SARS-CoV-2 spike protein antibody titers after the fourth dose of BNT162b2 vaccine among Japanese patients undergoing hemodialysis: a single-center study.

Patients undergoing hemodialysis are particularly vulnerable to severe outcomes of SARS-CoV-2 infection, with mortality rates higher than that of the general population. Vaccination reduces the risk of adverse outcomes, with booster doses being particularly beneficial. However, limited data are available on the effectiveness of subsequent vaccinations or their effect on increasing antibody levels. This single-center study aimed to investigate changes in SARS-CoV-2 IgG antibody titers following the fourth vaccination among 28 patients undergoing hemodialysis. Blood tests were conducted at various intervals post-vaccination, with a focus on identifying factors associated with antibody levels. The IgG antibody levels rapidly increased by Day 7 post-vaccination, with a median time to peak of 11 days. Antibody titers tended to be higher in male patients than in female patients. This study sheds light on the immune response to the fourth vaccination in patients undergoing hemodialysis. As this study included a small sample size, with a short observation period, further research is warranted to comprehensively understand the effectiveness of vaccination and the benefits of additional doses of vaccine.

Dahuang Zhechong Pill Improves Pulmonary Fibrosis through miR-29b-2-5p/HK2 Mediated Glycolysis Pathway.

OBJECTIVE: To explore the preventive and therapeutic effects of Dahuang Zhechong Pill (DZP) on pulmonary fibrosis and the underlying mechanisms. METHODS: The first key rate-limiting enzyme hexokinase 2 (HK2) of glycolysis was silenced and over-expressed through small interfering RNA and lentivirus using lung fibroblast MRC-5 cell line, respectively. The cell viability, migration, invasion and proliferation were detected by cell counting kit-8, wound healing assay, transwell assay, and flow cytometry. The mRNA and protein expression levels of HK2 were detected by RT-PCR and Western blotting, respectively. The contents of glucose, adenosine triphosphate (ATP) and lactate in MRC-5 cells were determined by enzyme-linked immunosorbnent assay (ELISA). Then, the relationship between miR-29b-2-5p and HK2 was explored by luciferase reporter gene assay. Pulmonary fibrosis cell model was induced by transforming growth factor-ß 1 (TGF-ß 1) in MRC-5 cells, and the medicated serum of DZP (DMS) was prepared in rats. MRC-5 cells were divided into control, TGF-ß 1, TGF-ß 1+10% DMS, TGF-ß 1+10% DMS+miR-29b-2-5p inhibitor, TGF-ß 1+10% DMS+inhibitor negative control, TGF-ß 1+10% DMS+miR-29b-2-5p mimic and TGF-ß 1+10% DMS+mimic negative control groups. After miR-29b-2-5p mimics and inhibitors were transfected into MRC-5 cells, all groups except control and model group were treated with DMS. The effect of DMS on MRC-5 cells were detected using aforementioned methods and immunofluorescence. Similarly, the contents of glucose, ATP and lactate in each group were measured by ELISA. RESULTS: The mRNA and protein expressions of HK2 in MRC-5 cells were successfully silenced and overexpressed through si-HK2-3 and lentiviral transfection, respectively. After silencing HK2, the mRNA and protein expressions of HK2 were significantly decreased (P<0.01), and the concentrations of glucose, ATP and lactate were also significantly decreased (P<0.05). The proliferation, migration and invasion of MRC-5 cells were significantly declined (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly increased (P<0.01). After overexpressing HK2, the mRNA and protein expressions of HK2 were significantly increased (P<0.05), and the concentrations of glucose, ATP and lactate were also significantly increased (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were significantly increased (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly decreased (P<0.05). The relative luciferase activity of 3'UTR-WT+hsa-miR-29b-2-5p transfected with HK2 was significantly decreased (P<0.01). After miR-29b-2-5p mimic and inhibitor were transfected into the MRC-5 cells, DMS intervention could significantly reduce the concentration of glucose, ATP and lactate, and the mRNA and proteins expressions of HK2, phosphofructokinase and pyruvate kinase isoform M2 (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were alleviated (P<0.05 or P<0.01), and the deposition of fibronectin, α-smooth muscle actin, and collagen I were significantly decreased (P<0.05 or P<0.01). CONCLUSIONS: Glycolysis is closely related to pulmonary fibrosis. DZP reduced glycolysis and inhibited fibroblasts' excessive differentiation and abnormal collagen deposition through the miR-29b-2-5p/HK2 pathway, which played a role in delaying the process of pulmonary fibrosis.

The descriptive epidemiology of adverse events following two doses of mRNA COVID-19 vaccination in Curaçao, the Caribbean.

BACKGROUND: BNT162b2 and mRNA-1273 COVID-19 vaccines have been used for mass vaccinations in Curaçao, the Caribbean but information on adverse events (AEs)in this population is unavailable. This study describes the characteristics of vaccinees that incurred AEs, explores the associations between AEs by vaccine and doses, and estimates the rate of AEs. METHODS: Vaccination and AEs data for all persons of age 5 years (range 5-105 years) and older who received two doses of COVID-19 vaccine at 71 centres in Curaçao between February 24, 2021, and April 5, 2023, were included in this retrospective observational study. RESULTS: The vaccines differed significantly in the frequency distribution of vaccinees by age, age groups, sex, AEs, and prior COVID-19 infection. Occurrence of AEs was strongly associated with mRNA vaccine brand, sex, number of doses, but not with age, age group, and prior COVID-19 infection. Of 209,720 doses, 84 persons (0.04%) incurred AEs following two doses of mRNA vaccines (overall rate of 40.1 per 100,000 persons (95% CI 32.4-49.6). AEs were also significantly higher in females compared to males.AE rates associated with BNT162b2, and mRNA-1273 vaccines were low, but BNT162b2 vaccinees incurred substantially significantly higher AE rates (58.3 per 100,000 persons, 95% CI 45.4-74.9) than mRNA-1273 vaccinees (21.9 per 100,000 persons, 95% CI 14.6-32.8). mRNA-1273 vaccine was associated with a significantly lower risk of AEs. CONCLUSIONS: AE reporting varied by age, sex, and vaccine used as well as the number of doses. Future studies with follow-up and longer-term reporting of AEs should be conducted.

Expression and significance of CEMIP and CYP11B2 in serum in women with foetal growth restriction.

BACKGROUND: Foetal growth restriction (FGR) occurs when a foetus fails to reach its growth potential. This observational study assessed the expression and significance of cell migration-including protein (CEMIP) and aldosterone synthase (CYP11B2) in the serum of pregnant women with FGR. METHODS: 40 singleton FGR-suffered pregnant women, as well as 40 normal singleton pregnant women, were enrolled. The expression of CEMIP and CYP11B2 in serum was detected in early pregnancy. The correlations between parameters were evaluated. The predictive variables for FGR were determined. The diagnostic value of CEMIP and CYP11B2 for FGR was analysed. RESULTS: CEMIP and CYP11B2 mRNA expression in the serum of pregnant women with FGR decreased (both P < 0.001). CEMIP (95%CI: 0.802-0.921, P < 0.001) and CYP11B2 (95%CI: 0.795-0.907, P < 0.001) mRNA expression in serum and soluble fms like tyrosine kinase-1 (sFLT1)/placental growth factor (PlGF) ratio (95%CI: 0.866-0.974, P < 0.001) were independent predictors of FGR, and CEMIP (r = -0.578, P = 0.001) and CYP11B2 (r = -0.602, P < 0.001) mRNA expression in serum were negatively correlated with sFLT1/PlGF ratio. CEMIP (AUC = 0.741) and CYP11B2 (AUC = 0.764) mRNA expression in serum had good diagnostic value for FGR. CONCLUSION: The expression of CEMIP and CYP11B2 is reduced in the serum of pregnant women with FGR and may become new diagnostic markers for FGR.

Foetal growth restriction is the inability of the foetus to reach its growth potential in the uterus due to various factors. This study aimed to investigate the expression and significance of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction. In our study, we found that the expression of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction were decreased. Cell migration-including protein and aldosterone synthase expression was negatively correlated with soluble fms like tyrosine kinase-1/placental growth factor ratio. In addition, the study also found that cell migration-including protein and aldosterone synthase expression in serum had good diagnostic value for foetal growth restriction.

Early Postoperative Functional Recovery in Older Patients With Periprosthetic Femoral Fractures: Comparison Between Cemented and Cementless Stem Revisions.

Background: Early postoperative functional recovery is important in older patients with lower-extremity fractures to prevent disuse, and periprosthetic femoral fractures (PFFs) are no exception. This study aimed to compare the postoperative functional recovery in the early phase after revision for PFF with loose stems between cemented and cementless stems. Methods: Eighteen patients with Unified Classification System type B2 PFF were included in this retrospective cohort study with a follow-up period of about 2 years. All patients underwent stem revision and were divided into 2 groups: the cemented stem group (n = 9) and the cementless stem group (n = 9). In postrevision, functional independence measure score, independent walk rate, activities of daily living recovery rate to the original level at 2 weeks postoperatively, the Beals and Tower classification for radiological status, and survival rate for readmission as endpoints were compared between the 2 groups. Results: Patients in the cemented group recovered functional mobility earlier than in the cementless group, with higher postoperative functional independence measure functional subscale values (73 vs 50 points, P = .02), higher independent walk rate (89 vs 11%, P < .01), and more postoperative activities of daily living recovery (100% vs 44%, P = .03) at 2 weeks postoperatively. The Beals and Tower classification and survival rates were similar in both groups. Conclusions: Revision using a cemented stem for PFF in older patients was a useful surgical procedure in terms of early postoperative functional recovery. Cemented stem revision was comparable with cementless in bone union and safety at 2 years postoperatively.

Fluoride induces hepatointestinal damage and vitamin B2 mitigation by regulating IL-17A and Bifidobacterium in ileum.

INTRODUCTION: Fluorosis is a global public health disease affecting more than 50 countries and 500 million people. Excessive fluoride damages the liver and intestines, yet the mechanisms and therapeutic approaches remain unclear. OBJECTIVES: To explore the mechanisms by which fluoride-induced intestinal-hepatic damage and vitamin B2 alleviation. METHODS: Fluoride and/or vitamin B2-treated IL-17A knockout and wild-type mouse models were established, the morphological and functional changes of liver and gut, total bile acid biosynthesis, metabolism, transport, and regulation of FXR-FGF15 signaling pathways were evaluated, the ileal microbiome was further analyzed by 16S rDNA sequence. Finally, Bifidobacterium supplementation mouse model was designed and re-examined the above indicators. RESULTS: The results demonstrated that fluoride induced hepatointestinal injury and enterohepatic circulation disorder by altering the synthesis, transporters, and FXR-FGF15 pathway regulation of total bile acid. Importantly, the ileum was found to be the most sensitive and fluoride changed ileal microbiome particularly by reducing abundance of Bifidobacterium. While vitamin B2 supplementation attenuated fluoride-induced enterohepatic circulation dysfunction through IL-17A and ileal microbiome, Bifidobacterium supplementation also reversed fluoride-induced hepatointestinal injury. CONCLUSION: Fluoride induces morphological and functional impairment of liver and gut tissues, as well as enterohepatic circulation disorder by altering total bile acid (TBA) synthesis, transporters, and FXR-FGF15 signaling regulation. Vitamin B2 attenuated fluoride-induced enterohepatic circulation disorder through IL-17A knockout and ileal microbiome regulation. The ileum was found to be the most sensitive to fluoride, leading to changes in ileal microbiome, particularly the reduction of Bifidobacterium. Furthermore, Bifidobacterium supplementation reversed fluoride-induced hepatointestinal injury. This study not only elucidates a novel mechanism by which fluoride causes hepatointestinal toxicity, but also provides a new physiological function of vitamin B2, which will be useful in the therapy of fluorosis and other hepatoenterological diseases.

SARS-CoV-2 mRNA vaccine-related myocarditis and pericarditis: An analysis of the Japanese Adverse Drug Event Report database.

BACKGROUND: The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines and myocarditis/pericarditis in the Japanese population has not been systematically investigated. This study was aimed at clarifying the association between SARS-CoV-2 mRNA vaccines (BNT162b2 and mRNA-1273) and myocarditis/pericarditis as well as influencing factors by using the Japanese Adverse Drug Event Report database. METHODS: Reporting odds ratios (RORs) and 95 % confidence intervals (95 % CIs) for the association between the vaccines and myocarditis/pericarditis were calculated using data from the database (April 2004-December 2023). Age, sex, onset time, and outcomes in symptomatic patients were evaluated. RESULTS: The total number of reports was 880,999 (myocarditis: 1846; pericarditis: 761). The adverse events associated with the vaccines included myocarditis (919 cases) and pericarditis (321 cases), with the ROR [95 % CIs] being significant for both (myocarditis: 30.51 [27.82-33.45], pericarditis: 21.99 [19.03-25.40]). Furthermore, the ROR [95 % CIs] of BNT162b2 and mRNA-1273 were 15.64 [14.15-17.28] and 54.23 [48.13-61.10], respectively, for myocarditis, and 15.78 [13.52-18.42] and 27.03 [21.58-33.87], respectively, for pericarditis. Furthermore, most cases were ≤30 years or male. The period from vaccination to onset was ≤8 days, corresponding to early failure type based on analysis using the Weibull distribution. Outcomes were recovery or remission for most cases; however, they were severe or caused death in some cases. CONCLUSION: In the Japanese population, SARS-CoV-2 mRNA vaccination was significantly associated with the onset of myocarditis/pericarditis. The influencing factors included age of ≤30 years and male. Furthermore, although most adverse events occurred early after vaccination, overall outcomes were good.

Acute extensive pulmonary embolism after mRNA SARS-CoV-2 immunization.

COVID-19 vaccines, a cornerstone of the fight against the disease have generally proven to be safe with most commonly reported side effects being mild and self-limiting. Uncommon severe adverse effects like thromboembolism have been reported during postmarketing surveillance. Viral-based vector vaccines have been most commonly implicated in these reports. Our report however portrays a case of a 26-year-old female who developed extensive pulmonary embolism following administration of the Pfizer- BNT162b2 mRNA COVID-19 vaccine. The patient did not have any risk factors for thromboembolism. She was admitted, put on enoxaparin, and given Altaplase thrombolytic therapy. Her condition improved and she was discharged on Apixaban. The Thrombophilia screen performed on the 6-month follow-up was negative and following the resolution of thrombosis, Apixaban was stopped. Our case highlights the importance of continued surveillance of uncommon adverse effects and the need for prompt diagnosis and management of such side effects.

Gene expression of aromatase, SF-1, and HSD17B2 in menstrual blood as noninvasive diagnostic biomarkers for endometriosis.

OBJECTIVE: Endometriosis diagnostic delays are still encountered due to the lack of a reliable, noninvasive diagnostic test. Besides, menstrual blood is a relatively untapped field for diagnostics, yet it provides a readily accessible source for investigating common gynecological conditions. In the present study, we aim to evaluate the expression levels of menstrual blood aromatase, SF-1, and HSD17B2 from women with and without endometriosis and their diagnostic performance. METHODS: A total of 40 subjects participated in this study, including 20 patients from each endometriosis and non-endometriosis group. The endometriosis group comprised patients with proven endometriosis confirmed by pathological diagnosis and pelvic ultrasound examination, then requiring endometrial biopsy determined by the clinicians. The non-endometriosis group consisted of women who had primary and secondary infertility and underwent endometrial examination without any visible endometriosis lesion. The menstrual blood and eutopic endometrial tissue of enrolled subjects were collected, and the relative expression of the genes was performed by quantitative real-time polymerase chain reaction (qPCR). ROC curve was used to evaluate the diagnostic efficacy of aromatase, SF-1, and HSD17B2. RESULTS: We found significantly higher expressions of aromatase, SF-1, and HSD17B2 in the menstrual blood of the endometriosis group compared to non-endometriosis (P < 0.05). In contrast, examination of eutopic endometrial tissue of both groups only found significant in HSD17B2 (P < 0.05), while aromatase and SF-1 showed no statistically significant variance. The Area Under Curve (AUC) of aromatase, SF-1, and HSD17B2 in the menstrual blood was 0.977, 0.862, and 0.807, respectively. The optimal cutoff value was determined to be >1.63 (sensitivity = 95 % and specificity = 90 %) for aromatase, >1.71 (sensitivity = 90 % and specificity = 80 %) for SF-1, and >1.83 (sensitivity = 80 % and specificity = 75 %) for HSD17B2. CONCLUSION: Our study showed that aromatase, SF-1, and HSD17B2 in the menstrual blood solidly discriminate between endometriosis and non-endometriosis patients with high diagnostic accuracy. However, further confirmation in larger cohorts is required to validate the reliability of these biomarkers to endometriosis.

Evaluating the role of aldosterone synthesis on adrenal cell fate.

Hypertension affects one-third of the adult population worldwide, with primary aldosteronism (PA) accounting for at least 5-10% of these cases. The aldosterone synthase enzyme (CYP11B2) plays a pivotal role in PA manifestation, as increased expression of CYP11B2 leads to excess aldosterone synthesis. Physiological expression of CYP11B2 in humans is normally limited to cells of the adrenal zona glomerulosa under tight homeostatic regulation. In PA, however, there are CYP11B2-positive lesions in the adrenal cortex that autonomously secrete aldosterone, highlighting the dysregulation of adrenal cortex zonation and function as a key aspect of PA pathogenesis. Thus, this review aims to summarize the development of the adrenal glands, the key regulators of adrenal cortex homeostasis, and the dysregulation of this homeostasis. It also discusses the development of CYP11B2 inhibitors for therapeutic use in patients with hypertension, as well as the current knowledge of the effects of CYP11B2 inhibition on adrenal cortex homeostasis and cell fate. Understanding the control of adrenal cell fate may offer valuable insights into both the pathogenesis of PA and the development of alternative treatment approaches for PA.

Effectiveness of Pfizer Vaccine BNT162b2 Against SARS-CoV-2 in Americans 16 and Older: A Systematic Review.

This systematic review evaluates the efficacy and long-term effectiveness of the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) across diverse clinical and observational settings within the United States in Americans aged 16 and older. We conducted an extensive literature search utilizing various types of studies to assess the vaccine's performance in preventing symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes. Our initial search in PubMed on March 14, 2022, yielded 6,725 potentially relevant articles, with 26 undergoing full-text assessment and eight meeting the inclusion criteria. To incorporate the most up-to-date findings, a secondary search was conducted on July 6, 2024, using improved and refined Medical Subject Headings (MeSH) terms within the PubMed and Scopus databases. This expanded approach resulted in 78 potentially relevant articles from PubMed and 1,567 from Scopus, with 40 articles undergoing full-text assessment and an additional 14 articles meeting the inclusion criteria. Early clinical trials reported initial vaccine effectiveness (VE) up to 95% with sustained immunity in various populations. Observational studies and systematic reviews further confirmed VE above 90% against symptomatic infections and highlighted nearly complete protection against hospitalizations and deaths. Recent research underscores the critical role of booster doses in maintaining high VE, especially against emerging variants, showing restored effectiveness up to 95% and supporting their strategic importance in ongoing pandemic responses. Despite observed waning immunity and breakthrough infections, the BNT162b2 vaccine continues to exhibit robust protection across different demographic groups and under varying epidemiological conditions. Our findings advocate for continuous booster updates and adaptive vaccination strategies to manage emerging SARS-CoV-2 variants, reinforcing the pivotal role of mRNA vaccine technology in addressing global health emergencies.

Monocarbonyl analogs of curcumin C66 and B2BrBC modulate oxidative stress, JNK activity, and pancreatic gene expression in rats with streptozotocin-induced diabetes.

The pathogenesis of type 1 diabetes mellitus (T1DM) involves oxidative stress and inflammation. Curcumin, a natural polyphenolic compound found in turmeric, known to exhibit antioxidative and anti-inflammatory properties, is characterized by poor chemical stability, low bioavailability, and rapid metabolism. Monocarbonyl analogs of curcumin (MACs) with a structural absence of ß-diketone and enhanced stability and bioavailability present a potential solution to the challenges associated with the use of curcumin. This study aimed to evaluate the effect of two MACs, C66 and B2BrBC, on oxidative stress markers, antioxidant enzyme activity, expression of diabetes-associated genes, and signaling pathway proteins in the context of T1DM. Streptozotocin (STZ)-induced male Wistar rats or rat pancreatic RIN-m cells were used for in vivo and in vitro experiments, respectively. C66 or B2BrBC were given either before or after STZ treatment. Oxidative stress markers and antioxidant enzyme activities were determined in various tissues. Expression of diabetes-associated genes was assessed using RT-qPCR, and the activity of signaling pathway proteins in the pancreas was determined through Western blot analysis. Treatment with C66 and B2BrBC significantly reduced oxidative stress markers and positively influenced antioxidant enzyme activities. Moreover, both compounds inhibited JNK activity in the pancreas while enhancing the expression of genes crucial for ß-cell survival and glucose and redox homeostasis. The findings highlight the multifaceted potential of C66 and B2BrBC in ameliorating oxidative stress, influencing gene expression patterns linked to diabetes, and modulating key signaling pathways in the pancreas. The findings suggest that these compounds can potentially address diabetes-related pathological processes.

Antibody responses post-booster COVID-19 vaccination: Insights from a single-center prospective cohort study.

The study aimed to evaluate the effect of booster dose COVID-19 vaccines on prevention and humoral immune response in individuals with different vaccination schemes during the period BA.4 and BA.5 omicron sub-variants were globally dominant. The study included 146 individuals who preferred different vaccination schemes for booster doses. Anti-spike/RBD-IgG and neutralizing antibody levels were measured 28 days after the booster dose vaccination upon their consent. There is no significant difference between median antibody titers detected according to different vaccination schemes. SARS-CoV-2 neutralizing antibody inhibition percentages were detected significantly higher in serum samples before and after the last booster dose in 2 BNT162b2+1 BNT162b2(99.42 %), 2 BNT162b2 + 2 BNT162b2(99.42 %), and 2 BNT162b2 + 3 BNT162b2(99.42 %) vaccination schemes (p = 0.004, p = 0.044, p = 0.002,respectively). The study indicated that a booster vaccination dose provides a high level of protection against severe COVID-19 and death. We think that the variant-specific pancoronavirus vaccines will be necessary to protect against breakthrough infections.

Stem revision vs. internal fixation in Vancouver B2/B3 periprosthetic hip fractures: systematic review and metanalysis.

INTRODUCTION: Vancouver B2 and B3 periprosthetic fractures (PFF) are associated with stem instability and often require a demanding stem implant revision (SR) or internal fixation (ORIF). This latter surgery is increasingly performed in the last few years instead of SR, but it is unclear which is the best treatment to manage PFF patients. The aim of this study is the compare the outcomes of B2/B3 PFF managed by either ORIF or SR, by performing a systematic review and meta-analysis of current literature. MATERIALS AND METHODS: Cochrane Database, PubMed, Google Scholar and MEDLINE were examined to find out relevant publications dealing with the different outcomes of SR vs. ORIF in B2/B3 PFF of the hip. The effect model (EM) was calculated using Cohen´s d index. RESULTS: Fifteen studies were included, reporting on a total of 1629 patients (564 ORIF and 1065 SR). The pooled random EM estimates for reoperation was 0.87 (95% CI, 0.39-1.96; I2 = 78%) in favor of ORIF surgery; EM for complications was 1.01 (95% CI, 0.45-2.27; I2 = 85%) without difference among procedures. The EM for transfusion was 0.72 (95% CI, 0.46-1.12; I2 = 62%) in favor of fixation. CONCLUSION: ORIF and SR were both suitable and effective options in PFF patients, being associated to similar complications rates. Our results show that ORIF performance in PFF patients is associated to significantly less in blood loss, surgical time and in-hospital stay. These advantages are particularly appealing in patients with multiple comorbidities.

The development and application of a novel E-commerce recommendation system used in electric power B2B sector.

The advent of the digital era has transformed E-commerce platforms into critical tools for industry, yet traditional recommendation systems often fall short in the specialized context of the electric power industry. These systems typically struggle with the industry's unique challenges, such as infrequent and high-stakes transactions, prolonged decision-making processes, and sparse data. This research has developed a novel recommendation engine tailored to these specific conditions, such as to handle the low frequency and long cycle nature of Business-to-Business (B2B) transactions. This approach includes algorithmic enhancements to better process and interpret the limited data available, and data pre-processing techniques designed to enrich the sparse datasets characteristic of this industry. This research also introduces a methodological innovation that integrates multi-dimensional data, combining user E-commerce activities, product specifics, and essential non-tendering information. The proposed engine employs advanced machine learning techniques to provide more accurate and relevant recommendations. The results demonstrate a marked improvement over traditional models, offering a more robust and effective tool for facilitating B2B transactions in the electric power industry. This research not only addresses the sector's unique challenges but also provides a blueprint for adapting recommendation systems to other industries with similar B2B characteristics.

Development of aldosterone biosynthesis during fetal and pediatric periods; Histological analysis of CYP11B2-positive cell distribution in the zona glomerulosa of human adrenal.

The distribution of CYP11B2-positive or aldosterone producing adrenocortical cells in human fetuses and children and their age-dependent changes has not been studied. We aimed to explore the changes of aldosterone biosynthesis and age-related histological alterations of the zona glomerulosa in human adrenal gland during fetal and pediatric periods. We first reviewed 125 fetal and pediatric autopsy cases and retrieved 78 adrenals from 70 cases. CYP11B2 immunohistochemistry and quantitative image analysis of its results were performed in all adrenal glands. The ratio of the definitive zone (DZ) or zona glomerulosa (ZG) / the whole adrenocortical areas started to increase in the 2nd trimester, subsequently decreased in the 3rd, increased after birth, peaked in infancy, and then gradually decreased. The ratio of CYP11B2-positive / whole adrenocortical areas remained low during the fetal period but increased after birth, peaked at infancy, and then decreased. The ratio of CYP11B2-positive / DZ or ZG areas and CYP11B2-positive areas / depth of DZ or ZG demonstrated a distinctive bimodal pattern, with one peak in the fetal period and another in the neonatal period to infancy. This is the first study to perform quantitative analysis of the distribution of CYP11B2-positive cells, the histological DZ or ZG, and the development of aldosterone biosynthesis in human adrenal glands during fetal and pediatric periods.

Mechanistic Interrogation on Wound Healing and Scar Removing by the Mo4/3B2-x Nanoscaffold Revealed Regulated Amino Acid and Purine Metabolism.

Wound rehabilitation is invariably time-consuming, scar formation further weakens therapeutic efficacy, and detailed mechanisms at the molecular level remain unclear. In this work, a Mo4/3B2-x nanoscaffold was fabricated and utilized for wound healing and scar removing in a mice model, while metabolomics was used to study the metabolic reprogramming of metabolome during therapy at the molecular level. The results showed that transition metal borides, called Mo4/3B2-x nanoscaffolds, could mimic superoxide dismutase and glutathione peroxidase to eliminate excess reactive oxygen species (ROS) in the wound microenvironment. During the therapeutic process, the Mo4/3B2-x nanoscaffold could facilitate the regeneration of wounds and removal of scars by regulating the biosynthesis of collagen, fibers, and blood vessels at the pathological, imaging, and molecular levels. Subsequent metabolomics study revealed that the Mo4/3B2-x nanoscaffold effectively ameliorated metabolic disorders in both wound and scar microenvironments through regulating ROS-related pathways including the amino acid metabolic process (including glycine and serine metabolism and glutamate metabolism) and the purine metabolic process. This study is anticipated to illuminate the potential clinical application of the Mo4/3B2-x nanoscaffold as an effective therapeutic agent in traumatic diseases and provide insights into the development of analytical methodology for interrogating wound healing and scar removal-related metabolic mechanisms.

CgIκB2 negatively regulates the expression of interferon-like protein by Rel/NF-κB signal in Crassostrea gigas.

Inhibitors of NF-κB (IκBs) have been implicated as major components of the Rel/NF-κB signaling pathway, playing an important negative regulatory role in host antiviral immunity such as in the activation of interferon (IFN) in vertebrates. In the present study, the immunomodulatory effect of IκB (CgIκB2) on the expression of interferon-like protein (CgIFNLP) was evaluated in Pacific oyster (Crassostrea gigas). After poly (I:C) stimulation, the mRNA expression level of CgIκB2 in haemocytes was significantly down-regulated at 3-12 h while up-regulated at 48-72 h. The mRNA expression of CgIκB2 in haemocytes was significantly up-regulated at 3 h after rCgIFNLP stimulation. In the CgIκB2-RNAi oysters, the mRNA expression of CgIFNLP, interferon regulatory factor-8 (CgIRF8) and NF-κB subunit (CgRel), the abundance of CgIFNLP and CgIRF8 protein in haemocytes, as well as the abundance of CgRel protein in nucleus were significantly increased after poly (I:C) stimulation. Immunofluorescence assay showed that nuclear translocation of CgIRF8 and CgRel protein was promoted in CgIκB2-RNAi oysters compared with that in EGFP-RNAi group. In the CgRel-RNAi oysters, the mRNA and protein expression level of CgIFNLP significantly down-regulated after poly (I:C) stimulation. The collective results indicated that CgIκB2 plays an important role in regulating CgIFNLP expression through its effects on Rel/NF-κB and IRF signaling pathways.

Discovery of NFκB2-Coordinated Dual Regulation of Mitochondrial and Nuclear Genomes Leads to an Effective Therapy for Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) has a poor survival rate for both pediatric and adult patients due to its frequent relapse. To elucidate the bioenergetic principle underlying AML relapse, we investigated the transcriptional regulation of mitochondrial-nuclear dual genomes responsible for metabolic plasticity in treatment-resistant blasts. Both the gain and loss of function results demonstrated that NFκB2, a noncanonical transcription factor (TF) of the NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) family, can control the expression of TFAM (mitochondrial transcription factor A), which is known to be essential for metabolic biogenesis. Furthermore, genetic tracking and promoter assays revealed that NFκB2 is in the mitochondria and can bind the specific "TTGGGGGGTG" region of the regulatory D-loop domain to activate the light-strand promoter (LSP) and heavy-strand promoter 1 (HSP1), promoters of the mitochondrial genome. Based on our discovery of NFκB2's novel function of regulating mitochondrial-nuclear dual genomes, we explored a novel triplet therapy including inhibitors of NFκB2, tyrosine kinase, and mitochondrial ATP synthase that effectively eliminated primary AML blasts with mutations of the FMS-related receptor tyrosine kinase 3 (FLT3) and displayed minimum toxicity to control cells ex vivo. As such, effective treatments for AML must include strong inhibitory actions on the dual genomes mediating metabolic plasticity to improve leukemia prognosis.