A systematic review of automated methods to perform white matter tract segmentation.

White matter tract segmentation is a pivotal research area that leverages diffusion-weighted magnetic resonance imaging (dMRI) for the identification and mapping of individual white matter tracts and their trajectories. This study aims to provide a comprehensive systematic literature review on automated methods for white matter tract segmentation in brain dMRI scans. Articles on PubMed, ScienceDirect [NeuroImage, NeuroImage (Clinical), Medical Image Analysis], Scopus and IEEEXplore databases and Conference proceedings of Medical Imaging Computing and Computer Assisted Intervention Society (MICCAI) and International Symposium on Biomedical Imaging (ISBI), were searched in the range from January 2013 until September 2023. This systematic search and review identified 619 articles. Adhering to the specified search criteria using the query, "white matter tract segmentation OR fiber tract identification OR fiber bundle segmentation OR tractography dissection OR white matter parcellation OR tract segmentation," 59 published studies were selected. Among these, 27% employed direct voxel-based methods, 25% applied streamline-based clustering methods, 20% used streamline-based classification methods, 14% implemented atlas-based methods, and 14% utilized hybrid approaches. The paper delves into the research gaps and challenges associated with each of these categories. Additionally, this review paper illuminates the most frequently utilized public datasets for tract segmentation along with their specific characteristics. Furthermore, it presents evaluation strategies and their key attributes. The review concludes with a detailed discussion of the challenges and future directions in this field.

Supervised contrastive learning enhances graph convolutional networks for predicting neurodevelopmental deficits in very preterm infants using brain structural connectome.

Very preterm (VPT) infants (born at less than 32 weeks gestational age) are at high risk for various adverse neurodevelopmental deficits. Unfortunately, most of these deficits cannot be accurately diagnosed until the age of 2-5 years old. Given the benefits of early interventions, accurate diagnosis and prediction soon after birth are urgently needed for VPT infants. Previous studies have applied deep learning models to learn the brain structural connectome (SC) to predict neurodevelopmental deficits in the preterm population. However, none of these models are specifically designed for graph-structured data, and thus may potentially miss certain topological information conveyed in the brain SC. In this study, we aim to develop deep learning models to learn the SC acquired at term-equivalent age for early prediction of neurodevelopmental deficits at 2 years corrected age in VPT infants. We directly treated the brain SC as a graph, and applied graph convolutional network (GCN) models to capture complex topological information of the SC. In addition, we applied the supervised contrastive learning (SCL) technique to mitigate the effects of the data scarcity problem, and enable robust training of GCN models. We hypothesize that SCL will enhance GCN models for early prediction of neurodevelopmental deficits in VPT infants using the SC. We used a regional prospective cohort of ∼280 VPT infants who underwent MRI examinations at term-equivalent age from the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS). These VPT infants completed neurodevelopmental assessment at 2 years corrected age to evaluate cognition, language, and motor skills. Using the SCL technique, the GCN model achieved mean areas under the receiver operating characteristic curve (AUCs) in the range of 0.72∼0.75 for predicting three neurodevelopmental deficits, outperforming several competing models. Our results support our hypothesis that the SCL technique is able to enhance the GCN model in our prediction tasks.

Thirty-eight cases of paraovarian cysts in children and adolescents: a retrospective study.

PURPOSE: Paraovarian cysts in children and adolescents can be challenging to accurately diagnose prior to surgery. Our objective is to outline the clinical characteristics of paraovarian cysts and enhance the precision of diagnosing paraovarian cysts in this age group. METHODS: We retrospectively analyzed all patients with paraovarian cysts who underwent surgery in our department from 2013 to 2021. The review focused on demographic characteristics, clinical manifestations, intraoperative findings, and postoperative pathology of these patients. RESULTS: This cohort was composed of 38 children with paraovarian cysts. The average diameter of the cysts was 4.8 cm (range 0.5-10 cm). Among the cases, 25 (65.8%) had adnexal torsion. Postoperative pathology showed that all cases were simple cysts with serous fluid. After the procedure, the patients were monitored for a period ranging from 12 to 108 months. B-ultrasound and physical examination did not reveal any significant abnormalities. CONCLUSIONS: B-ultrasound can help diagnose paraovarian cysts by detecting slight deviation movement between the cyst and the uterus. The presence of adnexa torsion in children and adolescents with paraovarian cysts does not depend on BMI, but rather on the size of cysts. Laparoscopic cyst removal has proven to be an effective surgical approach with favorable outcomes.

Effect evaluation of competency-based education (CBE) combined with multi-disciplinary team (MDT) teaching mode in respiratory rehabilitation nursing teaching：A randomized controlled trial.

AIM: To explore the application effect of competency-based education (CBE) combined with multi-disciplinary team (MDT) teaching mode in respiratory rehabilitation nursing teaching. BACKGROUND: Respiratory rehabilitation, as an important non drug treatment for chronic respiratory disease, started late in China, with low implementation rate in hospitals and insufficient knowledge of nursing staff. Therefore, it is urgent to cultivate high professional level nurses with strong professional ability. DESIGN: A randomized controlled trial. METHODS: We selected nurses from the respiratory and critical care department at a Grade III, Level A hospital in Beijing, who participated in the respiratory rehabilitation training program between March 2020 and August 2022, as our study participants. Participants were grouped using a random number method. Nurses who participated in the study from March 2020 to May 2021 were set as the control group, and the nurses who participated in the study from June 2021 to August 2022 were set as the test group. The control group used traditional teaching methods, and the test group used the CBE combined MDT teaching model. At the end of the test, the theory, operating skills, satisfaction and core competence were assessed. RESULTS: After training, the theoretical examination score of the test group (93.71 ± 1.94) was higher than that of the control group (92.37 ± 1.92), the operational examination score of the test group (93.11 ± 2.12) was higher than that of the control group (91.61 ± 1.93), the overall teaching satisfaction of the test group (4.45 ± 0.50) was higher than that of the control group (4.13 ± 0.57), and the total score of the core competence of the test group (148.73 ± 7.08) was higher than that of the control group (141.02 ± 6.41). The difference between the two groups was statistically significant (P<0.05). CONCLUSION: CBE combined with MDT teaching mode has a good effect in Pulmonary and Critical Care Medicine (PCCM) respiratory rehabilitation nursing teaching.

The main cause of tibial prosthesis malalignment after total knee arthroplasty in Southern Chinese population.

Objectives: This study aimed to determine the occurrence rate of malalignment of tibial prosthesis and explore the influencing factors. Methods: 296 patients from Southern China who underwent total knee arthroplasty (TKA) were selected as the research objects. Their general demographic data were recorded. The tibial bowing angle (TBA), tibial length, medial proximal tibial angle (MPTA), tibial plateau shift angle (TPSA), tibial bone loss, lateral distal tibial angle, and overall width of tibial plateau and widths of medial and lateral tibial plateau were measured before TKA. The tibial component coronal alignment angle (TCCA) was measured after the operation. Malalignment of the tibial prosthesis was defined as TCCA <87° or TCCA >93°. Tibial bowing was indicated by TBA >2°, and lateral bowing was recorded as +. The correlations of TCCA with demographic data and pre-operation imaging measurement parameters were statistically analyzed. Results: Bivariate correlation analysis revealed negative correlations between TCCA and TBA (r = -0.602, P < 0.001) and TPSA (r = -0.304, P < 0.001), and a positive correlation with MPTA (r = -0.318, P < 0.001). Multivariate linear regression analysis demonstrated a significant negative correlation between TCCA and TBA (P < 0.001). The occurrence rate of malalignment of tibial prosthesis was 12.37 %. The occurrence rates of malalignment were 22.54 % in the tibial bowing group and 6.87 % in the non-tibial bowing group, showing statistical differences (P < 0.001). Conclusion: The malalignment rate of tibial prosthesis among Southern Chinese patients is relatively high, possibly attributed to the tibial anatomy anomalies, particularly the tibial bowing. The entry point should be determined based on tibial morphology.

Comparison of Lipid Composition between Quasipaa spinosa Oil and Rana catesbeiana Oil and Its Effect on Lipid Accumulation in Caenorhabditis elegans.

Frog oil has been recognized for its nutritional and medicinal value. However, there is limited research on the role of frog oil in preventing obesity. In this study, we aimed to investigate the lipid composition of Quasipaa spinosa oil (QSO) and Rana catesbeiana oil (RCO) using lipidomics analysis. We compared the lipid accumulation effects of these two kinds of frog oils and soybean oil (SO) in Caenorhabditis elegans (C. elegans). Additionally, we determined the gene expression related to lipid metabolism and used the nhr-49 mutant (RB1716) and sir-2.1 mutant (VC199) for validation experiments. The results showed that the lipid composition of QSO and RCO was significantly different (p < 0.05), and QSO was rich in more polyunsaturated fatty acids (PUFAs). After feeding C. elegans, the lipid accumulation of the QSO group was the lowest among the three dietary oil groups. In addition, compared with RCO and SO, QSO significantly inhibited the production of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD). The effects of three kinds of dietary oils on the fatty acid composition of C. elegans were significantly different. Compared with SO and RCO, QSO significantly up-regulated (p < 0.05) the expression of sir-2.1 and ech-1 genes. The results showed that QSO might reduce lipid accumulation through the SIRT1 and nuclear hormone signaling pathways. Such a situation was verified experimentally by the nhr-49 mutant (RB1716) and sir-2.1 mutant (VC199). This study proposed a new functional oil, laying the groundwork for developing functional foods from Quasipaa spinosa.

Prenatal Opioid Exposure and Risk for Adverse Brain and Motor Outcomes in Infants Born Premature.

OBJECTIVE: To compare brain magnetic resonance imaging (MRI) biomarkers and neurodevelopmental test scores in infants born preterm with and without prenatal opioid exposure (POE). STUDY DESIGN: We examined 395 preterm infants (≤32 weeks gestational age) who had term-equivalent brain MRIs, composite scores from the Bayley Scales of Infant and Toddler Development-III at 2 years corrected age, and POE data. MRI parameters included total/regional brain volumes and severe punctate white matter lesions (PWMLs). We conducted bivariable analysis and multivariable logistic regression analyses. RESULTS: The mean ± SD gestational age was 29.3 ± 2.5 weeks; 35 (8.9%) had POE and 20 (5.1%) had severe PWML. Compared with unexposed infants, those with POE exhibited higher rates of severe PWML (17.1% vs 3.9%, respectively; P = .002); findings remained significant with an OR of 4.16 (95% CI, 1.26-13.68) after adjusting for confounders. On mediation analysis, the significant relationship between POE and severe PWML was not indirectly mediated through preterm birth/gestational age (OR, 0.93; 95% CI, 0.78-1.10), thus suggesting the association was largely driven by a direct adverse effect of POE on white matter. In multivariable analyses, POE was associated with a significantly lower score by -6.2 (95% CI, -11.8 to -0.6) points on the Bayley Scales of Infant and Toddler Development-III Motor subscale compared with unexposed infants. CONCLUSIONS: POE was associated with severe PWML; this outcome may be a direct effect of POE rather than being mediated by premature birth. POE was also associated with worse motor development. Continued follow-up to understand the long-term effects of POE is warranted.

Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats.

PURPOSE: To investigate the effects of canagliflozin (20 mg/kg) on Dahl salt-sensitive (DSS) rat gut microbiota and salt-sensitive hypertension-induced kidney injury and further explore its possible mechanism. METHODS: Rats were fed a high-salt diet to induce hypertension and kidney injury, and physical and physiological indicators were measured afterwards. This study employed 16S rRNA sequencing technology and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolic profiling combined with advanced differential and association analyses to investigate the correlation between the microbiome and the metabolome in male DSS rats. RESULTS: A high-salt diet disrupted the balance of the intestinal flora and increased toxic metabolites (methyhistidines, creatinine, homocitrulline, and indoxyl sulfate), resulting in severe kidney damage. Canagliflozin contributed to reconstructing the intestinal flora of DSS rats by significantly increasing the abundance of Corynebacterium spp., Bifidobacterium spp., Facklamia spp., Lactobacillus spp., Ruminococcus spp., Blautia spp., Coprococcus spp., and Allobaculum spp. Moreover, the reconstruction of the intestinal microbiota led to significant changes in host amino acid metabolite concentrations. The concentration of uremic toxins, such as methyhistidines, creatinine, and homocitrulline, in the serum of rats was decreased by canagliflozin, which resulted in oxidative stress and renal injury alleviation. CONCLUSION: Canagliflozin may change the production of metabolites and reduce the level of uremic toxins in the blood circulation by reconstructing the intestinal flora of DSS rats fed a high-salt diet, ultimately alleviating oxidative stress and renal injury.

Improved synthesis and evaluation of preclinical pharmacodynamic parameters of a new monocyclic ß-lactam DPI-2016.

Monocyclic ß-lactams are stable to a number of ß-lactamases and are the focus of researchers for the development of antibacterial drugs, particularly against Enterobacterales. We recently synthesized and reported the bactericidal activity of diverse series of aztreonam appended with amidine moieties as siderophores. One of the derivatives exhibiting the highest MIC value in vitro was selected for further preclinical studies. The compound DPI-2016 was reassessed for its synthetic routes and methods that were improved to find the maximum final yields aimed at large-scale synthesis. In addition, the results of the pharmacological studies were determined with reference to aztreonam. It has been found that the compound DPI-2016 showed comparable or slightly improved ADMET as well as pharmacokinetic parameters to aztreonam. It is estimated that the compound could be a potential lead for further clinical evaluation.

Branched fructo-oligosaccharides from Polygonatum Cyrtonema Hua as crosslinking agents for cellulose: A novel injectable and on-demand dissolution hydrogel for diabetic wound.

Oligosaccharide-containing macromolecular bio adhesives are emerging as highly promising eco-friendly materials to enhance the cytocompatibility of viscous hydrogels for wound healing applications. In our prior research, we extensively elucidated the properties of branch-structure fructo-oligosaccharides derived from Polygonatum Cyrtonema Hua (referred to as PCOS). However, the characteristics of hydrogels based on fructo-oligosaccharides remain to be fully explored. In present work, we developed an injectable, PCOS/carboxymethyl cellulose (CMC) hydrogel which is a dual ion-physical cross-linked hydrogel that can be considered as a potential diabetic wound dressing. The tests showed that the optimal ratios for hydrogel preparation were 2 % CBM 940 (Carbomer 940), 5 % CMC and 10 % PCOS. The resultant hydrogel was formulated into composite hydrogels that were then used for the treatment of full-thickness excisional wounds in a db/db diabetic mouse model. Wound closure and histological evaluation confirmed its beneficial effect on wound healing. Further morphological analysis through scanning electron microscopy images revealed a porous hydrogel structure, while Fourier-transform infrared spectroscopy provided structural insights on the crosslinking reaction. Physicochemical properties of the hybrid hydrogels determined by rheological properties, thermogravimetric, water loss rate, et al., indicated that the double crosslinking PCOS/CMC hybrid hydrogel showed enhanced dynamic mechanical properties and water retention capacity compared to the CMC cellulose matrix hydrogels. Thus, this novel PCOS-hybrid hydrogel exhibited good dissolvability and injectable properties, which was proved to facilitate for the diabetic wound healing both in vitro and in vivo test and holds a potential clinical application in the wound healing.

Machine Learning Diagnosis of Small-Bowel Crohn Disease Using T2-Weighted MRI Radiomic and Clinical Data.

BACKGROUND. Radiologists have variable diagnostic performance and considerable interreader variability when interpreting MR enterography (MRE) examinations for suspected Crohn disease (CD). OBJECTIVE. The purposes of this study were to develop a machine learning method for predicting ileal CD by use of radiomic features of ileal wall and mesenteric fat from noncontrast T2-weighted MRI and to compare the performance of the method with that of expert radiologists. METHODS. This single-institution study included retrospectively identified patients who underwent MRE for suspected ileal CD from January 1, 2020, to January 31, 2021, and prospectively enrolled participants (patients with newly diagnosed ileal CD or healthy control participants) from December 2018 to October 2021. Using axial T2-weighted SSFSE images, a radiologist selected two slices showing greatest terminal ileal wall thickening. Four ROIs were segmented, and radiomic features were extracted from each ROI. After feature selection, support-vector machine models were trained to classify the presence of ileal CD. Three fellowship-trained pediatric abdominal radiologists independently classified the presence of ileal CD on SSFSE images. The reference standard was clinical diagnosis of ileal CD based on endoscopy and biopsy results. Radiomic-only, clinical-only, and radiomic-clinical ensemble models were trained and evaluated by nested cross-validation. RESULTS. The study included 135 participants (67 female, 68 male; mean age, 15.2 ± 3.2 years); 70 were diagnosed with ileal CD. The three radiologists had accuracies of 83.7% (113/135), 88.1% (119/135), and 86.7% (117/135) for diagnosing CD; consensus accuracy was 88.1%. Interradiologist agreement was substantial (κ = 0.78). The best-performing ROI was bowel core (AUC, 0.95; accuracy, 89.6%); other ROIs had worse performance (whole-bowel AUC, 0.86; fat-core AUC, 0.70; whole-fat AUC, 0.73). For the clinical-only model, AUC was 0.85 and accuracy was 80.0%. The ensemble model combining bowel-core radiomic and clinical models had AUC of 0.98 and accuracy of 93.5%. The bowel-core radiomic-only model had significantly greater accuracy than radiologist 1 (p = .009) and radiologist 2 (p = .02) but not radiologist 3 (p > .99) or the radiologists in consensus (p = .05). The ensemble model had greater accuracy than the radiologists in consensus (p = .02). CONCLUSION. A radiomic machine learning model predicted CD diagnosis with better performance than two of three expert radiologists. Model performance improved when radiomic data were ensembled with clinical data. CLINICAL IMPACT. Deployment of a radiomic-based model including T2-weighted MRI data could decrease interradiologist variability and increase diagnostic accuracy for pediatric CD.

Unleashing Breast Cancer Progression: miR-455-5p's Targeting of SOCS3 Drives Proliferation, Migration, and Invasion.

OBJECTIVES: We aim to investigate the regulatory mechanisms of miR-455-5p/SOCS3 pathway that underlie the proliferation, migration, and invasion of triple-negative breast cancer (TNBC) cells. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-455-5p expression in breast cancer tissues and cell lines. CCK8 and Transwell assays were conducted to assess the effects of miR-455-5p on breast cancer line proliferation, migration, and invasion. SOCS3 expression level in breast cancer tissues and cell lines was determined by qPCR and western blotting. The targeting relationship between miR-455-5p and SOCS3 was determined by dual luciferase reporter gene assay in different breast cancer cell lines. Finally, the upstream and downstream regulatory association between miR-455-5p and SOCS3 was confirmed in breast cancer cells by CCK8, western blot, and Transwell assays. RESULTS: MiR-455-5p expression was up-regulated in breast cancer tissues; miR-455-5p regulates TNBC proliferation, migration, and invasion of TNBC. SOCS3 was the direct target of miR-455-5p and was down-regulated in breast cancer. Interference with SOCS3 reversed the inhibitory effect of the miR-455-5p inhibitor on breast cancer cells' malignant potential. CONCLUSION: MiR-455-5p promotes breast cancer progression by targeting the SOCS3 pathway and may be a potential therapeutic target for breast cancer.

Human papillomavirus infections among women with cervical lesions and cervical cancer in Yueyang, China: a cross-sectional study of 3674 women from 2019 to 2022.

PURPOSE: To investigate the distribution of the incidence and genotypes of human papillomavirus (HPV) among women with cervical cancer (CC) and precancerous cervical lesions in Yueyang City, China, to develop prevention and control strategies for CC. METHODS: A total of 3674 patients with cervical lesions and cervical cancer who attended 7 hospitals in Yueyang City between September 2019 and September 2022 were included. They included 1910 cervical intraepithelial neoplasia (CIN) I, 718 CIN II, 576 CIN II and 470 CC, respectively. The HPV genotyping of the above patients was detected by Real time-PCR in the laboratory department of each hospital. RESULTS: The total HPV prevalence was 74.69% (95% CI 73.28-76.09%) in 3674 patients. The incidence of high- and low-risk HPV was 73.46% and 7.21%, respectively. The prevalence of HPV in CIN I, CIN II, CIN III, and invasive CC (ICC) groups was 66.65% (1273/1910, 95% CI 64.53-68.77%), 80.78% (580/718, 95% CI 77.89-83.67%), 83.88% (483/576, 95% CI 80.84-86.87%), and 86.81% (408/470, 95% CI 83.74-89.88%), respectively. The top three HPV subtypes in ICC are HPV16, HPV52, and HPV58. The prevalence of HPV 16 increased with increasing disease severity, with this genotype being present in 12.57%, 20.89%, 36.98%, and 50.85% of CIN I, CIN II, CIN III, and ICC cases, respectively (p < 0.001). Single HPV infection was predominant in cervical lesions, with a prevalence of 48.50% (95% CI 46.89-50.12%). The HPV prevalence varied by age, being highest among women with ICC, CIN I, CIN II and CIN III aged ≥ 60 years, 50-59 years, 40-49 years, and 40-49 years, respectively. CONCLUSION: The prevalence of HPV in patients with cervical lesions in Yueyang City was very high, with HPV 16, 52, 58, 53, and 51 being the five most common HPV genotypes in patients with cervical lesions.

Quantifying the effect of non-ionic surfactant alkylphenol ethoxylates on the persistence of thiabendazole on fresh produce surface.

BACKGROUND: Understanding the role of adjuvants in pesticide persistence is crucial to develop effective pesticide formulations and manage pesticide residues in fresh produce. This study investigated the impact of a commercial non-ionic surfactant product containing alkylphenol ethoxylates (APEOs) on the persistence of thiabendazole on apple and spinach surfaces against the 30 kg m-3 baking soda (sodium bicarbonate, NaHCO3 ) soaking, which was used to remove the active ingredient (AI) in the cuticular wax layer of fresh produce through alkaline hydrolysis. Surface-enhanced Raman scattering (SERS) mapping method was used to quantify the residue levels on fresh produce surfaces at different experimental scenarios. Four standard curves were established to quantify surface thiabendazole in the absence and presence of APEOs, on apple and spinach leaf surfaces, respectively. RESULTS: Overall, the result showed that APEOs enhanced the persistence of thiabendazole over time. After 3 days of exposure, APEOs increased thiabendazole surface residue against NaHCO3 hydrolysis on apple and spinach surfaces by 5.39% and 10.47%, respectively. CONCLUSION: The study suggests that APEOs led to more pesticide residues on fresh produce and greater difficulty in washing them off from the surfaces using baking soda, posing food safety concerns. © 2023 Society of Chemical Industry.

Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

This study aims to summarize the available data and determine if the presence of venous thromboembolism (VTE) immune-related adverse event (irAE) in patients with immune checkpoint inhibitor (ICI) therapy is associated with improved treatment efficacy and clinical outcomes, which in turn was used to help optimize patient selection for anticoagulation therapy and inform rational treatment strategies for overcoming the mechanisms of ICI resistance. PubMed, Embase, Web of Science, and Cochrane Library were searched up to March 18, 2023, for studies assessing the relationship between VTE irAE development during ICI therapy and cancer outcomes. Seven primary articles with a total of 4437 patients were included in the overall survival (OS) meta-analysis. Patients with VTE had a significant increase in overall mortality compared to patients without VTE in adjusted hazard ratios (HRs 1.36, 95% confidence interval [CI] 1.06-1.75, P = .02). In the studies where immortal time bias (ITB) was accounted for, patients with VTE irAE also had poor OS than those without. HR and the corresponding 95% CI values in the non-ITB group were 2.53 (1.75-3.66, P < .00001) with low heterogeneity (P = .17, I2 = 48%) and 1.21 (1.06-1.37, P = .004) in the ITB group with no heterogeneity (P = .95, I2 = 0%), respectively. Despite the heterogeneity identified, the evidence does suggest that VTE irAE occurrence could be served as a prognostic indicator, with higher frequencies of occurrence associated with poorer OS. However, the fundamental role of this association with clinical consequences should be further investigated in large cohorts and clinical trials.

Canagliflozin and irbesartan ameliorate renal fibrosis via the TGF-ß1/Smad signaling pathway in Dahl salt-sensitive rats.

OBJECTIVES: This study assessed the antifibrotic effects of canagliflozin, with or without irbesartan, on renal injury in Dahl salt-sensitive (SS) rats fed a high-salt (HS) diet. METHODS: After the preconditioning stage, Dahl SS rats (n = 47) were divided into five experimental groups as follows: low-salt (LS, n = 7), HS (n = 10), HS with canagliflozin (n = 10), HS with irbesartan (n = 10), and HS with canagliflozin and irbesartan (n = 10). RESULTS: The HS diet increased systolic blood pressure (SBP), renal fibrosis, fibrotic protein expression, and transforming growth factor-ß1 (TGF-ß1)/Smad2/3 pathway protein expression compared with the findings in the LS group. Irbesartan reduced SBP and slowed the loss of renal function. Canagliflozin significantly reduced body weight and renal fibrosis and suppressed the TGF-ß1/Smad2/3 pathway. The combined therapy exerted better renoprotective effects on all outcome parameters. CONCLUSIONS: These results indicate that canagliflozin and irbesartan exert different effects on renal injury in SS hypertensive rats, and the combined regimen could have stronger effects than either monotherapy.

MrCreC, a carbon catabolite repression gene, is required for the growth, conidiation, stress tolerance and virulence of Metarhizium robertsii.

As a key component of carbon source metabolism in fungi, CreC WD40 repeat protein is regulated by carbon catabolite repression (CCR). However, the understanding of the functions of CreC in entomopathogenic fungi is currently limited. Here, CreC in Metarhizium robertsii (MrCreC) was identified, and its roles in fungal development, conidiation, environmental stress response, and insecticidal virulence were explored. MrCreC is localized to cytoplasm, and MrCreC deletion affects fungal growth on various nutrients. Compared to the wild type, the sporulation of ΔMrCreC strain was significantly decreased by 60.3%. Further qPCR analysis found that deletion of MrCreC resulted in repression of sporulation-related genes such as AbaA, FlbA, Flbc, MedA, FlbD, FluG, and wetA. In addition, MrCreC loss did not alter heat stress tolerance but resulted in enhanced tolerance to UV-B. Interestingly, bioassays showed that the virulence following exposures to topical applications or injection of conidial suspensions of both infection and injection was impaired compared with that of the wild type. Further analysis showed that the adhesion and cuticle penetration genes in ΔMrCreC was down-regulated during infection, and the appressorial formation rate was significantly reduced. A deletion of MrCreC significantly also reduced immune escape and nutrient utilization genes in insect hemocoel. In conclusion, MrCreC is involved in the growth, development and virulence of M. robertsii. These findings advance our understanding of the function of CCR pathway-related genes.

Electroacupuncture preconditioning protects against myocardial ischemia-reperfusion injury by modulating dynamic inflammatory response.

Background: The protective effects of electroacupuncture (EA) preconditioning against myocardial ischemia-reperfusion injury (MIRI) have been reported. However, the underlying mechanism remains unclear. Recent research has indicated that the dynamic inflammatory response following MIRI plays an essential role in the progression of myocardial injury. This study aimed to investigate the myocardial protective effects of EA preconditioning on MIRI in rats and to explore the relevant mechanism from the perspective of dynamic inflammatory response. Methods: A MIRI model was employed, and the rats were subjected to EA on Neiguan for four days prior to modeling. The myocardial protective effect of EA preconditioning was evaluated by echocardiography, Evans blue and triphenyltetrazolium chloride staining. Real-time polymerase chain reaction, Western blot, hematoxylin & eosin staining, and immunohistochemistry were utilized to detect the content of mitochondrial DNA, NOD receptor family protein 3 (NLRP3) inflammasome activation, neutrophil recruitment and macrophage infiltration in blood samples and myocardium below the ligation. Results: We found that EA preconditioning could accelerate the recovery of left ventricle function after MIRI and reduce the myocardial infarction area, thereby protecting the myocardium against MIRI. Furthermore, EA preconditioning was observed to ameliorate mitochondrial impairment, reduce the level of plasma mitochondrial DNA, modulate NLRP3 inflammasome activation, attenuate neutrophil infiltration, and promote the polarization of M1 macrophages towards M2 macrophages in the myocardium after MIRI. Conclusion: EA preconditioning could reduce plasma mtDNA, suppress overactivation of the NLRP3 inflammasome, facilitate the transition from the acute pro-inflammatory phase to the anti-inflammatory reparative phase after MIRI, and ultimately confer cardioprotective benefits.

Canagliflozin Ameliorates Ventricular Remodeling through Apelin/Angiotensin-Converting Enzyme 2 Signaling in Heart Failure with Preserved Ejection Fraction Rats.

INTRODUCTION: The aim of this study was to investigate the effect of canagliflozin (CANA) on ventricular remodeling in patients with preserved ejection fraction (HFpEF) heart failure and to further investigate its possible molecular mechanisms. METHODS: A high-salt diet was used to induce the formation of HFpEF model in salt-sensitive rats. The rats were fed with CANA and irbesartan, respectively. The mice were divided into control group, model group, CANA group, irbesartan group, and combined drug group. After 12 weeks of feeding, the rats were evaluated by measuring the relevant indexes and echocardiography for cardiac function. Histological analysis was performed using Masson trichrome staining and immunohistochemical staining. RT-qPCR and Western blot were used to quantify the relevant genes and proteins. RESULTS: In this study, CANA exhibited diuresis, decreased blood pressure, weight loss, and increased food and water intake. Following a high-salt diet, Dahl salt-sensitive rats developed hypertension followed by left ventricular diastolic dysfunction, myocardial fibrosis, and left ventricular remodeling. Myocardial hypertrophy and fibrosis were reduced, and left ventricular diastolic function and ventricular remodeling improved after CANA treatment. The combination of CANA and irbesartan was superior to monotherapy in reducing blood pressure and improving cardiac insufficiency and left ventricular diastolic dysfunction in rats. CANA improves myocardial fibrosis, left ventricular diastolic dysfunction, and ventricular remodeling by upregulating apelin, activating angiotensin-converting enzyme 2 (ACE2), and increasing ACE2/Ang (1-7)/MASR axis levels. CONCLUSION: CANA improves myocardial fibrosis, left ventricular diastolic dysfunction, and ventricular remodeling in HFpEF rats through upregulation of apelin/ACE2 signaling.

MiR-21 attenuates FAS-mediated cardiomyocyte apoptosis by regulating HIPK3 expression.

MicroRNA-21 (miR-21) plays an anti-apoptotic role following ischemia-reperfusion (I/R) injury (IRI) in vivo; however, its underlying mechanism remains unclear. The present study explored the effects of miR-21 and homeodomain interacting protein kinase 3 (HIPK3) on cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R) in vitro. To this end, the rat cardiomyocyte H9C2 cell line was exposed to H/R and the roles of miR-21 and HIPK3 in regulating cell viability and apoptosis were evaluated by cell counting kit-8 assay, terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling, and flow cytometry. Immunofluorescence and Western blotting were performed to detect the expression/phosphorylation of apoptosis-related proteins. miR-21 expression was measured with quantitative real-time polymerase chain reaction. The putative interaction between miR-21 and HIPK3 was evaluated using the luciferase reporter assay. Our results showed that (i) miR-21 overexpression or HIPK3 down-regulation significantly attenuated H9C2 cells apoptosis after H/R, (ii) suppression of miR-21 expression promoted apoptosis, (iii) miR-21 overexpression inhibited HIPK3 expression, (iv) HIPK3 was the direct and main target of miR-21, (v) miR-21/HIPK3 formed part of a reciprocal, negative feedback loop, and (vi) HIPK3 down-regulation decreased FAS-mediated apoptosis by inhibiting the phosphorylation of FADD, which subsequently inhibited the expression of BAX and cleaved caspase-3 and increased the expression of BCL2. Our study indicates that miR-21 attenuates FAS-mediated cardiomyocyte apoptosis by regulating HIPK3 expression, which could eventually have important clinical implications for patients with acute myocardial infarction.