that the Asn157 site is necessary for CD82 glycosylation in CRC cells migration and LN-dependent adhesion in vitro.

Homologous Recombination Deficiency Scar: Mutations and Beyond-Implications for Precision Oncology.

Homologous recombination deficiency (HRD) is a prevalent in approximately 17% of tumors and is associated with enhanced sensitivity to anticancer therapies inducing double-strand DNA breaks. Accurate detection of HRD would therefore allow improved patient selection and outcome of conventional and targeted anticancer therapies. However, current clinical assessment of HRD mainly relies on determining germline mutational status and is insufficient for adequate patient stratification as mechanisms of HRD occurrence extend beyond functional BRCA1/2 loss.

A Silent Biosynthetic Gene Cluster from a Methanotrophic Bacterium Potentiates Discovery of a Substrate Promiscuous Proteusin Cyclodehydratase.

Natural product-encoding biosynthetic gene clusters (BGCs) within microbial genomes far outnumber the known natural products; chemical products from such BGCs remain cryptic. These silent BGCs hold promise not only for the elaboration of new natural products but also for the discovery of useful biosynthetic enzymes. Here, we describe a genome mining strategy targeted toward the discovery of substrate promiscuous natural product biosynthetic enzymes.

Catalysts for the Enzymatic Lipidation of Peptides.

Biologically active peptides are a major growing class of drugs, but their therapeutic potential is constrained by several limitations including bioavailability and poor pharmacokinetics. The attachment of functional groups like lipids has proven to be a robust and effective strategy for improving their therapeutic potential. Biochemical and bioactivity-guided screening efforts have identified the cyanobactins as a large class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that are modified with lipids.

The Landscape of Coronavirus Disease 2019 (COVID-19) and Integrated Analysis SARS-CoV-2 Receptors and Potential Inhibitors in Lung Adenocarcinoma Patients.

The outbreak of novel coronavirus disease 2019 (COVID-19) has become the largest health threat worldwide, with more than 34.40 million positive cases and over 1.02 million deaths confirmed.

Dual Mechanisms of Novel CD73-Targeted Antibody and Antibody-Drug Conjugate in Inhibiting Lung Tumor Growth and Promoting Antitumor Immune-Effector Function.

Although tyrosine kinase inhibitor therapy and immunotherapy have significantly improved lung cancer management, many patients do not benefit or become resistant to treatment, highlighting the need for novel treatments. We found elevated CD73 expression to be prevalent in non-small cell lung cancer (NSCLC) including those harboring the RAS- or RTK (EGFR, EML4-ALK) oncogenes. CD73 expression is enriched closely with the transcriptome signature of epithelial-mesenchymal transition and the immune-tolerant tumor microenvironment, which are increasingly relevant for disease progression and therapy resistance.

mTOR Promotes Tissue Factor Expression and Activity in EGFR-Mutant Cancer.

Mechanistic target of rapamycin (mTOR) signaling pathway mediates the function of oncogenic receptor tyrosine kinases (RTKs). We aimed to elucidate new role of mTOR in EGFR-mutant (EGFR-mut) non-small cell lung cancer (NSCLC) and glioblastoma (GBM) with a focus on tumor microenvironments. Here, we report a novel regulatory link between mTOR complexes (mTORCs) and tissue factor (TF), an initiator of tumor-derived thrombosis.

Challenges and potential for improving the druggability of podophyllotoxin-derived drugs in cancer chemotherapy.

Covering: up to 2020As a main bioactive component of the Chinese, Indian, and American Podophyllum species, the herbal medicine, podophyllotoxin (PTOX) exhibits broad spectrum pharmacological activity, such as superior antitumor activity and against multiple viruses. PTOX derivatives (PTOXs) could arrest the cell cycle, block the transitorily generated DNA/RNA breaks, and blunt the growth-stimulation by targeting topoisomerase II, tubulin, or insulin-like growth factor 1 receptor. Since 1983, etoposide (VP-16) is being used in frontline cancer therapy against various cancer types, such as small cell lung cancer and testicular cancer.

Propane-2-sulfonic acid octadec-9-enyl-amide, a novel PPARα/γ dual agonist, reverses neuroinflammation in lipopolysaccharide-induced mice.

Our previous study showed that propane-2-sulfonic acid octadec-9-enyl-amide (N15), a novel peroxisome proliferator-activated receptor α and γ (PPARα/γ) dual agonist, inhibits inflammatory responses in tumor necrosis factor alpha (TNFα)-induced vascular endothelial cells or lipopolysaccharide (LPS)-induced human myeloid leukemia mononuclear cells-1. However, little is known about whether N15 applies to other pathological or neuroinflammatory conditions. In the present study, we detected the effect of N15 on the LPS-induced neuroinflammatory response in mice and further investigated whether the effect of N15 on neuroinflammation and neuronal cells survival was related to PPARα/γ dual pathways.

Propane-2-sulfonic acid octadec-9-enyl-amide alleviates scopolamine-induced spatial learning and memory deficits in mice.

Our previous reports demonstrated that the novel peroxisome proliferator-activated receptors α and γ (PPARα/γ) dual agonist propane-2-sulfonic acid octadec-9-enyl-amide (N15) alleviates cognitive ability in the chronic phase of ischemic stroke. However, the potential effects of N15 on Alzheimer's disease (AD) animal models have not been elucidated. In the present study, we investigated the effects of N15 on scopolamine-induced cognitive dysfunction and cholinergic system ability.

Influence of media intervention on AIDS transmission in MSM groups.

To explore the effects of propaganda and education on the prevention and control of AIDS infection, a model of AIDS transmission in MSM population is proposed and theoretically analyzed by introducing media impact factors. The basic reproduction number of AIDS transmission in MSM group without media intervention R = 1.5447 is obtained.

Lactonization of 2-Alkynylbenzoates for the Assembly of Isochromenones Mediated by BF·EtO.

A general and efficient lactonization method of readily available 2-alkynylbenzoates affording biologically important isochromenones has been realized via a solely BF·EtO-mediated 6-endo-dig cyclization process under mild conditions. An alternative mechanistic pathway in which BF·EtO activates the carbonyl of the ester moiety, rather than the alkyne triple bond, was postulated on the basis of control experiment results. Gram-scale reaction and further application for the assembly of more complex molecules demonstrated the practicability of the protocol.