Epigallocatechin gallate modification of physicochemical, structural and functional properties of egg yolk granules.

The aim of this study was to prepare protein-polyphenol covalent complexes by treating egg yolk granules (EYG) with alkali in the presence of epigallocatechin gallate (EGCG) and characterize the physicochemical, structural, and functional properties of these covalent complexes. Results revealed that the optimal covalent binding occurred when the concentration of EGCG reached 0.15% (w/w), resulting in a grafting rate of 1.51 ± 0.03%. As the amount of EGCG increased, corresponding increases were observed in the particle size and ζ-potential of the complexes, thereby enhancing their stability. Furthermore, our analysis using fluorescence spectroscopy, FTIR, SEM, and SDS-PAGE collectively demonstrated the formation of a covalent complex between EYG and EGCG. Notably, the covalent complexes exhibited improved antioxidant activity and emulsifying properties. Overall, this study establishes a theoretical framework for the future practical application of EYG, emphasizing the potential of EGCG to modify its structural and functional characteristics.

Probiotics are beneficial for liver cirrhosis: a systematic review and meta-analysis of randomized control trials.

Introduction: Gut dysbiosis may play a pivotal role in the pathogenesis of cirrhosis and the severity of complications. Numerous studies have investigated the probiotics as treatments for cirrhosis. However, there is still a lack of definitive evidence confirming the beneficial effects of probiotics on cirrhosis. Methods: Databases including PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for randomized controlled trials that compared the effects of probiotic intervention and control treatments, including placebo, no treatment, and active control, on cirrhosis, published from inception to February 2024. Outcomes included hepatic encephalopathy (HE) reversal, safety and tolerability of probiotics, liver function, quality of life, and other cirrhotic-related outcomes. A meta-analysis was conducted to synthesize evidence. Results: Thirty studies were included. The quantitative synthesis results showed that compared with the control group, probiotics significantly reverse minimal hepatic encephalopathy (MHE) (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.03 to 2.32) and improve HE (RR 1.94, 95% CI 1.24 to 3.06). Additionally, probiotics demonstrated higher safety and tolerability by causing a lower incidence of serious adverse events (RR 0.71, 95% CI 0.58 to 0.87). Probiotics could potentially improve liver function by reducing the Model for End-Stage Liver Disease (MELD) scores (standardized mean difference [SMD] -0.57, 95% CI -0.85 to -0.30), and displayed favorable changes in quality of life (SMD 0.51, 95% CI 0.27 to 0.75) and gut flora (SMD 1.67, 95% CI 1.28 to 2.06). Conclusion: This systematic review and meta-analysis offers compelling evidence that probiotics are beneficial for cirrhosis by demonstrating reversal of HE, potential for liver function improvements, enhancements in quality of life, and regulation of gut dysbiosis. Furthermore, the apparent safety profile suggests that probiotics are a promising intervention for treating cirrhosis. Clinical trial registration number: CRD42023478380.

A Prediction Model for Clinical Outcomes of COVID-19 Hospitalized Patients: Construction and Accuracy Assessment.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic spread rapidly with considerable morbidity nationwide since China's liberalization in December 2022. Our work has focused on identifying different predictive factors from the laboratory examination of critically ill patients, and forecasting the unfavorable outcome of critically ill patients with COVID-19 through a combined diagnosis of biological markers. METHODS: We conducted a retrospective study at the Department of First Affiliated Hospital of Wenzhou Medical University, China, from December 24, 2022, to January 10, 2023, where 434 critically ill patients who met the inclusion criteria were involved. Machine analysis was employed to search for the parameters with the highest predictive value to calculate COVID-19 mortality by exploiting 66 typical laboratory results. RESULTS: Combined diagnosis of serum albumin (ALB), lactate dehydrogenase (LDH), direct bilirubin (Dbil), ferritin, pulse oxygen saturation (SpO2), and neutrophil count (NEUT#) was evaluated, and the result with the highest predictive value (NEUT#) was selected as the predictor for COVID-19 mortality with a sensitivity of 89.2% and a specificity of 77.4%. CONCLUSIONS: The increased levels of LDH, Dbil, ferritin, and NEUT#, along with lowered ALB and SpO2 levels are the most decisive variables for forecasting the mortality for COVID-19 according to our machine-learning-based model. The combined diagnosis could be used to improve further diagnostic performance.

SIVA-1 enhances acquired chemotherapeutic drug resistance of gastric cancer in vivo by regulating the ARF/MDM2/p53 pathway.

SIVA-1 has been shown to affect apoptotic processes in various different cell lines, and SIVA-1 significantly contributes to the decreased responsiveness of cancer cells to some chemotherapy agents. However, whether SIVA-1 has potential application in gastric cancer remains unknown. Therefore, the objective of this investigation was to clarify the distinct function of SIVA-1 in chemotherapeutic drug resistance within a living murine model with gastric malignancy, and initially elucidate the underlying mechanisms. In an established multidrug-resistant gastric cancer xenograft mouse model, lentivirus, named Lv-SIVA-1, was injected into xenograft tumors, and increased the mRNA and protein expression of endogenous SIVA-1 in tumors. Immunohistochemical assays of xenograft tumor showed that SIVA-1 was significantly upregulated, and the protein expression levels of SIVA-1 were highly increased, as detected by Western blotting. In addition, we detected the role of SIVA-1 in cell proliferation and cell apoptosis in gastric cancer cells by TUNEL and found that SIVA-1 decreased tumor cell apoptosis and promoted tumor growth in vivo. Using a TMT assay between tumor tissues of experimental and control groups, differentially expressed proteins were examined and three potential biomarkers of multidrug resistance (ARF, MDM2, and p53) were screened. We further investigated the molecular mechanism by which SIVA-1 played an efficient role against chemotherapies and found that overexpressed SIVA-1 leads to increased ARF and MDM2 expression and suppressed expression of p53 in tumor tissue. In conclusion, SIVA-1 plays a significant role in the multidrug resistance of gastric tumors. In addition, overexpressed SIVA-1 positively regulates cell proliferation, adjusts cycle progression, and reduces the response to drug treatment for gastric cancer in an ARF/MDM2/p53-dependent manner. This novel research provides a basis for chemical management of gastric cancer through regulation of SIVA-1 expression.

Association between postoperative pathological results and non-sentinel nodal metastasis in breast cancer patients with sentinel lymph node-positive breast cancer.

OBJECTIVE: For patients with 1-2 positive sentinel lymph nodes (SLN) identified by biopsy, the necessity of axillary lymph node dissection (ALND) remains a matter of debate. The primary aim of this study was to investigate the association between postoperative pathological factors and non-sentinel lymph node (NSLN) metastases in Chinese patients diagnosed with sentinel node-positive breast cancer. METHODS: This research involved a total of 280 individuals with SLN-positive breast cancer. The relationship between postoperative pathological variables and non-sentinel lymph node metastases was scrutinized using univariate, multivariate, and stratified analysis. RESULTS: Among the 280 patients with a complete count of SLN positives, 126 (45.0%) exhibited NSLN metastasis. Within this group, 45 cases (35.71%) had 1 SLN positive, while 81 cases (64.29%) demonstrated more than 1 SLN positive. Multivariate logistic regression analysis revealed that HER2 expression status (OR 2.25, 95% CI 1.10-4.60, P = 0.0269), LVI (OR 6.08, 95% CI 3.31-11.14, P < 0.0001), and the number of positive SLNs (OR 4.17, 95% CI 2.35-7.42, P < 0.0001) were positively correlated with NSLNM. CONCLUSION: In our investigation, the risk variables for NSLN metastasis included LVI, HER2 expression, and the quantity of positive sentinel lymph nodes. However, further validation is imperative, including this institution, distinct institutions, and diverse patient populations.

Alteration of white matter microstructure in patients with sleep disorders after COVID-19 infection.

BACKGROUND: The pathophysiology of coronasomnia remains unclear. This study aimed to investigate changes in white matter (WM) microstructure and inflammatory factors in patients with sleep disorders (SD) characterized by poor sleep quantity, quality, or timing following coronavirus disease 2019 (COVID-19) infection in the acute phase (within one month) and whether these changes could be recovered at 3-month follow-up. METHODS: 29 acute COVID-19 patients with SD (COVID_SD) and 27 acute COVID-19 patients without SD (COVID_NonSD) underwent diffusion tensor imaging (DTI), tested peripheral blood inflammatory cytokines level, and measured Pittsburgh Sleep Quality Index (PSQI), and matched 30 uninfected healthy controls. Analyzed WM abnormalities between groups in acute phase and explored its changes in COVID_SD at 3-month follow-up by using tract-based spatial statistics (TBSS). Correlations between DTI and clinical data were examined using Spearman partial correlation analysis. RESULTS: Both COVID_SD and COVID_NonSD exhibited widespread WM microstructure abnormalities. The COVID_SD group showed specific WM microstructure changes in right inferior fronto-occipital fasciculus (IFOF) (lower fractional anisotropy [FA]/axial diffusivity [AD] and higher radial diffusivity [RD]) and left corticospinal tract (CST) (higher FA and lower RD) and higher interleukin-1ß (IL-1ß) compared with COVID_NonSD group. These WM abnormalities and IL-1ß levels were correlated PSQI score. After 3 months, the IFOF integrity and IL-1ß levels tended to return to normal accompanied by symptom improvement in the COVID_SD relative to baseline. CONCLUSION: Abnormalities in right IFOF and left CST and elevated IL-1ß levels were important neurophenotypes correlated with COVID_SD, which might provide new insights into the pathogenesis of neuroinflammation in SD patients induced by COVID-19.

Reconstructing cell lineage trees with genomic barcoding: approaches and applications.

In multicellular organisms, developmental history of cell divisions and functional annotation of terminal cells can be organized into a cell lineage tree (CLT). The reconstruction of the CLT has long been a major goal in developmental biology and other related fields. Recent technological advancements, especially those in editable genomic barcodes and single-cell high-throughput sequencing, have sparked a new wave of experimental methods for reconstructing CLTs. Here we review the existing experimental approaches to the reconstruction of CLT, which are broadly categorized as either image-based or DNA barcode-based methods. In addition, we present a summary of the related literature based on the biological insight provided by the obtained CLTs. Moreover, we discuss the challenges that will arise as more and better CLT data become available in the near future. Genomic barcoding-based CLT reconstructions and analyses, due to their wide applicability and high scalability, offer the potential for novel biological discoveries, especially those related to general and systemic properties of the developmental process.

Preoperative albumin-alkaline phosphatase ratio affects the prognosis of patients undergoing hepatocellular carcinoma surgery.

BACKGROUND: The correlation between the preoperative albuminalkaline phosphatase ratio (AAPR) and the prognosis of hepatocellular carcinoma (HCC) patients after radical resection is still not comprehensive. OBJECTIVE: This study aims to observe the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. METHODS: We constructed a retrospective cohort study and included 656 HCC patients who underwent radical resection. The patients were grouped after determining an optimum AAPR cut-off value. We used the Cox proportional regression model to assess the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. RESULTS: The optimal cut-off value of AAPR for assessing the prognosis of HCC patients after radical resection was 0.52 which was acquired by using X-tile software. Kaplan-Meier analysis curves showed that a low AAPR (⩽ 0.52) had a significantly lower rate of overall survival (OS) and recurrence-free survival (RFS) (P< 0.05). Multiple Cox proportional regression showed that an AAPR > 0.52 was a protective factor for OS (HR = 0.66, 95%CI 0.45-0.97, p= 0.036) and RFS (HR = 0.70, 95% CI 0.53-0.92, p= 0.011). CONCLUSIONS: The preoperative AAPR level was related to the prognosis of HCC patients after radical resection and can be used as a routine preoperative test, which is important for early detection of high-risk patients and taking personalized adjuvant treatment.

Abnormal prefrontal functional network in adult obstructive sleep apnea: A resting-state fNIRS study.

To assess prefrontal brain network abnormality in adults with obstructive sleep apnea (OSA), resting-state functional near infrared spectroscopy (rs-fNIRS) was used to evaluate 52 subjects, including 27 with OSA and 25 healthy controls (HC). The study found that patients with OSA had a decreased connection edge number, particularly in the connection between the right medial frontal cortex (MFG-R) and other right-hemisphere regions. Graph-based analysis also revealed that patients with OSA had a lower global efficiency, local efficiency, and clustering coefficient than the HC group. Additionally, the study found a significant positive correlation between the Montreal Cognitive Assessment (MoCA) score and both the connection edge number and the graph-based indicators in patients with OSA. These preliminary results suggest that prefrontal rs-fNIRS could be a useful tool for objectively and quantitatively assessing cognitive function impairment in patients with OSA.

Single-cell immune profiling of mouse liver aging reveals Cxcl2+ macrophages recruit neutrophils to aggravate liver injury.

BACKGROUND AND AIMS: Immune cells play a crucial role in liver aging. However, the impact of dynamic changes in the local immune microenvironment on age-related liver injury remains poorly understood. We aimed to characterize intrahepatic immune cells at different ages to investigate key mechanisms associated with liver aging. APPROACH AND RESULTS: We carried out single-cell RNA sequencing on mouse liver tissues at 4 different ages, namely, the newborn, suckling, young, and aged stages. The transcriptomic landscape, cellular classification, and intercellular communication were analyzed. We confirmed the findings by multiplex immunofluorescence staining, flow cytometry, in vitro functional experiments, and chimeric animal models. Nine subsets of 89,542 immune cells with unique properties were identified, of which Cxcl2+ macrophages within the monocyte/macrophage subset were preferentially enriched in the aged liver. Cxcl2+ macrophages presented a senescence-associated secretory phenotype and recruited neutrophils to the aged liver through the CXCL2-CXCR2 axis. Through the secretion of IL-1ß and TNF-α, Cxcl2+ macrophages stimulated neutrophil extracellular traps formation. Targeting the CXCL2-CXCR2 axis limited the neutrophils migration toward the liver and attenuated age-related liver injury. Moreover, the relationship between Cxcl2+ macrophages and neutrophils in age-related liver injury was further validated by human liver transplantation samples. CONCLUSIONS: This in-depth study illustrates that the mechanism of Cxcl2+ macrophage-driven neutrophil activation involves the CXCL2-CXCR2 axis and provides a potential therapeutic strategy for age-related liver injury.

Development of lymph node metastasis-related prognostic markers in breast cancer.

BACKGROUND: Lymph node metastasis (LNM) from Breast cancer (BC) is commonly seen in BC progression. Currently, the identification of genes linked with LNM in BC remains in mystery. METHODS: Genes related to BC LNM were screened, and a risk model was constructed based on LASSO-Cox analysis. Combined with the Kaplan-Meier curve, the ability of riskscore to distinguish different baseline characteristics was evaluated, and model was verified by the receiver operating characteristic (ROC) curve. The expression levels of prognostic marker genes were analyzed by qRT-PCR and western blot (WB). RESULTS: A higher survival rate and longer survival time in low-risk BC patients. The 1, 3 and 5 year AUC values of the training set were 0.79, 0.74, and 0.73, respectively. Results for the validation set was similar to the training set. The differentially expressed genes between the high- and low-risk groups were significantly enriched in immune pathways. In addition, the low-risk group had higher levels of immune infiltration. qRT-PCR and WB results showed that in BC, CDH10, SMR3A, POU3F2, and FABP7 were down-regulated, and LHX1 was up-regulated. CONCLUSIONS: We built a prognostic model of BC based on LNM-related genes, proffering evaluation for prognosis and precise cure of BC. SIGNIFICANCE: At present, the genes related to lymph node metastasis in BC are still largely unknown and need to be further explored. Searching for potential lymph node metastasis-related genes of BC will provide meaningful biomarkers for BC treatment. Based on TCGA-BRCA data, we established an effective 11-gene prognostic risk model that could predict patient outcomes independently. Our model could classify BC patients and distinguish patients with poor prognosis effectively. Besides, the feature genes we identified might exert a predictive function in immunotherapy. The results of this study provide a new reference for the prognosis and treatment of BC patients with lymph node metastasis.

Lymphovascular invasion is a significant risk factor for non-sentinel nodal metastasis in breast cancer patients with sentinel lymph node (SLN)-positive breast cancer: a cross-sectional study.

BACKGROUND: A connection between lymphovascular invasion and axillary lymph node metastases in breast cancer has been observed, but the findings are inconsistent and primarily based on research in Western populations. We investigated the association between lymphovascular invasion and non-sentinel lymph node (non-SLN) metastasis in breast cancer patients with sentinel lymph node (SLN) metastasis in western China. METHODS: This study comprised 280 breast cancer patients who tested positive for SLN through biopsy and subsequently underwent axillary lymph node dissection (ALND) at The People's Hospital of Guangxi Zhuang Autonomous Region between March 2013 and July 2022. We used multivariate logistic regression analyses to assess the association between clinicopathological characteristics and non-SLN metastasis. Additionally, we conducted further stratified analysis. RESULTS: Among the 280 patients with positive SLN, only 126 (45%) exhibited non-SLN metastasis. Multivariate logistic regression demonstrated that lymphovascular invasion was an independent risk factor for non-SLN in breast cancer patients with SLN metastasis (OR = 6.11; 95% CI, 3.62-10.32, p < 0.05). The stratified analysis yielded similar results. CONCLUSIONS: In individuals with invasive breast cancer and 1-2 positive sentinel lymph nodes, lymphovascular invasion is the sole risk factor for non-SLN metastases. This finding aids surgeons and oncologists in devising a plan for local axillary treatment, preventing both over- and undertreatment.

Age has a U-shaped relationship with breast cancer outcomes in women: a cohort study.

Background and Objectives: Age is a significant determinant of susceptibility to breast cancer. Currently, the available evidence regarding the non-linear correlation between the age of diagnosis and the prognosis of breast cancer patients is contradictory. Insufficient data currently exist regarding the influence of age at diagnosis on the prognosis of breast cancer. The objective of our investigation was to examine the relationship between age at diagnosis and overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). Methods: This retrospective cohort study included 1054 patients diagnosed with breast cancer between March 7, 2013 and December 31, 2019. The hazard ratios (HRs) and 95% confidence interval (CI) for OS, BCSS, DFS were assessed using Cox proportional hazard ratio models and restricted cubic splines (RCS). Results: The study included 1054 breast cancer patients who met the criteria. With a median follow-up of 4.86 years, 71 patients (6.74%) died and 144 patients (13.66%) relapsed. After multivariable adjustment, age showed a U-shaped association with OS, BCSS, and DFS, with significantly higher risk at two ends, with age inflection points of 44, 44, and 41 years for OS, BCSS, and DFS, respectively. For OS, Quartile 1 (HR, 2.09; 95% CI: 0.90-4.84), Quartile 3 (HR, 2.44; 95% CI: 1.05-5.65) and Quartile 4 (HR, 3.38; 95% CI: 1.51-7.54) had poorer OS compared with Quartile 2. Similar results were found for BCSS and DFS. Conclusions: This study confirmed a U-shaped association between age at diagnosis and breast cancer outcome.

Risk factors of prolonged intensive care unit stay following cardiac surgery for infective endocarditis.

INTRODUCTION: Prolonged intensive care unit (ICU) stay is common in serious patients undergoing cardiac surgery. Prolonged ICU stay is associated with increased mortality and worse prognosis. This study was conducted to determine the risk factors for prolonged ICU stay after cardiac surgery for infective endocarditis (IE) and we try to decrease the operative risk of mortality and morbidity of cardiac surgery for IE. METHODS: The retrospective study of patients with IE undergoing cardiac surgery between January 2006 and November 2022 at our hospital was performed. RESULTS: 896 patients undergoing cardiac surgery were divided into group of ICU stay ≤ 3d (n = 416) and group p of ICU stay > 3d (n = 480). There were 48 operative deaths (5.4%). Univariable and multivariable analyses showed that factors are associated with prolonged ICU stay following cardiac surgery for IE, including male (P < .001), age (P < .001), weight (P = .009), vegetation length (P < .001), paravalvular leak (P < .001), aortic cross-clamp time (P < .001), cardiopulmonary bypass (CPB) time (P < .001), mechanical ventilation time (P < .001), hospitalized time postoperative (P = .032), creatinine of serum before surgery (P < .001), creatinine of serum 24h after surgery (P = .005), creatinine of serum 48h after surgery (P < .001), fluid balance on operation day (P < .001), postoperative acute kidney injury (P < .001), left ventricular end diastolic dimension (LVEDD) preoperative (P < .001), LVEDD postoperative (P < .001), chest drainage (P = .032), frozen plasma (P = .016), preoperative aortic insufficiency (P < .001), and packed red cells (P < .001). CONCLUSIONS: In our study, shortness of ICU stay and optimization of pre-, peri-, and postoperative factors that can shorten ICU stay, therefore, contribute to a better postoperative outcome and leads to lower rates of mortality and morbidity.

Surgical treatment of left-sided infective endocarditis with symptomatic neurological complications before surgery in China.

Introduction: We aimed to investigate surgical treatment of left-sided infective endocarditis with symptomatic neurological complications before surgery. Methods: This was a retrospective study of patients with left-sided infective endocarditis and symptomatic neurological complications before surgery undergoing cardiac surgery between January 2006 and November 2022 at our hospital. Results: Eight hundred thirty-two patients were divided into group with symptomatic neurological complications before surgery (n = 112) and without symptomatic neurological complications before surgery (n = 720). There were 48 operative deaths (5.4%). Univariate and multivariate analyses showed that symptomatic neurological complications before surgery is statistically significantly associated with in-hospital mortality following cardiac surgery and prolonged intubation time. Conclusions: Our study showed that symptomatic neurological complications before surgery are associated with increased in-hospital mortality following cardiac surgery and prolonged intubation time.

Genome-wide probing of eukaryotic nascent RNA structure elucidates cotranscriptional folding and its antimutagenic effect.

The transcriptional intermediates of RNAs fold into secondary structures with multiple regulatory roles, yet the details of such cotranscriptional RNA folding are largely unresolved in eukaryotes. Here, we present eSPET-seq (Structural Probing of Elongating Transcripts in eukaryotes), a method to assess the cotranscriptional RNA folding in Saccharomyces cerevisiae. Our study reveals pervasive structural transitions during cotranscriptional folding and overall structural similarities between nascent and mature RNAs. Furthermore, a combined analysis with genome-wide R-loop and mutation rate approximations provides quantitative evidence for the antimutator effect of nascent RNA folding through competitive inhibition of the R-loops, known to facilitate transcription-associated mutagenesis. Taken together, we present an experimental evaluation of cotranscriptional folding in eukaryotes and demonstrate the antimutator effect of nascent RNA folding. These results suggest genome-wide coupling between the processing and transmission of genetic information through RNA folding.

Effect of preoperative peripheral blood platelet volume index on prognosis in patients with invasive breast cancer.

Aim: This study was designed to investigate the prognostic value of the platelet volume index in patients with invasive breast cancer (IBC). Methods: A total of 524 patients with IBC were enrolled in this study, with a median follow-up time of 6.76 years. The relationship between platelet volume indices and breast cancer prognosis was analyzed. Results: There is a strong correlation between a higher platelet distribution width-to-platelet count ratio (PDW/P) and poorer disease-free survival (DFS) in patients with IBC. The DFS rate was significantly lower among individuals with elevated PDW/P ratios compared with those with lower ratios. Conclusion: The PDW/P ratio is an independent risk factor for predicting DFS in patients with IBC.

Effects of NAD+ precursors on blood pressure, C-reactive protein concentration and carotid intima-media thickness: A meta-analysis of randomized controlled trials.

BACKGROUND: There are contradictory effects regarding the effect of NAD+ precursor on blood pressure and inflammation. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD+ precursor supplementation on blood pressure, C-reactive protein (CRP) and carotid intima-media thickness (CIMT). METHODS: PubMed/MEDLINE, Web of Science, SCOPUS and Embase databases were searched using standard keywords to identify all controlled trials investigating the effects of NAD+ precursor on blood pressure, CRP and CIMT. Pooled weighted mean difference (WMD) and 95% confidence intervals (95% CI) were achieved by random-effects model analysis for the best estimation of outcomes. RESULTS: Twenty-nine articles (with 8664 participants) were included in this article. Results from meta-analyses of RCTs from random-effects models indicated a significant reduction in systolic (SBP) (weighted mean difference (WMD): -2.54 mmHg, p < .001) and diastolic blood pressure (DBP) (WMD: -2.15 mmHg, p < .001), as well as in CRP (WMD: -.93 mg/L, 95% CI -1.47 to -.40, p < .001) concentrations and CIMT (WMD: -.01 mm, 95% CI -.02 to -.00, p = .005) with the NAD+ precursors supplementation compared with the control group. In addition, a greater effect of supplementation with NAD+ precursors in reducing blood pressure (BP) were observed with the highest dose (≥2 g) and duration of the intervention (>12 weeks), as well as with NA supplementation when compared to NE. CONCLUSIONS: Overall, these findings suggest that NAD+ precursor supplementation might have a beneficial effect on cardiovascular risk factors such as BP, CRP concentration and CIMT.

Wide-scale identification of novel/eliminated genes responsible for evolutionary transformations.

BACKGROUND: It is generally accepted that most evolutionary transformations at the phenotype level are associated either with rearrangements of genomic regulatory elements, which control the activity of gene networks, or with changes in the amino acid contents of proteins. Recently, evidence has accumulated that significant evolutionary transformations could also be associated with the loss/emergence of whole genes. The targeted identification of such genes is a challenging problem for both bioinformatics and evo-devo research. RESULTS: To solve this problem we propose the WINEGRET method, named after the first letters of the title. Its main idea is to search for genes that satisfy two requirements: first, the desired genes were lost/emerged at the same evolutionary stage at which the phenotypic trait of interest was lost/emerged, and second, the expression of these genes changes significantly during the development of the trait of interest in the model organism. To verify the first requirement, we do not use existing databases of orthologs, but rely purely on gene homology and local synteny by using some novel quickly computable conditions. Genes satisfying the second requirement are found by deep RNA sequencing. As a proof of principle, we used our method to find genes absent in extant amniotes (reptiles, birds, mammals) but present in anamniotes (fish and amphibians), in which these genes are involved in the regeneration of large body appendages. As a result, 57 genes were identified. For three of them, c-c motif chemokine 4, eotaxin-like, and a previously unknown gene called here sod4, essential roles for tail regeneration were demonstrated. Noteworthy, we established that the latter gene belongs to a novel family of Cu/Zn-superoxide dismutases lost by amniotes, SOD4. CONCLUSIONS: We present a method for targeted identification of genes whose loss/emergence in evolution could be associated with the loss/emergence of a phenotypic trait of interest. In a proof-of-principle study, we identified genes absent in amniotes that participate in body appendage regeneration in anamniotes. Our method provides a wide range of opportunities for studying the relationship between the loss/emergence of phenotypic traits and the loss/emergence of specific genes in evolution.

Impact of Vegetation Length on Clinical Complications During Surgical Intervention and Long-Term Survival in Infective Endocarditis.

We aimed to investigate the impact of vegetation length on clinical complications during surgical intervention and long-term survival in infective endocarditis. This was a retrospective study of patients with infective endocarditis who underwent cardiac surgery between January 2006 and November 2022 at our hospital. 896 patients were divided into 2 groups: group I (vegetation length <10 mm, n = 448) and group II (vegetation length ≥10 mm, n = 448). There were 48 operative deaths (5.4%). Univariate and multivariate analyses showed that vegetation length is statistically significantly associated with destruction of the annulus (p <0.001), neurological complications before surgery (p <0.001), acute renal injury (p <0.001), prolonged intubation time (intubation time >24 hours) (p <0.001), prolonged intensive care unit (ICU) retention time (ICU retention time >3 days) (p <0.001), and in-hospital mortality (p <0.001), respectively. Our study showed that vegetation length is statistically significantly associated with destruction of the annulus, neurological complications before surgery, acute renal injury, prolonged intubation time, prolonged ICU retention time, in-hospital mortality, and 1-year mortality, respectively.