Chinese Healthcare Workers' Knowledge, Attitudes, and Practices in Diabetic Kidney Management: A Multi-Centered Cross-Sectional Study.

Background: Given the importance of diabetic kidney disease (DKD) management, this study aims to explore the knowledge, attitudes, and practices in disease management demonstrated by healthcare workers from the nephrology department. Materials and Methods: This study is a multi-centered cross-sectional study, and adopts snowball sampling, with 530 healthcare workers being recruited to complete a questionnaire covering areas such as demographic characteristics, knowledge, attitude, and practices (KAP) of DKD management. This data was analyzed using descriptive statistics and binary logistics analysis. Results: In this study, 530 healthcare workers were studied, including 94 doctors and 436 nurses. The participants were mainly from general tertiary hospitals in 14 provinces. For Chinese nurse, the results indicate that both poor knowledge level (Odds Ratio (OR) =0.63, 95% Confidence Interval (CI): 0.42-0.94) and having experience in further medical training in nephrology (OR=1.92, 95% CI: 1.20-3.08) are associated with the practice levels. For Chinese doctors, having not experience in further medical training in nephrology (OR=0.36, 95% CI: 0.15-0.83) are associated with their practice levels. Conclusion: In summary, Chinese doctors and nurses in this study showed positive attitudes towards DKD management, but their knowledge and practical skills were lacking. This underscores a notable gap in achieving optimal DKD care. Notably, nurses' knowledge influenced their management practices, and additional nephrology training correlated with better engagement. To improve patient care, enhancing nephrology healthcare professional training and addressing knowledge-practice disparities are recommended.

Development and Validation of a Risk Prediction Model for Female Stress Urinary Incontinence in Rural Fujian, China.

Purpose: With China's rapidly aging population and the rising proportion of obese people, an increase in the number of women suffering from urinary incontinence (UI) is to be expected. In order to identify high-risk groups before leakage occurs, we aimed to develop and validate a model to predict the risk of stress UI (SUI) in rural women. Patients and methods: This study included women aged 20-70 years in rural Fujian who participated in an epidemiologic survey of female UI conducted between June and October 2022. Subsequently the data was randomly divided into training and validation sets in a ratio of 7:3. Univariate and multivariate logistic regression analyses were used to identify independent risk factors as well as to further construct a nomogram for risk prediction. Finally, concordance index (C-index), calibration curve and decision curve analysis were applied to evaluate the performance of the predictive models. Results: A total of 5290 rural females were enrolled, of whom 771 (14.6%) had SUI. Age, body mass index (BMI), postmenopausal status, number of vaginal deliveries, vaginal delivery of large infant, constipation and family history of pelvic organ prolapse (POP) and SUI were included in the nomogram. C-index of this prediction model for the training and validation sets was 0.835 (95% confidence interval [CI] = 0.818-0.851) and 0.829 (95% CI = 0.796-0.858), respectively, and the calibration curves and decision analysis curves for both the training and validation sets showed that the model was well-calibrated and had a positive net benefit. Conclusion: This model accurately estimated the SUI risk of rural women in Fujian, which may serve as an effective primary screening tool for the early identification of SUI risk and provide a basis for further implementation of individualized early intervention. Moreover, the model is concise and intuitive, which makes it more operational for rural women with scarce medical resources.

Cultivated Enterococcus faecium B6 from children with obesity promotes nonalcoholic fatty liver disease by the bioactive metabolite tyramine.

Gut microbiota plays an essential role in nonalcoholic fatty liver disease (NAFLD). However, the contribution of individual bacterial strains and their metabolites to childhood NAFLD pathogenesis remains poorly understood. Herein, the critical bacteria in children with obesity accompanied by NAFLD were identified by microbiome analysis. Bacteria abundant in the NAFLD group were systematically assessed for their lipogenic effects. The underlying mechanisms and microbial-derived metabolites in NAFLD pathogenesis were investigated using multi-omics and LC-MS/MS analysis. The roles of the crucial metabolite in NAFLD were validated in vitro and in vivo as well as in an additional cohort. The results showed that Enterococcus spp. was enriched in children with obesity and NAFLD. The patient-derived Enterococcus faecium B6 (E. faecium B6) significantly contributed to NAFLD symptoms in mice. E. faecium B6 produced a crucial bioactive metabolite, tyramine, which probably activated PPAR-γ, leading to lipid accumulation, inflammation, and fibrosis in the liver. Moreover, these findings were successfully validated in an additional cohort. This pioneering study elucidated the important functions of cultivated E. faecium B6 and its bioactive metabolite (tyramine) in exacerbating NAFLD. These findings advance the comprehensive understanding of NAFLD pathogenesis and provide new insights for the development of microbe/metabolite-based therapeutic strategies.

Barley Protein LFBEP-C1 from Lactiplantibacillus plantarum dy-1 Fermented Barley Extracts by Inhibiting Lipid Accumulation in a Caenorhabditis elegans Model.

Objective: This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans (C. elegans). Methods: In this study, the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C. elegans. The worms were fed Escherichia coli OP50 ( E. coli OP50), glucose, and different concentrations of LFBEP-C1. Body size, lifespan, movement, triglyceride content, and gene expression were analyzed. The results were analyzed using ANOVA and Tukey's multiple comparison test. Results: Compared with the model group, the head-swing frequency of C. elegans in the group of LFBEP-C1 at 20 µg/mL increased by 33.88%, and the body-bending frequency increased by 27.09%. This indicated that LFBEP-C1 improved the locomotive ability of C. elegans. The average lifespan of C. elegans reached 13.55 days, and the body length and width of the C. elegans decreased after LFBEP-C1 intake. Additionally, LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels. The expression levels of sbp-1, daf-2, and mdt-15 significantly decreased, while those of daf-16, tph-1, mod-1, and ser-4 significantly increased after LFBEP-C1 intake. Changes in these genes explain the signaling pathways that regulate lipid metabolism. Conclusion: LFBEP-C1 significantly reduced lipid deposition in C. elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development, lifespan, and exercise behavior of C. elegans. In addition, LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein, insulin, and 5-hydroxytryptamine signaling pathways.

Predictive potential of preoperative Naples prognostic score-based nomogram model for the prognosis in surgical resected thoracic esophageal squamous cell carcinoma patients: A retrospective cohort study.

The present study aimed to establish an effective prognostic nomogram model based on the Naples prognostic score (NPS) for resectable thoracic esophageal squamous cell carcinoma (ESCC). A total of 277 patients with ESCC, who underwent standard curative esophagectomy and designated as study cohort, were retrospectively analyzed. The patients were divided into different groups, including NPS 0, NPS 1, NPS 2, and NPS 3 or 4 groups, for further analysis, and the results were validated in an external cohort of 122 ESCC patients, who underwent surgery at another cancer center. In our multivariate analysis of the study cohort showed that the tumor-node-metastasis (TNM) stage, systemic inflammation score, and NPS were the independent prognostic factors for the overall survival (OS) and progression-free survival (PFS) durations. In addition, the differential grade was also an independent prognostic factor for the OS in the patients with ESCC after surgery (all P < .05). The area under the curve of receiver operator characteristics for the PFS and OS prediction with systemic inflammation score and NPS were 0.735 (95% confidence interval [CI] 0.676-0.795, P < .001) and 0.835 (95% CI 0.786-0.884, P < .001), and 0.734 (95% CI 0.675-0.793, P < .001) and 0.851 (95% CI 0.805-0.896, P < .001), respectively. The above independent predictors for OS or PFS were all selected in the nomogram model. The concordance indices (C-indices) of the nomogram models for predicting OS and PFS were 0.718 (95% CI 0.681-0.755) and 0.669 (95% CI 0.633-0.705), respectively, which were higher than that of the 7th edition of American Joint Committee on Cancer TNM staging system [C-index 0.598 (95% CI 0.558-0.638) for OS and 0.586 (95% CI 0.546-0.626) for PFS]. The calibration curves for predicting the 5-year OS or PFS showed a good agreement between the prediction by nomogram and actual observation. In the external validation cohort, the nomogram discrimination for OS was better than that of the 7th edition of TNM staging systems [C-index: 0.697 (95% CI 0.639-0.755) vs 0.644 (95% CI 0.589-0.699)]. The calibration curves showed good consistency in predicting the 5-year survival between the actual observation and nomogram predictions. The decision curve also showed a higher potential of the clinical application of predicting the 5-years OS of the proposed nomogram model as compared to that of the 7th edition of TNM staging systems. The preoperative NPS-based nomogram model had a certain potential role for predicting the prognosis of ESCC patients.

High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma.

Protein phosphatase 1 catalytic subunit gamma (PPP1CC) promotes DNA repair and tumor development and progression, however, its underlying mechanisms remain unclear. This study investigated the molecular mechanism of PPP1CC's involvement in DNA repair and the potential clinical implications. High expression of PPP1CC was significantly correlated with radioresistance and poor prognosis in human nasopharyngeal carcinoma (NPC) patients. The mechanistic study revealed that PPP1CC bound to Ku70/Ku80 heterodimers and activated DNA-PKcs by promoting DNA-PK holoenzyme formation, which enhanced nonhomologous end junction (NHEJ) -mediated DNA repair and led to radioresistance. Importantly, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) interacted with PPP1CC to enhance its stability by removing the K48-linked polyubiquitin chain at Lys234 to prevent PPP1CC degradation. Therefore, BRCC3 helped the overexpressed PPP1CC to maintain its high protein level, thereby sustaining the elevation of DNA repair capacity and radioresistance. Our study identified the molecular mechanism by which PPP1CC promotes NHEJ-mediated DNA repair and radioresistance, suggesting that the BRCC3-PPP1CC-Ku70 axis is a potential therapeutic target to improve the efficacy of radiotherapy.

P2X7 receptor is essential for ST36-attenuated cardiac fibrosis upon beta-adrenergic insult.

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1ß, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

Heterologous expression and enzymatic characteristics of sulfatase from Lactobacillus plantarum dy-1.

Barley, rich in bioactive components including dietary fiber, polyphenolic compounds and functional proteins, exhibits health benefits such as regulating glucose and lipid metabolism. Previous studies have found that the content and composition of free phenolic acids in barley may be significantly changed by fermentation with the laboratory patented strain Lactobacillus plantarum dy-1 (L. p dy-1), but the mechanism of enzymatic release of phenolic acid remains to be elucidated. Based on this, this study aimed to identify the key enzyme in L. p dy-1 responsible for releasing the bound phenolic acid and to further analyze its enzymatic properties. The Carbohydrate-Active enZYmes database revealed that L. p dy-1 encodes 7 types of auxiliary enzymes, among which we have identified a membrane sulfatase. The enzyme gene LPMS05445 was heterologous to that expressed in E. coli, and a recombinant strain was induced to produce the target protein and purified. The molecular weight of the purified enzyme was about 59.9 kDa, with 578.21 U mg-1 enzyme activity. The optimal temperature and pH for LPMS05445 expression were 40 °C and 7.0, respectively. Furthermore, enzymatic hydrolysis by LPMS05445 can obviously change the surface microstructure of dietary fiber from barley bran and enhance the release of bound phenolic acid, thereby increasing the free phenolic acid content and improving its physiological function. In conclusion, sulfatase produced by Lactobacillus plantarum dy-1 plays a key role in releasing bound phenolic acids during the fermentation of barley.

Interfacial OOH* mediated Fe(II) regeneration on the single atom Co-N-C catalyst for efficient Fenton-like processes.

Fe(II) regeneration is decisive for highly efficient H2O2-based Fenton-like processes, but the role of cobalt-containing reactive sites in promoting Fe(II) regeneration was overlooked. Herein, a single atom Co-N-C catalyst was employed in Fe(II)/H2O2 system to promote the degradation of diverse organic contaminants. The EPR and quenching experiments indicated Co-N-C significantly enhanced the generation of superoxide species, and accelerated hydroxyl radical generation for pollutant degradation. The electrochemical and surface composition analyses demonstrated the enhanced H2O2 activation and Fe(III)/Fe(II) recycling on the catalyst. Furthermore, in-situ Raman characterization with shell-isolated gold nanoparticles was employed to visualize the interfacial reactive intermediates and their time-resolved interaction. The accumulation of interfacial CoOOH* was confirmed when Co-N-C activated H2O2 alone, but it rapidly transformed into FeOOH* upon Fe(II) addition. Besides, the temporal variation of OOH* intermediates and the relative intensity of Co(III)-O and Co(IV)=O peaks depicted the dynamic interaction of reactive intermediates along the H2O2 consumption. With this basis, we proposed a mechanism of interfacial OOH* mediated Fe(II) regeneration, which overcame the kinetical limitation of Fe(II)/H2O2 system. Therefore, this study provided a primary effort to elucidate the overlooked role of interfacial CoOOH* in the Fenton-like processes, which may inspire the design of more efficient catalysts.

Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Association between lactate dehydrogenase and the risk of diabetic kidney disease in patients with type 2 diabetes.

Objective: This study aims to investigate the association between lactate dehydrogenase (LDH) and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Methods: The study enrolled patients with diagnosis of T2D between 2009 and 2018 from the National Nutrition and Health Examination Survey (NHANES) database. Demographic information, laboratory test, and diagnostic data were collected. Restricted cubic spline (RCS) plots were used to assess the dose-effect relationship between LDH levels and the risk of DKD in patients with T2D. Based on LDH levels, individuals were divided into higher and lower groups using dichotomy, and multivariate logistic regression analysis was conducted to explore the relationship between different LDH levels and the risk of DKD in T2D patients. Stratified analysis was performed to assess the consistency of the result. Results: A total of 4888 patients were included in the study, with 2976 (60.9%) patients without DKD and 1912 (39.1%) patients with DKD. RCS plots showed that the risk of DKD increased with increasing LDH levels. Multifactorial logistic regression analysis revealed that T2D patients with higher LDH levels had a 45% increased risk of DKD compared to those with lower LDH levels (OR=1.45; 95% CI: 1.11-1.89). Furthermore, each standard deviation increase in LDH level was associated with a 24% increase in DKD incidence among T2D patients (OR=1.24; 95% CI: 1.07-1.44). Stratified analysis consistently supported these findings. Conclusions: LDH can serve as a valuable biomarker for screening DKD in patients with T2D.

Eukaryotic translation initiation factor EIF4G1 p.Ser637Cys mutation in a family with Parkinson's disease with antecedent essential tremor.

Essential tremor (ET) and Parkinson's disease (PD) are common chronic movement disorders that can cause a substantial degree of disability. However, the etiology underlying these two conditions remains poorly understood. In the present study, Whole-exome sequencing of peripheral blood samples from the proband and Sanger sequencing of the other 18 family members, and pedigree analysis of four generations of 29 individuals with both ET and PD in a nonconsanguineous Chinese family were performed. Specifically, family members who had available medical information, including historical documentation and physical examination records, were included. A novel c.1909A>T (p.Ser637Cys) missense mutation was identified in the eukaryotic translation initiation factor 4γ1 (EIF4G1) gene as the candidate likely responsible for both conditions. In total, 9 family members exhibited tremor of the bilateral upper limbs and/or head starting from ages of ≥40 years, 3 of whom began showing evidence of PD in their 70s. Eukaryotic initiation factor 4 (eIF4)G1, a component of the translation initiation complex eIF4F, serves as a scaffold protein that interacts with many initiation factors and then binds to the 40S ribosomal subunit. The EIF4G1 (p.Ser637Cys) might inhibit the recruitment of the mRNA to the ribosome. In conclusion, the results from the present study suggested that EIF4G1 may be responsible for the hereditary PD with 'antecedent ET' reported in the family assessed.

Community integration and its predictors in people with stroke: a multicenter longitudinal study.

OBJECTIVE: To investigate the community integration of patients following stroke and determine the predictors of their level of community integration at 1-year follow-up. DESIGN: A multicenter, longitudinal, and observational study. SUBJECTS: Sixty-five inpatients (41 men) with a mean age of 56.9 (standard deviation = 17.0) years, who had their first stroke at least 1 month prior to this study were recruited from 4 rehabilitation inpatient wards in China. METHODS: In the initial assessment, the participants were evaluated using the Community Integration Questionnaire, the Fugl-Meyer Assessment, the Berg Balance Scale, the Modified Barthel Index, the Mini Mental State Examination, and the Modified Ashworth Scale. In the follow-up assessments, which were conducted via telephone no less than 1 year after discharge, the participants were evaluated using the Community Integration Questionnaire and also assessed for other disease-related conditions. RESULTS: The participants' scores on the Community Integration Questionnaire in the follow-up assessment were significantly greater than those at the initial assessment (p < 0.05). In addition, the participants' Community Integration Questionnaire scores in the follow-up assessment were significantly correlated with their ages, numbers of years of education, and Modified Barthel Index, Berg Balance Scale, Mini Mental State Examination scores in the initial assessment (p < 0.05), and marginally significantly correlated with their scores on Fugl-Meyer Assessment in the initial assessment (p = 0.058). The participants' ages, numbers of years of education, and Modified Barthel Index, Berg Balance Scale, Mini Mental State Examination, Fugl-Meyer Assessment of the lower extremity, and Fugl-Meyer Assessment scores in the initial assessment were predictive of their Community Integration Questionnaire scores at follow-up, with coefficients of determination ranging from 0.254 to 0.056 (p < 0.05). CONCLUSIONS: The level of community integration of the participants was generally low, but it was greater at 1-year follow-up than it was initially. Balance function and daily living ability may be key predictors of community integration of patients following stroke.

Stem Cells and Bone Tissue Engineering.

Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard for restoring function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in the incorporation with the host bone as well as its cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells that are delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells, including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells, urine-derived stem cells, stem cells from apical papilla, and induced pluripotent stem cells, for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles that are delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hoped that in the future, these preclinical results will translate into new regenerative therapies for bone defect repair.

Efficacy and Tolerability of a Scutellaria lateriflora L. and Cistus × incanus L.-Based Chewing Gum on the Symptoms of Gingivitis: A Monocentric, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Preclinical studies have shown that the combination of Cistus × incanus L. and Scutellaria lateriflora L. extracts exerts beneficial effects on oral health against gingivitis. Thus, this study aimed to assess the tolerability of a chewing gum and its efficacy on gingivitis in a double-blind, placebo-controlled clinical trial. Enrolled subjects (n = 60, 18-70 years) were randomized to receive two chewing gums or a placebo daily for 3 months. At baseline (t0) and monthly (t1, t2, and t3) timepoints, the Quantitative Gingival Bleeding Index (QGBI), the Modified Gingival Index (MGI), and the Oral Health 15 items (OH-15)] were employed to assess potential improvements in gingivitis. Pain was self-quantified via the Visual Analogue Scale (VAS), and the Clinical Global Impression Scale for Severity of illness (CGI-S) helped in evaluating the oral general conditions. This study is listed on the ISRCTN registry. At t3, the QGBI, MGI, OH-15, VAS, and CGI-S values decreased in the treated but not in the placebo group (ß = 0.6 ± 0.1, t176 = 3.680, p < 0.001; ß = 0.87 ± 0.21, t115 = 4.263, p < 0.001; ß = 5.3 ± 2.5, t172 = 2.086, p = 0.038; ß = 3.16 ± 0.51, t88 = 6.253, p < 0.001; and ß = 1.09 ± 0.32, t83 = 3.419, p < 0.001, respectively). A significant improvement in gingival health occurred after a 3-month intervention with the chewing gums containing S. lateriflora and C. incanus extracts.

Changes in the structural, physicochemical and functional properties and in vitro fecal fermentation characteristics of barley dietary fiber fermented by Lactiplantibacillus plantarum dy-1.

Fermentation is an effective method for improving the nutritional quality and functional characteristics of grains. This study investigated changes in the structural, physicochemical, and functional properties of fermented barley dietary fiber (FBDF) exerted by Lactiplantibacillus plantarum dy-1 (Lp. plantarum dy-1) as well as its in vitro fecal fermentation characteristics. Lp. plantarum dy-1 fermentation remarkably changed the structure of FBDF, including the microstructure and monosaccharide components, correlating with improved water or oil retaining and cholesterol adsorption capacities. Additionally, Lp. plantarum dy-1 fermentation significantly (p < 0.05) promoted the release of bound phenolics from 6.24 mg g-1 to 6.93 mg g-1 during in vitro digestion, contributing to the higher antioxidant capacity and inhibitory activity of α-amylase and pancreatic lipase compared with those of raw barley dietary fiber (RBDF). A total of 14 phenolic compounds were detected in the supernatants of digestion and fermentation samples. During colonic fermentation, FBDF significantly increased the production of acetate, propionate, and butyrate (p < 0.05), inhibited the growth of Escherichia-Shigella, and promoted the abundance of SCFA-producing microbiota such as Faecalibacterium and Prevotella_9. In conclusion, Lp. plantarum dy-1 fermentation enhanced the physicochemical properties and in vitro fermentation characteristics of barley dietary fiber, representing a promising bioprocessing technology for modifying barley bran.

Bacillus cereus G2 alleviate salt stress in Glycyrrhiza uralensis Fisch. by balancing the downstream branches of phenylpropanoids and activating flavonoid biosynthesis.

The salinity environment is one of the biggest threats to Glycyrrhiza uralensis Fisch. (G. uralensis) growth, resulting from the oxidative stress caused by excess reactive oxygen species (ROS). Flavonoids are the main pharmacodynamic composition and help maintain ROS homeostasis and mitigate oxidative damage in G. uralensis in the salinity environment. To investigate whether endophytic Bacillus cereus G2 can improve the salt-tolerance of G. uralensis through controlling flavonoid biosynthesis, the transcriptomic and physiological analysis of G. uralensis treated by G2 in the saline environment was conducted, focused on flavonoid biosynthesis-related pathways. Results uncovered that salinity inhibited flavonoids synthesis by decreasing the activities of phenylalanine ammonialyase (PAL) and 4-coumarate-CoA ligase (4CL) (42% and 39%, respectively) due to down-regulated gene Glyur000910s00020578 at substrate level, and then decreasing the activities of chalcone isomerase (CHI) and chalcone synthase (CHS) activities (50% and 42%, respectively) due to down-regulated genes Glyur006062s00044203 and Glyur000051s00003431, further decreasing isoliquiritigenin content by 53%. However, salt stress increased liquiritin content by 43%, which might be a protective mechanism of salt-treated G. uralensis seedlings. Interestingly, G2 enhanced PAL activity by 27% whereas reduced trans-cinnamate 4-monooxygenase (C4H) activity by 43% which could inhibit lignin biosynthesis but promote flavonoid biosynthesis of salt-treated G. uralensis at the substrate level. G2 decreased shikimate O-hydroxycinnamoyltransferase (HCT) activity by 35%, increased CHS activity by 54% through up-regulating the gene Glyur000051s00003431 encoding CHS, and increased CHI activity by 72%, thereby decreasing lignin (34%) and liquiritin (24%) content, but increasing isoliquiritigenin content (35%), which could mitigate oxidative damage and changed salt-tolerance mechanism of G. uralensis.

A causality-inspired generalized model for automated pancreatic cancer diagnosis.

Pancreatic cancer (PC) is a severely malignant cancer variant with high mortality. Since PC has no obvious symptoms, most PC patients are belatedly diagnosed at advanced disease stages. Recently, artificial intelligence (AI) approaches have demonstrated promising prospects for early diagnosis of pancreatic cancer. However, certain non-causal factors (such as intensity and texture appearance variations, also called confounders) tend to induce spurious correlation with PC diagnosis. This undermines the generalization performance and the clinical applicability of the AI-based PC diagnosis approaches. Therefore, we propose a causal intervention based automated method for pancreatic cancer diagnosis with contrast-enhanced computerized tomography (CT) images, where a confounding effects reduction scheme is developed for alleviating spurious correlations to achieve unbiased learning, thereby improving the generalization performance. Specifically, a continuous image generation strategy was developed to simulate wide variations of intensity differences caused by imaging heterogeneities, where Monte Carlo sampling is added to further enhance the continuity of simulated images. Then, to enhance the pancreatic texture variability, a texture diversification method was introduced in conjunction with gradient-based data augmentation. Finally, a causal intervention strategy was proposed to alleviate the adverse confounding effects by decoupling the causal and non-causal factors and combining them randomly. Extensive experiments showed remarkable diagnosis performance on a cross-validation dataset. Also, promising generalization performance with an average accuracy of 0.87 was attained on three independent test sets of a total of 782 subjects. Therefore, the proposed method shows high clinical feasibility and applicability for pancreatic cancer diagnosis.

Directed osteogenic differentiation of human bone marrow mesenchymal stem cells via sustained release of BMP4 from PBVHx-based nanoparticles.

Bone Morphogenetic Protein 4 (BMP4) is crucial for bone and cartilage tissue regeneration, essential in medical tissue engineering, cosmetology, and aerospace. However, its cost and degradation susceptibility pose significant clinical challenges. To enhance its osteogenic activity while reducing dosage and administration frequency, we developed a novel long-acting BMP4 delivery system using poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx) nanoparticles with soybean lecithin-modified BMP4 (sBP-NPs). These nanoparticles promote directed osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) through sustained BMP4 release. sBP-NPs exhibited uniform size (100-200 nm) and surface charges, with higher BMP4 entrapment efficiency (82.63 %) compared to controls. After an initial burst release within 24 h, sBP-NPs achieved 80 % cumulative BMP4 release within 20 days, maintaining levels better than control BP-NPs with unmodified BMP4. Co-incubation and nanoparticle uptake experiments confirmed excellent biocompatibility of sBP-NPs, promoting hBMSC differentiation towards osteogenic lineage with increased expression of type I collagen, calcium deposition, and ALP activity (> 20,000 U/g protein) compared to controls. Moreover, hBMSCs treated with sBP-NPs exhibited heightened expression of osteogenic genetic markers, surpassing control groups. Hence, this innovative strategy of sustained BMP4 release from sBP-NPs holds potential to revolutionize bone regeneration in minimally invasive surgery, medical cosmetology or space environments.