Integrated Computational Pipeline for the High-Throughput Discovery of Cell Adhesion Peptides.

Cell adhesion peptides (CAPs) often play a critical role in tissue engineering research. However, the discovery of novel CAPs for diverse applications remains a challenging and time-intensive process. This study presents an efficient computational pipeline integrating sequence embeddings, binding predictors, and molecular dynamics simulations to expedite the discovery of new CAPs. A Pro2vec model, trained on vast CAP data sets, was built to identify RGD-similar tripeptide candidates. These candidates were further evaluated for their binding affinity with integrin receptors using the Mutabind2 machine learning model. Additionally, molecular dynamics simulations were applied to model receptor-peptide interactions and calculate their binding free energies, providing a quantitative assessment of the binding strength for further screening. The resulting peptide demonstrated performance comparable to that of RGD in endothelial cell adhesion and spreading experimental assays, validating the efficacy of the integrated computational pipeline.

Self-assembly mechanism, physicochemical analyses and application performance investigations of branched alkyl glycosides with alcohol ether carboxylic acids of varied epoxide numbers.

Green surfactants, specifically alkyl glycosides and fatty alcohol ether carboxylic acids, are known for their biocompatibility, multiresponsiveness, and versatile applications, garnering significant attention in the realms of green and colloid chemistry. This study systematically investigated the mechanism underlying micelle formation within aqueous solutions comprising alcohol ether carboxylic acids featuring diverse EO group chain quantities (AEC-nH, where n equals 5, 7, and 9) and branched alkyl glycosides (IG). The elucidation of these mechanisms sheds light on their prospective application properties. It was observed that the self-assembly of micelles in these hybrid systems is predominantly influenced by hydrogen bonding, electrostatic interactions, and hydrophobic forces. The spherical-rod morphology of the micelles responds to the varying numbers of EO group chains, with an increased number of EO leading to the formation of rod-like micelles, which exhibit relative instability, while a decreased number of EO results in the formation of spherical micelles with relative stability. Additionally, by means of kinetic analysis, it was determined that the micelle formation process of the three hybrid systems is driven by enthalpy, and a mixed diffusion-kinetics adsorption mechanism is involved in the adsorption process. These findings significantly impact their application properties. This report stands as the first exploration of the synergistic mechanisms and application performance of two types of green surfactants in aqueous solutions, considering the influence of different numbers of EO group chains. Not only does it provide fundamental insights into their properties, but it also offers novel perspectives on the applications of green surface activation.

Life-course adiposity and severe liver disease: a Mendelian randomization analysis.

OBJECTIVE: There is little evidence on the genetic associations between life-course adiposity (including birth weight, childhood BMI, and adulthood BMI) and severe liver disease (SLD; including cirrhosis and liver cancer). The current study aimed to examine and contrast these associations. METHODS: Genetic variants were obtained from genome-wide association studies. Two-sample Mendelian randomization (MR) analyses were performed to assess the genetic associations of life-course adiposity with SLD and liver biomarkers. Cox regression was used to estimate adjusted hazard ratios for SLD associated with genetic risk scores of life-course adiposity and adulthood weight change in the China Kadoorie Biobank. RESULTS: In observational analyses, genetic predispositions to childhood adiposity and adulthood adiposity were each associated with SLD. There was a U-shaped association between adulthood weight change and risk of SLD. In meta-analyses of MR results, genetically predicted 1-standard deviation increase in birth weight was inversely associated with SLD at a marginal significance (odds ratio: 0.81 [95% CI: 0.65-1.00]), whereas genetically predicted 1-standard deviation higher childhood BMI and adulthood BMI were positively associated with SLD (odds ratio: 1.27 [95% CI: 1.05-1.55] and 1.79 [95% CI: 1.59-2.01], respectively). The results of liver biomarkers mirrored those of SLD. CONCLUSIONS: The current study provided genetic evidence on the associations between life-course adiposity and SLD.

Post-infectious inflammatory response syndrome in an HIV-negative patient after Cryptococcus gattii meningoencephalitis: a case report and review of the literature.

BACKGROUND: Cryptococcal meningitis (CM) is an inflammatory mycosis of the central nervous system caused by meninge infection or brain parenchyma with Cryptococcus species. It is associated with high morbidity and mortality, and patients with acquired immune deficiency syndrome are particularly susceptible. There have been increasing reports of CM in HIV-negative patients in China over the last few years. CASE PRESENTATION: A 31-year-old healthy Chinese male presented with fever and gradually developed headache, projectile vomiting, and other manifestations that were later confirmed as Cryptococcus gattii meningoencephalitis. However, multiple disease changes occurred during the course of treatment, and the regimen was accordingly modified after the diagnosis of post-infectious inflammatory response syndrome (PIIRS). The patient eventually recovered. CONCLUSION: There has been a growing trend in the incidence of C. gattii meningoencephalitis in HIV-negative patients. It shows rapid onset and severe prognosis. This case report can provide a reference to treat PIIRS following CM in HIV-negative patients.

The Antimicrobial, Hemostatic, and Anti-Adhesion Effects of a Peptide Hydrogel Constructed by the All-d-Enantiomer of Antimicrobial Peptide Jelleine-1.

Peptide hydrogels are believed to be potential biomaterials with wide application in the biomedical field because of their good biocompatibility, injectability, and 3D printability. Most of the previously reported polypeptide hydrogels are composed of l-peptides, while the hydrogels formed by self-assembly of d-peptides are rarely reported. Herein, a peptide hydrogel constructed by D-J-1, which is the all-d-enantiomer of antimicrobial peptide Jelleine-1 (J-1) is reported. Field emission scanning electron microscope (FE-SEM) and rheologic study are performed to characterize the hydrogel. Antimicrobial, hemostatic, and anti-adhesion studies are carried out to evaluate its biofunction. The results show that D-J-1 hydrogel is formed by self-assembly and cross-linking driven by hydrogen bonding, hydrophobic interaction, and π-π stacking force of aromatic ring in the structure of D-J-1. It exhibits promising antimicrobial activity, hemostatic activity, and anti-adhesion efficiency in a rat sidewall defect-cecum abrasion model. In addition, it also exhibits good biocompatibility. Notably, D-J-1 hydrogel shows improved in vitro and in vivo stability when compared with its l-enantiomer J-1 hydrogel. Therefore, the present study will provide new insight into the application of d-peptide hydrogel, and provides a new peptide hydrogel with antibacterial, hemostatic, and anti-adhesion efficacy for clinical use.

Longitudinal Association of DNA Methylation With Type 2 Diabetes and Glycemic Traits: A 5-Year Cross-Lagged Twin Study.

Investigators of previous cross-sectional epigenome-wide association studies (EWAS) in adults have reported hundreds of 5'-cytosine-phosphate-guanine-3' (CpG) sites associated with type 2 diabetes mellitus (T2DM) and glycemic traits. However, the results from EWAS have been inconsistent, and longitudinal observations of these associations are scarce. Furthermore, few studies have investigated whether DNA methylation (DNAm) could be modified by smoking, drinking, and glycemic traits, which have broad impacts on genome-wide DNAm and result in altering the risk of T2DM. Twin studies provide a valuable tool for epigenetic studies, as twins are naturally matched for genetic information. In this study, we conducted a systematic literature search in PubMed and Embase for EWAS, and 214, 33, and 117 candidate CpG sites were selected for T2DM, HbA1c, and fasting blood glucose (FBG). Based on 1,070 twins from the Chinese National Twin Registry, 67, 17, and 16 CpG sites from previous studies were validated for T2DM, HbA1c, and FBG. Longitudinal review and blood sampling for phenotypic information and DNAm were conducted twice in 2013 and 2018 for 308 twins. A cross-lagged analysis was performed to examine the temporal relationship between DNAm and T2DM or glycemic traits in the longitudinal data. A total of 11 significant paths from T2DM to subsequent DNAm and 15 paths from DNAm to subsequent T2DM were detected, suggesting both directions of associations. For glycemic traits, we detected 17 cross-lagged associations from baseline glycemic traits to subsequent DNAm, and none were from the other cross-lagged direction, indicating that CpG sites may be the consequences, not the causes, of glycemic traits. Finally, a longitudinal mediation analysis was performed to explore the mediation effects of DNAm on the associations of smoking, drinking, and glycemic traits with T2DM. No significant mediations of DNAm in the associations linking smoking and drinking with T2DM were found. In contrast, our study suggested a potential role of DNAm of cg19693031, cg00574958, and cg04816311 in mediating the effect of altered glycemic traits on T2DM.

Fabrication of hexagonal boron carbonitride nanoplates using for in vitro photodynamic therapy and chemo therapy.

Carbon nanomaterials and boron nitride nanomaterials have been proved to be very potential for biomedical applications. However, as an analog of them, boron carbonitride nanomaterials are rarely reported in biomedical field. In this study, the fabrication of visible light-responsive boron carbonitride nanoplates (BCNNPs) and their application in photodynamic therapy and chemo therapy were demonstrated. BCNNPs with an average size of 46 nm were fabricated via hydrogen peroxide treatment from bulk BCN. Cytotoxicity tests showed that the as-prepared BCNNPs are biocompatible and have no cytotoxicity to human breast cancer cells and human hepatocyte carcinoma cells. After conjunction with doxorubicin and folic acid, the BCNNPs were adopted as a targeted drug carrier, presenting pH-responsive release and tumor-targeting property for chemo therapy. Moreover, under certain intensity of visible light irradiation (45 mW/cm2), the BCNNPs can generate reactive oxygen species including superoxide radical, hydroxyl radical and singlet oxygen, so that synergistic photodynamic/chemo therapy effects were achieved. This work may be a groundbreaking discovery for utilizing BCNNPs as photosensitizer for photodynamic therapy and drug carrier for chemo therapy.

Clinical significance of interleukin-10 concentration in the cerebrospinal fluid of patients with primary central nervous system lymphoma.

The diagnostic and prognostic evaluation of primary central nervous system lymphoma (PCNSL) is challenging due to the lack of sensitive biomarkers. The present study aimed to evaluate the value of interleukin (IL)-10 in this context. Between October 2016 and December 2018, 91 patients with suspected intracranial neoplasms were recruited, and the concentrations of IL-10 or IL-6 in both the cerebrospinal fluid (CSF) and blood were measured and analyzed by the Kruskal-Wallis test. The correlation between CSF IL-6 or IL-10 levels and tumor size was determined by Spearman's coefficient analysis. The receiver operating characteristic curve was used to evaluate the diagnostic value of CSF IL-6 and IL-10 levels. Median progression-free survival (PFS) and overall survival time were calculated using Kaplan-Meier survival analysis. Among the 91 patients, 3 were diagnosed with PCNSL on the basis of neuroimaging data and CSF IL-10 levels. A total of 35 cases were verified to show diffuse large B-cell lymphoma on histological assessment, 17 of which were diagnosed as PCNSL by MRI. The median PFS and OS were 8.00 months [95% confidence interval (CI), 3.94-12.06) and 17.5 months (95% CI, 11.55-23.45) respectively in the 12 PNCSL cases with regular follow up. The diagnostic efficiency of serum IL-6 levels was lower than that of serum IL-10 levels (P=0.030), which, in turn, was lower than that of CSF IL-10 levels (P<0.001). The decline and increase in CSF IL-10 levels was concurrent with improvement and deterioration in manifestation, respectively, which predated the MRI variation. High CSF IL-10 levels indicated low Karnofsky performance scale scores and shortened PFS times. CSF IL-10 levels higher than 1,000 pg/ml signified disease progression. CSF IL-10 levels could be a sensitive biomarker guiding the differential diagnosis, early recurrence detection, prognostic evaluation and therapeutic strategy establishment in cases of PCNSL.

Establishment of reference intervals for serum [-2]proPSA (p2PSA), %p2PSA and prostate health index in healthy men.

BACKGROUND: Prostate cancer (PCa) is the second most common cancer among men worldwide. Recent research has identified [-2]proPSA (p2PSA), %p2PSA and prostate health index (phi) as new biomarkers for the early diagnosis and grading of PCa. However, few studies have used these parameters in a healthy population. In this study, we aimed to establish reference intervals (RIs) for p2PSA, %p2PSA and phi in healthy men based on age stratification. METHODS: Between April 2016 and March 2018, healthy subjects were recruited. Healthy men were then stratified into four age groups: <40 years, 40-49 years, 50-59 years and ≥60 years. Total PSA (tPSA), free PSA (fPSA), %fPSA, p2PSA, %p2PSA and phi were measured and RIs were established for p2PSA, %p2PSA and phi. RESULTS: In total, 732 healthy men were used for analysis. The RIs of phi were 9.77-48.44 for <40 years of age, 9.85-65.28 for 40-49 years of age, 9.98-39.72 for 50-59 years of age and 8.16-40.76 for ≥60 years of age. The reference values at the age of 40-49 years were generally higher than those at ≥60 years of age. CONCLUSIONS: Age-specific RIs for p2PSA, %p2PSA and phi were established in this study. This first set of established RIs will be invaluable for physicians to make precise medical decisions and carry out appropriate medical interventions.

Effect of CXCL12/CXCR4 on migration of decidua-derived mesenchymal stem cells from pregnancies with preeclampsia.

PROBLEM: Systemic immuno-inflammatory response caused by maternal immune imbalance is central to the pathogenesis of preeclampsia (PE). We hypothesized that changes in the number of decidual mesenchymal stem cells (dMSCs) may be associated with maternal immune imbalance. We aimed to evaluate the expression of CXCL12/CXCR4 axis in patients with PE and its influence on the migration behavior of dMSCs, to further clarify the pathogenesis of PE. METHOD OF STUDY: Fourteen women with PE and 11 controls were included. DMSCs were extracted from decidual tissue by type II collagenase digestion and adherence. ELISA and immunohistochemistry analysis were used to measure serum and tissue levels of CXCL12. Q-PCR and Western blotting were used to detect CXCR4 expression on dMSCs, whereas transwell assay was used to measure the migration ability of dMSCs. RESULTS: Decidual mesenchymal stem cells from women with PE showed higher expressions of CXCR4 and HIF-1α than the dMSCs of controls did. Tissues from women with PE showed the highest CXCL12 levels in the decidua, followed by the placenta and umbilical cord, whereas tissues from controls showed the highest CXCL2 levels in the umbilical cord, followed by the placenta and decidua. dMSCs from women with PE showed possibly higher migration ability than that of dMSCs from controls, under the induction of CXCL12, whereas dMSCs showed a decreasing trend in hypoxic than in normoxic environment. CONCLUSION: Decidual mesenchymal stem cells from women with PE can migrate to the decidua layer with the concentration gradient of CXCL12, which may play a role in the occurrence and development of PE.

Risk factors of surgical site infection in geriatric orthopedic surgery: A retrospective multicenter cohort study.

AIM: As we are experiencing the progressive aging of our population, risk management of geriatric orthopedic patients is extremely important. The present study was carried out to identify independent predictors of surgical site infection and to better define the threshold value of serum albumin on postoperative wound infection in older patients. METHODS: This retrospective multicenter study was carried out from January 2015 to June in 2017. A total of 3378 older patients (aged ≥60 years) were enrolled. We extracted the patients' demographics, characteristics of disease, treatment-related variables and indexes of laboratory examination. Receiver operating characteristic analysis was carried out to find the optimum cut-off value for serum albumin. Univariate and multivariate logistic analysis models were carried out, respectively, to determine independent predictors of surgical site infection. RESULTS: A total of 123 patients developed wound infection in the present study. Surgical site infection prolonged hospitalization of patients by a mean of 14.2 days. The overall incidence was 3.64%, with 0.47% for deep infection and 3.16% for superficial infection. Independent predictors of surgical site infection identified by multivariate analysis were traumatic injury (odds ratio 12.42, 95% CI 6.80-22.12; P = 0.000), serum albumin <32.6 g/L (odds ratio 2.54, 95% CI 1.22-5.29; P = 0.013) and American Society of Anesthesiologists physical status index class 3 or higher (odds ratio 2.14, 95% CI = 1.24-3.69; P = 0.006). CONCLUSIONS: We recommend that surgeons evaluate the nutritional status of older patients and optimize the perioperative strategy of supplementary nutrition support to reduce the risk of postoperative wound infection. Geriatr Gerontol Int 2019; 19: 213-217.

[Clinical analysis of curative resection with hemihepatectomy for advanced hilar cholangiocarcinoma].

OBJECTIVE: To investigate the superiority of curative resection with hemihepatectomy in treatment of hilar cholangiocarcinoma and the strategy to lower the incidence of complications and mortality. METHODS: The clinical data of 50 patients with hilar cholangiocarcinoma who underwent surgical procedures in Peking University School of Oncology from January 1998 to May 2006 were retrospectively analyzed. RESULTS: Forty-one patients (56.9%) underwent surgical resection. Twenty-two (53.6%) received a radical operation (RO). Thirty patients underwent preoperative percutaneous transhepatic cholangio-drainage (PTCD) to reduce the jaundice. Curative resection with hemihepatectomy was performed on 19 cases including 14 cases undergoing RO. Two patients who had undergone hemihepatectomy died of liver failure. The postoperative morbidity rate was 62% in all 50 cases, 78% in the hemihepatectomy group. The 1- and 2-year survival rates of the hemihepatectomy group were 57.1% and 27.3% respectively. CONCLUSION: Curative resection with hemihepatectomy is a safe and effective option for hilar cholangiocarcinoma, especially for Bismuth III or IV type. Preoperative biliary drainage is necessary before a major hepatic resection.