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Glutathione (GSH) plays a crucial role in several physiological processes, including anti-oxidation and heavy metal detoxification. GSH is produced endogenously in the human body and can also be obtained through diet. The development of fast, highly sensitive, and multi-application fluorescent probes remains a challenging task. In this study, we have designed and synthesized a coumarin-based fluorescent probe (NFRF) for the sensitive and rapid detection of GSH in 100 % aqueous solution. By loading probe NFRF on the filter paper, the real-time visual detection of GSH is achieved in both daylight and fluorescence modes, providing a convenient, economical and rapid on-site detection tool. Probe NFRF could be used for the detection of GSH in real samples, with recoveries rates of 81.74 %-115.12 %. Notably, the probe imaged changes in GSH concentrations in oxidative stress environments and during ferroptosis. This work provides a prospective method for GSH detection in food and complex biological systems.

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Janus TiPX (X = F, Cl, and Br) monolayers were systematically investigated through first-principles calculations. The Janus TiPX monolayers exhibit mechanical and dynamic stability. Two monolayers are indirect bandgap semiconductors, except the TiPBr monolayer, which has the features of a quasi-direct bandgap semiconductor. Biaxial strain can modify the band gap of single layers. The Janus TiPX monolayers have remarkable flexibility and piezoelectric properties. In particular, the TiPF monolayer shows high horizontal (44.18 pm V-1) and vertical piezoelectric coefficients (-3.59 pm V-1). These values exceed those of conventional bulk materials, like GaN (3.1 pm V-1) and α-quartz (2.3 pm V-1). All of the monolayers have absorption coefficients of 105 cm-1 for visible and ultraviolet (UV) light, which are one order of magnitude greater than that of MoSSe. Furthermore, TiPX monolayers have high carrier mobility. Janus TiPX monolayers represent a class of two-dimensional (2D) materials with exceptional properties and multifunctionality, holding significant promise for various applications in piezoelectric sensors, solar cells, and nano-electronic devices.

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Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) have the potential application in evaluating pathological structural change of the optic nerve. We aimed to evaluate the value of the OCT and OCTA parameters of the optic disk and macular in differentiating early chronic primary angle-closure glaucoma (CPACG) and early pituitary adenoma (PA) in case of mild visual field defects (the mean defect (MD) > 6 dB). The results showed that regarding OCTA parameters, CPACG patients had lower retinal blood flow density of most layers of the optic disk and macular than PA patients. Regarding OCT parameters, CPACG patients had thinner circumpapillary retinal nerve fiber layer (CP-RNFL) in all quadrants and average CP-RNFL, ganglion cell layer (GCL) and macular ganglion cell complex (GCC) in each quadrant of macular inner and outer rings, and inner plexus layer (IPL) of macular inner ring, superior-outer ring and temporal-outer ring than PA patients. The Z test indicated that OCTA parameters and OCT parameters had similar value in the diagnosis of disease. In conclusion, in the case of similar visual field damage, early CPACG patients have smaller blood flow density and thinner optic disk and macular than early PA. OCTA has similar performance to OCT in diagnosing CPACG and PA.

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Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma and has a poor prognosis. Despite the impressive advancements in treating ccRCC using immune checkpoint (IC) blockade, such as PD-1/PD-L1 inhibitors, a considerable number of ccRCC patients experience adaptive resistance. Therefore, exploring new targetable ICs will provide additional treatment options for ccRCC patients. We comprehensively analyzed multi-omics data and performed functional experiments, such as pathologic review, bulk transcriptome data, single-cell sequencing data, Western blotting, immunohistochemistry and in vitro/in vivo experiments, to explore novel immunotherapeutic targets in ccRCC. It was found that immune-related genes VSIG4, SAA1, CD7, FOXP3, IL21, TNFSF13B, BATF, CD72, MZB1, LTB, CCL25 and KLRK1 were significantly upregulated in ccRCC (Student's t test and p-value < 0.05; 36 normal and 267 ccRCC tissues in raining cohort; 36 normal and 266 ccRCC tissues in validation cohort) and correlated with the poor prognosis of ccRCC patients (Wald test and p-value < 0.05 in univariate cox analysis; log-rank test and p-value < 0.05 in Kaplan-Meier method; 267 patients in training cohort and 266 in validation cohort). In particular, we found the novel IC target VSIG4 was specifically expressed in inhibitory immune cells M2-biased tumor-associated macrophages (TAMs), conventional dendritic cell 2 (cDC2) cells, and cycling myeloid cells in ccRCC microenvironment. Moreover, VSIG4 showed a closely relation with resistance of Ipilimumab/Nivolumab immunotherapy in ccRCC. Furthermore, VSIG4 promoted the infiltration of M2 macrophages, Tregs, and cDC2 in ccRCC tissues. VSIG4+ TAMs and VSIG4+ cDC2s may be a kind of immune cell subtypes related to immunosuppression. VSIG4 may play similar roles with other IC ligands, as it is highly expressed on the surface of antigen-presenting cells and ccRCC cells to inhibit T cells activity and facilitate immune escape. Targeting IC gene VSIG4 may provide a novel immunotherapeutic strategy to ccRCC patients with resistance to existing targeted therapy options.

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INTRODUCTION: The molecular basis of cognitive resilience (CR) among pathologically confirmed Alzheimer's disease (AD) cases is not well understood. METHODS: Abundance of 13 cell types and neuronal subtypes in brain bulk RNA-seq data from the anterior caudate, dorsolateral prefrontal cortex (DLPFC), and posterior cingulate cortex (PCC) obtained from 434 AD cases, 318 cognitively resilient AD cases, and 188 controls in the Religious Orders Study and Rush Memory and Aging Project was estimated by deconvolution. RESULTS: PVALB+ neuron abundance was negatively associated with cognitive status and tau pathology in the DLPFC and PCC (Padj < 0.001) and the most reduced neuronal subtype in AD cases compared to controls in DLPFC (Padj = 8.4 × 10-7) and PCC (Padj = 0.0015). We identified genome-wide significant association of neuron abundance with TMEM106B single nucleotide polymorphism rs13237518 in PCC (p = 6.08 × 10-12). rs13237518 was also associated with amyloid beta (p = 0.0085) and tangles (p = 0.0073). DISCUSSION: High abundance of PVALB+ neurons may be a marker of CR. TMEM106B variants may influence CR independent of AD pathology. HIGHLIGHTS: Neuron retention and a lack of astrocytosis are highly predictive of Alzheimer's disease (AD) resilience. PVALB+ GABAergic and RORB+ glutamatergic neurons are associated with cognitive status. A TMEM106B single nucleotide polymorphism is related to lower AD risk, higher neuron count, and increased AD pathology.

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AIM: To assess the research capacity of 3014 clinical nurses in northeastern China, examining their participation in research and self-assessed competencies to advance nursing practice. BACKGROUND: Nursing research is essential for the development of the nursing discipline, yet significant progress in enhancing the research capabilities of nursing staff has been limited over the past decades. Clinical nurses, central to the execution of research activities, need improved research skills to identify relevant topics and synthesise clinical experiences with the literature. DESIGN: A cross-sectional survey. METHODS: In 2023, using a convenience sampling method, a cross-sectional questionnaire survey was conducted on 3014 nurses in a Grade A tertiary hospital. The questionnaire included questions on basic information and scientific research, as well as a self-evaluation scale assessing the nurses' capability for conducting scientific research. RESULTS: Among the nurses participating in the survey, 29.66% (894) had published academic papers in Chinese, 2.06% (62) had published papers in Science Citation Index journals, 2.39% (72) had hosted nursing research projects, 5.87% (177) had participated in nursing research projects and 71% (2140) expressed their willingness to participate in nursing research activities. The average score on the self-evaluation of research capability was 54.08 ± 24.55, with scores ranging from 0 to 120. CONCLUSION: The clinical nurses' research capacity scores are at the midpoint of the scale (0-120), indicating basic research capabilities with room for improvement. There is a high willingness to engage in research. Nursing managers should consider these factors in training programmes and promote research activities to improve the team's scientific capability. RELEVANCE TO CLINICAL PRACTICE: This study reveals a critical gap between nurses' willingness and actual involvement in research, emphasising the need for enhanced research skills to improve nursing practice. PATIENT OR PUBLIC CONTRIBUTION: This study did not require patient or public involvement in its design, outcome measures or execution. The contribution of patients/members of the public was limited solely to data collection.

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The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp3)-rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is a scarcity of catalytic asymmetric cycloadditions of BCBs to fulfill the need for enantioenriched saturated bicycles in drug design and development. In this study, an efficient synthesis of valuable azabicyclo[2.1.1]hexanes (aza-BCHs) by an enantioselective zinc-catalyzed (3+2) cycloadditions of BCBs with imines is reported. The reaction proceeds effectively with a novel type of BCB that incorporates a 2-acyl imidazole group and a diverse array of alkynyl- and aryl-substituted imines. The target aza-BCHs, which consist of α-chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94% yield and 96.5:3.5 er under mild conditions. Experimental and computational studies reveal that the reaction follows a concerted nucleophilic ring-opening mechanism of BCBs with imines. This mechanism is distinct from previous studies on Lewis acid-catalyzed cycloadditions of BCBs.

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The potential of circular RNAs (circRNAs) as biomarkers and therapeutic targets is becoming increasingly evident, yet their roles in cardiac regeneration and myocardial renewal remain largely unexplored. Here, we investigated the function of circIGF1R and related mechanisms in cardiac regeneration. Through analysis of circRNA sequencing data from neonatal and adult cardiomyocytes, circRNAs associated with regeneration were identified. Our data showed that circIGF1R expression was high in neonatal hearts, decreased with postnatal maturation, and up-regulated after cardiac injury. The elevation was validated in patients diagnosed with acute myocardial infarction (MI) within 1 week. In human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and myocardial tissue from mice after apical resection and MI, we observed that circIGF1R overexpression enhanced cardiomyocyte proliferation, reduced apoptosis, and mitigated cardiac dysfunction and fibrosis, while circIGF1R knockdown impeded endogenous cardiac renewal. Mechanistically, we identified circIGF1R binding proteins through circRNA precipitation followed by mass spectrometry. RNA pull-down Western blot and RNA immunoprecipitation demonstrated that circIGF1R directly interacted with DDX5 and augmented its protein level by suppressing ubiquitin-dependent degradation. This subsequently triggered the ß-catenin signaling pathway, leading to the transcriptional activation of cyclin D1 and c-Myc. The roles of circIGF1R and DDX5 in cardiac regeneration were further substantiated through site-directed mutagenesis and rescue experiments. In conclusion, our study highlights the pivotal role of circIGF1R in facilitating heart regeneration and repair after ischemic insults. The circIGF1R/DDX5/ß-catenin axis emerges as a novel therapeutic target for enhancing myocardial repair after MI, offering promising avenues for the development of regenerative therapies.

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OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic prompted a rapid shift from in-person to virtual learning in dental education. This study aims to assess the perceptions of virtual education learning among dental residents and faculty and employ regulatory focus theory (RFT) to understand the impact of motivational orientations on virtual learning during the COVID-19 pandemic. METHODS: In total, 46 dental residents and 10 faculty members in a dental institution participated in the study (June-August 2021). Questionnaires were used to obtain data on demographics, perceptions of virtual learning, burnout, and RFT types (promotion and prevention focus). Multiple regression analyses were used to examine factors associated with perceptions of virtual learning and burnout. RESULTS: Overall, 70% of residents and 44% of faculty found virtual learning effective. Younger residents with less experience preferred virtual learning more than their older, experienced peers. Residents trained outside the U.S. and Canada favored in-person learning more than those trained within. Furthermore, residents with a higher promotion focus score found virtual learning more interactive for didactic courses. Additionally, 52% of residents experienced burnout, with a higher incidence among females (p = 0.044). CONCLUSIONS: Virtual learning is well received by dental residents and faculty, with potential for continued use post-pandemic. Future efforts should focus on creating an inclusive and supportive educational environment that meets the motivational and well-being needs of dental residents and faculty.

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Maternal age is one of the most important factors affecting the success of maternal pregnancy. Uterine aging is the leading cause of pregnancy failure in older women. However, how uterine aging affects uterine receptivity and decidualization is unclear. In this study, naturally aged one-year-old female mice were used to investigate effects of maternal age on embryo implantation during early pregnancy. In our study, we found abnormal uterine receptivity in aged mice. Aged mouse uterus indicates a decrease in nuclear LAMIN A, and an increase in PRELAMIN A and PROGERIN. In aged mouse uterus, double-stranded DNA (dsDNA) in cytoplasmic fraction is significantly increased. PROGERIN overexpression in mouse uterine epithelial cells and epithelial organoids leads to nuclear DNA leakage and impaired uterine receptivity. DNase I, DNase II, and TREX1 are obviously reduced in aged mouse uterus. Treatments with foreign DNA or STING agonist significantly downregulate uterine receptivity markers and activate cGAS-STING pathway. Uterine estrogen (E2) concentration is significantly increased in aged mice. After ovariectomized mice are treated with a high level of E2, there are significant increase of PROGERIN and cytoplasmic DNA, and activation of cGAS-STING pathway. CD14 is significantly increased in aged uterus. Intrauterine CD14 injection inhibits embryo implantation. In vitro CD14 treatment of cultured epithelial cells or epithelial organoids decreases uterine receptivity. Uterine abnormality in aged mouse can be partially rescued by STING inhibitor. In conclusion, uterine PROGERIN increase in aged mouse uterus results in cytoplasmic DNA accumulation and cGAS-STING pathway activation. CD14 secretion in aged uterus impairs uterine receptivity.

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OBJECTIVE: To assess the role of Machine Learning (ML) in identification critical factors of dementia and mild cognitive impairment. METHODS: 371 elderly individuals were ultimately included in the ML analysis. Demographic information (including gender, age, parity, visual acuity, auditory function, mobility, and medication history) and 35 features from 10 assessment scales were used for modeling. Five machine learning classifiers were used for evaluation, employing a procedure involving feature extraction, selection, model training, and performance assessment to identify key indicative factors. RESULTS: The Random Forest model, after data preprocessing, Information Gain, and Meta-analysis, utilized three training features and four meta-features, achieving an area under the curve of 0.961 and a accuracy of 0.894, showcasing exceptional accuracy for the identification of dementia and mild cognitive impairment. CONCLUSIONS: ML serves as a identification tool for dementia and mild cognitive impairment. Using Information Gain and Meta-feature analysis, Clinical Dementia Rating (CDR) and Neuropsychiatric Inventory (NPI) scale information emerged as crucial for training the Random Forest model.

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In moiré crystals resulting from the stacking of twisted two-dimensional (2D) layered materials, a subtle adjustment in the twist angle surprisingly gives rise to a wide range of correlated optical and electrical properties. Herein, we report the synthesis of supertwisted WS2 spirals and the observation of giant second harmonic generation (SHG) in these spirals. Supertwisted WS2 spirals featuring different twist angles are synthesized on a Euclidean or step-edge particle-induced non-Euclidean surface using carefully designed water-assisted chemical vapor deposition. We observed an oscillatory dependence of SHG intensity on layer number, attributed to atomically phase-matched nonlinear dipoles within layers of supertwisted spiral crystals where inversion symmetry is restored. Through an investigation into the twist angle evolution of SHG intensity, we discovered that the stacking model between layers plays a crucial role in determining the nonlinearity, and the SHG signals in supertwisted spirals exhibit enhancements by a factor of 2 to 136 when compared with the SHG of the single-layer structure. These findings provide helpful perspectives on the rational growth of 2D twisted structures and the implementation of twist angle adjustable endowing them great potential for exploring strong coupling correlation physics and applications in the field of twistronics.

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The objective of this study was to examine the effects of varying levels of dietary chitosan supplementation on mitigating cadmium stress and its influence on growth performance, serum biochemical indices, antioxidant capacity, immune response, inflammatory response, and the expression of related genes in juvenile Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus). Five groups of juvenile tilapias (initial body weight 21.21 ± 0.24 g) were fed five diets with different levels (0%, 0.5%, 1.0%, 1.5%, and 2.0%) of chitosan supplementation for 60 days under cadmium stress (0.2 mg/L Cd2+). The findings indicated that, compared with the 0% chitosan group, dietary chitosan could significantly increase (p < 0.05) the final weight (Wf), weight gain rate (WGR), specific growth rate (SGR), daily growth index (DGI), and condition factor (CF), while the feed conversion ratio (FCR) expressed the opposite trend in juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of cholinesterase (CHE), albumin (ALB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP), and lysozyme (LZM), while glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and complement 3 (C3) in the serum of juvenile GIFT expressed the opposite trend. Dietary chitosan could significantly increase (p < 0.05) the activities of superoxide dismutase (SOD) and catalase (CAT) and significantly decrease (p < 0.05) the activities (contents) of glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in the serum of juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of CAT, GST, GSH-Px, and total antioxidant capacity (T-AOC) and significantly decrease (p < 0.05) the contents of MDA in the liver of juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of SOD, GSH-Px, T-AOC, Na+-K+-ATPase, and Ca2+-ATPase and significantly decrease (p < 0.05) the activities (contents) of CAT, GST, and MDA in the gills of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of cat, sod, gst, and gsh-px in the liver of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of interferon-γ (inf-γ) in the gills and spleen and significantly down-regulate (p < 0.05) the gene expression of inf-γ in the liver and head kidney of juvenile GIFT. Dietary chitosan could significantly down-regulate (p < 0.05) the gene expression of interleukin-6 (il-6), il-8, and tumor necrosis factor-α (tnf-α) in the liver, gills, head kidney, and spleen of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of il-10 in the liver, gills, head kidney, and spleen of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of transforming growth factor-ß (tgf-ß) in the liver and significantly down-regulate (p < 0.05) the gene expression of tgf-ß in the head kidney and spleen of juvenile GIFT. In conclusion, dietary chitosan could mitigate the impact of cadmium stress on growth performance, serum biochemical indices, antioxidant capacity, immune response, inflammatory response, and related gene expression in juvenile GIFT. According to the analysis of second-order polynomial regression, it was found that the optimal dietary chitosan levels in juvenile GIFT was approximately 1.42% to 1.45%, based on its impact on Wf, WGR, SGR, and DGI.

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Background: Traditional observational studies exploring the association between air pollution and infections have been limited by small sample sizes and potential confounding factors. To address these limitations, we applied Mendelian randomization (MR) to investigate the potential causal relationships between particulate matter (PM2.5, PM2.5-10, and PM10), nitrogen dioxide, and nitrogen oxide and the risks of infections. Methods: Single nucleotide polymorphisms (SNPs) related to air pollution were selected from the genome-wide association study (GWAS) of the UK Biobank. Publicly available summary data for infections were obtained from the FinnGen Biobank and the COVID-19 Host Genetics Initiative. The inverse variance weighted (IVW) meta-analysis was used as the primary method for obtaining the Mendelian randomization (MR) estimates. Complementary analyses were performed using the weighted median method, MR-Egger method, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) test. Results: The fixed-effect IVW estimate showed that PM2.5, PM2.5-10 and Nitrogen oxides were suggestively associated with COVID-19 [for PM2.5: IVW (fe): OR 3.573(1.218,5.288), PIVW(fe) = 0.021; for PM2.5-10: IVW (fe): OR 2.940(1.385,6.239), PIVW(fe) = 0.005; for Nitrogen oxides, IVW (fe): OR 1.898(1.318,2.472), PIVW(fe) = 0.010]. PM2.5, PM2.5-10, PM10, and Nitrogen oxides were suggestively associated with bacterial pneumonia [for PM2.5: IVW(fe): OR 1.720 (1.007, 2.937), PIVW(fe) = 0.047; for PM2.5-10: IVW(fe): OR 1.752 (1.111, 2.767), P IVW(fe) = 0.016; for PM10: IVW(fe): OR 2.097 (1.045, 4.208), PIVW(fe) = 0.037; for Nitrogen oxides, IVW(fe): OR 3.907 (1.209, 5.987), PIVW(fe) = 0.023]. Furthermore, Nitrogen dioxide was suggestively associated with the risk of acute upper respiratory infections, while all air pollution were not associated with intestinal infections. Conclusions: Our results support a role of related air pollution in the Corona Virus Disease 2019, bacterial pneumonia and acute upper respiratory infections. More work is need for policy formulation to reduce the air pollution and the emission of toxic and of harmful gas.

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BACKGROUND: Emerging evidence suggested that S-adenosylhomocysteine (SAH) may be a better serum biomarker for cardiovascular disease than homocysteine (Hcy). However, the role of SAH in hepatocellular carcinoma (HCC) prognosis remains unclear. OBJECTIVES: We aimed to prospectively explore the relationships between serum SAH and related metabolites [Hcy, S-adenosylmethionine (SAM)] with HCC survival, and to evaluate the effect modifications by gene polymorphisms in one-carbon metabolism key enzymes. METHODS: We included 1080 newly diagnosed patients with HCC from the Guangdong Liver Cancer Cohort. Serum SAH, Hcy, and SAM were measured utilizing high-performance liquid chromatography-tandem mass spectrometry. Gene polymorphisms in one-carbon metabolism key enzymes were identified using kompetitive allele-specific polymerase chain reaction. Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariate Cox proportional hazards models. RESULTS: After a median follow-up of 3.6 y, 601 deaths occurred, with 552 (92%) attributed to HCC. Multivariable analysis revealed that patients in the highest quartile of serum SAH concentrations were significantly associated with worse survival compared with those in the lowest quartile, with HRs of 1.58 (95% CI: 1.19, 2.10; P-trend = 0.002) for LCSS and 1.54 (95% CI: 1.18, 2.02; P-trend = 0.001) for OS. There were no significant interactions between serum SAH concentrations and genetic variants of one-carbon metabolism key enzymes. No significant associations were found between serum Hcy, SAM concentrations, and SAM/SAH ratio with LCSS or OS. CONCLUSIONS: Higher serum SAH concentrations, rather than Hcy, were independently associated with worse survival in patients with HCC, regardless of the genetic variants of one-carbon metabolism key enzymes. These findings suggest that SAH may be a novel metabolism-related prognostic biomarker for HCC.

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BACKGROUND: Peripherally Inserted Central Catheter (PICC) is essential in neonatal care, especially for critically ill infants. Traditional training for neonatal PICC insertion faces challenges such as high costs and limited practice opportunities. Virtual simulation technology has emerged as a potential training tool, providing a realistic, risk-free learning environment. OBJECTIVES: The study aimed to assess the effectiveness of a virtual simulation teaching system in neonatal PICC care training, focusing on improving nursing students' knowledge， skills and interest in pediatric nursing. DESIGN: A quasi-experimental design was used, with assessments conducted before and after the activity. PARTICIPANTS: The study involved 58 graduate nursing students from China Medical University, divided into experimental and control groups. METHODS: The System Usability Scale (SUS) was utilized to assess teachers' experiences with the PICC virtual simulation software. Students' perceptions of the software and their interest in pediatric nursing were measured using Self-Administered Questionnaires. Furthermore, Theoretical and Operational Assessments were applied to determine the extent of students' knowledge and practical skills before and after experimentation. RESULTS: Teachers and students have favorably evaluated the software system, with notable improvements in theoretical scores following testing. While the virtual simulation system does not enhance practical skills, it does increase student interest in pediatric nursing and employment. CONCLUSIONS: This neonatal virtual simulation software serves as a complement to, rather than a replacement for, traditional clinical training. Its integration into educational programs significantly enhances learning outcomes.

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PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

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Cytosine modifications, particularly 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), play crucial roles in numerous biological processes. Current analytical methods are often constrained to the separate detection of either 5mC or 5hmC, or the combination of both modifications. The ability to simultaneously detect C, 5mC, and 5hmC at the same genomic locations with precise stoichiometry is highly desirable. Herein, we introduce a method termed engineered deaminase-assisted sequencing (EDA-seq) for the simultaneous quantification of C, 5mC, and 5hmC at the same genomic sites. EDA-seq utilizes a specially engineered protein, derived from human APOBEC3A (A3A), known as eA3A-M5. eA3A-M5 exhibits distinct deamination capabilities for C, 5mC, and 5hmC. In EDA-seq, C undergoes complete deamination and is sequenced as T. 5mC is partially deaminated resulting in a mixed readout of T and C, and 5hmC remains undeaminated and is read as C. Consequently, the proportion of T readouts (P T) reflects the collective occurrences of C and 5mC, regulated by the deamination rate of 5mC (R 5mC). By determining R 5mC and P T values, we can deduce the precise levels of C, 5mC, and 5hmC at particular genomic locations. We successfully used EDA-seq to simultaneously measure C, 5mC, and 5hmC at specific loci within human lung cancer tissue and their normal counterpart. The results from EDA-seq demonstrated a strong concordance with those obtained from the combined application of BS-seq and ACE-seq methods. EDA-seq eliminates the need for bisulfite treatment, DNA oxidation or glycosylation and uniquely enables simultaneous quantification of C, 5mC and 5hmC at the same genomic locations.

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Pathological examination of nasopharyngeal carcinoma (NPC) is an indispensable factor for diagnosis, guiding clinical treatment and judging prognosis. Traditional and fully supervised NPC diagnosis algorithms require manual delineation of regions of interest on the gigapixel of whole slide images (WSIs), which however is laborious and often biased. In this paper, we propose a weakly supervised framework based on Tokens-to-Token Vision Transformer (WS-T2T-ViT) for accurate NPC classification with only a slide-level label. The label of tile images is inherited from their slide-level label. Specifically, WS-T2T-ViT is composed of the multi-resolution pyramid, T2T-ViT and multi-scale attention module. The multi-resolution pyramid is designed for imitating the coarse-to-fine process of manual pathological analysis to learn features from different magnification levels. The T2T module captures the local and global features to overcome the lack of global information. The multi-scale attention module improves classification performance by weighting the contributions of different granularity levels. Extensive experiments are performed on the 802-patient NPC and CAMELYON16 dataset. WS-T2T-ViT achieves an area under the receiver operating characteristic curve (AUC) of 0.989 for NPC classification on the NPC dataset. The experiment results of CAMELYON16 dataset demonstrate the robustness and generalizability of WS-T2T-ViT in WSI-level classification.

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To explore the association between fluoride exposure and depression / anxiety in adults, the 1,169 participants were recruited. The demographic information of participants was obtained through questionnaire survey and physical measurements. Morning urine samples were collected, and urinary fluoride (UF) level was determined. Changes in depression and anxiety levels were evaluated using the Patient Health Questionnaire-2 and General Anxiety Disorder-2 scales. The association between psychiatric disorders and UF levels was analyzed. In the total population, the prevalence of depression and anxiety were 3.17% and 4.19%, respectively. These results showed no significant association between depression / anxiety scale scores and UF levels. Logistic regression suggested no significant association between depression / anxiety levels, and UF levels, but there was an interaction between UF and income on depression. Our findings highlighted the interaction between fluoride exposure and monthly income, which may affect depression in adults.