Miracle-dz/UniFAR-FTUs huggingface dataset:
NcRNA-regulated CAPZA1 associated with prognostic and immunological effects across lung adenocarcinoma

Recent discoveries have suggested that the F-actin capping protein α1 subunit (CAPZA1) in various human tumors could play a significantly important role in regulating cell proliferation, metastasis, and epithelial–mesenchymal transition. However, the immune-regulating role of CAPZA1 in the initiation and development of lung adenocarcinoma (LUAD) remains unclear. In our research, we first found that CAPZA1 serves as an oncogene in pan-cancers from the TCGA data and higher CAPZA1 expression process unfavorably prognostic value in LUAD based on starBase database, PrognoScan, and LOGpc database. Then, in our analyses, lncRNAs AC026356.1 in LUAD acted as a competitive endogenous RNA (ceRNA) of miR-30d-5p, which might be the possible regulatory miRNA of CAPZA1 based on the starBase database. Finally, we confirmed that CAPZA1 expression had a tightly positive correlation with immune infiltration cells, immune infiltration markers, TMB, MSI, immune score, stromal score, and immune checkpoints, indicating that CAPZA1 was a markedly reliable therapeutic target for immunological antitumor strategies. In conclusion, our investigations revealed that CAPZA1 might function as an immune-associated biomarker in the development and treatment of LUAD, thereby acting as a promising prognostic and therapeutic target against LUAD.
The influence of gold mining wastes on the migration-transformation behavior and health risks of arsenic in the surrounding soil of mined-area

Understanding the characteristic heavy metals and their migration-transformation behavior in mining areas is essential for the prevention and control of mining pollution. This study selected a gold mine in the Anqing-Guichi ore-cluster region in the Middle-Lower Yangtze metallogenic belt as the research area, the concentrations, and migration-transformation mechanisms of metalloid As and typical heavy metals (Cd, Zn, Pb, Cu, Cr, and Ni) in gold mining wastes (mine tailings and sewage sludge) and the surrounding soil (farmland soil and soil a mining area) were investigated. The results showed that the concentration of As was high in both mining wastes and soils, and the geo-accumulation index values of As in soils ranging from 1.44–6.70, indicated that As pollution was severe in the soil. Besides, a close correlation between the concentration of As and the content of iron was observed by XRF analysis, in conjunction with SEM observations, most As-bearing phases are embedded in Fe, O, and Si compounds. According to EDS and XPS results, the Fe-O-As particle was suggested to be Fe-(oxy)hydroxides with absorbed or co-precipitated As. Furthermore, the arsenic phase observed in the soils were consistent with the weathering oxidation products in the tailings, demonstrating that the mineral particles in the tailings could migrate into soils via atmospheric transport, rainwater leaching, surface runoff, etc., and consequently result in heavy metal accumulation. The sequential chemical extraction result showed that the residual state of As in the soil exceeded 60%, and As posed no risk to low risk according to the Risk assessment code result. However, due to the high concentration and high mobility of arsenic, its environmental impact cannot be ignored even if its bio-accessibility in mined area soil is low.
Mannose-modified erythrocyte membrane-encapsulated chitovanic nanoparticles as a DNA vaccine carrier against reticuloendothelial tissue hyperplasia virus

Introduction The erythrocyte membranes used in nanovaccines include high membrane stability, long circulation life, adaptability and extremely good bio compatibility. Nanoparticles encapsulated by erythrocyte membranes are widely used as ideal drug delivery vehicles because of their high drug loading, long circulation time, and excellent biocompatibility. The mannose modification of delivery materials can help target mannose receptors (MRs) to deliver antigens to antigen-presenting cells (APCs). Methods In this study, the antigen gene gp90 of avian reticuloendotheliosis virus (REV) was encapsulated with carboxymethyl chitosan (CS) to obtain CSgp90 nanoparticles, which were coated with mannose-modied fowl erythrocyte membranes to yield CS-gp90@M-M nanoparticles. The physicochemical characterization and immune response of the CS-gp90@M-M nanoparticles were investigated in vitro and in vivo. Results CS-gp90@M-M nanoparticles were rapidly phagocytized in vitro by macrophages to induce the production of cytokines and nitric oxide. In vivo, CS-gp90@M-M nanoparticles increased cytokine levels, the CD4+/8+ ratio, REV-specific antibodies in the peripheral blood of chicks, and the mRNA levels of immune-related genes in the spleen and bursa of immunized chicks. CS-gp90@M-M nanoparticles could be targeted to lymphoid organs to prolong the retention time of the nanoparticles at the injection site and lymphatic organs, leading to a strong, sustained immune response. Moreover, the CS-gp90@M-M nano-vaccine showed a lasting immunoprotective effect and improved the body weight of chicks after the challenge. Conclusion Overall, CS-gp90@M-M nanoparticles can be used in vaccine designs as an effective delivery carrier with immune response-enhancing effects.
Impact of malnutrition evaluated by the mini nutritional assessment on the prognosis of acute hospitalized older adults

Background Malnutrition is prevalent among hospitalized older patients. Therefore, this study aimed to investigate the association between nutritional status [assessed using the Mini Nutritional Assessment (MNA) and serum albumin levels] and adverse outcomes in hospitalized older patients. We also aimed to compare the predictive utility of our findings. Methods This retrospective cohort study was conducted between January 2016 and June 2020. In total, 808 older patients (aged ≥ 65 years, mean age 82.8 ± 6.70 years, 45.9% male) admitted to the acute geriatric unit were included in our sample. Comprehensive geriatric assessments, including the MNA, were performed. Malnutrition and risk of malnutrition were defined as MNA < 17, albumin < 3.5 g/dL and 17 ≤ MNA ≤ 24, 3.5 g/dL ≤ albumin < 3.9 g/dL, respectively. The primary outcome was that patients could not be discharged to their own homes. The secondary outcomes were overall all-cause mortality, 3-month all-cause mortality, and incidence of geriatric syndrome, including delirium, falls, and newly developed or worsening pressure sores during hospitalization. Results Poor nutritional status was associated with older age; female sex; admission from the emergency room; high risk of pressure sores and falls; lower physical and cognitive function; higher depressive score; and lower serum albumin, protein, cholesterol, and hemoglobin levels. In the fully adjusted model, malnutrition assessed using the MNA predicted discharge to nursing homes or long-term care hospitals [odds ratio (OR) 5.822, 95% confidence interval (CI): 2.092–16.199, P = 0.001], geriatric syndrome (OR 2.069, 95% CI: 1.007–4.249, P = 0.048), and 3-month mortality (OR 3.519, 95% CI: 1.254–9.872, P = 0.017). However, malnutrition assessed using albumin levels could only predict 3-month mortality (OR 3.848, 95% CI: 1.465–10.105, P = 0.006). The MNA predicted 3-month mortality with higher precision than serum albumin levels (P = 0.034) when comparing the areas under the receiver operating characteristic curve. Conclusion Nutritional risk measured by the MNA was an independent predictor of various negative outcomes in hospitalized older patients. Poor nutritional status assessed by serum albumin levels, the most widely used biochemical marker, could predict mortality, but not the development of geriatric syndrome or discharge location reflecting functional status.
The moderating effect of the COVID-19 pandemic on the mental wellbeing of health care workers on sustainable employability: A scoping review

Sustainable employability (SE) amongst healthcare workers (HCW) is an important asset for healthcare institutions. However, SE is under strain due to high work pressure, a shortage of employees, and absenteeism amongst employees based on mental problems. These developments had already started before the COVID-19 pandemic. The aim of this review is to explore whether there is a moderating effect of the COVID-19 pandemic on the mental wellbeing of HCW in the context of SE. A double blinded systematic review was conducted for this article in accordance with preferred reporting items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies were subjected to quality evaluation and narrative synthesis. The analysis of the selected literature led to the understanding that mental problems amongst HCW were already abundantly present before the COVID-19 pandemic. Mental health problems have increased in prevalence, severity, and variation. In general, a negative relation between (mental) health and SE exists. Our findings show that mental health problems have heavily impacted the SE of HCW: absenteeism has increased and perspective on work has changed. It is time to prioritize the mental health of HCW to prevent acute care capacity from declining even further and ending up in a vicious circle.
Transcriptome and single-cell analysis reveal the contribution of immunosuppressive microenvironment for promoting glioblastoma progression

Graphical Abstract Overview of the study design. (A) We firstly identified five GBM progression related pathways. By performing functional enrichment analysis on gene sets obtained from three perspectives, such as genes co-survival in TCGA-GBM and CGGA cohort, DEGs of high and low risk groups, and DEGs of IDH1 mutation compared with wild type, we identified five pathways significantly associated with poor prognosis in GBM patients. (B) Secondly, GBM TME-associated functional gene signatures were constructed. Based on the activity profile of these signatures, GBM patients were classified into four distinct subtypes and immunosuppressive subtypes were found. (C) the expression of hub genes from immunosuppressive subtypes were validated in three single-cell RNA-seq datasets, and cell types significantly associated with TME subtypes were identified. The interactions between certain cell types were also elaborated. Background and objectives GBM patients frequently exhibit severe local and systemic immunosuppression, limiting the possible efficacy of immunotherapy strategies. The mechanism through which immunosuppression is established in GBM tumors is the key to successful personalized immunotherapies. Methods We divided GBM patients into subtypes according to the expression characteristics of the TME typing-related signature matrix. WGCNA analysis was used to get co-expressed gene modules. The expression activity of hub genes retrieved from co-expressed modules was validated in two single-cell datasets. Then, cell–cell interaction was calculated. Results Four subtypes were identified in the TCGA and CGGA RNA-seq datasets simultaneously, one of which was an immunosuppressive subtype rich in immunosuppressive factors with low lymphocyte infiltration and an IDH1 mutation. Three co-expressed gene modules related to the immunosuppressive subtype were identified. These three modules are associated with the inflammatory response, angiogenesis, hypoxia, and carbon metabolism, respectively. The genes of the inflammatory response were mainly related to myeloid cells, especially TAM, angiogenesis was related to blood vessels; hypoxia and glucose metabolism were related to tumors, TAM, and blood vessels. Moreover, there was enhanced interaction between tumor cells and TAM. Discussion This research successfully found the immunosuppressive subtype and the major cell types, signal pathways, and molecules involved in the formation of the immunosuppressive subtype and will provide new clues for the improvement of GBM personalized immunotherapy in the future.
Drug repurposing screening validated by experimental assays identifies two clinical drugs targeting SARS-CoV-2 main protease

The COVID-19 pandemic prompted several drug repositioning initiatives with the aim to rapidly deliver pharmacological candidates able to reduce SARS-CoV-2 dissemination and mortality. A major issue shared by many of the in silico studies addressing the discovery of compounds or drugs targeting SARS-CoV-2 molecules is that they lacked experimental validation of the results. Here we present a computer-aided drug-repositioning campaign against the indispensable SARS-CoV-2 main protease (MPro or 3CLPro) that involved the development of ligand-based ensemble models and the experimental testing of a small subset of the identified hits. The search method explored random subspaces of molecular descriptors to obtain linear classifiers. The best models were then combined by selective ensemble learning to improve their predictive power. Both the individual models and the ensembles were validated by retrospective screening, and later used to screen the DrugBank, Drug Repurposing Hub and Sweetlead libraries for potential inhibitors of MPro. From the 4 in silico hits assayed, atpenin and tinostamustine inhibited MPro (IC50 1 µM and 4 μM, respectively) but not the papain-like protease of SARS-CoV-2 (drugs tested at 25 μM). Preliminary kinetic characterization suggests that tinostamustine and atpenin inhibit MPro by an irreversible and acompetitive mechanisms, respectively. Both drugs failed to inhibit the proliferation of SARS-CoV-2 in VERO cells. The virtual screening method reported here may be a powerful tool to further extent the identification of novel MPro inhibitors. Furthermore, the confirmed MPro hits may be subjected to optimization or retrospective search strategies to improve their molecular target and anti-viral potency.
Prism adaptation combined with eye movement training for unilateral spatial neglect after stroke: Study protocol for a single-blind prospective, randomized controlled trial

Background Unilateral spatial neglect (USN) is a complex neurological syndrome that often reduces rehabilitation outcomes, prolongs patients' hospital stays, and decreases their quality of life. However, the current therapies for USN have varying efficacy. We will explore a new treatment option that combines prism adaptation (PA) with eye movement training (EMT) for the treatment of USN after stroke. Methods We will conduct a single-blind, prospective, randomized controlled trial to assess the efficacy of the combined intervention (PA & EMT) on USN in an inpatient rehabilitation setting. The study aims to recruit 88 patients with USN after an ischemic or hemorrhagic stroke. Participants will be randomly assigned to the following four groups: (1) PA group (n = 22), (2) EMT group (n = 22), (3) PA and EMT group (n = 22), and (4) control group (n = 22). All groups will receive 10 sessions of interventions over 2 weeks, 5 times per week. Blinded assessors will conduct a baseline assessment, a post-intervention assessment, and a follow-up assessment (2 weeks post-intervention). The primary outcome measure will use the Behavioral Inattention Test-Conventional Subset (BIT-C) and Catherine Bergego Scale (CBS) to assess the levels of USN. Secondary outcome measures will assess the patient's ability to perform activities of daily living using the Modified Barthel Index (MBI). Patients who completed all treatment and assessment sessions will be included in the final analysis. Discussion This study will explore the effects of 10 sessions of combined interventions (PA & EMT) on USN and functional capacity. This study has the potential to identify a new, evidence-based treatment option and provide new ideas for the treatment of USN. Ethics and dissemination The study protocol has been approved by the Nanchong Central Hospital. Written informed consent will be obtained from all the participants. The results of this study will be disseminated to the public through scientific conferences and a peer-reviewed journal. Trial registration ChiCTR, ChiCTR2100049482. Registered on 2 August 2021, http://www.chictr. org.cn/showproj.aspx? proj=130823.
Label-free multimodal non-linear optical imaging of three-dimensional cell cultures

3D cell cultures recapitulate tissue-specific diversity and better mimic the in vivo conditions compared to 2D cell cultures. Although confocal fluorescence microscopy is probably the most commonly used optical imaging technique to characterize 3D cell cultures, the limited imaging depth greatly hinders its application. Moreover, due to difficult diffusion of fluorescent probes into thick 3D cultures, the optical imaging techniques that rely on exogeneous fluorescent probes are not desirable. To address these problems, non-linear optical (NLO) microscopy uses near infrared light excitation to achieve significant larger imaging depth and gains molecular selectivity in a label-free manner. Taking advantages of 3D optical sectioning capability, submicron resolution, and high speed, label-free multimodal NLO microscopy has offered great promise for regenerative medicine, tumor microenvironment research, and drug discovery. This article overviews and discusses the latest applications of label-free multimodal NLO microscopy as an emerging platform to facilitate 3D cell culture research.
A study of site response in the Longmen Shan and adjacent regions and site response models for the Sichuan Basin

We investigated the regional attenuation and site responses in the Sichuan Basin and adjacent Songpan-Ganze terrane of the Tibetan Plateau using seismic data recorded at 41 stations from regional earthquakes occurring between January 2009 and October 2020. Fourier amplitude spectra of Lg waves were computed and binned into 18 frequency bins with center frequencies ranging from 0.1 Hz to 20.4 Hz. The quality factor is estimated as Q ( f ) = 313 f 0.74 for the Sichuan Basin and Q ( f ) = 568 f 0.34 for the Songpan-Ganze terrane, reflecting significant differences in the crustal structure beneath these two regions. Relative to the Songpan-Ganze terrane, site responses in the Sichuan Basin are characterized by strong amplification effects at frequencies lower than 6 Hz and obvious attenuation at higher frequencies (>10 Hz). κ 0 of stations in the Sichuan Basin show clearly geographical dependence with an average value of 0.045 s, whereas stations in the Songpan-Ganze terrane generally have smaller κ 0 values with an average value of 0.028 s. In particular, site response and κ 0 of stations in the Sichuan Basin are found to be dependent on the geographically variable thickness of the sedimentary deposits (sediment thickness). These units are comprised of sedimentary rock and semi-consolidated sediments, with a maximum thickness reaching approximately 10 km. Site response terms in the Sichuan Basin derived from the Lg Fourier spectra exhibit consistent patterns versus sediment thickness as frequency increases. We developed site response models as functions of sediment thickness for stations in the Sichuan Basin. The site response model derived from Lg site terms is consistent with that based on site response terms from coda amplitude spectra and horizontal to vertical (H/V) spectral ratios. The models were then incorporated in the stochastic method of ground motion predictions in the Sichuan Basin for six earthquakes occurring between October 2020 and June 2022. Residual analysis suggests that incorporating the site response models as functions of sediment thickness can improve the ground motion prediction model for the Sichuan Basin from moderate earthquakes.
Public beliefs about trauma and its consequences: Profiles and correlates of stigma

Public stereotypes about trauma exposure and its likely consequences have the potential to influence levels of support extended to survivors in the larger community. The current project sought to examine unique profiles of stereotype endorsement both within and across participants sampled from distinct populations. Trauma-related stereotypes involving symptom course, dangerousness, employability, social functioning, predictability, character, and treatment need were examined in undergraduate (N1 = 404; N2 = 502) and MTurk (N3 = 364) samples. Sympathizing [low overall endorsement], Fearful [high overall endorsement], Pejorative [high endorsement + moralizing beliefs], Safety-Focused [intermediate endorsement + dangerousness], and Performance-Focused [intermediate endorsement + employability] groups were replicated in latent profile models across all samples. Stereotype profiles demonstrated hypothesized associations with general perspectives of mental illness although support for consistent relations with respondent characteristics (e.g., sex; personal exposure to trauma; reported exposure in friends/family) was limited. Data suggest that trauma stereotypes are endorsed at high frequencies in the general community and conform to systematic patterns of prejudice that may be overlooked in more global assessments of stigma.
Comparative genome analysis reveals high-level drug resistance markers in a clinical isolate of Mycobacterium fortuitum subsp. fortuitum MF GZ001

Introduction Infections caused by non-tuberculosis mycobacteria are significantly worsening across the globe. M. fortuitum complex is a rapidly growing pathogenic species that is of clinical relevance to both humans and animals. This pathogen has the potential to create adverse effects on human healthcare. Methods The MF GZ001 clinical strain was collected from the sputum of a 45-year-old male patient with a pulmonary infection. The morphological studies, comparative genomic analysis, and drug resistance profiles along with variants detection were performed in this study. In addition, comparative analysis of virulence genes led us to understand the pathogenicity of this organism. Results Bacterial growth kinetics and morphology confirmed that MF GZ001 is a rapidly growing species with a rough morphotype. The MF GZ001 contains 6413573 bp genome size with 66.18 % high G+C content. MF GZ001 possesses a larger genome than other related mycobacteria and included 6156 protein-coding genes. Molecular phylogenetic tree, collinearity, and comparative genomic analysis suggested that MF GZ001 is a novel member of the M. fortuitum complex. We carried out the drug resistance profile analysis and found single nucleotide polymorphism (SNP) mutations in key drug resistance genes such as rpoB, katG, AAC(2')-Ib, gyrA, gyrB, embB, pncA, blaF, thyA, embC, embR, and iniA. In addition, the MF GZ001strain contains mutations in iniA, iniC, pncA, and ribD which conferred resistance to isoniazid, ethambutol, pyrazinamide, and para-aminosalicylic acid respectively, which are not frequently observed in rapidly growing mycobacteria. A wide variety of predicted putative potential virulence genes were found in MF GZ001, most of which are shared with well-recognized mycobacterial species with high pathogenic profiles such as M. tuberculosis and M. abscessus. Discussion Our identified novel features of a pathogenic member of the M. fortuitum complex will provide the foundation for further investigation of mycobacterial pathogenicity and effective treatment.
Exposure region of the Kawase approach and its correlation with skull base anatomy: An evaluation with digital models

The Kawase approach is one of the most used trajectories in skull base surgery. The exposure range of the approach and its correlation with skull base anatomy still demand more exploration. With the help of digital rebuilding, analysis, and measurement, we evaluated the exposure range of the Kawase and extended Kawase approaches and analyzed the correlation between the exposure range and the variants of the petrosal and clival anatomy. The finding of the study demonstrated that compared to the sub-temporal approach, the Kawase approach and the extended Kawase approach significantly added the exposure range in the upper, middle, and partial inferior regions of the clivus. The gains in the exposure volume and area are more when the manipulation angle is less than 135°.