Comprehensive prognostic and immune analysis of sterol O-acyltransferase 1 in patients with hepatocellular carcinoma.

BACKGROUND: Sterol O-acyltransferase 1 (SOAT1) is an important target in the diagnosis and treatment of liver cancer. However, the prognostic value of SOAT1 in patients with hepatocellular carcinoma (HCC) is still not clear. AIM: To investigate the correlation of SOAT1 expression with HCC, using RNA-seq and gene expression data of The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) and pan-cancer. METHODS: The correlation between SOAT1 expression and HCC was analyzed. Cox hazard regression models were conducted to investigate the prognostic value of SOAT1 in HCC. Overall survival and disease-specific survival were explored based on TCGA-LIHC data. Biological processes and functional pathways mediated by SOAT1 were characterized by gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes. In addition, the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this malignancy. RESULTS: SOAT1 and SOAT2 were highly expressed in unpaired samples, while only SOAT1 was highly expressed in paired samples. The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748, while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676. Patients with higher SOAT1 expression had lower survival rates. Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway, the IL-18 signaling pathway, the calcium signaling pathway, secreted factors, the Wnt signaling pathway, the Jak/STAT signaling pathway, the MAPK family signaling pathway, and cell-cell communication were involved in such association. SOAT1 expression was positively associated with the abundance of macrophages, Th2 cells, T helper cells, CD56bright natural killer cells, and Th1 cells, and negatively linked to the abundance of Th17 cells, dendritic cells, and cytotoxic cells. CONCLUSION: Our findings demonstrate that SOAT1 may serve as a novel target for HCC treatment, which is helpful for the development of new strategies for immunotherapy and metabolic therapy.

Comprehensive geriatric assessment of older patients with renal disease: a cross-sectional survey.

Multidimensional health function impairments are common in older patients with chronic kidney disease (CKD). The purpose of this study was to explore whether the risk or severity of geriatric syndrome increased with a decline in renal function. This survey was conducted for CKD patients aged ≥ 60 years and hospitalized at West China Hospital of Sichuan University (Center of Gerontology and Geriatrics, Nephrology, and Endocrinology) and Chengdu Kangfu Kidney Disease Hospital from September 01, 2013 to June 30, 2014. Patients underwent multidimensional individualized assessments by trained doctors. Logistic regression analysis found that the risk of assisted walking (P = 0.001) and urinary incontinence (P = 0.039) increased with a decline in renal function. Regression analysis revealed that the scores of activities of daily living (P = 0.024), nutritional status (P = 0.000), total social support (P = 0.014), and objective support (P = 0.000) decreased with a decline in renal function.

Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease (GD) and Parkinson's disease (PD). Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.

Segment selection for fusion and artificial disc replacement in the hybrid surgical treatment of noncontiguous cervical spondylosis: a finite element analysis.

Introduction: The treatment of skip-level cervical degenerative disease (CDD) with no degenerative changes observed in the intervening segment (IS) is complicated. This research aims to provide a reference basis for selecting treatment approaches for noncontiguous CDD. Methods: To establish accurate finite element models (FEMs), this study included computed tomography (CT) data from 21 patients with CDD (10 males and 11 females) for modeling. The study primarily discusses four cross-segment surgical approaches: upper (C3/4) anterior cervical discectomy and fusion (ACDF) and lower (C5/6) cervical disc arthroplasty (CDA), FA model; upper CDA (C3/4) and lower ACDF (C5/6), AF model; upper ACDF (C3/4) and lower ACDF (C5/6), FF model; upper CDA (C3/4) and lower CDA (C5/6), AA model. An initial axial load of 73.6 N was applied at the motion center using the follower load technique. A moment of 1.0 Nm was applied at the center of the C2 vertebra to simulate the overall motion of the model. The statistical analysis was conducted using STATA version 14.0. Statistical significance was defined as a p value less than 0.05. Results: The AA group had significantly greater ROM in flexion and axial rotation in other segments compared to the FA group (p < 0.05). The FA group consistently exhibited higher average intervertebral disc pressure in C2/3 during all motions compared to the AF group (p < 0.001); however, the FA group displayed lower average intervertebral disc pressure in C6/7 during all motions (p < 0.05). The AA group had lower facet joint contact stresses during extension in all segments compared to the AF group (p < 0.05). The FA group exhibited significantly higher facet joint contact stresses during extension in C2/3 (p < 0.001) and C6/7 (p < 0.001) compared to the AF group. Discussion: The use of skip-level CDA is recommended for the treatment of non-contiguous CDD. The FA construct shows superior biomechanical performance compared to the AF construct.

Efficacy of Wearable low-intensity pulsed Ultrasound treatment in the Movement disorder in Parkinson's disease (the SWUMP trial): protocol for a single-site, double-blind, randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is a progressive, neurodegenerative illness marked by the loss of dopaminergic neurons, causing motor symptoms. Oral levodopa replacement therapy remains the gold standard in the treatment of PD. It is, nevertheless, a symptomatic treatment. There is currently no effective treatment for PD. Therefore, new therapies for PD are highly desirable. Low-intensity pulsed ultrasound (LIPUS) has been shown to improve behavioral functions in PD animal models. It is a new type of neuromodulation approach that combines noninvasiveness with high spatial precision. The purpose of this study is to establish a new clinical protocol for LIPUS in the treatment of movement disorders in patients with PD. METHODS: This protocol is a single-site, prospective, double-blind, randomized controlled trial (RCT). Forty-eight participants with clinically confirmed PD will be randomly allocated to one of two groups: LIPUS group or sham group. All of the participants continue to use pharmacological therapy as a fundamental treatment. The primary outcome is the difference between groups from baseline to 4 months in the change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score (part III). The secondary outcomes include the rating scales such as the Mini-Mental State Examination (MMSE), and other three rating scales, and medical examinations including high-density electroencephalography (hdEEG) and functional magnetic resonance imaging (fMRI). The primary safety outcome will be assessed at 4 months, and adverse events will be recorded. DISCUSSION: This study represents the clinical investigation into the efficacy of therapeutic LIPUS in the treatment of PD for the first time. If LIPUS is determined to be effective, it could offer a practical and innovative means of expanding the accessibility of ultrasound therapy by using a wearable LIPUS device within a home setting. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100052093. Registered on 17 October 2021.

Nuclear and mitochondrial genomes of Polylopha cassiicola: the first assembly in Chlidanotinae (Tortricidae).

Tortricidae is one of the largest families in Lepidoptera, including subfamilies of Tortricinae, Olethreutinae, and Chlidanotinae. Here, we assembled the gap-free genome for the subfamily Chlidanotinae using Illumina, Nanopore, and Hi-C sequencing from Polylopha cassiicola, a pest of camphor trees in southern China. The nuclear genome is 302.03 Mb in size, with 36.82% of repeats and 98.4% of BUCSO completeness. The karyotype is 2n = 44 for males. We identified 15412 protein-coding genes, 1052 tRNAs, and 67 rRNAs. We also determined the mitochondrial genome of this species and annotated 13 protein-coding genes, 22 tRNAs, and one rRNA. These high-quality genomes provide valuable information for studying phylogeny, karyotypic evolution, and adaptive evolution of tortricid moths.

Laparoscopic liver resection versus radiofrequency ablation for small hepatocellular carcinoma: randomized clinical trial.

BACKGROUND: The aim of this study was to compare the efficacy of laparoscopic liver resection versus radiofrequency ablation for treatment of small hepatocellular carcinoma. METHODS: This single-centre RCT was conducted at a tertiary referral centre in China. Patients with small hepatocellular carcinoma who had a single nodule no larger than 5 cm, or up to three nodules of 3 cm or smaller, were eligible. Patients were assigned randomly in a 1 : 1 ratio to either laparoscopic liver resection or radiofrequency ablation. Blinding was not attempted. Sample size calculations led to 75 patients per group. The primary outcome was overall survival, and the secondary outcome was recurrence-free survival. RESULTS: Seventy-five patients were included in each group. Overall survival (HR 1.26, 95% c.i. 0.69 to 2.30; P = 0.451) and recurrence-free survival (HR 1.34, 0.86 to 2.08; P = 0.189) did not differ between the resection and ablation groups. The 1-, 3- and 5-year overall survival rates were 94.7, 80.0, and 74.7% respectively after laparoscopic liver resection versus 93.3, 78.7, and 67.9% after radiofrequency ablation. Corresponding recurrence-free survival rates were 78.7, 61.3, and 51.6%, and 69.3, 53.3, and 41.0%, respectively. CONCLUSION: For small hepatocellular carcinoma, percutaneous radiofrequency ablation provides therapeutic effects similar to those of laparoscopic liver resection. REGISTRATION NUMBER: NCT02243384 (http://www.clinicaltrials.gov).

Percutaneous radiofrequency ablation may provide similar therapeutic effects to laparoscopic liver resection for patients with small hepatocellular carcinoma. This study compared the two treatments. Survival was similar after the two treatments. The choice of treatment may depend on the patient's preference and local availability.

Phase Engineering of Zirconium MOFs Enables Efficient Osmotic Energy Conversion: Structural Evolution Unveiled by Direct Imaging.

Creating structural defects in a controlled manner within metal-organic frameworks (MOFs) poses a significant challenge for synthesis, and concurrently, identifying the types and distributions of these defects is also a formidable task for characterization. In this study, we demonstrate that by employing 2-sulfonylterephthalic acid as the ligand for synthesizing Zr (or Hf)-based MOFs, a crystal phase transformation from the common fcu topology to the rare jmt topology can be easily facilitated using a straightforward mixed-solvent strategy. The jmt phase, characterized by an extensively open framework, can be considered a derivative of the fcu phase, generated through the introduction of missing-cluster defects. We have explicitly identified both MOF phases, their intermediate states, and the novel core-shell structures they form using ultralow-dose high-resolution transmission electron microscopy. In addition to facilitating phase engineering, the incorporation of sulfonic groups in MOFs imparts ionic selectivity, making them applicable for osmotic energy harvesting through mixed matrix membrane fabrication. The membrane containing the jmt-phase MOF exhibits an exceptionally high peak power density of 10.08 W m-2 under a 50-fold salinity gradient (NaCl: 0.5 M|0.01 M), which surpasses the threshold of 5 W m-2 for commercial applications and can be attributed to the combination of large pore size, extensive porosity, and abundant sulfonic groups in this novel MOF material.

Advancements in research on the effects of panax notoginseng saponin constituents in ameliorating learning and memory disorders.

Learning and memory disorder is a cluster of symptoms caused by neuronal aging and other diseases of the central nervous system (CNS). Panax notoginseng saponins (PNS) are a series of saponins derived from the natural active ingredients of traditional Chinese medicine (TCM) that have neuroprotective effects on the central nervous system. In this paper, we review the ameliorative effects and mechanisms of Panax notoginseng saponin-like components on learning and memory disorders to provide valuable references and insights for the development of new drugs for the treatment of learning and memory disorders. Our summary results suggest that Panax ginseng saponins have significant effects on improving learning and memory disorders, and these effects and potential mechanisms are mediated by their anti-inflammatory, anti-apoptotic, antioxidant, ß-amyloid lowering, mitochondrial homeostasis in vivo, neuronal structure and function improving, neurogenesis promoting, neurotransmitter release regulating, and probiotic homeostasis in vivo activities. These findings suggest the potential of Panax notoginseng saponin-like constituents as drug candidates for improving learning and memory disorders.

Ninety-day postoperative mortality and complications in continuous and unselected single-stage revisions for chronic periprosthetic joint infection.

PURPOSE: Single-stage revision has gained significant attention as a major surgical approach for periprosthetic joint infection (PJI). However, the 90-day mortality and complication profile of single-stage revision is poorly characterized. The purposes of this study were to determine the incidence rates of and identify the risk factors for 90-day postoperative mortality and complications of single-stage revision for chronic PJI. METHODS: A retrospective review was conducted on patients who underwent single-stage revision for PJI between August 2000 and May 2022. Patient demographics, 90-day mortality, and postoperative complications were recorded. Complications were categorized into systemic and local complications. Patients in this study were further categorized into knee and hip revision groups. Univariate and multivariate logistic regression analyses were performed to identify significant independent predictors of the outcome measures. RESULTS: 348 patients (144 knees and 204 hips) were included in this study. The 90-day mortality rate was 0.9%. The incidence rates of postoperative complications in knee and hip surgeries were 31.3% and 19.6%, respectively. The most common complication was deep-vein thrombosis (DVT). Rheumatoid arthritis (RA) was the independent predictor of mortality. In the knee revision group, fungal infection was identified as the independent predictor of recurrent PJI; regular alcohol use was predictive of wound dehiscence. Among hip PJI patients, age ≥ 80 years was independently associated with DVT; RA was found to be a predictor of dislocation and wound dehiscence. CONCLUSION: For continuous and unselected patients with chronic PJI, single-stage revision demonstrated a satisfactory 90-day mortality. Nevertheless, the 90-day postoperative complication rates after single-stage revision in both knee and hip groups were relatively high.

Regulation of morphogenesis and pathogenicity by OsMep2, OsCph1, and OsPes1 in dimorphic entomopathogenic fungus Ophiocordyceps sinensis (Hypocreales: Ophiocordycipitaceae).

Polarized growth plays a key role in all domains of their biology, including morphogenesis and pathogenicity of filamentous fungi. However, little information is available about the determinants of polarized growth. The fungal Mep2, Pes1, and Cph1 proteins were identified to be involved in the dimorphic transition between yeast and hyphal forms in Candida albicans. In this study, evidence that the dimorphic fungal entomopathogen Ophiocordyceps sinensis Mep2, Pes1, and Cph1 proteins are involved in polarized growth is presented. OsMep2 was significantly upregulated at aerial hyphae and conidia germination stages. OsCph1 was significantly upregulated at aerial hyphae, conidia initiation, and conidia germination stages, and OsPes1 was significantly upregulated at the conidia germination stage. Deletions of OsMep2, OsCph1, and OsPes1 provoked defects in the polarized growth. The abilities of hyphal formation and the yields of blastospores and conidia for the ∆ OsMep2, ∆OsCph1, and ∆ OsPes1 mutants were significantly reduced. The conidia yields of the ΔOsMep2, ΔOsCph1, and ΔOsPes1 mutants were decreased by 69.17%, 60.90%, and 75.82%, respectively. Moreover, the pathogenicity of the ∆ OsMep2, ∆OsCph1, and ∆ OsPes1 mutants against Thitarodes xiaojinensis was significantly reduced. The mummification rate caused by wide type and ΔOsMep2, ΔOsCph1, and ΔOsPes1 mutants were 36.98% ± 8.52%, 0.31% ± 0.63%, 1.15% ± 1.57%, and 19.69% ± 5.6%, respectively. These results indicated that OsMep2, OsCph1, and OsPes1 are involved in the regulation of hyphal formation, sporulation, and pathogenicity of O. sinensis. This study provided a basis for the understanding of the fungal dimorphic development and improving the efficiency of artificial cultivation of O. sinensis.

HOXD3 promotes the migration and angiogenesis of hepatocellular carcinoma via modifying hepatocellular carcinoma cells exosome-delivered CCR6 and regulating chromatin conformation of CCL20.

Angiogenesis plays an essential role in the microenvironment of hepatocellular carcinoma (HCC). HOXD3 is involved in the metastasis and invasion of HCC cells; Whereas the underlying molecular mechanisms in the microenvironment of HCC remain unknown. Wound healing, transwell invasion, tube formation and spheroid sprouting assays were carried out to identify the effects of HCC-HOXD3-exosomes and genes on the migration of HCC cells. ChIP-PCR was applied to test the binding region of HOXD3 on CCR6, Med15, and CREBBP promoter. Exosome isolation and mRNA-seq were applied to examine the morphological characteristics of exosomes and the contained mRNA in exosomes. Co-IP and Immunofluorescence assays were used to demonstrate the role of CREBBP in the chromatin conformation of CCL20. The nude mice were used to identify the function of genes in regulating migration of HCC in vivo. In this study, integrated cellular and bioinformatic analyses revealed that HOXD3 targeted the promoter region of CCR6 and induced its transcription. CCR6 was delivered by exosomes to endothelial cells and promoted tumour migration. Overexpression of CCR6 promoted metastasis, invasion in HCCs and angiogenesis in endothelial cells (ECs), whereas its downregulation suppressed these functions. The role of HOXD3 in the metastasis and invasion of HCC cells was reversed after the suppression of CCR6. Furthermore, CCL20 was demonstrated as the ligand of CCR6, and its high expression was found in HCC tissues and cells, which was clinically associated with the poor prognosis of HCC. Mechanistically, HOXD3 targets the promoter regions of CREBBP and Med15, which affect CCL20 chromatin conformation by regulating histone acetylation and expression of Pol II to enhance the migration of HCCs. This study demonstrated the function of the HOXD3-CREBBP/Med15-CCL20-CCR6 axis in regulating invasion and migration in HCC, thus providing new therapeutic targets for HCC.

DNA Nanospheres Assisted Spatial Confinement Signal Amplification for MicroRNA Imaging in Live Cancer Cells.

DNA assemblies are commonly used in biosensing, particularly for the detection and imaging of microRNAs (miRNAs), which are biomarkers associated with tumor progression. However, the difficulty lies in the exploration of high-sensitivity analytical techniques for miRNA due to its limited presence in living cells. In this study, we introduced a DNA nanosphere (DS) enhanced catalytic hairpin assembly (CHA) system for the detection and imaging of intracellular miR-21. The single-stranded DNA with four palindromic portions and extending sequences at the terminal was annealed for assembling DS, which avoided the complex sequence design and high cost of long DNA strands. Benefiting from the multiple modification sites of DS, functional hairpins H1 (modified with Cy3 and BHQ2) and H2 were grafted onto the surface of DS for assembling DS-H1-H2 using a hybridization reaction. The DS-H1-H2 system utilized spatial confinement and the CHA reaction to amplify fluorescence signals of Cy3. This enabled highly sensitive and rapid detection of miR-21 in the range from 0.05 to 3.5 nM. The system achieved a limit of determination (LOD) of 2.0 pM, which was 56 times lower than that of the control CHA circuit with freedom hairpins. Additionally, the sensitivity was improved by 8 times. Moreover, DS-H1-H2 also showed an excellent imaging capability for endogenous miR-21 in tumor cells. This was due to enhanced cell internalization efficiency, accelerated reaction kinetics, and improved biostability. The imaging strategy was shown to effectively monitor the dynamic content of miR-21 in live cancer cells and differentiate various cells. In general, the simple nanostructure DS not only enhanced the detection and imaging capability of the conventional probe but also could be easily integrated with the reported DNA-free probe, indicating a wide range of potential applications.

The performance of artificial intelligence models in generating responses to general orthodontic questions: ChatGPT vs Google Bard.

INTRODUCTION: This study aimed to evaluate and compare the performance of 2 artificial intelligence (AI) models, Chat Generative Pretrained Transformer-3.5 (ChatGPT-3.5; OpenAI, San Francisco, Calif) and Google Bidirectional Encoder Representations from Transformers (Google Bard; Bard Experiment, Google, Mountain View, Calif), in terms of response accuracy, completeness, generation time, and response length when answering general orthodontic questions. METHODS: A team of orthodontic specialists developed a set of 100 questions in 10 orthodontic domains. One author submitted the questions to both ChatGPT and Google Bard. The AI-generated responses from both models were randomly assigned into 2 forms and sent to 5 blinded and independent assessors. The quality of AI-generated responses was evaluated using a newly developed tool for accuracy of information and completeness. In addition, response generation time and length were recorded. RESULTS: The accuracy and completeness of responses were high in both AI models. The median accuracy score was 9 (interquartile range [IQR]: 8-9) for ChatGPT and 8 (IQR: 8-9) for Google Bard (Median difference: 1; P <0.001). The median completeness score was similar in both models, with 8 (IQR: 8-9) for ChatGPT and 8 (IQR: 7-9) for Google Bard. The odds of accuracy and completeness were higher by 31% and 23% in ChatGPT than in Google Bard. Google Bard's response generation time was significantly shorter than that of ChatGPT by 10.4 second/question. However, both models were similar in terms of response length generation. CONCLUSIONS: Both ChatGPT and Google Bard generated responses were rated with a high level of accuracy and completeness to the posed general orthodontic questions. However, acquiring answers was generally faster using the Google Bard model.

Remodeling the Electronic Structure of Metallic Nickel and Ruthenium via Alloying in a Molecular Template for Sustainable Hydrogen Evolution.

The reasonably constructed high-performance electrocatalyst is crucial to achieve sustainable electrocatalytic water splitting. Alloying is a prospective approach to effectively boost the activity of metal electrocatalysts. However, it is a difficult subject for the controllable synthesis of small alloying nanostructures with high dispersion and robustness, preventing further application of alloy catalysts. Herein, we propose a well-defined molecular template to fabricate a highly dispersed NiRu alloy with ultrasmall size. The catalyst presents superior alkaline hydrogen evolution reaction (HER) performance featuring an overpotential as low as 20.6 ± 0.9 mV at 10 mA·cm-2. Particularly, it can work steadily for long periods of time at industrial-grade current densities of 0.5 and 1.0 A·cm-2 merely demanding low overpotentials of 65.7 ± 2.1 and 127.3 ± 4.3 mV, respectively. Spectral experiments and theoretical calculations revealed that alloying can change the d-band center of both Ni and Ru by remodeling the electron distribution and then optimizing the adsorption of intermediates to decrease the water dissociation energy barrier. Our research not only demonstrates the tremendous potential of molecular templates in architecting highly active ultrafine nanoalloy but also deepens the understanding of water electrolysis mechanism on alloy catalysts.

Clinical analysis of nonsyndromic oligodontia phenotypes.

OBJECTIVES: To provide references, this study investigated the clinical characteristics of patients with nonsyndromic oligodontia. METHODS: The information of 178 patients with oligodontia was collected, including histories, oral examinations, and panoramic radiographs. Tooth agenesis characteristics were calculated and evaluated. All the data were statistically analyzed with SPSS 24.0 software. RESULTS: No significant difference in the number of missing teeth was found between sexes nor between the right and left sides, and congenitally missing teeth affected the maxillary arch (P<0.05). The highest prevalence of tooth agenesis was observed in the mandibular second premolars. In the maxillary arch, the most common pattern of tooth agenesis was agenesis of the bilateral first and second premolars. The agenesis of the bilateral second premolars was observed in the mandibular arch. The prevalence of a symmetric pattern between the right and left quadrants was significantly higher than that of matched patterns between the maxillary and mandibular antagonistic quadrants. Approximately 16.85% of patients with nonsyndromic oligodontia were affected by other tooth-related anomalies. CONCLUSIONS: The common patterns of tooth agenesis were successfully identified in patients with nonsyndromic oligodontia. Dentists need to provide multidisciplinary treatments for patients with nonsyndromic oligodontia because of variations in occluding and full-mouth tooth agenesis patterns.

Gorilla optimization algorithm combining sine cosine and cauchy variations and its engineering applications.

To address the issues of lacking ability, loss of population diversity, and tendency to fall into the local extreme value in the later stage of optimization searching, resulting in slow convergence and lack of exploration ability of the artificial gorilla troops optimizer algorithm (AGTO), this paper proposes a gorilla search algorithm that integrates the positive cosine and Cauchy's variance (SCAGTO). Firstly, the population is initialized using the refractive reverse learning mechanism to increase species diversity. A positive cosine strategy and nonlinearly decreasing search and weight factors are introduced into the finder position update to coordinate the global and local optimization ability of the algorithm. The follower position is updated by introducing Cauchy variation to perturb the optimal solution, thereby improving the algorithm's ability to obtain the global optimal solution. The SCAGTO algorithm is evaluated using 30 classical test functions of Test Functions 2018 in terms of convergence speed, convergence accuracy, average absolute error, and other indexes, and two engineering design optimization problems, namely, the pressure vessel optimization design problem and the welded beam design problem, are introduced for verification. The experimental results demonstrate that the improved gorilla search algorithm significantly enhances convergence speed and optimization accuracy, and exhibits good robustness. The SCAGTO algorithm demonstrates certain solution advantages in optimizing the pressure vessel design problem and welded beam design problem, verifying the superior optimization ability and engineering practicality of the SCAGTO algorithm.

Whole transcriptome mapping reveals the lncRNA regulatory network of TFP5 treatment in diabetic nephropathy.

BACKGROUND: TFP5 is a Cdk5 inhibitor peptide, which could restore insulin production. However, the role of TFP5 in diabetic nephropathy (DN) is still unclear. OBJECTIVE: This study aims to characterize the transcriptome profiles of mRNA and lncRNA in TFP5-treated DN mice to mine key lncRNAs associated with TFP5 efficacy. METHODS: We evaluated the role of TFP5 in DN pathology and performed RNA sequencing in C57BL/6J control mice, C57BL/6J db/db model mice, and TFP5 treatment C57BL/6J db/db model mice. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were analyzed. WGCNA was used to screen hub-gene of TFP5 in treatment of DN. RESULTS: Our results showed that TFP5 therapy ameliorated renal tubular injury in DN mice. In addition, compared with the control group, the expression profile of lncRNAs in the model group was significantly disordered, while TFP5 alleviated the abnormal expression of lncRNAs. A total of 67 DElncRNAs shared among the three groups, 39 DElncRNAs showed a trend of increasing in the DN group and decreasing after TFP treatment, while the remaining 28 showed the opposite trend. DElncRNAs were enriched in glycosphingolipid biosynthesis signaling pathways, NF-κB signaling pathways, and complement activation signaling pathways. There were 1028 up-regulated and 1117 down-regulated DEmRNAs in the model group compared to control group, and 123 up-regulated and 153 down-regulated DEmRNAs in the TFP5 group compared to the model group. The DEmRNAs were involved in PPAR and MAPK signaling pathway. We confirmed that MSTRG.28304.1 is a key DElncRNA for TFP5 treatment of DN. TFP5 ameliorated DN maybe by inhibiting MSTRG.28304.1 through regulating the insulin resistance and PPAR signaling pathway. The qRT-PCR results confirmed the reliability of the sequencing data through verifying the expression of ENSMUST00000211209, MSTRG.31814.5, MSTRG.28304.1, and MSTRG.45642.14. CONCLUSION: Overall, the present study provides novel insights into molecular mechanisms of TFP5 treatment in DN.

Association of vaccination status and severity of SARS-CoV-2 infections in hospitalized patients.

Vaccination is considered the most promising approach for addressing the COVID-19 pandemic. However, even vaccinated people remain at risk. In this study, we examined the association between levels of vaccination and clinical outcomes in hospitalized patients. We conducted a retrospective review of adults hospitalized with COVID-19 infection. Of 484 patients, fully vaccinated (OR = 0.49, p = 0.001) and updated patients (OR = 0.46, p = 0.004) had significantly lower probability of critical severity compared to unvaccinated. Vaccination status is significantly related with 30-day mortality (p = 0.005) but not significantly associated with need for respiratory support or ICU stay. Mean length of stay (LOS) of 6.6 days among boosted patients is significantly lower than patients with no vaccination status (10.7 d, p < 0.001). Our study findings provide real-world evidence of the benefit of booster vaccinations against critical infection and death as well as shortcomings in ICU stay, length of stay or need for ventilatory support.

Identification of a novel Scn3b mutation in a Chinese Brugada syndrome pedigree: implications for Nav1.5 electrophysiological properties and intracellular distribution of Nav1.5 and Navß3.

Background: The Scn3b gene encodes for Navß3, a pivotal regulatory subunit of the fast sodium channel in cardiomyocytes. However, its mutation status in the Chinese population suffering from Brugada Syndrome (BrS) has not been characterized, and the contributory pathophysiological mechanisms to disease pathology remain undefined. Methods and Results: A Scn3b (c.260C>T, p.P87l) mutation was identified in a patient with BrS of Chinese descent. Functional analyses demonstrated that sodium channel activation for the wild type, mutant samples, and co-expression of both commenced at -55 mv and peaked at -25 mv. The mutant group exhibited a notable reduction, approximately 60%, in peak sodium channel activation current (INa) at -25 mv. The parameters for half-maximal activation voltages (V1/2) and slope factors (k) showed no significant differences when comparing wild type, mutant, and combined expression groups (P = 0.98 and P = 0.65, respectively). Additionally, no significant disparities were evident in terms of the steady-state sodium channel inactivation parameters V1/2 and k (with P-values of 0.85 and 0.25, respectively), nor were there significant differences in the activation time constant τ (P = 0.59) and late sodium current density (P = 0.23) across the wild-type, mutant, and co-expressed groups. Confocal imaging and Western blot analysis demonstrated decreased plasma membrane localization of SCN3B and SCN5A in the P87l group. Computational simulations of cardiac action potentials suggested that SCN3B P87l can alter the morphology of the action potentials within the endocardium and epicardium while reducing the peak of depolarization. Conclusions: The pathogenic impact of the Scn3b P87l mutation predominantly originates from a reduction in peak INa activation current coupled with decreased cell surface expression of Nav1.5 and Navß3. These alterations may influence cardiac action potential configurations and contribute to the risk of ventricular arrhythmias in individuals with BrS.