The Characteristics and Expression Analysis of the Tomato SlRBOH Gene Family under Exogenous Phytohormone Treatments and Abiotic Stresses.

Respiratory burst oxidase homologs (RBOHs), also known as NADPH oxidases, contribute significantly to the production of ROS in plants, alongside other major sources such as photosynthesis and electron transport in chloroplasts. It has been shown that plant RBOHs play an active role in plant adversity response and electron transport. However, the phylogenetic analysis and characterization of the SlRBOH gene family in tomatoes have not been systematically studied. This study identified 11 SlRBOH genes in the tomato genome using a genome-wide search approach. The physicochemical properties, chromosomal localization, subcellular localization, secondary structure, conserved motifs, gene structure, phylogenetics, collinear relationships, cis-acting elements, evolutionary selection pressures, tissue expressions, and expression patterns under exogenous phytohormones (ABA and MeJA) and different abiotic stresses were also analyzed. We found that the SlRBOHs are distributed across seven chromosomes, collinearity reflecting their evolutionary relationships with corresponding genes in Arabidopsis thaliana and rice. Additionally, all the SlRBOH members have five conserved domains and 10 conserved motifs and have similar gene structures. In addition, the results of an evolutionary selection pressure analysis showed that SlRBOH family members evolved mainly by purifying selection, making them more structurally stable. Cis-acting element analyses showed that SlRBOHs were responsive to light, hormone, and abiotic stresses. Tissue expression analysis showed that SlRBOH family members were expressed in all tissues of tomato to varying degrees, and most of the SlRBOHs with the strongest expression were found in the roots. In addition, the expressions of tomato SlRBOH genes were changed by ABA, MeJA, dark period extension, NaCl, PEG, UV, cold, heat, and H2O2 treatments. Specifically, SlRBOH4 was highly expressed under NaCl, PEG, heat, and UV treatments, while SlRBOH2 was highly expressed under cold stress. These results provide a basis for further studies on the function of SlRBOHs in tomato.

Pharmacokinetics and pharmacodynamics of intravenous delafloxacin in healthy subjects: model-based dose optimization.

Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical trial was conducted to assess the safety and pharmacokinetics (PK) of intravenous delafloxacin in the Chinese population. A population pharmacokinetic (PopPK) model based on the clinical trial was conducted by NONMEM software. Monte Carlo simulation was performed to evaluate the antibacterial effects of delafloxacin at different doses in different Chinese populations. The PK characteristics of delafloxacin were best described by a three-compartment model with mixed linear and nonlinear clearance. Body weight was included as a covariate in the model. We simulated the AUC0-24h in a steady state at five doses in patient groups of various weights. The results indicated that for patients weighing 70 kg and treated with methicillin-resistant Staphylococcus aureus (MRSA) infections, a minimum dose of 300 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, suggesting an ideal bactericidal effect. For patients weighing less than 60 kg, a dose of 200 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, also suggesting an ideal bactericidal effect. Additionally, this trial demonstrated the high safety of delafloxacin in single-dose and multiple-dose groups of Chinese. Delafloxacin (300 mg, q12h, iv) was recommended for achieving optimal efficacy in Chinese bacterial skin infections patients. To ensure optimal efficacy, an individualized dose of 200 mg (q12h, iv) could be advised for patients weighing less than 60 kg, and 300 mg (q12h, iv) for those weighing more than 60 kg.

Cardiovascular events of Bruton's tyrosine kinase inhibitors: A real-world study based on the United States Food and Drug Administration Adverse Event Reporting System database.

AIMS: Bruton's tyrosine kinase inhibitors (BTKIs), including first-generation ibrutinib, second-generation acalabrutinib and zanubrutinib, may be involved in the mechanisms of action related to adverse events (AEs) of the cardiovascular system. We aimed to characterize the cardiovascular AEs of BTKIs reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System, and to compare the cardiovascular risks of BTKIs. METHODS: Across all indications of three FDA-approved BTKIs, primary suspect drugs were extracted over two periods: from January 2013 to December 2022 (after the approval of the first BTKI), and from January 2020 to December 2022 (all three BTKIs on the market). Disproportionality was measured by reporting odds ratios (RORs) and information components. Additional analyses were performed without incorporating patients with underlying cardiovascular disease (CVD). RESULTS: A total of 10 353 cases included the uses of ibrutinib, acalabrutinib and zanubrutinib. Ibrutinib was significantly associated with 47 cardiovascular AEs. Acalabrutinib was associated with new signals, including cardiac failure (ROR = 1.82 [1.13-2.93]), pulmonary oedema (ROR = 2.15 [1.19-3.88]), ventricular extrasystoles (ROR = 5.18 [2.15-12.44]), heart rate irregular (ROR = 3.05 [1.53-6.11]), angina pectoris (ROR = 3.18 [1.71-5.91]) and cardiotoxicity (ROR = 25.22 [17.14-37.10]). In addition, cardiovascular events had an earlier onset in acalabrutinib users. Zanubrutinib was only associated with atrial fibrillation. Acalabrutinib and zanubrutinib had lower ROR values than ibrutinib. The AE signals were generally consistent between the population receiving and not receiving CVD medications. CONCLUSIONS: Potential cardiovascular risks identified in this study were not clearly noted on the label of marketed acalabrutinib. Caution should be paid to the cardiovascular risks of BTKIs having been or being developed.

Novel therapeutic perspectives for wet age-related macular degeneration: RGD-modified liposomes loaded with 2-deoxy-D-glucose as a promising nanomedicine.

Choroidal neovascularization (CNV), characterized as a prominent feature of wet age-related macular degeneration (AMD), is a primary contributor to visual impairment and severe vision loss globally, while the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells is dictated by angiogenic growth factors alone. Even though treatments targeting vascular endothelial growth factor (VEGF), like Ranibizumab, are widely administered, more than half of the patients still exhibit inadequate or null responses, emphasizing the imperative need for solutions to this problem. Here, aiming to explore therapeutic strategies from a novel perspective of endothelial cell metabolism, a biocompatible nanomedicine delivery system is constructed by loading RGD peptide-modified liposomes with 2-deoxy-D-glucose (RGD@LP-2-DG). RGD@LP-2-DG displayed good targeting performance towards endothelial cells and excellent in vitro and in vivo inhibitory effects on neovascularization were demonstrated. Moreover, our mechanistic studies revealed that 2-DG interfered with N-glycosylation, leading to the inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling. Notably, the remarkable inhibitory effect on neovascularization and biocompatibility of RGD@LP-2-DG render it a highly promising and clinically translatable therapeutic candidate for the treatment of wet AMD and other angiogenic diseases, particularly in patients who are unresponsive to currently available treatments.

Investigating the molecular mechanism of Mori Cortex against osteosarcoma by bioinformatics analysis and in vitro experimental.

OBJECTIVE: To explore the therapeutic mechanism of Mori Cortex against osteosarcoma (OS), we conducted bioinformatics prediction followed by in vitro experimental validation. METHODS: Gene expression data from normal and OS tissues were obtained from the GEO database and underwent differential analysis. Active Mori Cortex components and target genes were extracted from the Traditional Chinese Medicine System Pharmacology database. By intersecting these targets with differentially expressed genes in OS, we identified potential drug action targets. Using the STRING database, a protein-protein interaction network was constructed. Subsequent analyses of these intersected genes, including Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, were performed using R software to elucidate biological processes, molecular functions, and cellular components, resulting in the simulation of signaling pathways. Molecular docking assessed the binding capacity of small molecules to signaling pathway targets. In vitro validations were conducted on U-2 OS cells. The CCK8 assay was used to determine drug-induced cytotoxicity in OS cells, and Western Blotting was employed to validate the expression of AKT, extracellular signal-regulated kinases (ERK), Survivin, and Cyclin D1 proteins. RESULTS: Through differential gene expression analysis between normal and OS tissues, we identified 12,364 differentially expressed genes. From the TCSMP database, 39 active components and 185 therapeutic targets related to OS were derived. The protein-protein interaction network indicated that AKT1, IL-6, JUN, VEGFA, and CASP3 might be central targets of Mori Cortex for OS. Molecular docking revealed that the active compound Morusin in Mori Cortex exhibits strong binding affinity to AKT and ERK. The CCK8 assay showed that Morusin significantly inhibits the viability of U-2 OS cells. Western Blot demonstrated a reduction in the p-AKT/AKT ratio, the p-ERK/ERK ratio, Survivin, and Cyclin D1. CONCLUSION: Mori Cortex may exert its therapeutic effects on OS through multiple cellular signaling pathways. Morusin, the active component of Mori Cortex, can inhibit cell cycle regulation and promote cell death in OS cells by targeting AKT/ERK pathway.

Bioinformatics-based discovery of biomarkers and immunoinflammatory targets in children with cerebral palsy: An observational study.

Cerebral palsy (CP) is the most common disabling disease in children, and motor dysfunction is the core symptom of CP. Although relevant risk factors have been found to be closely associated with CP: congenital malformations, multiple gestation, prematurity, intrauterine inflammation and infection, birth asphyxia, thrombophilia, and perinatal stroke. Its important pathophysiological mechanism is amniotic fluid infection and intraamniotic inflammation leading to fetal developing brain damage, which may last for many years. However, the molecular mechanism of CP is still not well explained. This study aimed to use bioinformatics to identify key biomarker-related signaling pathways in CP. The expression profile of children with CP was selected from the Gene Expression Comprehensive Database, and the CP disease gene data set was obtained from GeneCards. A protein-protein interaction network was established and functional enrichment analysis was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. A total of 144 differential key intersection genes and 10 hub genes were identified through molecular biology. Gene Ontology functional enrichment analysis results show that differentially expressed genes are mainly concentrated in biological processes, such as immune response and neurogenesis. The cellular components involved mainly include axons, postsynaptic membranes, etc, and their molecular functions mainly involve proteoglycan binding, collagen binding, etc. Kyoto Encyclopedia of Genes and Genomes analysis shows that the intersection genes are mainly in signaling pathways related to the immune system, inflammatory response, and nervous system, such as Th17 cell differentiation, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, NF-κB signaling pathway, axon guidance, PI3K-Akt signaling pathway, HIF-1 signaling pathway, gap junction, etc. Jak-STAT signaling pathway, mTOR signaling pathway, and related hub genes regulate immune cells and inflammatory factors and play an important role in the development and progression of CP.

Safety and immunogenicity of heterologous boosting with a bivalent SARS-CoV-2 mRNA vaccine (XBB.1.5/BQ.1) in Chinese participants aged 18 years or more: A randomised, double-blinded, active-controlled phase 1 trial.

Continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants urges the development of new vaccines. We assessed the safety and immunogenicity of SYS6006.32, a bivalent vaccine (XBB.1.5/BQ.1), in healthy adults who had received SARS-CoV-2 primary vaccination. In a randomised, double-blinded, active-controlled trial, 200 participants were randomised to receive one dose of SYS6006.32 (N = 100) or a prototype-based, monovalent control vaccine SYS6006 (N = 100). Adverse events (AEs) were collected through the study. Immunogenicity was assessed by live-virus neutralising antibody (Nab) and pseudovirus Nab. 61 (61.0 %) and 60 (60.0 %) participants reported AE in the SYS6006.32 and SYS6006 groups, respectively. Most AEs were grade 1 or 2. Pain and fever were the most common injection-site and systemic AEs, respectively. No serious AEs were observed. SYS6006.32 heterologous boosting induced robust Nab responses against BA.5, XBB.1.5 and EG.5 with live-virus Nab geometric mean titres (GMTs) increased by 17.1-, 34.0-, and 48.0-fold, and pseudovirus Nab GMTs increased by 12.2-, 32.0-, and 35.1-fold, respectively, 14 days after vaccination. SYS6006.32 demonstrated a superior immunogenicity to SYS6006. SYS6006.32 also induced robust pseudovirus Nab responses against XBB.1.16, XBB.2.3, and BA.2.86, with GMTs 3- to 6-fold higher than those induced by SYS6006. In conclusion, SYS6006.32 showed good safety profile and superior immunogenicity to the monovalent vaccine SYS6006.

Genome-Wide Identification and Characterization of Tomato Fatty Acid ß-Oxidase Family Genes KAT and MFP.

Fatty acids and their derivatives play a variety of roles in living organisms. Fatty acids not only store energy but also comprise membrane lipids and act as signaling molecules. There are three main proteins involved in the fatty acid ß-oxidation pathway in plant peroxisomes, including acyl-CoA oxidase (ACX), multifunctional protein (MFP), and 3-ketolipoyl-CoA thiolase (KAT). However, genome-scale analysis of KAT and MFP has not been systemically investigated in tomatoes. Here, we conducted a bioinformatics analysis of KAT and MFP genes in tomatoes. Their physicochemical properties, protein secondary structure, subcellular localization, gene structure, phylogeny, and collinearity were also analyzed. In addition, a conserved motif analysis, an evolutionary pressure selection analysis, a cis-acting element analysis, tissue expression profiling, and a qRT-PCR analysis were conducted within tomato KAT and MFP family members. There are five KAT and four MFP family members in tomatoes, which are randomly distributed on four chromosomes. By analyzing the conserved motifs of tomato KAT and MFP family members, we found that both KAT and MFP members are highly conserved. In addition, the results of the evolutionary pressure selection analysis indicate that the KAT and MFP family members have evolved mainly from purifying selection, which makes them more structurally stable. The results of the cis-acting element analysis show that SlKAT and SlMFP with respect may respond to light, hormones, and adversity stresses. The tissue expression analysis showed that KAT and MFP family members have important roles in regulating the development of floral organs as well as fruit ripening. The qRT-PCR analysis revealed that the expressions of SlKAT and SlMFP genes can be regulated by ABA, MeJA, darkness, NaCl, PEG, UV, cold, heat, and H2O2 treatments. These results provide a basis for the involvement of the SlKAT and SlMFP genes in tomato floral organ development and abiotic stress response, which lay a foundation for future functional study of SlKAT and SlMFP in tomatoes.

Immunogenicity and safety of a SARS-CoV-2 mRNA vaccine (SYS6006) in healthy Chinese participants: A randomized, observer-blinded, placebo-controlled phase 2 clinical trial.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine enables quick upgrade of antigen sequence to combat emerging new variants. In an observer-blinded, randomized, placebo-controlled phase 2 trial, immunologically naïve 300 adults and 150 older participants were enrolled and randomized (1:1:1) to receive two doses of 20 µg or 30 µg of a SARS-CoV-2 mRNA vaccine (SYS6006) or placebo. Adverse events (AEs) were recorded through 30 days after the second dose. Live virus neutralizing antibody (Nab), S1 protein-specific binding antibody (S1-IgG) and cellular immunity were tested. Results showed that robust wild-type Nab response was elicited with geometric mean titers of 91.3 and 84.9 in the adults, and 74.0 and 115.9 in the elders, 14 days following the second dose (Day 35) in the 20-µg and 30-µg groups, respectively. All seroconverted for wild-type Nab except two participants. Nab against Omicron BA.5 was mild. Robust wild-type S1-IgG response was induced with geometric mean concentrations of 2751.0 and 3142.2 BAU/mL in adults, and 2474.1 and 2993.5 BAU/mL in elders at Day 35 in the 20-µg and 30-µg groups, respectively. S1-IgG against Omicron BA.2 was induced. Cellular immunity was elicited, particularly in enzyme-linked immunospot assay. The most frequent AEs were injection-site pain and fever. Most reported AEs were grade 1 or grade 2. The AE incidences were similar following the first dose and second dose. No vaccination-associated serious AE was reported. In conclusion, two-dose vaccination with SYS6006 demonstrated good safety, tolerability and immunogenicity in immunologically naïve healthy participants aged 18 years or more.

Mefenamic acid exhibits antitumor activity against osteosarcoma by impeding cell growth and prompting apoptosis in human osteosarcoma cells and xenograft mice model.

The study investigates the anticancer activity of mefenamic acid against osteosarcoma, shedding light on its underlying mechanisms and therapeutic potential. Mefenamic acid exhibited robust inhibitory effects on the proliferation of MG-63, HOS, and H2OS osteosarcoma cells in a dose-dependent manner. Moreover, mefenamic acid induced cellular toxicity in MG63 cells, as evidenced by LDH leakage, reflecting its cytotoxic impact. Furthermore, mefenamic acid effectively suppressed the migration and invasion of MG-63 cells. Mechanistically, mefenamic acid induced apoptosis in MG-63 cells through mitochondrial depolarization, activation of caspase-dependent pathways, and modulation of the Bcl-2/Bax axis. Additionally, mefenamic acid promoted autophagy and inhibited the PI3K/Akt/mTOR pathway, further contributing to its antitumor effects. The molecular docking studies provide compelling evidence that mefenamic acid interacts specifically and strongly with key proteins in the PI3K/AKT/mTOR pathway, suggesting a novel mechanism by which mefenamic acid could exert anti-osteosarcoma effects. In vivo studies using a xenograft mouse model demonstrated significant inhibition of MG-63 tumor growth without adverse effects, supporting the translational potential of mefenamic acid as a safe and effective therapeutic agent against osteosarcoma. Immunohistochemistry staining corroborated the in vivo findings, highlighting mefenamic acid's ability to suppress tumor proliferation and inhibit the PI3K/AKT/mTOR pathway within the tumor microenvironment. Collectively, these results underscore the promising therapeutic implications of mefenamic acid in combating osteosarcoma, warranting further investigation for clinical translation and development.

Analysis of the relationship between color and natural pigments of tobacco leaves during curing.

Color is one of the most important indicators for the flue-cured tobacco quality. The color change of tobacco has a great relationship with the natural pigments in the tobacco. The relationship between color characteristics and the content of natural pigments in tobacco leaves during curing was investigated. The middle part of variety K326 tobacco was taken at each key time point during the curing process to determine the changes of color characteristics, moisture, pigment and polyphenol content. The results showed that moisture content of wet basis of tobacco gradually decreased from 72 to 18% during the curing process, the b* value increased and then decreased, and the a* value increased significantly. The lutein and ß-carotene content decreased to 63.83 µg/g and 28.3 µg/g, respectively. The total polyphenols content increased to 50.19 mg/g. Meanwhile, the a* value was significantly and positively correlated with polyphenols content and negatively correlated with pigments content. Cluster analysis showed that the samples were divided into three categories: samples with the curing time of 0 h, 24-72 h, and 84-132 h. These results demonstrated that the color change of tobacco during curing process can be divided into three stages from the perspective of chemical composition, which are strongly related to the degradation of pigments and the transformation of polyphenols.

Exploration and breakthrough in the mode of chondrocyte death - A potential new mechanism for osteoarthritis.

Osteoarthritis (OA) is a frequent chronic joint disease in orthopedics that effects individuals and society significantly. Obesity, aging, genetic susceptibility, and joint misalignment are all known risk factors for OA, but its pathomechanism is still poorly understood. Researches have revealed that OA is a much complex process related to inflammation, metabolic and chondrocyte death. It can affect all parts of the joint and is characterized by causing chondrocyte death and extracellular matrix descent. Previously, OA was thought to develop from excessive mechanical loading leading to the destruction of articular cartilage. Since some programmed cell deaths and OA share a pattern of chondrocyte destruction, it is likely that OA also involves programmed cell death. Even though chondrocyte apoptosis and pyroptosis have been investigated in OA, clarifing solely conventional cell death pathways is still insufficient to understand the pathophysiology of osteoarthritis. With more researches, it has been discovered that osteoarthritis and other new cell death processes, including PANoptosis, ferroptosis, and cell senescence, are strongly associated. Among these, PANoptosis combines the key traits of pyroptosis, cell apoptosis, and necrotic apoptosis into a highly coordinated and dynamically balanced programmed inflammatory cell death mechanism. Furthermore, we think that PANopotosis might obstruct necroptosis and cell senescence. Therefore, in order to offer direction for therapeutic treatment, we evaluate the development of research on multiple cell death of chondrocytes in OA.

Sesquiterpene from Artemisia argyi seed extracts: A new anti-acute peritonitis agent that suppresses the MAPK pathway and promotes autophagy.

To find novel anti-inflammatory drugs, we screened anti-inflammatory compounds from 18 different types of Artemisia argyi seed extracts. The in vitro and in vivo anti-inflammatory activities of the screened compounds and their mechanisms were characterized. We first detected the cytotoxic effect of the compounds on RAW264.7 cells and the inhibitory effect on LPS-induced NO release. It was found that sesquiterpenoids CA-2 and CA-4 had low cytotoxic and strong NO inhibitory activity with an IC50 of 4.22 ± 0.61 µM and 2.98 ± 0.23 µM for NO inhibition, respectively. Therefore, compound CA-4 was studied in depth. We found that compound CA-4 inhibited LPS-induced pro-inflammatory factor production and M1 macrophage differentiation in RAW264.7 cells. Additionally, CA-4 inhibited the expression of p-ERK1/2, p-JNK, iNOS, and COX-2 by blocking the MAPK signaling pathway. CA-4 also promoted the expression of autophagy-related proteins such as LC3 II and Beclin-1 by inhibiting activation of the PI3K/AKT/mTOR signaling pathway, and promoted the generation of autophagosomes. Finally, CA-4 significantly inhibited the degree of inflammation in mice with acute peritonitis, showing good anti-inflammatory activity in vivo. Consequently, compound CA-4 may be a promising drug for the treatment of acute inflammatory diseases and provide new ideas for the synthesis of novel anti-inflammatory compounds.

Safety and immunogenicity of primary vaccination with a SARS-CoV-2 mRNA vaccine (SYS6006) in Chinese participants aged 18 years or more: Two randomized, observer-blinded, placebo-controlled and dose-escalation phase 1 clinical trials.

Vaccination plays a key role in preventing morbidity and mortality caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the safety and immunogenicity of a SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine SYS6006. In the two randomized, observer-blinded, placebo-controlled phase 1 trials, 40 adult participants aged 18-59 years and 40 elderly participants aged 60 years or more were randomized to receive two doses of SYS6006 or placebo (saline). Adverse events (AEs) were collected through 30 days post the second vaccination. Immunogenicity was assessed by live-virus neutralizing antibody (Nab), spike protein (S1) binding antibody (S1-IgG), and cellular immunity. The result showed that 7/15, 9/15 and 4/10 adult participants, and 9/15, 8/15 and 4/10 elderly participants reported at least one AE in the 20-µg, 30-µg and placebo groups, respectively. Most AEs were grade 1. Injection-site pain was the most common AE. Two adults and one elder reported fever. No vaccination-related serious AE was reported. SYS6006 elicited wild-type Nab response with a peak geometric mean titer of 232.1 and 130.6 (adults), and 48.7 and 66.7 (elders), in the 20-µg and 30-µg groups, respectively. SYS6006 induced moderate-to-robust Nab response against Delta, and slight Nab response against Omicron BA.2 and BA.5. Robust IgG response against wild type and BA.2 was observed. Cellular immune response was induced. In conclusion, two-dose primary vaccination with SYS6006 demonstrated good safety and immunogenicity during a follow-up period of 51 days in immunologically naive population aged 18 years or more. (Trial registry: Chictr.org.cn ChiCTR2200059103 and ChiCTR2200059104).

Research progress of small-molecule drugs in targeting telomerase in human cancer and aging.

Telomeres are unique structures located at the ends of linear chromosomes, responsible for stabilizing chromosomal structures. They are synthesized by telomerase, a reverse transcriptase ribonucleoprotein complex. Telomerase activity is generally absent in human somatic cells, except in stem cells and germ cells. Every time a cell divides, the telomere sequence is shortened, eventually leading to replicative senescence and cell apoptosis when the telomeres reach a critical limit. However, most human cancer cells exhibit increased telomerase activity, allowing them to divide continuously. The importance of telomerase in cancer and aging has made developing drugs targeting telomerase a focus of research. Such drugs can inhibit cancer cell growth and delay aging by enhancing telomerase activity in telomere-related syndromes or diseases. This review provides an overview of telomeres, telomerase, and their regulation in cancer and aging, and highlights small-molecule drugs targeting telomerase in these fields.

Fulfilling global climate pledges can lead to major increase in forest land on Tibetan Plateau.

The UN Climate Change Conference in Glasgow spawned the enhancement and updating of many nations' climate pledges. Previous research has investigated the effects of these pledges on limiting planetary warming, but their spatially explicit effects on land use/cover are unknown. Here, we linked the Glasgow pledges and the spatially explicit responses of the Tibetan Plateau's land systems. We found that while fulfilling global climate pledges may not significantly affect the global shares of forestland, grassland/pasture, shrubland, and cropland, it needs a 9.4% increase in the forest area of the Tibetan Plateau. This need is an area 11.4 times the increase of the plateau's forest in the 2010s, or greater than the size of Belgium. The new forest comes mainly from the medium-density grassland in the Yangtze River basin, calling for more proactive environmental management for the headwaters area of this longest river in Asia.

Effects of glutenin and gliadin on the surface tackiness of frozen cooked noodles.

The mechanism of glutenin and gliadin on the surface tackiness of recooked frozen cooked noodles (FCNs) is unclear. In this study, the effects of glutenin and gliadin addition on the surface tackiness of FCNs were investigated. The addition of glutenin and gliadin reduced the surface tackiness (3.60 and 3.50 N) of recooked FCNs stored for 0 min. The addition of glutenin increased the rigidity of the gluten network and the compactness of FCNs and made the FCNs have a moisture-distribution with multilayers. The addition of gliadin increased the tensile distance of FCNs, restricted water migration during frozen storage, and increased the membranous structure of the gluten network to wrap starch particles. Glutenin had a stronger effect on reducing the surface tackiness of FCNs than gliadin. In the future, the synergistic effects of different proportions of glutenin and gliadin on the gluten network of FCNs could be further studied.

Corylin inhibits the progression of Non-small cell lung cancer cells by regulating NF-κB signaling pathway via targeting p65.

BACKGROUND: Lung cancer is characterized by high-risk and high mortality, among which non-small cell lung cancer (NSCLC) conquers a dominant position. Previous studies have reported that corylin has anti-inflammatory, anti-oxidant, and anti-tumor effects; however, its role in NSCLC cells remains unclear. HYPOTHESIS: Corylin inhibits the progression of NSCLC cells. METHODS: A lentivector NF-κB luciferase reporter was constructed by molecular cloning. Corylin was screened and identified as an NF-κB pathway inhibitor by luciferase reporter assay. Corylin inhibited the expression of NF-κB downstream genes, which was detected by qRT-PCR. The effect of corylin on NSCLC cells was detected by colony formation assay, cell apoptosis, cell proliferation, in vitro invasion, and cell scratch assay. Corylin inhibited p65 nuclear translocation and was detected by molecular docking, immunofluorescence assay, and Western blot analysis. RESULTS: We constructed a lentiviral expression vector, containing an NF-κB luciferase reporter and established a stable A549 cell line for its expression. Using this cell line, corylin was screened and identified as an NF-κB pathway inhibitor. It was found that corylin inhibited the expression of NF-κB downstream genes and inhibited the proliferation and migration of NSCLC cells. Meanwhile, it was also found that corylin significantly reversed the increased proliferation of NSCLC cell lines induced by p65 overexpression. Molecular docking analysis showed that corylin could bind to p65 by hydrogen bonding. Further study showed that corylin inhibited the NF-κB signaling pathway by blocking p65 nuclear translocation. CONCLUSIONS: Our study screened and identified corylin as an NF-κB inhibitor and elucidated the molecular mechanism by which corylin inhibits the growth of NSCLC cells. The present study provides a novel strategy for improving the prognosis and treatment of NSCLC patients.

P2Y6R: A Promising New Target in Inflammatory Diseases and Advances in its Antagonists.

P2Y receptors (P2YRs) are G protein-coupled receptors that are activated by extracellular nucleotides. The P2Y6 receptor (P2Y6R) is specifically activated by UDP, causing PKC activation and intracellular calcium ion release through the PLC pathway. Based on receptor tissue distribution and related pathways, several studies have reported that P2Y6R plays a physiological role in mediating inflammation, which suggests that P2Y6R could be a promising molecular target for the treatment of inflammatory diseases. In the past ten years, several P2Y6R antagonists have been discovered as new therapeutic strategies for inflammatory diseases. In this article, we systematically summarize the role of P2Y6R in inflammation and highlight the anti-inflammatory mechanism of a key P2Y6R antagonist, MRS2578. Insight into recent progress on the discovery of P2Y6R antagonists is also discussed.

Pharmacological Activity of Quercetin: An Updated Review.

Quercetin, a natural flavonoid compound with a widespread occurrence throughout the plant kingdom, exhibits a variety of pharmacological activities. Because of the wide spectrum of health-promoting effects, quercetin has attracted much attention of dietitians and medicinal chemists. An updated review of the literature on quercetin was performed using PubMed, Embase, and Science Direct databases. This article presents an overview of recent developments in pharmacological activities of quercetin including anti-SARS-CoV-2, antioxidant, anticancer, antiaging, antiviral, and anti-inflammatory activities as well as the mechanism of actions involved. The biological activities of quercetin were evaluated both in vitro and in vivo, involving a number of cell lines and animal models, but metabolic mechanisms of quercetin in the human body are not clear. Therefore, further large sample clinical studies are needed to determine the appropriate dosage and form of quercetin for the treatment of the disease.