Posttranslational modification dramatically enhances protein complexity, but the function and precise mechanism of novel lysine acylation modifications remain unknown. Chemoresistance remains a daunting challenge to successful treatment. We found that lysine butyrylation (Kbu) is specifically upregulated in chemoresistant tumor cells and tissues. By integrating butyrylome profiling and gain/loss-of-function experiments, lysine 754 in HSP90 (HSP90 K754) was identified as a substrate for Kbu. Kbu modification leads to overexpression of HSP90 in esophageal squamous cell carcinoma (ESCC) and its further increase in relapse samples. Upregulation of HSP90 contributes to 5-FU resistance and can predict poor prognosis in cancer patients. Mechanistically, HSP90 K754 is regulated by the cooperation of KAT8 and HDAC11 as the writer and eraser, respectively; SDCBP increases the Kbu level and stability of HSP90 by binding competitively to HDAC11. Furthermore, SDCBP blockade with the lead compound V020-9974 can target HSP90 K754 to overcome 5-FU resistance, constituting a potential therapeutic strategy.

The snap bean is the most commonly grown vegetable legume worldwide, and its pod size is both an important yield and appearance quality trait. However, the improvement of pod size in snap beans grown in China has been largely hindered by a lack of information on the specific genes that determine pod size. In this study, we identified 88 snap bean accessions and evaluated their pod size traits. Through a genome-wide association study (GWAS), 57 single nucleotide polymorphisms (SNPs) significantly associated with pod size were detected. Candidate gene analysis showed that cytochrome P450 family genes, WRKY, and MYB transcription factors were the predominant candidate genes for pod development, and eight of these 26 candidate genes showed relatively higher expression patterns in flowers and young pods. A significant pod length (PL) SNP and a single pod weight (SPW) SNP were successfully converted into kompetitive allele-specific polymerase chain reaction (KASP) markers and validated in the panel. These results enhance our understanding of the genetic basis of pod size, and also provide genetic resources for the molecular breeding of pod size in snap beans.

PurposeTo determine the role of Lactobacillus strains and their combinations in inhibiting the colonization of H. pylori and gastric mucosa inflammation.MethodsHuman gastric adenocarcinoma AGS cells were incubated with H. pylori and six probiotic strains (Lactobacillus acidophilus NCFM, L. acidophilus La-14, Lactiplantibacillus plantarum Lp-115, Lacticaseibacillus paracasei Lpc-37, Lacticaseibacillus rhamnosus Lr-32, and L. rhamnosus GG) and the adhesion ability of H. pylori in different combinations was evaluated by fluorescence microscopy and urease activity assay. Male C57BL/6 mice were randomly divided into five groups (uninfected, H. pylori, H. pylori+NCFM, H. pylori+Lp-115, and H. pylori+NCFM+Lp-115) and treated with two lactobacilli strains (NCFM and Lp-115) for six weeks. H. pylori colonization and tissue inflammation statuses were determined by rapid urease test, Hematoxylin-Eosin (HE) staining, immunohistochemistry, and qRT-PCR and ELISA.ResultsL. acidophilus NCFM, L. acidophilus La-14, L. plantarum Lp-115, L. paracasei Lpc-37, L. rhamnosus Lr-32, and L. rhamnosus GG reduced H. pylori adhesion and inflammation caused by H. pylori infection in AGS cells and mice. Among all probiotics L. acidophilus NCFM and L. plantarum, Lp-115 showed significant effects on the H. pylori eradication and reduction of inflammation in-vitro and in-vivo. Compared with the H. pylori infection group, the mRNA and protein expression levels of IL-8 and TNF-α in the six Lactobacillus intervention groups were significantly reduced. The changes in the urease activity (ureA and ureB) for 1-7h in each group showed that L. acidophilus NCFM, L. acidophilus La-14, L. plantarum Lp-115, and L. rhamnosus GG effectively reduced the colonization of H. pylori. We observed a higher ratio of lymphocyte and plasma cell infiltration into the lamina propria of the gastric mucosa and neutrophil infiltration in H. pylori+NCFM+Lp-115 mice. The infiltration of inflammatory cells in lamina propria of the gastric mucosa was reduced in the H. pylori+NCFM+Lp-115 group. Additionally, the expression of IFN-γ was decreased significantly in the NCFM and Lp-115 treated C57BL/6 mice.ConclusionsL. acidophilus NCFM and L. plantarum Lp-115 can reduce the adhesion of H. pylori and inhibit the gastric inflammatory response caused by H. pylori infection.

BackgroundAlthough interleukin-2 (IL-2) has long been associated with cancer development, its roles in the development of cervical cancer remains unclear. Few studies examined the associations between IL-2 and high-risk human papillomavirus (HPV) with risk of cervical intraepithelial neoplasia (CIN).ObjectiveWe aimed to assess the association of IL-2 and high-risk HPV infection with risk of CIN as well as their interactions on the risk of CIN.DesignWe performed a cross-sectional analysis of screening data in 2285 women aged 19-65 years who participated in an ongoing community-based cohort of 40,000 women in Shanxi, China in 2014-2015. Both categorical and spline analyses were used to evaluation the association between IL-2 in the local vaginal fluids and prevalence of CIN. In addition, 1503 controls were followed up until January 31, 2019), the nested case-control study design was adopted to evaluate the association of vaginal lavage IL-2 levels and the risk of CIN progression.ResultsAfter adjusting for potential confounders, IL-2 levels were statistically inversely associated with prevalence of CIN (the 1st versus 4th quartile IL-2 levels: the respective odds ratio [OR] and 95% confidence intervals [CI] was: = 1.75 [1.37, 2.23] for CIN, 1.32 [1.01, 1.73] for CIN I, and 3.53 [2.26, 5.52] for CIN II/III). Increased IL-2 levels were inversely associated with prevalence of CIN (P-overall<0.01, P-nonlinearity<0.01 for CIN; P-overall<0.01, P-nonlinearity = 0.01 for CIN I; P-overall <0.01, P-nonlinearity = 0.62 for CIN II/III). The highest prevalence of CIN was observed in women with high-risk HPV, who also had the lowest IL-2 levels (P-interaction < 0.01). Nested case-control study observed an inverse association between IL-2 levels and risk of CIN progression (OR=3.43, [1.17, 10.03]).ConclusionsIL-2 levels in the local vaginal fluids were inversely associated with the risk of CIN in Chinese women either with or without high-risk HPV infection.

Hypocalcemic cardiomyopathy is a rare etiology of heart failure. It is considered highly reversible with a relatively favorable prognosis. This case reports a 52-year-old housewife diagnosed with hypocalcemic cardiomyopathy who presented with acute decompensated heart failure and hypocalcemia symptoms with a history of thyroidectomy. Shortness of breath and edema were relieved after diuresis and prompt electrolyte correction. The left ventricular ejection fraction increased from 27% to 53%, and the left ventricular end-diastolic dimension shortened from 58 to 50 mm in echocardiographic re-examinations, while repeat cardiac magnetic resonance imaging revealed evidence of non-reversible cardiac fibrosis after 1-year follow-up. Cardioprotective agents with close follow-ups were called for in this entity of patients.

BackgroundPOD places a heavy burden on the healthcare system as the number of elderly people undergoing surgery is increasing annually because of the aging population. As a large country with a severely aging population, China's elderly population has reached 267 million. There has been no summary analysis of the pooled incidence of POD in the elderly Chinese population.MethodsSystematic search databases included PubMed, Web of Science, EMBASE, Cochrane Library Databases, China Knowledge Resource Integrated Database (CNKI), Chinese Biomedical Database (CBM), WanFang Database, and Chinese Science and Technology Periodicals (VIP). The retrieval time ranged from the database's establishment to February 8, 2023. The pooled incidence of delirium after non-cardiac surgery was calculated using a random effects model. Meta-regression, subgroup, and sensitivity analyses were used to explore the source of heterogeneity.ResultsA total of 52 studies met the inclusion criteria, involving 18,410 participants. The pooled incidence of delirium after non-cardiac surgery in the elderly Chinese population was 18.6% (95% CI: 16.4–20.8%). The meta-regression results revealed anesthesia method and year of publication as a source of heterogeneity. In the subgroup analysis, the gender subgroup revealed a POD incidence of 19.6% (95% CI: 16.9–22.3%) in males and 18.3% (95% CI: 15.7–20.9%) in females. The year of publication subgroup analysis revealed a POD incidence of 20.3% (95% CI: 17.4–23.3%) after 2018 and 14.6 (95% CI: 11.6–17.6%) in 2018 and before. In the subgroup of surgical types, the incidence of hip fracture surgery POD was 20.7% (95% CI: 17.6–24.3%), the incidence of non-cardiac surgery POD was 18.4% (95% CI: 11.8–25.1%), the incidence of orthopedic surgery POD was 16.6% (95% CI: 11.8–21.5%), the incidence of abdominal neoplasms surgery POD was 14.3% (95% CI: 7.6–21.1%); the incidence of abdominal surgery POD was 13.9% (95% CI: 6.4–21.4%). The anesthesia methods subgroup revealed a POD incidence of 21.5% (95% CI: 17.9–25.1%) for general anesthesia, 15.0% (95% CI: 10.6–19.3%) for intraspinal anesthesia, and 8.3% (95% CI: 10.6–19.3%) for regional anesthesia. The measurement tool subgroup revealed a POD incidence of 19.3% (95% CI: 16.7–21.9%) with CAM and 16.8% (95% CI: 12.6–21.0%) with DSM. The sample size subgroup revealed a POD incidence of 19.4% (95% CI: 16.8–22.1%) for patients ≤ 500 and 15.3% (95% CI: 11.0–19.7%) for patients > 500. The sensitivity analysis suggested that the pooled incidence of postoperative delirium in this study was stable.ConclusionOur systematic review of the incidence of delirium after non-cardiac surgery in elderly Chinese patients revealed a high incidence of postoperative delirium. Except for cardiac surgery, the incidence of postoperative delirium was higher for hip fracture surgery than for other types of surgery. However, this finding must be further explored in future large-sample studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: PROSPERO CRD42023397883.