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.

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.

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.

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.

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.

Association between circulatory complement activation and hypertensive renal damage: a case-control study.

OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.

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.

Synergistic solidification and mechanism research of electrolytic manganese residue and coal fly ash based on C-A-S-H gel material.

Electrolytic manganese residue (EMR) is known for high concentrations of Mn2+, NH4+, and heavy metals. Failure to undergo benign treatment and landfill disposal would undeniably lead to negative impacts on the quality of the surrounding ecological environment. This study sought to mitigate the latent environmental risks associated with EMR using a cooperative solidification/stabilization (S/S) method involving coal fly ash (CFA). Leveraging leaching toxicity tests, the leaching behavior of pollutants in electrolytic manganese residue-based geopolymer materials (EMRGM) was determined. At the same time, mechanistic insights into S/S processes were explored utilizing characterization techniques such as XRF, XRD, FT-IR, SEM-EDS, and XPS. Those results confirmed significant reductions in the leaching toxicities of Mn2+ and NH4+ to 4.64 µg/L and 0.99 mg/L, respectively, with all other heavy metal ions falling within the permissible limits set by relevant standards. Further analysis shows that most of NH4+ volatilizes into the air as NH3, and a small part is fixed in the EMRGM in the form of struvite; in addition to being oxidized to MnOOH and MnO2, Mn2+ will also be adsorbed and wrapped by silicon-aluminum gel together with other heavy metal elements in the form of ions or precipitation. This research undeniably provides a solid theoretical foundation for the benign treatment and resourceful utilization of EMR and CFA, two prominent industrial solid wastes.

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.

A novel collaborative self-supervised learning method for radiomic data.

The computer-aided disease diagnosis from radiomic data is important in many medical applications. However, developing such a technique relies on labeling radiological images, which is a time-consuming, labor-intensive, and expensive process. In this work, we present the first novel collaborative self-supervised learning method to solve the challenge of insufficient labeled radiomic data, whose characteristics are different from text and image data. To achieve this, we present two collaborative pretext tasks that explore the latent pathological or biological relationships between regions of interest and the similarity and dissimilarity of information between subjects. Our method collaboratively learns the robust latent feature representations from radiomic data in a self-supervised manner to reduce human annotation efforts, which benefits the disease diagnosis. We compared our proposed method with other state-of-the-art self-supervised learning methods on a simulation study and two independent datasets. Extensive experimental results demonstrated that our method outperforms other self-supervised learning methods on both classification and regression tasks. With further refinement, our method will have the potential advantage in automatic disease diagnosis with large-scale unlabeled data available.

Canagliflozin ameliorates epithelial-mesenchymal transition in high-salt diet-induced hypertensive renal injury through restoration of sirtuin 3 expression and the reduction of oxidative stress.

Hypertensive nephropathy is characterized by long-term damage to renal tissues by chronic uncontrolled hypertension, and ultimately leads to the development of renal fibrosis. The epithelial-mesenchymal transition (EMT) potentially contributes to the promotion of renal fibrosis in chronic kidney disease (CKD). In this study, we investigated the potential roles of canagliflozin (Cana) on renal EMT and oxidative stress through its effects on sirtuin 3 (SIRT3) expression. High-salt diet (HSD)-induced Dahl salt-sensitive rats hypertensive renal injury led to decreased SIRT3 expression and an increase in EMT and oxidative stress. In contrast, Cana administration rescued SIRT3 expression, decreased both EMT and levels of oxidative stress, and ameliorated renal injury. Furthermore, we compared the antihypertensive and renoprotective properties of Cana when combined with irbesartan (Irb), a renin-angiotensin system (RAS) blocker. We concluded that administration of Cana in combination with Irb had a significantly greater effect in lowering systolic blood pressure when compared to Cana monotherapy. However, no statistical differences were observed between combined therapy and monotherapy groups with regards to the lowering of diastolic blood pressure and renoprotection. Utilizing the human renal proximal tubular epithelial cell line (HK-2), Angiotensin II (AngⅡ) induced HK-2 negatively regulated the expression of SIRT3, FOXO3a, catalase, and promoted EMT, all of which were reversed by Cana. Furthermore, SIRT3 silencing abolished Cana-mediated rescue of forkhead box O3a (FOXO3a) and catalase expression and Cana-mediated suppression of EMT in AngⅡ induced HK-2. Taken together, Cana acts as a renoprotective agent by suppressing EMT in the pathology of renal fibrosis via interaction with the SIRT3-FOXO3a pathway.

Differences and biocontrol potential of haustorial endophytic fungi from Taxillus Chinensis on different host plants.

BACKGROUND: To explore the community composition and diversity of the endophytic fungi in Taxillus chinensis, samples of the parasites growing on seven different hosts, Morus alba, Prunus salicina, Phellodendron chinense, Bauhinia purpurea, Dalbergia odorifera, Diospyros kaki and Dimocarpus longan, were isolated. The strains were identified by their morphological characteristics and their internal transcribed spacer (ITS) sequences. RESULTS: 150 different endophytic fungi were isolated from the haustorial roots of the seven hosts with a total isolation rate of 61.24%. These endophytic fungi were found to belong to 1 phylum, 2 classes, 7 orders, 9 families, 11 genera and 8 species. Among of them, Pestalotiopsis, Neopestalotiopsis and Diaporthe were the dominant genera, accounting for 26.67, 17.33 and 31.33% of the total number of strains, respectively. Diversity and similarity analyses showed that the endophytic fungi isolated from D. longan (H'=1.60) had the highest diversity index. The highest richness indexes were found in M. alba and D. odorifera (both 2.23). The evenness index of D. longan was the highest (0.82). The similarity coefficient of D. odorifera was the most similar to D. longan and M. alba (33.33%), while the similarity coefficient of P. chinense was the lowest (7.69%) with M. alba and D. odorifera. Nine strains showed antimicrobial activities. Among them, Pestalotiopsis sp., N. parvum and H. investiens showed significant antifungal activity against three fungal phytopathogens of medicinal plants. At the same time, the crude extracts from the metabolites of the three endophytic fungi had strong inhibitory effects on the three pathogens. Pestalotiopsis sp., N. parvum and H. investiens had the strongest inhibitory effects of S. cucurbitacearum, with inhibitory rates of 100%, 100% and 81.51%, respectively. In addition, N. parvum had a strong inhibitory effect on D. glomerata and C. cassicola, with inhibitory rates of 82.35% and 72.80%, respectively. CONCLUSIONS: These results indicate that the species composition and diversity of endophytic fungi in the branches of T. chinensis were varied in the different hosts and showed good antimicrobial potential in the control of plant pathogens.

RGD and Scutellarin Conjugate (WK001) Targeting Platelet Glycoprotein IIb/IIIa Receptor Protects from Myocardial Ischemia/Reperfusion Injury: Synthesis, Characterization, and Bioactivity Evaluation.

Myocardial ischemia/reperfusion (MI/R) injury is an unresolved clinical challenge. The blockade of binding fibrinogen by glycoprotein IIb/IIIa (GPIIb-IIIa) inhibitors has become a new therapeutic approach against MI/R injury. In this study, we modified the RGD structure to combine with scutellarin and synthesized a novel peptide, scutellarin-HomoArg-Gly-Asp-Trp-NH2 (WK001). Herein, reported experimental and docking evidence indicates that WK001 provides immediate and potent platelet inhibition, with stronger inhibition of platelet aggregation than eptifibatide and scutellarin. In particular, it is administered intravenously to prevent thrombus formation and attenuate myocardial fibrosis progression in vivo. Therefore, WK001 could be developed as an antiplatelet drug to treat thrombosis-associated diseases, such as stroke and myocardial infarction.

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.

Human Serum Albumin-enriched Clopidogrel Bisulfate Nanoparticle Alleviates Cerebral Ischemia-Reperfusion Injury in Rats.

PURPOSE: Cerebral ischemia-reperfusion (I/R) injury remains a leading cause of mobility and mortality among patients with ischemic stroke. This study aims to develop a human serum albumin (HSA)-enriched nanoparticle platform for solubilizing clopidogrel bisulfate (CLP) for intravenous administration, and to explore the protective effect of HSA-enriched nanoparticles loaded with CLP (CLP-ANPs) against cerebral I/R injury in transient middle cerebral artery occlusion (MCAO) rat model. METHODS: CLP-ANPs were synthesized via a modified nanoparticle albumin-bound technology, lyophilized, and then characterized by morphology, particle size, zeta potential, drug loading capacity, encapsulation efficiency, stability and in vitro release kinetics. In vivo pharmacokinetic studies were conducted using Sprague-Dawley (SD) rats. Also, an MCAO rat model was established to explore the therapeutic effect of CLP-ANPs on cerebral I/R injury. RESULTS: CLP-ANPs remained spherical particles with a layer of proteins forming protein corona. Lyophilized CLP-ANPs after dispersion displayed an average size of about 235.6 ± 6.6 nm (PDI = 0.16 ± 0.08) with a zeta potential of about - 13.5 ± 1.8 mV. CLP-ANPs achieved sustained release for up to 168 h in vitro. Next, a single injection of CLP-ANPs dose-dependently reversed the histopathological changes induced by cerebral I/R injury possibly via attenuating apoptosis and reducing oxidative damages in the brain tissues. CONCLUSIONS: CLP-ANPs represent a promising and translatable platform system for the management of cerebral I/R injury during ischemic stroke.

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.

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.

Efficacy of Deep Brain Stimulation for Camptocormia in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Camptocormia is one of the most common postural disorders of Parkinson's disease (PD) which has limited treatment options. In this review, we summarize the efficacy of deep brain stimulation (DBS) for camptocormia in PD. METHODS: The PubMed (https://pubmed.ncbi.nlm.nih.gov/) and EMBASE databases (https://www.embase.com/) were searched for the terms "Parkinson Disease" and "camptocormia" in combination with "deep brain stimulation". We then explored the efficacy of DBS for camptocormia by statistical analysis of the bending angle, the Unified Parkinson's Disease Rating Scale III (UPDRS-III) and L-dopa equivalent daily dose (LEDD), and by evaluating the prognosis after DBS. RESULTS: Twenty articles that reported results for 152 patients were included in this review. These comprised 136 patients from 16 studies who underwent subthalamic nucleus deep brain stimulation (STN-DBS), and 13 patients from 3 studies who underwent globus pallidus internus deep brain stimulation (GPi-DBS). One study used both STN-DBS (2 patients) and GPi-DBS (one patient). After 3-21 months of follow-up, the mean bending angle during the Off-period was significantly reduced compared to pre-DBS (31.5 ± 21.4 vs. 53.6 ± 22.7, respectively; p < 0.0001). For the STN-DBS trials, the mean post-operative bending angles during both Off- and On-periods were significantly reduced compared to pre-operative (32.1 ± 22.7 vs. 55.4 ± 24.1, p = 0.0003; and 33.1 ± 21.5 vs. 43.7 ± 20.6, p = 0.0003, respectively). For GPi-DBS, the mean bending angle post-DBS during the Off-period was considerably lower than pre-DBS (28.5 ± 10.7 vs. 42.9 ± 9.9, p < 0.001). The decrease in bending angle after DBS was negatively correlated with the duration of camptocormia (R = - 0.433, p = 0.013), whereas positively associated with the pre-bending angle (R = 0.352, p = 0.03). CONCLUSIONS: DBS is an effective treatment for camptocormia in PD. Patients in the early stage of camptocormia with more significant bending angle may benefit more from DBS.

Effect of Ag Modification on the Structure and Photocatalytic Performance of TiO2/Muscovite Composites.

Ag/TiO2/muscovite (ATM) composites were prepared by the sol-gel method and the effects of Ag modification on the structure and photocatalytic performance were investigated. The photocatalysts were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer-Emmett-Teller surface area (BET), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectra (FTIR), photoluminescence spectra (PL) and ultraviolet-visible diffuse reflectance spectra (DRS). The photocatalytic activity of the obtained composites was evaluated by taking 100 mL (10 mg/L) of Rhodamine B (RhB) aqueous solution as the target pollutant. The muscovite (Mus) loading releases the agglomeration of TiO2 particles and the specific surface area increases from 17.6 m2/g (pure TiO2) to 39.5 m2/g (TiO2/Mus). The first-order reaction rate constant increases from 0.0009 min-1 (pure TiO2) to 0.0074 min-1 (150%TiO2/Mus). Ag element exists in elemental silver. The specific surface area of 1-ATM further increases to 66.5 m2/g. Ag modification promotes the separation of photogenerated electrons and holes and increases the visible light absorption. 1%Ag-TiO2/Mus (1-ATM) exhibits the highest photocatalytic activity. After 100 min, the rhodamine B (RhB) degradation degrees of PT, 150%TiO2/Mus and 1-ATM are 10.4%, 48.6% and 90.6%, respectively. The first-order reaction rate constant of 1-ATM reaches 0.0225 min-1, which is 25 times higher than that of pure TiO2.

A novel Ontology-guided Attribute Partitioning ensemble learning model for early prediction of cognitive deficits using quantitative Structural MRI in very preterm infants.

Structural magnetic resonance imaging studies have shown that brain anatomical abnormalities are associated with cognitive deficits in preterm infants. Brain maturation and geometric features can be used with machine learning models for predicting later neurodevelopmental deficits. However, traditional machine learning models would suffer from a large feature-to-instance ratio (i.e., a large number of features but a small number of instances/samples). Ensemble learning is a paradigm that strategically generates and integrates a library of machine learning classifiers and has been successfully used on a wide variety of predictive modeling problems to boost model performance. Attribute (i.e., feature) bagging method is the most commonly used feature partitioning scheme, which randomly and repeatedly draws feature subsets from the entire feature set. Although attribute bagging method can effectively reduce feature dimensionality to handle the large feature-to-instance ratio, it lacks consideration of domain knowledge and latent relationship among features. In this study, we proposed a novel Ontology-guided Attribute Partitioning (OAP) method to better draw feature subsets by considering the domain-specific relationship among features. With the better-partitioned feature subsets, we developed an ensemble learning framework, which is referred to as OAP-Ensemble Learning (OAP-EL). We applied the OAP-EL to predict cognitive deficits at 2 years of age using quantitative brain maturation and geometric features obtained at term equivalent age in very preterm infants. We demonstrated that the proposed OAP-EL approach significantly outperformed the peer ensemble learning and traditional machine learning approaches.