Canagliflozin mediates mitophagy through the AMPK/PINK1/PARKIN pathway to alleviate isoprenaline-induced cardiac remodelling.

Heart failure has always been a prevalent, disabling, and potentially life-threatening disease. For the treatment of heart failure, controlling cardiac remodeling is very important. In recent years, clinical trials have shown that SGLT-2 inhibitors not only excel in lowering glucose levels but also demonstrate favorable cardiovascular protective effects. However, the precise mechanisms behind the cardiovascular benefits of SGLT-2 inhibitors remain elusive. In our current research, we assessed the impact of canagliflozin (CANA, an SGLT-2 inhibitor) on cardiac remodeling progression in mice, and preliminarily elucidated the possible mechanism of action of SGLT-2 inhibitor. Our results indicate that the administration of canagliflozin significantly attenuates myocardial hypertrophy and fibrosis and enhances cardiac ejection function in mice with isoprenaline (ISO)-induced cardiac remodeling. Notably, excessive mitophagy, along with mitochondrial structural abnormalities observed in ISO-induced cardiac remodeling, were mitigated by canagliflozin treatment, thereby attenuating cardiac remodeling progression. Furthermore, the differential expression of AMPK/PINK1/Parkin pathway-related proteins in ISO-induced cardiac remodeling was effectively reversed by canagliflozin, suggesting the therapeutic potential of targeting this pathway with the drug. Thus, our study indicates that canagliflozin holds promise in mitigating cardiac injury, enhancing cardiac function, and potentially exerting cardioprotective effects by modulating mitochondrial function and mitophagy through the AMPK/PINK1/Parkin pathway.

Overall clinical course of indeterminate dendritic cell tumor patients without skin lesions: A rare case report.

BACKGROUND: Indeterminate dendritic cell tumor (IDCT) is a rare tumor of immune cells, and IDCT patients without skin lesions are rarely reported. Therefore, the clinical course in this type of patient is unclear, and further research on the underlying pathological mechanisms and appropriate treatments is needed. CASE SUMMARY: This study describes a female IDCT patient with bile duct lesions. The strong mimicry of IDCT lesions confused doctors, and consequently, this patient, who had no skin lesions, was first diagnosed with cholangiocarcinoma. Then, she presented with persistent abdominal distension without jaundice. Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination. However, no tumor cells or pathogens were found in the three subsequent ascites analyses. It took 2 years to reach the correct diagnosis, which was eventually obtained by performing surgery for biopsy of the patient's abdominal lymph nodes. However, by then, she was already in a cachexic state. Finally, she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases. CONCLUSION: For IDCT patients without skin lesions, early biopsy is the key to obtaining a correct diagnosis. Moreover, the collective management of IDCT patients is important. Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.

The association between vascular access satisfaction and all-cause mortality in maintenance hemodialysis patients.

BACKGROUND: The mortality is significantly higher in patients undergoing maintenance hemodialysis (MHD) than in the general population. It is well-known that vascular access (VA) is critical for MHD patients. But the association between VA satisfaction and all-cause mortality in MHD patients is still not clear. The aim of this study was to explore the relationship between VA satisfaction and all-cause mortality in MHD patients with a 30-month follow-up. METHODS: Two hundred twenty-nine MHD patients in two dialysis centers were enrolled in this observational prospective study. VA satisfaction was assessed using the Short Form Vascular Access Questionnaire (VAQ). Health-related quality of life (HRQoL) score was calculated with Short Form 36 (SF-36) questionnaire. Multiple logistic regression analysis was used to evaluate the influencing factors of all-cause mortality. RESULTS: During the 30-month follow-up period, 35 patients dropped out of the study. Among them, 31 patients died, and 4 patients stopped MHD treatment after renal transplantation. Multivariable analyses showed that the age, VAQ total score, social functioning score and dialysis-related complication score of the VAQ, the total score and MCS of the SF-36 were factors influencing all-cause mortality in MHD patients. The Kaplan-Meier curve further showed that the cumulative survival probability was significantly higher in the MHD patients with VAQ scores <7 at baseline than in patients with VAQ scores ⩾7 (p = 0.031). INCLUSION: The present study showed that VA satisfaction was significantly associated with all-cause mortality in MHD patients. These findings suggest that a holistic approach is required for VA choice.

The emergence of natural products as potential therapeutics for male infertility.

Infertility is a major reproductive health problem. Approximately 50% of all documented cases of infertility are attributable to male factors, such as poor testicular function and semen quality. The recent significant global decline in sperm counts has serious implications for male fertility, but the armamentarium for improving testicular function and semen quality is limited. Natural products have a wide range of activities and are a major source of drugs for disease prevention and treatment. To provide ideas and a theoretical basis for the research and development of therapeutic drugs for male infertility, this review summarizes natural products (mostly monomers) that have been shown to improve testicular function and semen quality and their possible mechanisms of action. These natural products primarily improve testicular function and semen quality via antioxidant, antiapoptotic, and anti-inflammatory effects, in addition to increasing serum testosterone and reducing DNA damage in spermatozoa and testicular cells. Prospects for the application of natural products in the treatment of male infertility are discussed.

No Pairwise Interactions of GmSNAP18, GmSHMT08 and AtPR1 with Suppressed AtPR1 Expression Enhance the Susceptibility of Arabidopsis to Beet Cyst Nematode.

GmSNAP18 and GmSHMT08 are two major genes conferring soybean cyst nematode (SCN) resistance in soybean. Overexpression of either of these two soybean genes would enhance the susceptibility of Arabidopsis to beet cyst nematode (BCN), while overexpression of either of their corresponding orthologs in Arabidopsis, AtSNAP2 and AtSHMT4, would suppress it. However, the mechanism by which these two pairs of orthologous genes boost or inhibit BCN susceptibility of Arabidopsis still remains elusive. In this study, Arabidopsis with simultaneously overexpressed GmSNAP18 and GmSHMT0 suppressed the growth of underground as well as above-ground parts of plants. Furthermore, Arabidopsis that simultaneously overexpressed GmSNAP18 and GmSHMT08 substantially stimulated BCN susceptibility and remarkably suppressed expression of AtPR1 in the salicylic acid signaling pathway. However, simultaneous overexpression of GmSNAP18 and GmSHMT08 did not impact the expression of AtJAR1 and AtHEL1 in the jasmonic acid and ethylene signaling pathways. GmSNAP18, GmSHMT08, and a pathogenesis-related (PR) protein, GmPR08-Bet VI, in soybean, and AtSNAP2, AtSHMT4, and AtPR1 in Arabidopsis could interact pair-wisely for mediating SCN and BCN resistance in soybean and Arabidopsis, respectively. Both AtSNAP2 and AtPR1 were localized on the plasma membrane, and AtSHMT4 was localized both on the plasma membrane and in the nucleus of cells. Nevertheless, after interactions, AtSNAP2 and AtPR1 could partially translocate into the cell nucleus. GmSNAP18 interacted with AtSHMT4, and GmSHMT4 interacted with AtSNAP2. However, neither GmSNAP18 nor GmSHMT08 interacted with AtPR1. Thus, no pairwise interactions among α-SNAPs, SHMTs, and AtPR1 occurred in Arabidopsis overexpressing either GmSNAP18 or GmSHMT08, or both of them. Transgenic Arabidopsis overexpressing either GmSNAP18 or GmSHMT08 substantially suppressed AtPR1 expression, while transgenic Arabidopsis overexpressing either AtSNAP2 or AtSHMT4 remarkably enhanced it. Taken together, no pairwise interactions of GmSNAP18, GmSHMT08, and AtPR1 with suppressed expression of AtPR1 enhanced BCN susceptibility in Arabidopsis. This study may provide a clue that nematode-resistant or -susceptible functions of plant genes likely depend on both hosts and nematode species.

Synergy and Mechanism of Leflunomide Plus Fluconazole Against Resistant Candida albicans: An in vitro Study.

Objective: The global rise in the resistance of Candida albicans to conventional antifungals makes Candida albicans infections harder to treat. The main objective of this study was to investigate the antifungal effects and underlying mechanisms of leflunomide in combination with triazoles against resistant Candida albicans. Methods: In this study, the microdilution method was used to determine the antifungal effects of leflunomide in combination with three triazoles on planktonic cells in vitro. The morphological transition from yeast to hyphae was observed under a microscope. The effects on ROS, metacaspase, efflux pumps, and intracellular calcium concentration were investigated, respectively. Results: Our findings suggested that leflunomide + triazoles showed a synergistic effect against resistant Candida albicans in vitro. Further study concluded that the synergistic mechanisms were resulted from multiple factors, including the inhibited efflux of triazoles, the inhibition of yeast-to-hyphae transition, ROS increasing, metacaspase activation, and [Ca2+]i disturbance. Discussion: Leflunomide appears to be a potential enhancer of current antifungal agents for treating candidiasis caused by resistant Candida albicans. This study can also serve as an example to inspire the exploration of new approaches to treating resistant Candida albicans.

NanoSIMS sulfur isotopic analysis at 100 nm scale by imaging technique.

NanoSIMS has been widely used for in-situ sulfur isotopic analysis (32S and 34S) of micron-sized grains or complex zoning in sulfide in terrestrial and extraterrestrial samples. However, the conventional spot mode analysis is restricted by depth effects at the spatial resolution < 0.5-1 µm. Thus sufficient signal amount cannot be achieved due to limited analytical depths, resulting in low analytical precision (1.5‰). Here we report a new method that simultaneously improves spatial resolution and precision of sulfur isotopic analysis based on the NanoSIMS imaging mode. This method uses a long acquisition time (e.g., 3 h) for each analytical area to obtain sufficient signal amount, rastered with the Cs+ primary beam of ∼100 nm in diameter. Due to the high acquisition time, primary ion beam (FCP) intensity drifting and quasi-simultaneous arrival (QSA) significantly affects the sulfur isotopic measurement of secondary ion images. Therefore, the interpolation correction was used to eliminate the effect of FCP intensity variation, and the coefficients for the QSA correction were determined with sulfide isotopic standards. Then, the sulfur isotopic composition was acquired by the segmentation and calculation of the calibrated isotopic images. The optimal spatial resolution of ∼ 100 nm (Sampling volume of 5 nm × 1.5 µm2) for sulfur isotopic analysis can be implemented with an analytical precision of ∼1‰ (1SD). Our study demonstrates that imaging analysis is superior to spot-mode analysis in irregular analytical areas where relatively high spatial resolution and precision are required and may be widely applied to other isotopic analyses.

Angiotensin II-induced calcium overload affects mitochondrial functions in cardiac hypertrophy by targeting the USP2/MFN2 axis.

Ubiquitination, a common type of post-translational modification, is known to affect various diseases, including cardiac hypertrophy. Ubiquitin-specific peptidase 2 (USP2) plays a crucial role in regulating cell functions, but its role in cardiac functions remains elusive. The present study aims to investigate the mechanism of USP2 in cardiac hypertrophy. Animal and cell models of cardiac hypertrophy were established using Angiotensin II (Ang II) induction. Our experiments revealed that Ang II induced USP2 downregulation in the in vitro and in vivo models. USP2 overexpression suppressed the degree of cardiac hypertrophy (decreased ANP, BNP, and ß-MHC mRNA levels, cell surface area, and ratio of protein/DNA), calcium overload (decreased Ca2+ concentration and t-CaMKⅡ and p-CaMKⅡ, and increased SERCA2), and mitochondrial dysfunction (decreased MDA and ROS and increased MFN1, ATP, MMP, and complex Ⅰ and II) both in vitro and in vivo. Mechanically, USP2 interacted with MFN2 and improved the protein level of MFN2 through deubiquitination. Rescue experiments confirmed that MFN2 downregulation neutralized the protective role of USP2 overexpression in cardiac hypertrophy. Overall, our findings suggested that USP2 overexpression mediated deubiquitination to upregulate MFN2, thus alleviating calcium overload-induced mitochondrial dysfunction and cardiac hypertrophy.

Fungi-enabled pore channel regulation and defect engineering of a novel micro-reactor for treating complex effluents.

Defect engineering has become a significant research area in recent years; however, little has been reported on the biological method for modulating the intrinsic carbon defects of the biochar framework. Herein, a fungi-enabled method for the fabrication of porous carbon/Fe3O4/Ag (PC/Fe3O4/Ag) composites was developed, and the mechanism underlying the hierarchical structure is elucidated for the first time. By regulating the cultivation process of fungi on water hyacinth biomass, a well-developed interconnected structure and carbon defects acting as potential catalytic active sites were formed. This new material with antibacterial, adsorption and photodegradation properties could be an excellent choice for treating the mixed dyestuff effluents with oils and bacteria, also guiding pore channel regulation and defect engineering in materials science. Numerical simulations were carried out to demonstrate the remarkable catalytic activity.

The impact of vascular access satisfaction on health-related quality of life in patients receiving maintenance hemodialysis: A 2-year follow-up study.

BACKGROUND: Health-related quality of life (HRQoL) has been demonstrated to predict mortality in patients receiving maintenance hemodialysis (MHD). Vascular access (VA) is critical for MHD patients. The aim of this study was to investigate the change in HRQoL among MHD patients with a 2-year follow-up and to explore the impact of VA satisfaction on HRQoL in this population. METHODS: 229 MHD patients in two dialysis centers were included in this observational prospective study. VA satisfaction was assessed using the Vascular Access Questionnaire (VAQ). The 36 Item Short-Form Health Survey (SF-36) questionnaire was employed to evaluate HRQoL scores. Multiple logistic regression analysis was used to evaluate the influencing factors of HRQoL. RESULTS: A total of 229 MHD patients were enrolled in the study, and 198 individuals (86.46%) completed the 2-year follow-up. HRQoL decreased statistically significantly from baseline to the 2-year follow-up across all dimensions. Multivariable analyses showed that the overall score, social functioning score, dialysis-related complication score of VAQ influenced HRQoL in the study population. Furthermore, HRQoL total scores and scores on the physical component summary (PCS) and mental component summary (MCS) domains were significantly higher in the satisfied VA group than in the dissatisfied group at baseline. After the 2-year follow-up, patients with a higher level of VA satisfaction reported higher HRQoL than patients with lower VA satisfaction. CONCLUSION: Our data suggested that VA satisfaction was significantly associated with HRQoL in MHD patients. These findings imply that surgeons and nephrologists should incorporate patient satisfaction into VA surgical decision-making.

Sarcopenia and echocardiographic parameters for prediction of cardiovascular events and mortality in patients undergoing maintenance hemodialysis.

Background: Sarcopenia is prevalent and is associated with the occurrence of cardiovascular complications in patients undergoing maintenance hemodialysis (MHD). It is unknown how skeletal muscle may be associated with aspects of myocardial structure and function. This study aimed to evaluate the association between sarcopenia and cardiac structure and function in patients undergoing MHD. We also examined the prognostic role of sarcopenia for mortality and cardiovascular events (CVE) in this population. Methods: Participants from a single center underwent bioimpedance body composition analysis to measure skeletal muscle and echocardiography to assess myocardial structure and function. Sarcopenia was diagnosed based on the Asian Working Group for Sarcopenia criteria. The end points were all-cause mortality and CVE. Results: Of the 158 participants, 46 (29.1%) had sarcopenia, 102 (64.6%) had left ventricular diastolic dysfunction (LVDD), and 106 (67.0%) had left ventricular hypertrophy (LVH). Participants with sarcopenia had smaller right ventricular sizes (2.54 ± 0.77 vs 2.76 ± 0.28; P < 0.01), inter-ventricular thickness (1.07 ± 0.19 vs 1.14 ± 0.20; P = 0.039), and left ventricular posterior wall thickness (0.96, 0.89-1.10 vs 1.06, 0.95-1.20; P = 0.018). Skeletal muscle mass was strongly correlated with left ventricular mass (LVM) (r = 0.577; P < 0.0001). Furthermore, the risk of LVDD (OR: 4.92, 95% confidence interval (CI) [1.73-13.95]) and LVH (OR: 4.88, 95% CI [1.08-21.96]) was much higher in the sarcopenic group than in the non-sarcopenic group. During a follow-up period of 18 months, 11 (6.9%) patients died, of which seven died (4.4%) of CVE, and 36 (22.8%) experienced CVE. The presence of sarcopenia (adjusted hazard ratio (HR), 6.59; 95% CI [1.08-39.91]; P = 0.041) and low skeletal muscle index (HR, 3.41; 95% CI [1.01-11.57]; P = 0.049) and handgrip strength (HR, 0.88; 95% CI [0.78-0.99]; P = 0.037) independently predicted death. Sarcopenia was a significant predictor of CVE (HR, 10.96; 95% CI [1.14-105.10]; P = 0.038). Conclusion: Our findings demonstrated that sarcopenia is associated with LVDD and LVH, and is associated with a higher probability of death and CVE.

The prevalence of constipation in end-stage kidney disease patients: A cross-sectional observation study.

The aim of our study was to determine the prevalence, distribution, and risk factors for constipation in peritoneal dialysis (PD) and hemodialysis (HD) patients in our center. In this cross-sectional study, 858 dialysis patients over 18 years of age (681 HD cases and 177 PD cases from our hospital) were enrolled. A constipation assessment scale (CAS) questionnaire was used to evaluate constipation status. Logistic regression analysis was performed to define independent risk factors for CAS scores. The prevalence of constipation in HD and PD patients was 52.7% and 77.4%, respectively. The mean CAS score in HD and PD patients was 1.73 ± 2.31 and 2.42 ± 2.34, respectively. Age ≥ 65 and diabetic kidney disease for renal failure were independent risk factors associated with constipation in the HD population (OR = 1.67, 95% CI: 1.15-2.90, P = .019; OR = 3.31, 95% CI: 1.65-6.11, P < .001, respectively). In the PD population, only serum prealbumin was independently associated with constipation (OR = 0.88, 95% CI: 0.79-0.96, P = .007). The multivariable logistic regression analysis demonstrated that PD modality, age ≥ 65 and diabetic kidney disease for renal failure were independent risk factors for constipation (OR = 2.15, 95% CI: 1.41-3.32, P < .001; OR = 1.65, 95% CI: 1.13-2.33, P = .003; OR = 3.19, 95% CI: 1.76-5.093, P < .001, respectively). The prevalence of constipation in PD patients was higher than that in HD patients in our center. PD modality for renal replacement therapy, age ≥ 65 and diabetic kidney disease for renal failure were closely associated with constipation in dialysis patients.

The triglyceride-glucose index as a novel marker associated with sarcopenia in non-diabetic patients on maintenance hemodialysis.

OBJECTIVE: Sarcopenia is a common complication in patients with end-stage kidney disease. Insulin resistance is present in non-diabetic patients undergoing maintenance hemodialysis (MHD) and is an important factor leading to sarcopenia. The triglyceride-glucose (TyG) index, a reliable indicator for evaluating insulin resistance, is widely used in clinical practice. The present study investigated the association between the TyG index and sarcopenia in non-diabetic patients undergoing MHD. METHODS: Relevant clinical data of non-diabetic patients undergoing MHD at our center were collected. The TyG index was calculated using the following formula: ln(fasting triglycerides(mg/dL)×fasting blood glucose(mg/dL)/2). Multivariate logistic regression analyses were used to evaluate the associations. The receiver-operating characteristic curve was used to analyze the predictive value of the TyG index in sarcopenia. RESULTS: Of the 142 patients undergoing MHD who were included, 75 (52.82%) were men, the mean age was 54.05 ± 13.97 years, and 40 (28.17%) patients satisfied the diagnostic criteria for sarcopenia. The TyG index of participants with sarcopenia was higher compared with those without sarcopenia (8.83 ± 0.45 vs. 8.49 ± 0.50, p < 0.001). The prevalence of sarcopenia increased with increasing TyG index tertile (T1, 8.51%; T2, 31.91%; T3, 43.75%; p = 0.001). Logistic regression analysis indicated that the TyG index was an independent risk factor for sarcopenia (odds ratio, 4.21 [95% confidence interval, 1.85-9.59], p = 0.001). CONCLUSION: A higher TyG index was associated with an increased risk of sarcopenia in non-diabetic patients undergoing MHD; it may be used as a novel marker to reflect the presence of sarcopenia.

The association between vascular access satisfaction and quality of life and depression in maintained hemodialysis patients.

BACKGROUND: Vascular access (VA) is known to be critical for the survival of patients on maintained hemodialysis (MHD) treatment. However, the association between VA satisfaction and psychiatric state in MHD patients is still not fully elucidated. Thus, the aim of this study is to evaluate the relationship among VA satisfaction, health-related quality of life (HRQOL) and depression in MHD patients with different VA types. METHODS: This cross-sectional study was conducted at two dialysis centers with MHD-dependent patients. The Short Form Vascular Access Questionnaire (VAQ) was administered to estimate the level of MHD patients' satisfaction with their VA. HRQOL was assessed using the Short Form 36 (SF-36) questionnaire. Depression was assessed using the Zung's self-rating depression scale (SDS). RESULTS: Of the total 252 patients, AVF was used by 84.13%, AVG was used by 2.78%, and TCC was used by 13.09%. There was no significant difference in satisfaction and SDS scores by access type in patients with AVF, AVG, and TCC. However, HRQOL was worst in patients with TCC, and highest in the AVF group. Further analysis showed that VAQ scores in the domains of overall and dialysis-related complications exhibited a negative correlation with HRQOL. And SF-36 HRQOL scores, including the total score, PCS and MCS, were all negatively correlated with SDS scores (p < 0.05). The results of multivariable analyses found that VAQ scores in the domains of overall score and physical symptom, and total score of HRQOL influenced the depression. CONCLUSIONS: In the present study, no significant difference in satisfaction scores by access type was found in patients with AVF, AVG, and TCC. The HRQOL score was higher in patients with AVF than in those with AVG or TCC. And the result suggested a negative association between HRQOL and depression. Vascular access satisfaction and HRQOL might be risk factors for the presence of depression in MHD patients.

Prevalence and Clinical Characteristics of Calciphylaxis in Chinese Hemodialysis Patients.

Background: Calciphylaxis is a grievous life-threatening vascular disease that commonly affects dialysis population. This is the first epidemiological survey of calciphylaxis initiated in China. Methods: In the cross-sectional survey, a stratified sampling method was used to select 24 dialysis centers in Jiangsu Province. The participants were all adult patients in each center who had been on hemodialysis for more than 6 months. Calciphylaxis patients were uniformly diagnosed based on characteristic skin lesions and histopathological features. Results: A total of 3,867 hemodialysis patients (average age of 55.33 ± 13.89 years; 61.81% of males) were included. Forty eight cases were diagnosed with calciphylaxis, and prevalence was 1.24%. Among calciphylaxis patients, 33 cases were male, and the average age and median dialysis duration were 53.85 ± 15.17 years and 84.00 (48.00, 138.75) months, respectively. Skin biopsy was performed in 70.83% of calciphylaxis patients, and positive rate was 64.71%. Meanwhile, the positive rate of bone scintigraphy in the diagnosis of calciphylaxis was 62.5%. The prevalence of hyperparathyroidism in case group was as high as 72.92% with longer duration, and 42.86% had undergone parathyroidectomy. Multivariate analysis indicated that increased BMI, prolonged dialysis duration, warfarin therapy, hyperparathyroidism, diabetes, tumors, low serum albumin and high serum alkaline phosphatase levels were high-risk factors for calciphylaxis. Conclusions: The prevalence of calciphylaxis in Chinese hemodialysis patients was 1.24% according to regional epidemiological survey, but its actual prevalence would be presumably far beyond present data. It's urgent to improve clinical understanding of calciphylaxis, and multifaceted diagnostic methods should be applied for early screening.

Construction of Novel Gene Signature-Based Predictive Model for the Diagnosis of Acute Myocardial Infarction by Combining Random Forest With Artificial Neural Network.

Background: Acute myocardial infarction (AMI) is one of the most common causes of mortality around the world. Early diagnosis of AMI contributes to improving prognosis. In our study, we aimed to construct a novel predictive model for the diagnosis of AMI using an artificial neural network (ANN), and we verified its diagnostic value via constructing the receiver operating characteristic (ROC). Methods: We downloaded three publicly available datasets (training sets GSE48060, GSE60993, and GSE66360) from Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified between 87 AMI and 78 control samples. We applied the random forest (RF) and ANN algorithms to further identify novel gene signatures and construct a model to predict the possibility of AMI. Besides, the diagnostic value of our model was further validated in the validation sets GSE61144 (7 AMI patients and 10 controls), GSE34198 (49 AMI patients and 48 controls), and GSE97320 (3 AMI patients and 3 controls). Results: A total of 71 DEGs were identified, of which 68 were upregulated and 3 were downregulated. Firstly, 11 key genes in 71 DEGs were screened with RF classifier for the classification of AMI and control samples. Then, we calculated the weight of each key gene using ANN. Furthermore, the diagnostic model was constructed and named neuralAMI, with significant predictive power (area under the curve [AUC] = 0.980). Finally, our model was validated with the independent datasets GSE61144 (AUC = 0.900), GSE34198 (AUC = 0.882), and GSE97320 (AUC = 1.00). Conclusion: Machine learning was used to develop a reliable predictive model for the diagnosis of AMI. The results of our study provide potential gene biomarkers for early disease screening.

Breeding a Soybean Cultivar Heinong 531 with Peking-Type Cyst Nematode Resistance, Enhanced Yield, and High Seed-Oil Contents.

Soybean cyst nematode (SCN) is a destructive threat to soybean production. It is economically important to develop a new SCN-resistant soybean cultivar with high yield and other good agronomic traits. In this study, a yellow-seed-coated and yellow-hilum-pigmented cultivar Heinong 531 belonging to maturity group I was developed by a pedigree breeding method through a test-cross between a female parental SCN-resistant soybean cultivar Pengdou 158 and a male parental line F1 (high-yield but SCN-susceptible Hefeng 55 × SCN-resistant Kangxian 12). Heinong 531 was evaluated for SCN resistance in both SCN-infested field and autoclaved soil inoculated with hatched second-stage juveniles of SCN HG Type 0. The results indicated that SCN development at all stages in Heinong 531 was suppressed and the female index was only 1.6 to 5.6%. Heinong 531 as well as Pengdou 158 and Kangxian 12 were identified as carrying the Peking-type resistance with both rhg1-a GmSNAP18 and Rhg4 GmSHMT08 genes. In the 2-year regional trials, the average yield of Heinong 531 reached 2805.0 kg/ha, and the 1-year production trial demonstrated an average yield of 2,751.5 kg/ha with yield increase of >12.0% when compared with the local cultivars. The average seed-fat (oil) contents of Heinong 531 reached up to 22.3%. The Peking-type SCN-resistant Heilong 531 with enhanced yield and high seed-oil contents was released in China in June 2021 with the certified number of 'Heishendou 20210004'. These agronomic traits make Heinong 531 a good prospect in a wide attempt to control SCN in the main soybean-producing areas of Northeast China.

Laparoscopic right hemicolectomy with complete mesocolic excision plus D3 lymphadenectomy (CME + D3): a new medial approach for central vascular ligation.

Due to the high risk of vascular injuries, it remains a technical challenge and time-consuming procedure for surgeons to perform CME and D3 lymph node dissection in laparoscopic right hemicolectomy. To overcome this difficulty, we developed a novel method of the vessel's management for central vascular ligation (CVL). The key feature of this new approach focused on vascular dissection in two aspects. The first one was to expose the superior mesentery vein (SMV) and the branches of the superior mesentery artery (SMA) at their roots from left to right after dividing the peritoneum near the left border of SMV, which has the advantage of exposing SMV and controlling bleeding. The second was to selectively ligate the colic tributaries of gastrocolic trunk of Henle (GTH) after expanding its surrounding spaces. We named this technique the "new approach (NA)". Thirty-eight patients who underwent laparoscopic right hemicolectomy with the new approach (NA) were retrospectively analyzed and compared with data from 35 patients, who underwent the conventional medial approach (TA) performed by the same surgical team from April 2017 to March 2021. There was no significant difference between the two groups in baseline data (all p > 0.05). All 38 operations were completed with this procedure successfully. The NA approach was associated with a shorter operation time (190.5 min vs.215.5 min; P < 0.05) and a smaller blood loss (50 ml vs. 95 ml; P < 0.05) compared with the conventional approach. Two cases of vascular injuries occurred in the TA group and had been managed laparoscopically. The lymph nodes count (15 vs. 16; P > 0.05) was not significantly different; additionally, no difference was observed regarding anastomotic leakage (both n = 0) and postoperative complications (3/31 vs. 3/30; P > 0.05). No mortality was observed. NA is feasible and can be an optional method of vessel's management in laparoscopic CME and D3 lymphadenectomy for right-sided colon cancer.

The impact of hemodiafiltration on cognitive function in patients with end-stage renal disease.

Background: Patients with end-stage renal disease are more likely to suffer cognitive impairment. Cognitive impairment may lead to long-term severe adverse consequences. Purpose: To explore the impact of different blood purification therapy on cerebral blood flow and cognitive functions in end-stage renal disease. Materials and methods: This prospective study evaluated patients with end-stage renal disease undergoing blood purification from January to March 2021. Matched healthy controls were also included. Participants performed neurocognitive measurements, including a mini-mental state examination, logical memory test-20-minutes delayed, verbal fluency test, digit span test, clock drawing test, and stroop color and word test C. In addition, we tested plasma amyloid-ß protein levels, serum Fe and hemoglobin levels in blood samples. Cerebral blood flow was measured using pulsed pseudocontinuous arterial spin labeling. We analyzed and compared the correlation between cognitive function, biomarkers, and cerebral blood flow between patients and healthy subjects, as well as between patients with different treatments. Results: A total of 44 patients with end-stage renal disease (mean age, 57.39 years ± 8.63) and 46 healthy controls (mean age, 56.15 years ± 6.40) were recruited. Patients receive hemodialysis three times a week, and 27 of them have been replaced hemodialysis for hemodiafiltration twice a month. The cognitive function of patients was worse than healthy controls (P < 0.05). The patients showed higher plasma concentrations of amyloid-ß40, amyloid-ß42, Tau, and pTau181 than healthy controls (P < 0.05). The group receiving both hemodialysis and hemodiafiltration had higher cerebral blood flow signal values in the left caudate nucleus (chuster-level P < 0.05, voxel-level P < 0.001). They also exhibited better verbal fluency function than the hemodialysis-only group (P < 0.05). Conclusion: Patients with the end-stage renal disease showed widespread cognitive declines. Cerebral blood flow generally decreased in the cerebral cortex and increased in subcortical regions. The hemodiafiltration may protect verbal function by increasing cerebral blood flow in the left caudate.