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Background: China has one third of the worldwide indigenous pig breeds. The Henan province is one of the earliest pig domestication centers of China (about 8000 years ago). However, the precise genetic characteristics of the Henan local pig breeds are still obscure. To understand the origin and the effects of selection on these breeds, we performed various analyses on lineage composition, genetic structure, and detection of selection sweeps and introgression in three of these breeds (Queshan, Nanyang and Huainan) using genotyping data on 125 Queshan, 75 Nanyang, 16 Huainan pigs and 878 individuals from 43 Eurasian pig breeds., Results: We found no clear evidence of ancestral domestic pig DNA lineage in the Henan local breeds, which have an extremely complicated genetic background. Not only do they share genes with some northern Chinese pig breeds, such as Erhualian, Hetaodaer, and Laiwu, but they also have a high admixture of genes from foreign pig breeds (33-40%). Two striking selection sweeps in small regions of chromosomes 2 and 14 common to the Queshan and Nanyang breeds were identified. The most significant enrichment was for lipid kinase activity (GO:0043550) with the genes FII, AMBRA1, and PIK3IP1. Another interesting 636.35-kb region on chromosome 14 contained a cluster of spermatogenesis genes (OSBP2, GAL3ST1, PLA2G3, LIMK2, and PATZ1), a bisexual sterility gene MORC2, and a fat deposition gene SELENOM. Reproduction and growth genes LRP4, FII, and ARHGAP1 were present in a 238.05-kb region on SSC2 under selection. We also identified five loci associated with body length (P = 0.004) on chromosomes 1 and 12 that were introgressed from foreign pig breeds into the Henan breeds. In addition, the Chinese indigenous pig breeds fell into four main types instead of the previously reported six, among which the Eastern type could be divided into two subgroups., Conclusions: Admixture of North China, East China and foreign pigs contributed to high genetic diversity of Henan local pigs. Ontology terms associated with lipid kinase activity and spermatogenesis and growth shaping by introgression of European genes in Henan pigs were identified through selective sweep analyses., (© 2023. ’Institut National de Recherche en Agriculture, Alimentation et Environnement (INRAE).)

To identify novel bioactive compounds, an image-based, cell culture screening of natural product extracts was conducted. Specifically, our screen was designed to identify phytochemicals that might phenocopy inhibition of the chromosomal passenger protein complex in eliciting mitotic and cytokinetic defects. A known alkaloid, scoulerine, was identified from the rhizomes of the plant Corydalis decumbens as being able to elicit a transient mitotic arrest followed by either apoptosis induction or polyploidy. In examining the mitotic abnormality further, we observed that scoulerine could elicit supernumerary centrosomes during mitosis, but not earlier in the cell cycle. The localization of NUMA1 at spindle poles was also inhibited, suggesting diminished potential for microtubule recruitment and spindle-pole focusing. Polyploid cells emerged subsequent to cytokinetic failure. The concentration required for scoulerine to elicit all its cell division phenotypes was similar, and an examination of related compounds highlighted the requirement for proper positioning of a hydroxyl and a methoxy group about an aromatic ring for activity. Mechanistically, scoulerine inhibited AURKB activity at concentrations that elicited supernumerary centrosomes and polyploidy. AURKA was only inhibited at higher concentrations, so AURKB inhibition is the likely mechanism by which scoulerine elicited division defects. AURKB inhibition was never complete, so scoulerine may be a suboptimal AURK inhibitor or work upstream of the chromosomal passenger protein complex to reduce AURKB activity. Scoulerine inhibited the viability of a variety of human cancer cell lines. Collectively, these findings uncover a previously unknown activity of scoulerine that could facilitate targeting human cancers. Scoulerine, or a next-generation analogue, may be useful as a nontoxic component of combination therapies where inhibiting the chromosomal passenger protein complex is desired.

Type A insulin resistance syndrome (TAIRS) is a rare subtype of congenital insulin resistance (IR), which is characterized by specific clinical manifestations without clear diagnostic criteria and is easily misdiagnosed or overlooked. Herein we present a case of TAIRS with acanthosis nigricans (AN), severe IR, polycystic ovaries, hyperandrogenism and its consequence such as menstrual disturbances, acne and hirsutism. A heterozygous mutation, p.Arg1201Gln, in the insulin receptor (INSR) was detected. This mutation in the tyrosine kinase domain has been described before and shown to impair tyrosine kinase activity and is responsible for IR.

Noodles are a staple food in China, and their quality and sensory characteristics directly affect the consumer's quality of life. Therefore, dissecting the main traits affecting noodle quality at the molecular level by improving wheat quality breeding is of great significance. In this study, a genome-wide association study (GWAS) focusing on the sensory and textural properties of Chinese white noodles (CWNs) was conducted at two different locations over a 2-year period using a high-density genetic map constructed with 90 K single nucleotide polymorphism (SNP) arrays in a panel of 205 elite winter wheat accessions. A total of 80 marker-trait associations (MTAs) (P < 10−4) for 17 sensory and textural properties were mapped on 17 chromosomes, except for chromosomes 1A, 3D, 4B, and 7D. The phenotypic variation explained by a single associated locus ranged from 5.93 to 15.81%. Of these, 34 major quantitative trait loci (QTLs) were identified. Seven quantitative trait locus (QTL) clusters (QTLs ≥ 3) were found on chromosomes 1B, 2A, 3A, 3B, 5A, 6A, and 7A. On chromosome 5A, the QTLs at 93 cM were associated with both the adhesiveness and the extension travel of CWNs. The QTLs at the genetic position 99 cM on chromosome 2A were consistently associated with chewiness, cohesiveness, and gumminess. In addition, the QTLs consistently associated with color, appearance, firmness, stickiness, smoothness, and taste of the noodles were detected on chromosomes 1B, 3A, 4A, 5B, and 6B, respectively. These QTLs were pleiotropic effect loci. The wsnp_Ex_rep_c80588_75758453 locus on chromosome 2A associated with springiness was detected in both E2 and E4 environments. Sixteen new candidate genes related to the sensory and textural qualities of CWNs were predicted in wheat. Of these, six genes (TraesCS7A01G477900, TraesCS5A02G402100, TraesCS6D02G002200, TraesCS1B02G050600.1, TraesCS6A01G000400, and TraesCS2A01G475200) were important in determining CWN quality by regulating glutathione transferase activity, serine-type endopeptidase activity, protein serine/threonine kinase activity, triglyceride lipase activity, glycerate dehydrogenase activity, and phosphoglycerate kinase activity. These results provide important genes/loci in wheat breeding populations involved in enhancing the quality of CWNs by marker-assisted selection (MAS). [ABSTRACT FROM AUTHOR]

Grape ripe rot (Colletotrichum viniferum) causes huge losses in grape production in vineyards in southern China. However, the molecular mechanism against ripe rot in grape species and the responsive genes implicated in these processes are relatively unknown. Here, we present the transcriptome analysis of berries from a C. viniferum-resistant species (Vitis davidii Föex). Uninfected berries at day zero were used as control samples (CK), an inoculation was made at day zero, and the berries were subsequently analyzed at 1 day, 3 days, and 7 days post inoculation (dpi), which exhibited a sequential disease-progression stage. There were a total of 1810 differentially expressed genes, including 1315 up-regulated and 495 down-regulated transcripts. At 7 dpi, these differentially expressed genes (DEGs) were predominantly enriched in berries. In addition, in C. viniferum-infected grape fruits at 7 dpi, considerable changes in gene expression were induced, and those up-regulated genes involved in MAPK cascade, calcium ion binding, and serine/threonine kinase activity were enriched. According to our KEGG pathway analysis, numerous enriched biological processes, such as plant–pathogen interaction, phenylpropanoid biosynthesis, and metabolism, were implicated in grape–fungus interactions. Our research also revealed alterations in the expression pattern of phenylalanine-pathway-related transcription factors (TFs) and genes. We proposed a model in which C. viniferum invasion produces intracellular and extracellular Ca2+ deregulation to stimulate the MAPK pathway to activate TFs' (WRKY, ERF, and MYB) up-regulation, thus initiating disease-resistant responses in the tolerant Vitis species. Our results offer comprehensive transcriptomic data about molecular responses in C. viniferum-infected grape, and these data will aid in understanding of processes underlying plant responses to C. viniferum. [ABSTRACT FROM AUTHOR]

Background: Since December 2019, 2019 novel coronavirus pneumonia emerged in Wuhan city and rapidly spread throughout China and even the world. We sought to analyse the clinical characteristics and laboratory findings of some cases with 2019 novel coronavirus pneumonia .Methods: In this retrospective study, we extracted the data on 95 patients with laboratory-confirmed 2019 novel coronavirus pneumonia in Wuhan Xinzhou District People's Hospital from January 16th to February 25th, 2020. Cases were confirmed by real-time RT-PCR and abnormal radiologic findings. Outcomes were followed up until March 2th, 2020.Results: Higher temperature, blood leukocyte count, neutrophil count, neutrophil percentage, C-reactive protein level, D-dimer level, alanine aminotransferase activity, aspartate aminotransferase activity, α - hydroxybutyrate dehydrogenase activity, lactate dehydrogenase activity and creatine kinase activity were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and so were lower lymphocyte count, lymphocyte percentage and total protein level. Age below 40 or above 60 years old, male, higher Creatinine level, and lower platelet count also seemed related to severe 2019 novel coronavirus pneumonia and composite endpoint, however the P values were greater than 0.05, which mean under the same condition studies of larger samples are needed in the future.Conclusion: Multiple factors were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and more related studies are needed in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: We show that CLU, especially cytoplasmic precursor CLU, is downregulated in lung cancer and correlates with poor survival. The silencing of CLU promotes lung cancer cell migration and invasion, while the overexpression of CLU potently inhibits these phenomena. Interestingly, secretory CLU proteins are slightly decreased in lung cancer tissue and fail to exert similar anti-metastatic effects like cytoplasmic precursor CLU, demonstrating that cytoplasmic precursor CLU is the primary functional isoform of CLU, which exerts the anti-metastatic effects of lung cancer. Mechanistically, cytoplasmic precursor CLU binds ROCK1 to decrease phosphorylation of ERK1/2 by inhibiting the kinase activity of ROCK1, leading to an anti-metastatic effect in lung cancer cells. These findings reveal a novel insight into the function and regulation of cytoplasmic CLU in lung cancer, which might be a potential target for the diagnosis and treatment of metastatic lung cancer. Clusterin (CLU) is a heterodimeric glycoprotein that has been detected in diverse human tissues and implicated in many cellular processes. Accumulating evidence indicates that the expression of secreted CLU correlates with the progression of cancers. However, the molecular mechanisms underlying its tumor-suppressive roles are incompletely uncovered. In this study, we demonstrate that precursor CLU is widely downregulated in lung cancer tissue, in which secretory CLU proteins are slightly decreased. Impressively, overexpressing CLU potently inhibits the migration, invasion and metastasis of lung cancer cells, whereas silencing CLU promotes this behavior; however, it appears that secretory CLU fails to exert similar anti-metastatic effects. Interestingly, the cytoplasmic precursor CLU binds ROCK1 to abrogate the interaction between ROCK1 and ERK and impair ERK activity, leading to the suppression of lung cancer invasiveness. Meanwhile, the expression of CLU was remarkably diminished in lung cancer bone metastasis loci when compared with subcutaneous tumors in the mouse model and hardly detected in the bone metastasis loci of lung cancer patients when compared with the primary. These findings reveal a novel insight into the function and regulation of cytoplasmic CLU in lung cancer, which might be a potential target for the diagnosis and treatment of metastatic lung cancer. [ABSTRACT FROM AUTHOR]

Compound XiongShao Capsule (CXSC), a traditional herb mixture, has shown significant clinical efficacy against diabetic peripheral neuropathy (DPN). However, its multicomponent and multitarget features cause difficulty in deciphering its molecular mechanisms. Our study aimed to identify the key active ingredients and potential pharmacological mechanisms of CXSC in treating DPN by network pharmacology and provide scientific evidence of its clinical efficacy. CXSC active ingredients were identified from both the Traditional Chinese Medicine Systems Pharmacology database, with parameters of oral bioavailability ≥ 30% and drug-likeness ≥ 0.18, and the Herbal Ingredients' Targets (HIT) database. The targets of those active ingredients were identified using ChemMapper based on 3D-structure similarity and using HIT database. DPN-related genes were acquired from microarray dataset GSE95849 and five widely used databases (TTD, Drugbank, KEGG, DisGeNET, and OMIM). Next, we obtained candidate targets with therapeutic effects against DPN by mapping active ingredient targets and DPN-related genes and identifying the proteins interacting with those candidate targets using STITCH 5.0. We constructed an "active ingredients-candidate targets-proteins" network using Cytoscape 3.61 and identified key active ingredients and key targets in the network. We identified 172 active ingredients in CXSC, 898 targets of the active ingredients, 110 DPN-related genes, and 38 candidate targets with therapeutic effects against DPN. Three key active ingredients, namely, quercetin, kaempferol, and baicalein, and 25 key targets were identified. Next, we input all key targets into ClueGO plugin for KEGG enrichment and molecular function analyses. The AGE-RAGE signaling pathway in diabetic complications and MAP kinase activity were determined as the main KEGG pathway and molecular function involved, respectively. We determined quercetin, kaempferol, and baicalein as the key active ingredients of CXSC and the AGE-RAGE signaling pathway and MAP kinase activity as the main pharmacological mechanisms of CXSC against DPN, proving the clinical efficacy of CXSC against DPN. [ABSTRACT FROM AUTHOR]

Metorchis orientalis is a neglected zoonotic parasite of the gallbladder and bile duct of poultry, mammals, and humans. It has been widely reported in Asian, including China, Japanese, and Korea, where it is a potential threat to public health. Despite its significance as an animal and human pathogen, there are few published transcriptomic and proteomics data available. Transcriptome Illumina RNA sequencing and label-free protein quantification were performed to compare the gene and protein expression of adult and metacercariae-stage M. orientalis , resulting in 100,234 unigenes and 3,530 proteins. Of these, 13,823 differentially expressed genes and 1,445 differentially expressed proteins were identified in adult versus metacercariae. In total, 570 genes were differentially expressed consistent with the mRNA and protein level in the adult versus metacercariae stage. Differential gene transcription analyses revealed 34,228 genes to be expressed in both stages, whereas 66,006 genes showed stage-specific expression. Compared with adults, the metacercariae stage was highly transcriptional. GO and KEGG analyses based on transcriptome and proteome revealed numerous up-regulated genes in adult M. orientalis related to microtubule-based processes, microtubule motor activity, and nucleocytoplasmic transport. The up-regulated genes in metacercariae M. orientalis were mainly related to transmembrane receptor protein serine/threonine kinase activity, transmembrane receptor protein serine/threonine kinase signaling pathway. Transcriptome and proteome comparative analyses showed numerous up-regulated genes in adult stage were mainly enriched in actin filament capping, spectrin, and glucose metabolic process, while up-regulated genes in metacercariae stage were mainly related to cilium assembly, cilium movement, and motile cilium. These results highlight changes in protein and gene functions during the development of metacercariae into adults, and provided evidence for the mechanisms involved in morphological and metabolic changes at both the protein and gene levels. Interestingly, many genes had been proved associated with liver fibrosis and carcinogenic factors were identified highly expressed in adult M. orientalis , which suggests that M. orientalis is a neglected trematode with potential carcinogenic implications. These data provide attractive targets for the development of therapeutic or diagnostic interventions for controlling M. orientalis. [ABSTRACT FROM AUTHOR]

Introduction: The effect of icotinib on non-small cell lung cancer (NSCLC) patients with EGFR exon 19 deletions (19-Del) or L858R point mutation in exon 21 (21-L858R) remains inconsistent. This study aimed to evaluate the efficacy and safety of icotinib in patients with advanced NSCLC harboring these 2 EGFR mutations. Methods: We retrospectively assessed the clinical effects of first-line icotinib on advanced NSCLC patients with 2 classic EGFR mutations. Kinase activity assays were used to reaffirm the preclinical efficacy. Results: Among 2,757 patients, 2,365 (86%) harbored 19-Del (1,346/2,757, 49%) or 21-L858R (1,019/2,757, 37%) mutation. Patients with 19-Del had a higher response rate (ORR; 67.8 vs. 62.1%; p = 0.0039) and disease control rate (98.5 vs. 97.2%; p = 0.0223) than those with 21-L858R mutation. The median progression-free survival (PFS) in the 19-Del group (22.3 months, 95% confidence interval [CI]: 21.3–23.4) was significantly longer than that in the 21-L858R group (20.4 months, 95% CI: 19.5–21.7) (p = 0.004). In multivariate analysis, mutation types, clinical stage, and smoking history were significant factors for PFS. Additionally, an in vitro study indicated the 50% inhibitory concentrations (IC50) of icotinib was lower for EGFR 19-Del than 21-L858R. Conclusion: These results suggest that EGFR 19-Del confers superior PFS and response to the icotinib treatment compared to 21-L858R. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor receptor 1 (FGFR1) is an idiopathic hypogonadotropic hypogonadism (IHH)‐associated gene, mutated in approximately 10% of the patients with this condition. Through targeted gene sequencing of 153 males with IHH and 100 healthy controls, we identified 10 mutations in FGFR1 from IHH patients with a frequency of 5.9% in the Chinese population of central China. These included nine missense mutations(NM_023110.2, p.Gly687Arg, p.Ala608Asp, p.Gly348Glu, p.Asn296Ser, p.Gly226Asp, p.Arg209Cys, p.Gly97Arg, p.Val71Met, p.Gly70Arg) and a splicing mutation c.1430 + 1G > T. in vitro and in silico analyses of FGFR1 variants were conducted to study the impact of the identified mutations. Our findings indicated that the splicing mutation dramatically affected premRNA processing, causing exon 10 and 6 nucleotides in the 3′ end of exon 9 to be completely skipped. Two variants (p.Gly687Arg and p.Ala608Asp) markedly impaired tyrosine kinase activity, while the other variants had limited impact on the mitogen‐activated protein kinase (MAPK) signaling pathway. However, the functional impairment of the mutant receptors was not always consistent with the phenotypes, indicating that FGFR1 mutations might cause IHH in conjunction with other mutant genes. In this study, we expanded the knowledge on the mutation spectrum of FGFR1 in IHH patients and explored the genotype‐phenotype relationship. [ABSTRACT FROM AUTHOR]

Sentrin/small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) perform pivotal roles in SUMO maturation and recycling, which modulate the balance of SUMOylation/de-SUMOylation and spatiotemporal functions of SUMOylation targets. The malfunction of SENPs often results in cellular dysfunction and various diseases. However, studies rarely investigated the correlation between SENP2 and lung cancer. This study revealed that SENP2 is a required contributor to lung cancer-cell growth and targets nuclear Dbf2-related 2 (NDR2, also known as serine/threonine kinase 38L or STK38L) for de-SUMOylation, which improves NDR2 kinase activity. This condition leads to the instability of downstream target p21 in accelerating the G 1 /S cell cycle transition and suggests SENP2 as a promising therapeutic target for lung cancer in the future. Specifically, astragaloside IV, an active ingredient of Jinfukang Oral Liquid (JOL, a clinical combination antilung cancer drug approved by the National Food and Drug Administration (FDA) of China), can repress lung cancer-cell growth via the SENP2–NDR2–p21 axis, which provides new insights into the molecular mechanism of JOL for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Cipangopaludina chinensis is a common freshwater mollusk that is widely distributed worldwide, especially in China. In our research, 1,382 proteins and 1,039 phosphorylated proteins were identified from C. chinensis carcasses, and 690 differentially expressed proteins (DEPs) were quantified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the DEPs are involved in cellular processes, single-organism processes, metabolic processes, developmental processes, localization, and biological regulation. The phosphorylated proteins were found to be related to the Rap1 signaling pathway, Ras signaling pathway, calcium signaling pathway, and longevity-regulating pathways. Moreover, we also identified important regulatory enzymes, such as guanylate cyclase, tyrosine protein kinase, receptor protein tyrosine kinase, and glyoxylate reductase/hydroxypyruvate reductase. Notably, we found guanylate cyclase to be present in multiple signaling pathways, including the Rap1 signaling pathway, calcium signaling pathway, Ras signaling pathway, insulin secretion, longevity regulating pathway, glutamatergic synapse, circadian entrainment, and gap junction. This enzyme may play a crucial role in regulating molecular mechanisms in C. chinensis. In summary, proteomic and phosphoproteomic analyses of C. chinensis carcasses displayed significant differences among different geographical isolates, which helps enhance our understanding of food nutrition, signaling pathways, and metabolic mechanisms in C. chinensis. [ABSTRACT FROM AUTHOR]

The barbel chub (Squaliobarbus curriculus), the only species in the genus, is widely distributed in freshwater lakes and rivers at different latitudes in East Asia, with fishery and biodiversity importance, and is an emerging commercially important fish in China. However, the resource of this species has dramatically declined due to anthropogenic activities such as over-exploitation, as well as water pollution. Genomic resources for S. curriculus are useful for the management and sustainable utilization of this important fish species, and also for a better understanding of its genetic variation in the region. Here, we report the chromosome-level assembly of the S. curriculus genome obtained from the integration of PacBio long sequencing and Hi-C technology. A total of 155.34 Gb high-quality PacBio sequences were generated, and the preliminary genome assembly was 894.95 Mb in size with a contig N50 being 20.34 Mb. By using Hi-C data, 99.42% of the assembled sequences were anchored to 24 pseudochromosomes, with chromosome lengths ranging from 27.22 to 58.75 Mb. A total of 25,779 protein-coding genes were predicted, 94.70% of which were functionally annotated. Moreover, S. curriculus shows resistance to grass carp haemorrhagic disease (GCHD) caused by grass carp reovirus (GCRV), which seriously hinders the status and future perspectives of commercial grass carp production. Phylogenetic analysis indicated that S. curriculus diverged with grass carp (Ctenopharyngodon idellus) approximately 20.80 million years ago. Annotations of the expanded gene families were found to be largely enriched in immune-related KEGG pathway categories. Moreover, a total of 18 Toll-like receptor (TLR) genes were identified from the whole genome of S. curriculus. The high-quality genome assembled in this study will provide a valuable resource for accelerating ecological, evolutionary, and genetic research on S. curriculus. [ABSTRACT FROM AUTHOR]

Background: Unfavourable lipid and glucose levels may play a crucial role in the pathogenesis of gestational diabetes mellitus (GDM). However, there is a lack of prospective studies on the relationship between lipid profiles, lipid ratios and GDM during pregnancy. Aims: To prospectively investigate the relationship between lipid profile and lipid ratios in early and mid-pregnancy and their pattern of change from early to mid-pregnancy and the risk of GDM. Methods: This nested case-control study was based on maternal and child healthcare hospitals from Fujian Province, China. We included pregnant women who delivered in the hospital from January 2021 to June 2023. Lipid profiles (TC, TG, ApoA1, ApoB, HDL-c, LDL-c) and fasting glucose were measured before 14 weeks of gestation and between 20 and 28 weeks of gestation, and lipid ratios (triglyceride glucose index, TG/HDL-c and TC/HDL-c) was constructed. Logistic regression was used to assess the relationship between lipid profile, lipid ratios and GDM. Results: Of 1586 pregnant women, 741 were diagnosed with GDM. After adjusting for potential confounders, TG, ApoA1, ApoB, LDL-c, triglyceride glucose index, TG/HDL-c, and TC/HDL-c in early pregnancy were positively associated with the risk of GDM (odds ratios [95% CI] for extreme interquartile comparisons were 2.040 (1.468–2.843), 1.506 (1.091–2.082), 1.529 (1.110–2.107), 1.504 (1.086–2.086), 1.952 (1.398–2.731), 2.127 (1.526–2.971), and 2.370 (1.700-3.312), all trend P < 0.05). HDL-c was negatively associated with the risk of GDM (0.639: 0.459–0.889, trend P all less than 0.05). Similarly, in mid-pregnancy, lower levels of HDL-c, higher levels of triglyceride glucose index, TG/HDL-c ratio, and TC/HDL-c ratio were associated with increased risk of GDM (all trends P < 0.05). Stably high levels (both ≥ median for early and mid-pregnancy) of triglyceride glucose index, TG/HDL-c and TC/HDL-c were associated with increased risk of GDM (OR [95% CI]: 2.369 (1.438–3.940), 1.588 (1.077–2.341), 1.921 (1.309–2.829), respectively). The opposite was true for HDL-c, where stable high levels were negatively associated with GDM risk (OR [95% CI]: 0.599 (0.405–0.883)). Conclusion: Increases in triglyceride glucose index, TG/HDL-c ratio, and TC/HDL-c ratio in early and mid-pregnancy, as well as their stable high levels from early to mid-pregnancy, are associated with a higher risk of GDM. In contrast, increased levels of HDL-c, both in early and mid-pregnancy, and their stable high levels from early to mid-pregnancy were associated with a lower risk of GDM. That highlighted their possible clinical relevance in identifying those at high risk of GDM. [ABSTRACT FROM AUTHOR]

Cerasus humilis, a small shrub of the Cerasus genus within the Rosaceae family, is native to China and renowned for its highly nutritious and medicinal fruits, robust root system, and remarkable drought resistance. This study primarily employed association transcriptome and metabolome analyses to assess changes in abscisic acid (ABA) levels and identify key regulatory genes in C. humilis subjected to varying degrees of drought stress. Notably, we observed distinct alterations in transcription factors across different drought intensities. Specifically, our transcriptome data indicated noteworthy shifts in GATA, MYB, MYC, WRKY, C2H2, and bHLH transcription factor families. Furthermore, combined transcriptomic and metabolomic investigations demonstrated significant enrichment of metabolic pathways, such as 'Carbon metabolism', 'Biosynthesis of amino acids', 'Biosynthesis of cofactors', 'Phenylpropanoid biosynthesis', 'Starch and sucrose metabolism', and 'Plant hormone signal transduction' under moderate (Mod) or severe (Sev) drought conditions. A total of 11 candidate genes involved in ABA biosynthesis and signaling pathways were identified. The down-regulated genes included secoisolariciresinol dehydrogenase-like and PYL2. Conversely, genes including FAD-dependent urate hydroxylase-like, cytochrome P450 97B2, carotenoid cleavage dioxygenase 4 (CCD4), SnRK2.2, ABI 5-like protein 5, PP2C 51, and SnRK2.3, were up-regulated under Mod or Sev drought stress. This study lays the genetic foundation for ABA biosynthesis to enhance drought tolerance and provides genetic resources for plant genetic engineering and breeding efforts. [ABSTRACT FROM AUTHOR]

The holly Ilex dabieshanensis K. Yao & M. B. Deng, a tree endemic to the Dabieshan Mountains region in China, is a commonly used landscaping plant. Like other crops, its growth is affected by salt stress. The molecular mechanism underlying salt tolerance in holly is still unclear. In this study, we used NaCl treatment and RNA sequencing (RNA-seq) at different times to identify the salt stress response genes of holly. A total of 4775 differentially expressed genes (DEGs) were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the DEGs obtained at different salt treatment times (3, 6, 9, 12, and 24 h), as compared to control (ck, 0 h), showed that plant hormone signal transduction and carotenoid biosynthesis were highly enriched. The mechanism by which holly responds to salt stress involves many plant hormones, among which the accumulation of abscisic acid (ABA) and its signal transduction may play an important role. In addition, ion homeostasis, osmotic metabolism, accumulation of antioxidant enzymes and nonenzymatic antioxidant compounds, and transcription factors jointly regulate the physiological balance in holly, providing important guarantees for its growth and development under conditions of salt stress. These results lay the foundation for studying the molecular mechanisms of salt tolerance in holly and for the selection of salt-tolerant varieties. [ABSTRACT FROM AUTHOR]

Pueraria lobata (P. lobata), a traditional anti-diabetic medicine mainly composed of flavonoids and isoflavones, has a long history in diabetes treatment in China. However, the anti-diabetic active component is still unclear. Recently, protein tyrosine phosphatase 1B (PTP1B) has been a hot therapeutic target by negatively regulating insulin signaling pathways. In this study, the spectrum–effect relationship analysis method was first used to identify the active components of P. lobata that inhibit PTP1B. The fingerprints of 12 batches of samples were established using high-performance liquid chromatography (HPLC), and sixty common peaks were identified. Meanwhile, twelve components were identified by a comparison with the standards. The inhibition of PTP1B activity was studied in vitro by using the p-nitrophenol method, and the partial least squares discriminant analysis, grey relational analysis, bivariate correlation analysis, and cluster analysis were used to analyze the bioactive compounds in P. lobata. Peaks 6, 9 (glycitin), 11 (genistin), 12 (4′-methoxypuerarin), 25, 34, 35, 36, 53, and 59 were considered as potentially active substances that inhibit PTP1B. The in vitro PTP1B inhibitory activity was confirmed by glycitin, genistin, and 4′-methoxypuerarin. The IC50s of the three compounds were 10.56 ± 0.42 μg/mL, 16.46 ± 0.29 μg/mL, and 9.336 ± 0.56 μg/mL, respectively, indicating the obvious PTP1B inhibitory activity. In brief, we established an effective method to identify PTP1B enzyme inhibitors in P. lobata, which is helpful in clarifying the material basis of P. lobata on diabetes. Additionally, it is evident that the spectrum–effect relationship method serves as an efficient approach for identifying active compounds, and this study can also serve as a reference for screening bioactive constituents in traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Camellia oleifera is a native woody oil plant in southern China and is infected with anthracnose wherever it is grown. We previously identified Colletotrichum fructicola as the major causal agent of anthracnose on C. oleifera and found that CfAtg8 regulates the pathogenicity and development of C. fructicola. Here, we revealed that CfAtg4 interacts with CfAtg8, contributing to the formation of autophagosomes. The CfAtg81–160 allele, which only contains 1–160 amino acids of the CfAtg8, partially recovered the autophagosome numbers and autophagy defects of the ΔCfatg4 mutant. Consequently, these recoveries resulted in the restoration of the defects of the ΔCfatg4 mutant in growth and responses to different external stresses, albeit to an extent. Importantly, we illustrated the critical roles of CfAtg81–160 in appressoria formation, and pathogenicity. Collectively, our findings provide new insights into the importance of the interaction between CfAtg8 and CfAtg4 in the growth, autophagy and pathogenicity of the phytopathogenic fungi. [ABSTRACT FROM AUTHOR]

Paeonia lactiflora Pall. is a perennial herb of the buttercup family with a long history of medicinal use in China. With population migration and geographical changes, it gradually differentiates into different species, namely Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). This study established an integrated strategy to investigate the different species of Paeonia lactiflora Pall. through ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), chemometric analysis combined with network pharmacology. Firstly, a total of 36 compounds were identified using UPLC-Q-TOF/MS, mainly including monoterpene glycosides, polyphenols, and phenolic acids. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) indicated that the studied samples were classified into PRA and PRR based on their species, while PRA or PRR could be classified as corresponding to geographical origins and morphological characteristics. Moreover, the orthogonal partial least squares discriminant analysis (OPLS-DA) and counter propagation artificial neural networks (CP-ANN) were applied to confirm classification results and obtain the chemical markers on different samples. Network pharmacology and molecular docking techniques demonstrated that active molecules have a higher affinity for ACTB and AKT1. The results of the content of representative components demonstrated differences between the two species. In conclusion, the methodology and results of this study provided a reliable basis for the identification and rational utilization of PRA and PRR, which were important for the appropriate clinical use and quality assurance of pharmaceutical materials. [ABSTRACT FROM AUTHOR]

Background: The promising efficacy of novel anti-HER2 antibody-drug conjugates (ADC) in HER2-low breast cancer has made HER2-low a research hotspot. However, controversy remains regarding the neoadjuvant chemotherapy (NAC) efficacy, prognosis, and the relationship with hormone receptor (HR) status of HER2-low. Methods: A retrospective analysis was conducted on 975 patients with HER2-negative breast cancer undergoing NAC at Tianjin Medical University Cancer Institute and Hospital, evaluating pathological complete response (pCR) rate and prognosis between HER2-low and HER2-zero in the overall cohort and subgroups. Results: Overall, 579 (59.4%) and 396 (40.6%) patients were HER2-low and HER2-zero disease, respectively. Compared with HER2-zero, the HER2-low cohort consists of more postmenopausal patients, with lower histological grade and higher HR positivity. In the HR-positive subgroup, HER2-low cases remain to exhibit lower histological grade, while in the HR-negative subgroup, they show higher grade. The HER2-low group had lower pCR rates than the HER2-zero group (16.4% vs. 24.0%). In the HR-positive subgroup, HER2-low consistently showed lower pCR rate (8.1% vs. 15.5%), and served as an independent suppressive factor for the pCR rate. However, no significant difference was observed in the pCR rates between HER2-low and HER2-zero in the HR-negative breast cancer. In the entire cohort and in stratified subgroups based on HR and pCR statuses, no difference in disease-free survival were observed between HER2-low and HER2-zero. Conclusions: In the Chinese population, HER2-low breast cancer exhibits distinct characteristics and efficacy of NAC in different HR subgroups. Its reduced pCR rate in HR-positive subgroup is particularly important for clinical decisions. However, HER2-low is not a reliable factor for assessing long-term survival outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Bacillus amyloliquefaciens DGL1, isolated from the arid sandy areas in Dagler, Qinghai Province, China, promotes the growth of Avena sativa variety "Qing Yan 1". Methods: To elucidate the transcriptomic changes in the oat root system following interaction with DGL1 and to reveal the molecular mechanism by which DGL1 promotes oat growth, treatment and control groups of oat roots at 2, 4, 8, and 12 h after inoculation with a suspension of strain DGL1 were analyzed using Illumina high-throughput transcriptome sequencing technology. The differentially expressed genes were determined through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and the metabolic pathways and key genes were analyzed. Results: The results showed that 7874, 13,392, 13,169, and 19,026 diffrentially expressed genes were significantly enriched in the glycolysis/gluconeogenesis pathway, amino acid metabolism, nitrogen metabolism, plant hormone signal transduction, and other related metabolic pathways in the oat roots at 2, 4, 8, and 12 h after inoculation with a DGL1 suspension. The GO and KEGG enrichment analyses revealed that the genes encoding plasma membrane ATPase, phosphoglycerate kinase gene PGK, ammonium transporter protein gene AMT, cellulose synthase gene CSLF6, and growth hormone response family gene IAA18 were significantly upregulated. Discussion: It is hypothesized that the pro-growth mechanism of strain DGL1 in oats is the result of the coordination of multiple pathways through the promotion of oat energy metabolism, phytohormone signaling, secondary metabolite synthesis, and amino acid metabolism. [ABSTRACT FROM AUTHOR]

Introduction: P. candolleana Wight et Arn. Is a traditional Chinese herbal medicine used by the Gelao nationality in southwest China, has been historically applied to treat various gastrointestinal disorders. Despite its traditional usage, scientific evidence elucidating its efficacy and mechanisms in treating ulcerative colitis (UC) remains sparse. This study aimed to determine the quality and chemical composition of Pimpinella candolleana and to identify its potential therapeutic targets and mechanisms in acetic acid-induced ulcerative colitis (UC) rats through integrated approaches. Methods: Morphological and microscopic characteristics, thin layer chromatography (TLC) identification, and quantitative analysis of P. candolleana were performed. UPLC-Q-TOF-MS, network pharmacology, and molecular docking were used to identify its chemical composition and predict its related targets in UC. Furthermore, a rat model was established to evaluate the therapeutic effect and potential mechanism of P. candolleana on UC. Results: Microscopic identification revealed irregular and radial arrangement of the xylem in P. candolleana, with a light green cross-section and large medullary cells. UPLC-Q-TOF-MS analysis detected and analyzed 570 metabolites, including flavonoids, coumarins, and terpenoids. Network pharmacology identified 12 effective components and 176 target genes, with 96 common targets for P. candolleana-UC, including quercetin, luteolin, and nobiletin as key anti-inflammatory components. GO and KEGG revealed the potential involvement of their targets in RELA, JUN, TNF, IKBKB, PTGS2, and CHUK, with action pathways such as PI3K-Akt, TNF, IL-17, and apoptosis. Molecular docking demonstrated strong affinity and binding between these key components (quercetin, luteolin, and nobiletin) and the key targets of the pathway, including JUN and TNF. Treatment with P. candolleana improved body weight loss, the disease activity index, and colonic histological damage in UC rats. Pimpinella candolleana also modulated the levels of IL-2 and IL-6 in UC rats, reduced the expression of pro-inflammatory cytokines such as IL-6, MAPK8, TNF-a, CHUK, and IKBKB mRNA, and decreased the expression of TNF, IKBKB, JUN, and CHUK proteins in the colon of UC rats, thereby reducing inflammation and alleviating UC symptoms. Conclusion: P. candolleana exerts its protective effect on UC by reducing the expression of proinflammatory cytokines and inhibiting inflammation, providing scientific evidence for its traditional use in treating gastrointestinal diseases. This study highlights the potential of P. candolleana as a natural therapeutic agent for UC and contributes to the development of novel medicines for UC treatment. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis is a group of chronic, progressive, and irreversible interstitial lung diseases, which are common to most end-stage lung diseases and are one of the most difficult diseases of the respiratory system. In recent years, due to the frequent occurrence of air pollution and smog, the incidence of pulmonary fibrosis in China has increased year by year, the morbidity and mortality rates of pulmonary fibrosis have gradually increased and the age of the disease tends to be younger. However, the pathogenesis of pulmonary fibrosis is not yet fully understood and is needed to further explore new drug targets. Studies have shown that non-coding RNAs play an important role in regulating the process of pulmonary fibrosis, non-coding RNAs and their specifically expressed can promote or inhibit the process. Here, we review the role of some in the regulation of pulmonary fibrosis signaling pathways and provide new ideas for the clinical diagnosis and treatment of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

In the past 11 years, there has been a surge in studies exploring the regulatory effect of Traditional Chinese Medicine (TCM) on ferroptosis. However, a significant gap persists in comprehensive scientometric analysis and scientific mapping research, especially in tracking the evolution, primary contributors, and emerging research focal points. This study aims to comprehensively update the advancements in targeting ferroptosis with various TCMs during the previous 11 years. The data, covering the period from 1 January 2012, to 30 November 2023, were retrieved from the Web of Science database. For in-depth scientometric and visualized analyses, a series of advanced analytical instruments were employed. The findings highlight China's predominant role, accounting for 71.99% of total publications and significantly shaping research in this domain. Noteworthy productivity was observed at various institutions, including Guangzhou University of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, and Zhejiang University. Thomas Efferth emerged as the foremost author within this field, while Frontiers in Pharmacology boasted the highest publication count. This study pinpointed hepatocellular carcinoma, chemical and drug-induced liver injury, mitochondrial diseases, acute kidney injury, and liver failure as the most critical disorders addressed in this research realm. The research offers a comprehensive bibliometric evaluation, enhancing our understanding of the present status of TCM therapy in managing ferroptosisrelated diseases. Consequently, it aids both seasoned researchers and newcomers by accelerating access to vital information and fostering innovative concept extraction within this specialized field. [ABSTRACT FROM AUTHOR]

Runs of Homozygosity (ROH) are continuous homozygous DNA segments in diploid genomes, which have been used to estimate the genetic diversity, inbreeding levels, and genes associated with specific traits in livestock. In this study, we analyzed the resequencing data from 10 local goat breeds in Yunnan province of China and five additional goat populations obtained from a public database. The ROH analysis revealed 21,029 ROH segments across the 15 populations, with an average length of 1.27 Mb, a pattern of ROH, and the assessment of the inbreeding coefficient indicating genetic diversity and varying levels of inbreeding. iHS (integrated haplotype score) was used to analyze high-frequency Single-Nucleotide Polymorphisms (SNPs) in ROH regions, specific genes related to economic traits such as coat color and weight variation. These candidate genes include OCA2 (OCA2 melanosomal transmembrane protein) and MLPH (melanophilin) associated with coat color, EPHA6 (EPH receptor A6) involved in litter size, CDKAL1 (CDK5 regulatory subunit associated protein 1 like 1) and POMC (proopiomelanocortin) linked to weight variation and some putative genes associated with high-altitude adaptability and immune. This study uncovers genetic diversity and inbreeding levels within local goat breeds in Yunnan province, China. The identification of specific genes associated with economic traits and adaptability provides actionable insights for utilization and conservation efforts. [ABSTRACT FROM AUTHOR]

Mongolian oak (Quercus mongolica) is a common building material and landscaping tree species in northern China, with significant economic and ecological value. Its seedling growth is inhibited by high light intensity, but the mechanism by which light stress affects the growth and development of its seedlings remains unclear. In this study, we investigated the phenotypes, physiological processes, and molecular responses of 3-year-old Mongolian oak seedlings under different light treatments: full light (Sck), light shading (S1; 40% light), moderate shading (S2; 20% light), and severe shading (S3; 3% light). Compared to Sck, the S1 and S2 treatments resulted in higher leaf area, photosynthetic pigment content, photosynthesis rates, soluble sugar contents, and soluble protein contents in Mongolian oak seedlings. The S1 and S2 treatments also promoted seedling height and diameter growth and resulted in lower degrees of membrane lipid peroxidation, cell membrane permeability, and antioxidant enzyme activity. In contrast, severe shading (S3) significantly inhibited seedling height and diameter growth due to the lower net photosynthetic rate, and exhibiting higher degrees of membrane lipid peroxidation and cell membrane permeability. Shading treatments (S1 and S2) alleviated the negative effects of strong light on the growth and development of Mongolian oak seedlings, with the S2 treatment having the greatest effect. However, severe shading (S3) inhibited growth and development. A total of 3726 differentially expressed genes (DEGs) were detected in leaves under different shading treatments in RNA sequencing analysis. Among these, 1691, 3150, and 824 DEGs were detected in the Sck-S1, Sck-S2, and S1-S2 comparison groups, respectively. The different shading treatments determined common expression regulation pathways, including carotenoid biosynthesis, photosynthetic antenna proteins, and mitogen activated protein kinase (MAPK) signal transduction. Shading induced increases in gene expression levels in light harvesting complexes, which are related to changes in gene expression in the photosynthetic system, leading to changes in photosynthetic physiology. The expression levels of genes related to reactive oxygen species signal perception and activation enzymes were upregulated in Sck. Together, these findings revealed the response mechanisms of Mongolian oak seedlings to different shading levels at the physiological and molecular levels, providing a scientific basis and technical support for the cultivation and large-scale production of Mongolian oak seedlings. [ABSTRACT FROM AUTHOR]

Sweet clover (Melilotus albus) is a high-quality leguminous forage grass with salinity tolerance, drought tolerance, and cold hardiness. We selected four varieties of sweet clover with different sensitivities (061898, 061930, No. 55 white flower, and Ningxia white flower) and analyzed the effects of different concentrations of three sodium salts (Na2CO3, NaHCO3, and NaCl) on their physiology and biochemistry responses. Growth and development indexes (such as germination rate, root length, shoot length), chlorophyll content, osmotic regulators (proline, soluble sugar), malondialdehyde (MDA), superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were determined under saline–alkali stress. Seed germination and seedling growth of all four clover species were significantly inhibited under saline–alkali stress. During germination, seed germination rate, root length, and shoot length decreased with increasing saline and alkaline concentration. Under saline–alkali stress, chlorophyll content tended to increase and then decrease, cell damage and death increased, and malondialdehyde, soluble sugar, and proline content tended to increase and then decrease. Moreover, the activities of SOD, POD, and CAT all increased and then decreased. Under Na2CO3 stress, the decrease in chlorophyll content of the resistant variety 061898 was less than in the sensitive Ningxia white flower variety. As the concentrations of Na2CO3, NaHCO3, and NaCl increased, the maximum photochemical efficiency of PSII was significantly affected. The resistant 061898 is capable of maintaining higher photosynthetic efficiency. Furthermore, under treatments with the three kinds of saline–alkali solutions, cell damage and death for Ningxia white flower were greater than in 061898. For 061898, the increases in soluble sugar and proline content were greater and the increase in malondialdehyde content was less, while the antioxidant enzyme activities were higher than those in Ningxia white flower. All four sweet clover varieties had higher stress resistance with neutral than with alkaline salts. When stressed by medium to high saline–alkali concentrations, sweet clover seedlings had increased osmotic substance content, enhanced antioxidant enzyme activity, and regulated physiological metabolism. Additionally, sweet clovers regulated the expression of WRKY33, GH3, CYCD3, OXI1, MKK2, MYC2, JAZ, COI1, PYL, PP2C, TGA, and MPK3 to adapt to the saline–alkali environment and improve saline–alkali tolerance. Our analysis of the sweet clover salinity tolerance mechanism contributes to its further use and is of significant importance for addressing land salinization and promoting sustainable agricultural and pastoral practices in China. [ABSTRACT FROM AUTHOR]

Aim: Patients with advanced gastrointestinal stromal tumors (GISTs) exhibiting an imatinib plasma trough concentration (IM Cmin) under 1100 ng/ml may show a reduced drug response rate, leading to the suggestion of monitoring for IM Cmin. Consequently, the objective of this research was to create a customized IM Cmin classification model for patients with advanced GISTs from China. Methods: Initial data and laboratory indicators from patients with advanced GISTs were gathered, and the above information was segmented into a training set, validation set, and testing set in a 6:2:2 ratio. Key variables associated with IM Cmin were identified to construct the classification model using the least absolute shrinkage and selection operator (LASSO) regression and forward stepwise binary logistic regression. Within the training and validation sets, nine ML classification models were constructed via the resampling method and underwent comparison through the Brier scores, the areas under the receiver-operating characteristic curve (AUROC), the decision curve, and the precision-recall (AUPR) curve to determine the most suitable model for this dataset. Two methods of internal validation were used to assess the most suitable model's classification performance: tenfold cross-validation and random split-sample validation (test set), and the value of the test set AUROC was used to evaluate the model's classification performance. Results: Six key variables (gender, daily IM dose, metastatic site, red blood cell count, platelet count, and percentage of neutrophils) were ultimately selected to construct the classification model. In the validation set, it is found by comparison that the Extreme Gradient Boosting (XGBoost) model has the largest AUROC, the lowest Brier score, the largest area under the decision curve, and the largest AUPR value. Furthermore, as evaluated via internal verification, it also performed well in the test set (AUROC = 0.725). Conclusion: For patients with advanced GISTs who receive IM, initial data and laboratory indicators could be used to accurately estimate whether the IM Cmin is below 1100 ng/ml. The XGBoost model may stand a chance to assist clinicians in directing the administration of IM. [ABSTRACT FROM AUTHOR]

Aphidius gifuensis is a parasitoid wasp and primary endoparasitoid enemy of the peach potato aphid, Myzus persicae. Artificially reared, captive wasps of this species have been extensively and effectively used to control populations of aphids and limit crop loss. However, the consequences of large-scale releasing of captive A. gifuensis, such as genetic erosion and reduced fitness in wild populations of this species, remains unclear. Here, we sequence the genomes of 542 A. gifuensis individuals collected across China, including 265 wild and 277 human-intervened samples. Population genetic analyses on wild individuals recovered Yunnan populations as the ancestral group with the most complex genetic structure. We also find genetic signature of environmental adaptation during the dispersal of wild populations from Yunnan to other regions. While comparative genomic analyses of captive wasps revealed a decrease in genetic diversity during long-term rearing, population genomic analyses revealed signatures of natural selection by several biotic (host plants) or abiotic (climate) factors, which support maintenance of the gene pool of wild populations in spite of the introduction of captive wasps. Therefore, the impact of large-scale release is reduced. Our study suggests that A. gifuensis is a good system for exploring the genetic and evolutionary effects of mass rearing and release on species commonly used as biocontrol agents. Parasitoid wasps are reared and released as biocontrol agents to manage aphids and protect crops. Here, the authors use genomes from 542 wasps to show that, in spite of wide scale release of low-diversity captive individuals, diversity in wild populations is maintained. [ABSTRACT FROM AUTHOR]

The sterility advantages of triploids make them paramount for oyster aquaculture. Tetraploids are always used as male parents for triploid industrial breeding in current hatcheries, thus they are the core asset for triploid oyster culture. The oyster Crassostrea angulata is the most productive oyster species in China. However, the optimal conditions for tetraploid induction have never been examined. In this study, we investigated the effectiveness of three induction methods (Method I, 2n ♀ × 2n ♂ + inducer abbreviated as DD + ind; Method II, 3n ♀ × 2n ♂ + inducer abbreviated as TrD + ind; Method III, 2n ♀ × 4n ♂ + inducer abbreviated as DT + ind) and three inducers (salinity; cytochalasin B, CB; and 6-dimethylaminopurine, 6-DMAP) for tetraploid induction in C. angulata. The optimal induction conditions for the three induction methods were a CB concentration of 0.5 mg/L treated for 20 min, 0.75 mg/L CB for a constant induction treatment of 20 min and 6-DMAP at a concentration of 100 mg/L for 20 min, respectively. When the optimal induction conditions were applied to a single pair of oysters, the D-larval tetraploid rate for the three methods were 18.93 ± 1.46%, 58.32 ± 1.03% and 51.61 ± 1.37%, respectively. After 30 days, the survival rates of the experimental groups were only 10.36 ± 2.51%, 28.07 ± 2.03% and 21.99 ± 1.27%, respectively, at day 30. The tetraploid rates in DD + ind and DT + ind were both decreased significantly over time, but they still reached 11.81% and 21.99% at 30 days, and 8% and 16% at day 180, respectively. Tetraploid rates in TrD + ind were 58.32 − 71.28% at the larval stage and 80% at day 180. In summary, despite very different induction rates, surviving tetraploids of C. angulata could be obtained in all three methods. Method II (TrD + inducer) was regarded as the optimal method to induce C. angulata tetraploids, and the optimal induction condition was a CB concentration of 0.75 mg/L and treated for 20 min under this method. [ABSTRACT FROM AUTHOR]

Background and Purpose: Penetrance estimates of the leucine-rich repeat kinase 2 (LRRK2) variants for Parkinson disease (PD) vary widely. G2385R is one of the most common LRRK2 variants in Asian populations, and its penetrance is currently unknown. We aimed to estimate the penetrance of G2385R in the Chinese population., Methods: The G2385R variant was tested by Sanger sequencing in 6386 participants older than 50 years, all from the community cohort established by Shanghai Ruijin Hospital in 2009-2011. G2385R carriers and matched noncarriers underwent a brief questionnaire survey (including sex, current age, PD diagnosis, and age at onset) and face-to-face PD assessment during 2020-2021. The penetrance of PD was estimated by the Kaplan-Meier method., Results: A total of 396 G2385R carriers and 415 noncarriers were included, after excluding those with a baseline diagnosis of PD or unwilling to participate. In G2385R carriers, the penetrance of PD was 1.64% at 70 years, 10.26% at 80 years, and 18.49% at 90 years, and reached 25.90% at 95 years. The penetrance of PD in G2385R carriers was higher than in noncarriers (p = 0.0071). In noncarriers, only 0%, 3.72%, and 9.66% developed parkinsonism by 70, 80, and 90 years of age. Among carriers and noncarriers, there were no statistically significant differences in penetrance comparisons between males and females, or between urban and rural., Conclusions: The lifetime penetrance of LRRK2 G2385R in the Chinese population was 25.9%. The penetrance modifier of G2385R in our study was age-related. Further investigation of genetic and environmental modifiers affecting G2385R penetrance is warranted., (© 2022 European Academy of Neurology.)

Cucumber corynespora leaf spot, caused by Corynespora cassiicola , is the primary disease of cucumber leaves in greenhouses in China. Fludioxonil is a phenylpyrrole fungicide that inhibits C. cassiicola growth. We studied the sensitivity of 170 isolates of C. cassiicola to fludioxonil and evaluated resistance risk. All of the isolates were sensitive to fludioxonil. The EC 50 values ranged from 0.082 to 0.539 μg/mL with a mean of 0.207 ± 0.0053 μg/mL. Laboratory-created mutants with a high resistance factor to fludioxonil were genetically stable after 10 transfers and showed positive cross-resistance to iprodione and procymidone but not to azoxystrobin, carbendazim, pydiflumetofen, and prochloraz. There was no significant difference in mycelial growth and temperature adaptation between the mutant s and the sensitive isolates, except for pathogenicity and sporulation. The resistant isolates accumulated less glycerol than their parental isolates and were more sensitive to osmotic stress. The histidine kinase activity of the sensitive isolates was significantly inhibited compared to that of the resistant mutants. Sequence alignment of the histidine kinase gene CCos revealed that the mutants RTL4, RXM5, and RFS102 had point mutations at different sites that resulted in amino acid changes at G934E, S739F, and A825P in the CCos protein. The mutant RFS102 had an alanine deletion at site 824. After fludioxonil treatment, CCos expression by RFS20 was significantly lower than that of the parental isolate. Our findings demonstrate that C. cassiicola exhibits moderate resistance to fludioxonil. [Display omitted] • Fludioxonil has a strong inhibitory activity against Corynespora cassiicola. • The adaptability of the fludioxonil-resistant mutants in pathogenicity and osmotic stress decreased. • The resistance mechanism of fludioxonil is associated with the point mutation of CCos. [ABSTRACT FROM AUTHOR]

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia., (© 2024 UICC.)

The incidence of diabetes and related mortality rate increase yearly in modern cities. Additionally, elevated glucose levels can result in an increase of reactive oxygen species (ROS), ferroptosis, and the disruption of protective pathways in the heart. These factors collectively heighten the vulnerability of diabetic individuals to myocardial ischemia. Reperfusion therapies have been effectively used in clinical practice. There are limitations to the current clinical methods used to treat myocardial ischemia-reperfusion injury. As a result, reducing posttreatment ischemia/reperfusion injury remains a challenge. Therefore, efforts are underway to provide more efficient therapy. Salvia miltiorrhiza Bunge (Danshen) has been used for centuries in ancient China to treat cardiovascular diseases (CVD) with rare side effects. Salvianolic acid is a water-soluble phenolic compound with potent antioxidant properties and has the greatest hydrophilic property in Danshen. It has recently been discovered that salvianolic acids A (SAA) and B (SAB) are capable of inhibiting apoptosis by targeting the JNK/Akt pathway and the NF-kB pathway, respectively. This review delves into the most recent discoveries regarding the therapeutic and cardioprotective benefits of salvianolic acid for individuals with diabetes. Salvianolic acid shows great potential in myocardial protection in diabetes mellitus. A thorough understanding of the protective mechanism of salvianolic acid could expand its potential uses in developing medicines for treating diabetes mellitus related myocardial ischemia-reperfusion. [ABSTRACT FROM AUTHOR]

The pathogen Cytospora chrysosperma is the causal agent of poplar canker disease and causes considerable economic losses in China. Mitogen-activated protein kinase (MAPK) cascades play a crucial role in mediating cellular responses and Pmk1-MAPKs are indispensable for pathogenic related processes in plant pathogenic fungi. In previous studies, we demonstrated that the CcPmk1 acts as a core regulator of fungal pathogenicity by modulating a small number of master downstream targets, such as CcSte12. In this study, we identified and characterized two upstream components of CcPmk1: MAPKKK CcSte11 and MAPKK CcSte7. Deletion of CcSte11 and CcSte7, resulted in slowed growth, loss of sporulation and virulence, similar to the defects observed in the CcPmk1 deletion mutant. In addition, CcSte11, CcSte7 and CcPmk1 interact with each other, and the upstream adaptor protein CcSte50 interact with CcSte11 and CcSte7. Moreover, we explored the global regulation network of CcSte12 by transcriptional analysis between CcSte12 deletion mutants and wild-type during the simulated infection process. Two hydrolase activity GO terms (GO:0004553 and GO:0016798) and starch and sucrose metabolism (mgr00500) KEGG pathway were significantly enriched in the down-regulated genes of CcSte12 deletion mutants. In addition, a subset of glycosyl hydrolase genes and putative effector genes were significantly down-regulated in the CcSte12 deletion mutant, which might be important for fungal pathogenicity. Especially, CcSte12 bound to the CcSp84 promoter region containing the TGAAACA motif. Moreover, comparison of CcSte12-regulated genes with CcPmk1-regulated genes revealed 116 overlapping regulated genes in both CcSte12 and CcPmk1, including some virulence-associated genes. Taken together, the protein complexes CcSte11-CcSte7-CcPmk1 receive signals transmitted by upstream CcSte50 and transmit signals to downstream CcSte12, which regulates hydrolase, effectors and other genes to promote virulence. Overall, these results indicate that the CcPmk1-MAPK signaling pathway of C. chrysosperma plays a key role in the pathogenicity. [ABSTRACT FROM AUTHOR]

Purpose: This research designeded to: 1. Analyze the efficacy and safety of Palbociclib treatment in HR-positive and HER2-negative (HR + /HER2-) metastatic breast cancer(MBC) patients. 2. Establish and validate a nomogram model for predicting the progression-free survival (PFS) rates of 6 months, 12 months, and 18 months in HR + /HER2- MBC patients after receiving Palbociclib plus endocrine therapy (ET). Patients and methods: 1. This research retrospectively analyzed the efficacy and safety of Palbociclib combined with ET in 214 patients with HR + /HER2- MBC. 2. A nomogram was designed and constructed with the retrospective clinical data of 214 patients with HR + /HER2- MBC who received Palbociclib plus ET at Zhejiang Cancer Hospital in China from August 2018 to August 2022. Among these patients, 161 were randomly assigned to the training cohort, while 53 to the validation cohort. The predictive accuracy of the nomogram was assessed through the analysis the area under the receiver operating characteristic(ROC) curve, calibration curve, and decision curve analysis(DCA). Results: 1. Median PFS was 7.17 months (95% CI: 7.61—10.05 months), with an objective response rate (ORR) of 2.80% and a disease control rate (DCR) of 34.58%. The most prevalent grade 3–4 adverse event was neutropenia (38.79%). 2. Multiple variable analysis of the training set revealed that age < 60 years old, PR < 20%, Ki-67 ≥ 20%, luminal B molecular subtype, primary resistance to ET, receipt of late-stage chemotherapy, and presence of liver metastasis or ≥ 2 visceral metastases were independent prognostic factors associated with poor PFS (P < 0.05). Then, the predictive model underwent development and validation utilizing the aforementioned parameters. On the one hand, the area under the ROC curve (AUC) values of the training set at 6 months, 12 months, and 18 months were 0.771, 0.783, and 0.790, respectively, indicating a strong predictive ability of the developed model. On the other hand, the AUC of the validation set at 6 months, 12 months, and 18 months were 0.720, 0.766, and 0.754, respectively, suggesting the favorable discriminatory ability of the model. The calibration curves also exhibited a good fit with the ideal curves, and the DCA demonstrated the clinical applicability of the model. The nomogram's different scores could distinguish PFS. Conclusion: This retrospective study demonstrates the efficacy of Palbociclib in Chinese breast cancer patients. Moreover, the clinical parameters showed a significant association with the prognosis of HR + /HER2- MBC, and the prognostic models constructed based on these variables also displayed robust predictive power, which could offer more intuitive and convenient references for clinical doctors to formulate follow-up treatment plans. [ABSTRACT FROM AUTHOR]

Approximately 6% of adults worldwide suffer from peripheral artery disease (PAD), primarily caused by atherosclerosis of lower limb arteries. Despite optimal medical care and revascularization, many PAD patients remain symptomatic and progress to critical limb ischemia (CLI) and risk major amputation. Delivery of pro-angiogenic factors as proteins or DNA, stem, or progenitor cells confers vascular regeneration and functional recovery in animal models of CLI, but the effects are not well replicated in patients and no pro-angiogenic biopharmacological procedures are approved in the US, EU, or China. The reasons are unclear, but animal models that do not represent clinical PAD/CLI are implicated. Consequently, it is unclear whether the obstacles to clinical success lie in the toxic biochemical milieu of human CLI, or in procedures that were optimized on inappropriate models. The question is significant because the former case requires abandonment of current strategies, while the latter encourages continued optimization. These issues are discussed in the context of relevant preclinical and clinical data, and it is concluded that preclinical mouse models that include age and atherosclerosis as the only comorbidities that are consistently present and active in clinical trial patients are necessary to predict clinical success. Of the reviewed materials, no biopharmacological procedure that failed in clinical trials had been tested in animal models that included advanced age and atherosclerosis relevant to PAD/CLI. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) exhibits significant geoethnic disparities as reflected by distinct variations in the cancer genome and disease progression. Here, we perform a comprehensive proteogenomic characterization of localized high-risk PCa utilizing paired tumors and nearby tissues from 125 Chinese male patients, with the primary objectives of identifying potential biomarkers, unraveling critical oncogenic events and delineating molecular subtypes with poor prognosis. Our integrated analysis highlights the utility of GOLM1 as a noninvasive serum biomarker. Phosphoproteomics analysis reveals the crucial role of Ser331 phosphorylation on FOXA1 in regulating FOXA1-AR-dependent cistrome. Notably, our proteomic profiling identifies three distinct subtypes, with metabolic immune-desert tumors (S-III) emerging as a particularly aggressive subtype linked to poor prognosis and BCAT2 catabolism-driven PCa progression. In summary, our study provides a comprehensive resource detailing the unique proteomic and phosphoproteomic characteristics of PCa molecular pathogenesis and offering valuable insights for the development of diagnostic and therapeutic strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The monocytes to high-density lipoprotein cholesterol ratio (MHR) has been identified as a potential biomarker for cardiovascular and cerebrovascular diseases. In this population-based cross-sectional study, we explored the relationships among carotid artery disease (CAD), including the presence of carotid atherosclerotic plaque (CAP) and carotid artery intima-media thickness (CIMT), the MHR, and related parameter changes. Methods: This cross-sectional study, Conducted from April to June 2019 in a rural area of Tianjin, involved middle-aged and elderly participants. Based on carotid ultrasound examinations, participants were divided into CAP and non-CAP groups. Logistic regression and Receiver Operating Characteristic (ROC) curve analyses were utilized to assess MHR's predictive value for CAP. Gender-specific analyses were also performed to examine predictive variations. The relationship between CIMT and MHR was evaluated using linear regression. Results: Of the 2109 participants meeting the inclusion criteria, 51.6% were identified with CAP. Multivariate analysis revealed a significant association between MHR and CAP prevalence, (OR, 9.670; 95% CI, 2.359–39.631; P = 0.002), particularly in females (OR, 5.921; 95% CI, 1.823–19.231; P = 0.003), after adjusting for covariates. However, no significant correlation was found between CIMT and MHR when adjusted for other factors. The ROC analysis showed the area under the curve for MHR and CAP to be 0.569 (95% CI: 0.544–0.593; P < 0.001). Conclusions: These findings suggested that it is crucial to enhance early screening and intervention for CAD, specifically focusing on the prevention and progression of CAP, to address the unique health challenges faced by low-income groups in rural settings. Emphasizing these preventive measures could significantly contribute to improving cardiovascular health outcomes in this vulnerable population. [ABSTRACT FROM AUTHOR]

Introduction: Body measurement traits are integral in cattle production, serving as pivotal criteria for breeding selection. Wenshan cattle, a local breed in China’s Yunnan province, exhibit remarkable genetic diversity. However, the molecular mechanisms regulating body measurement traits in Wenshan cattle remain unexplored. Methods: In this study, we performed a genome-wide association method to identify genetic architecture for body height body length hip height back height (BAH), waist height and ischial tuberosity height using the Bovine 50 K single nucleotide polymorphism Array in 1060 Wenshan cattles. Results: This analysis reveals 8 significant SNPs identified through the mixed linear model (MLM), with 6 SNPs are associated with multiple traits and 4 SNPs are associated with all 6 traits. Furthermore, we pinpoint 21 candidate genes located in proximity to or within these significant SNPs. Among them, Scarb1, acetoacetyl-CoA synthetase and HIVEP3 were implicated in bone formation and rarely encountered in livestock body measurement traits, emerge as potential candidate genes regulating body measurement traits in Wenshan cattle. Discussion: This investigation provides valuable insights into the genetic mechanisms underpinning body measurement traits in this unique cattle breed, paving the way for further research in this domain. [ABSTRACT FROM AUTHOR]

Pig growth involves multiple genes and coordinated regulatory mechanisms. The large Diqing Tibetan pigs (TPs) are a unique plateau pig breed in China. Data on the mechanisms of muscle growth and development in TPs are limited, and its transcriptional regulation mechanism remains unclear. This study identifies important genes and proteins involved in muscle growth in TPs. We obtained transcriptomic and proteomic data from the longissimus dorsi muscle tissues of TPs and Duroc pigs (DPs) via RNA-seq and isobaric tags for relative and absolute quantitation analyses, respectively. Comparative analyses of TPs and DPs yielded 557 differentially expressed genes (DEGs) and 56 differentially abundant proteins (DAPs). Functional annotation of these DEGs and DAPs was enriched in metabolic processes, metabolic pathways, cytoskeletal protein binding, AMPK signaling pathway, insulin signaling pathway, PPAR signaling pathway, and other related pathways. Ten genes were identified as key candidate regulators (FASN, PPARG, PCK1, ACTA2, TXN, SNU13, APOA1, ATP8, ALDH2, and IGFN1) that may play important roles in the muscle growth traits of TPs. This study provides a reference for analyzing the genetic regulation mechanism underlying muscle growth in pigs and improving the meat yield of TPs via molecular marker-assisted selection. [ABSTRACT FROM AUTHOR]

Background: In China, individuals diagnosed with esophageal cancer are confronted with an elevated risk of nutritional inadequacy or malnutrition throughout the course of their disease, a condition that contributes to various adverse clinical outcomes. A vast corpus of data are burgeoning at an unprecedented rate, primarily due to the revolutionary growth of digitalization technologies and artificial intelligence, notably within the domains of health care and medicine. The purpose of this investigation is to initiate the development of a nutritional screening and assessment indicator framework for patients with esophageal cancer within the Chinese context. We seek to furnish an instrumental reference to facilitate preparations for the forthcoming era of advanced, "deep," evidence‐based medicine. Methods: An integrative methodology was employed to forge the preliminary draft of the nutritional screening and assessment indicator system for preoperative patients with esophageal cancer. This encompassed a rigorous literature survey, in‐depth clinical practice investigation, and the facilitation of expert panel discussions. Thereafter, two iterative consultation phases were conducted using the Delphi method in China. The analytic hierarchy process was deployed to ascertain the weighting of each index within the definitive evaluation indicator system. Results: The effective response rates for the dual rounds of expert consultation were 91.7% and 86.4%, with commensurate authority coefficients of 0.97 and 0.91. The Kendall harmony coefficients were ascertained to be 0.19 and 0.14 (p < 0.01), respectively. The culminating nutritional screening and assessment indicator system for patients with esophageal cancer comprised 5 primary‐level indicators and 38 secondary‐level indicators. Conclusions: The nutritional screening and assessment indicator system contrived for patients with esophageal cancer is underpinned by cogent theoretical principles, leverages an astute research methodology, and manifests dependable outcomes. This system may be appositely utilized as a meaningful reference for the nutritional screening and assessment process in patients afflicted with esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: The prevalence of obese children in China is increasing, which poses a great challenge to public health. Gut microbes play an important role in human gut health, and changes in gut status are closely related to obesity. However, how gut microbes contribute to obesity in children remains unclear. In our study, we performed shotgun metagenomic sequencing of feces from 23 obese children, 8 overweight children and 22 control children in Chengdu, Sichuan, China. Results: We observed a distinct difference in the gut microbiome of obese children and that of controls. Compared with the controls, bacterial pathogen Campylobacter rectus was significantly more abundant in obese children. In addition, functional annotation of microbial genes revealed that there might be gut inflammation in obese children. The guts of overweight children might belong to the transition state between obese and control children due to a gradient in relative abundance of differentially abundant species. Finally, we compared the gut metagenomes of obese Chinese children and obese Mexican children and found that Trichuris trichiura was significantly more abundant in the guts of obese Mexican children. Conclusions: Our results contribute to understanding the changes in the species and function of intestinal microbes in obese Chinese children. [ABSTRACT FROM AUTHOR]

Background: Breast cancer, the most prevalent malignancy in women worldwide, presents diverse onset patterns and genetic backgrounds. This study aims to examine the genetic landscape and clinical implications of rare mutations in Chinese breast cancer patients. Methods: Clinical data from 253 patients, including sporadic and familial cases, were analyzed. Comprehensive genomic profiling was performed, categorizing identified rare variants according to the American College of Medical Genetics (ACMG) guidelines. In silico protein modeling was used to analyze potentially pathogenic variants' impact on protein structure and function. Results: We detected 421 rare variants across patients. The most frequently mutated genes were ALK (22.2%), BARD1 (15.6%), and BRCA2 (15.0%). ACMG classification identified 7% of patients harboring Pathogenic/Likely Pathogenic (P/LP) variants, with one case displaying a pathogenic BRCA1 mutation linked to triple-negative breast cancer (TNBC). Also identified were two pathogenic MUTYH variants, previously associated with colon cancer but increasingly implicated in breast cancer. Variants of uncertain significance (VUS) were identified in 112 patients, with PTEN c.C804A showing the highest frequency. The role of these variants in sporadic breast cancer oncogenesis was suggested. In-depth exploration of previously unreported variants led to the identification of three potential pathogenic variants: ATM c.C8573T, MSH3 c.A2723T, and CDKN1C c.C221T. Their predicted impact on protein structure and stability suggests a functional role in cancer development. Conclusion: This study reveals a comprehensive overview of the genetic variants landscape in Chinese breast cancer patients, highlighting the prevalence and potential implications of rare variants. We emphasize the value of comprehensive genomic profiling in breast cancer management and the necessity of continuous research into understanding the functional impacts of these variants. [ABSTRACT FROM AUTHOR]

Straw return (SR) plus nitrogen (N) fertilizer has become a practical field management mode to improve soil fertility and crop yield in North China. This study aims to explore the relationship among organic waste, mineral nutrient utilization, and crop yield under SRN mode. The fertilizer treatments included unfertilized (CK), SR (straws from wheat and corn), N fertilizer (N), and SR plus N fertilizer (SRN). SRN treatment not only significantly increased the grain yield, net photosynthetic rate, and transpiration rate but also enhanced the contents of chlorophyll, soluble sugar, and soluble protein and increased the activities of antioxidant enzymes but reduced intercellular CO2 concentration and malondialdehyde (MDA) content when compared to other treatments. There were 2572, 1258, and 3395 differentially expressed genes (DEGs) identified from the paired comparisons of SRvsCK, NvsCK, and SRNvsCK, respectively. The transcript levels of many promising genes involved in the transport and assimilation of potassium, phosphate, and nitrogen, as well as the metabolisms of sugar, lipid, and protein, were down-regulated by straw returning under N treatment. SRN treatment maintained the maximum maize grain yield by regulating a series of genes' expressions to reduce nutrient shortage stress and to enhance the photosynthesis of ear leaves at the maize grain filling stage. This study would deepen the understanding of complex molecular mechanisms among organic waste, mineral nutrient utilization, crop yield, and quality. [ABSTRACT FROM AUTHOR]

Lonicerae Japonicae Caulis is the aboveground stem part of the Lonicera Japonica Thunb, which belongs to the medicine food homology species in China. It has the effects of clearing away heat, toxic material, dredging wind and unblocking collaterals. Modern research shows that it contains various active metabolites and a wide range of pharmacological effects, which is of great research and clinical application value. It mainly contains organic acids, volatile oils, flavonoids, triterpenes, triterpene saponins and other active metabolites. Its pharmacological effects mainly include anti-inflammatory, antibacterial, antitumor, antioxidant, and repairing bone and soft tissue. Based on the literature reports in recent years, the active metabolites, pharmacological effects and mechanisms of Lonicerae Japonicae Caulis were sorted out and summarized. It lays a foundation for explaining the efficacy material basis and application value of Lonicerae Japonicae Caulis. It aims to provide a reference for the in-depth research, development and utilization of Lonicerae Japonicae Caulis. [ABSTRACT FROM AUTHOR]

Coronary artery spasm (CAS) is one of the mechanisms of angina pectoris. Unlike the diagnosis of acute myocardial infarction which is based on the elevation of cardiac markers, the diagnosis of CAS is difficult and sometimes requires sophisticated and risky provocative test which is not widely accepted in China. There is no well-established biomarker for the diagnosis or prediction of CAS. However, there are some biomarkers proven to be associated with the occurrence of CAS. For example, inflammatory factors including C-reactive protein and cytokines, lipoprotein (a), and cystatin-C might be precipitating factor for CAS. Rho-kinase as a mediator involved in multiple mechanisms of CAS, serotonin, and endothelin-1 as powerful vasoconstrictors leading to vasospasm were all observed being elevated in patients with CAS. Thioredoxin and nitrotyrosine reflected the oxidative status and could be observed to be elevated after the occurrence of CAS. In some cases doubted to be CAS without the evidence of provocative test, the blood test for the biomarkers mentioned above could be useful for the diagnosis of CAS. [ABSTRACT FROM AUTHOR]

Cordycepin is an efficient component of Cordyceps spp, a traditional Chinese medicine widely used for healthcare in China, and has been recently acted as a strong anticancer agent for clinic. However, whether and how it may play a role in combating tuberculosis, caused by Mycobacterium tuberculosis, remains unknown. Here we report that cordycepin can kill Mycobacterium by hijacking the bacterial adenosine kinase (AdoK), a purine salvage enzyme responsible for the phosphorylation of adenosine (Ado) to adenosine monophosphate (AMP). We show that cordycepin is a poor AdoK substrate but it competitively inhibits the catalytic activity of AdoK for adenosine phosphorylation. Cordycepin does not affect the activity of the human adenosine kinase (hAdoK), whereas hAdoK phosphorylates cordycepin to produce a new monophosphate derivative. Co-use of cordycepin and deoxycoformycin, an inhibitor of adenosine deaminase (ADD), more efficiently kills M. bovis and M. tuberculosis. The add-deleted mycobacterium is more sensitive to cordycepin. This study characterized cordycepin as a new mycobactericidal compound and also uncovered a potential anti-mycobacterial mechanism. [ABSTRACT FROM AUTHOR]

Targeted therapy with Bruton tyrosine kinase (BTK) inhibitors have revolutionized the treatment of patients with various B-cell malignancies. BTK inhibitors such as ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib have shown good clinical efficacy and better safety profiles than those of traditional chemotherapy and chemoimmunotherapy regimens. Multiple studies on new BTK inhibitors are ongoing, which may provide more therapeutic options for the treatment of B-cell malignancies. Considering the unmet need of evidence on BTK inhibitors in all clinical settings and to standardize the use of BTK inhibitors available in mainland China, Taiwan, Hong Kong, and Macau regions, this consensus has been formulated for the treatment of various B-cell malignancies based on the clinical practice and available evidences on the use of BTK inhibitors. The recommendations of this consensus will provide guidance to physicians and clinical researchers on the effective treatment of B-cell malignancies with BTK inhibitors. [ABSTRACT FROM AUTHOR]