Residential quality, physical activity, and restorative perceptions: A seasonal longitudinal study.

While the restorative benefits of residential environments are known, the influence of residents' physical activity on their perceptions of restorativeness in different settlements is unclear. This study aimed to investigate the mediating and moderating roles of residents' physical activities and seasons on restorative perceptions using survey data from three settlements in Harbin, China, involving a baseline survey conducted in June 2023 and questionnaires administered at 30-day intervals from July to December 2023 (534 interviews). Residents' restorative perceptions and physical activity levels were highest in autumn, with settlement quality having a seasonal moderating effect and physical activity having a mediating effect.

Dynamics of Long-Term Quality of Life After Treatment for Esophageal Cancer: A Community-Based Patient Study.

PURPOSE: To characterize the pattern of post-treatment quality of life (QoL) for esophageal cancer (EC) survivors and construct models predicting their long-term QoL. METHODS: On the basis of a randomized trial in an EC high-risk region in China, we interviewed 363 EC survivors and 25,245 permanent residents matched with the survivors on age, sex, and township as the baseline. QoL was measured using three-level version of European Quality of Life 5-Dimensions instrument. We constructed piecewise mixed models estimating the QoL of EC survivors that varied by age, sex, patient type, hospital level, and therapy to ascertain QoL determinants. RESULTS: The post-treatment QoL of EC survivors dropped by 15.7% within the first year and recovered by 9.3% between 1 and 9 years compared with the baseline. Therapy was found to be a determinant of QoL, and a series of therapy-specific models were fitted accordingly, which all showed the pattern of decreasing rapidly and recovering gradually. Endoscopic treatment had the least impact on post-treatment QoL (7.5% drop within 5 years) compared with esophagectomy (12.2% drop within 1 year) and chemoradiotherapy (37.8% drop within 2 years). The usual activities dimension showed the greatest impairment among those patients (34.4% drop within 1 year). CONCLUSION: This community-based study described the long-term QoL trajectory for EC survivors after different therapeutic modalities and constructed models to predict therapy-specific QoL at different time points after treatment. It provided new insights into decision making in treatment for EC from the perspective of QoL protection, offering a convenient tool for estimating quality-adjusted life-years.

Pharmacokinetics and Safety of Estradiol Valerate Tablet and Its Generic: A Phase 1 Bioequivalence Study in Healthy Chinese Postmenopausal Female Subjects.

Purpose: Estradiol valerate (Progynova®) is used as hormone therapy to supplement estrogen deficiency. This study aimed to assess the bioequivalence of an estradiol valerate tablet and its generic form, under fasting and fed conditions. Methods: A randomized, open-label, single-dose, 2-period crossover study was conducted on healthy postmenopausal Chinese female volunteers under fasting and fed conditions. For each period, the subjects received either a 1 mg tablet of estradiol valerate or its generic. Blood samples were collected before dosing and up to 72 hours after administration. Plasma levels of total estrone, estradiol, and unconjugated estrone were quantified using a validated liquid chromatography-tandem mass spectrometry method. Results: A total of 54 volunteers were enrolled in this study. The primary pharmacokinetic parameters, including Cmax, AUC0-t, and AUC0-∞, were similar for the two drugs under both fasting and fed conditions, with 90% confidence intervals for the geometric mean ratios of these parameters, all meeting the bioequivalence criterion of 80-125%. A total of 48 adverse events (AEs) were reported in the fed study compared with 24 AEs in the fasting study. Conclusion: Estradiol valerate and its generic form were bioequivalent and well tolerated under both fasting and fed conditions.

A comprehensive analysis of imaging features and clinical characteristics to differentiate malignant from non-malignant mammographic architectural distortion.

Background: Mammographic architectural distortion (AD) is usually subtle and has variable presentations and causes, which poses a diagnostic challenge for breast radiologists and consequently a complex decision-making challenge for clinicians and patients. Presently, there is no reliable imaging standard to differentiate between malignant and benign ADs preoperatively. This study aimed to perform a comprehensive analysis of detailed mammographic and ultrasonographic features and clinical characteristics to enhance the diagnostic and differential efficacy for AD lesions. The findings have the potential to boost the diagnostic confidence of breast radiologists when encountering with AD lesions and could be instrumental in refining clinical management strategies for ADs. Methods: This retrospective study included consecutive female patients with ADs on screening or diagnostic mammography from January 6, 2015, to December 28, 2018. The patient's clinical data, mammographic and ultrasonographic or "second look" ultrasonographic findings, and pathological results were reviewed. The continuous variables were analyzed using the t-test. The categorical variables were assessed using the Chi-square test or two-tailed Fisher's exact test. Logistic regression analyses were conducted to evaluate potential risk factors for pathologically proven malignant ADs. Machine learning model based on multimodal clinical and imaging features was constructed using R software. Results: Ultimately, 344 patients with 346 AD lesions were enrolled in the study (mean age: 47.40±10.07 years; range, 19-84 years). Of the ADs, 228 were malignant and 118 were non-malignant. Palpable AD on mammography was more likely to indicate malignancy than non-palpable AD (83.43% vs. 49.15%, P<0.001). AD associated with other mammographic findings was more likely to be malignant than pure AD (73.58% vs. 59.36%, P=0.005). Ultrasonography (US) correlates were observed in 345 of these 346 AD lesions. Among these US correlates, 63 (18.26%, 63/345) were detected by "second look" ultrasound. For the US correlates, the mammographic ADs that appeared as non-mass-like hypoechoic areas and masses on US were more likely to be malignant than those that appeared as other abnormalities (P<0.001). The sensitivity, specificity and diagnostic accuracy of the eXtreme Gradient Boosting (XGBoost) model based on clinical and comprehensive imaging features in differentiation of AD lesions in the validation set were 66.46%, 94.23% and 78.9%, respectively, and the AUC was 0.886 (95% confidence interval: 0.825-0.947). Conclusions: The application of mammograms-guided "second-look" ultrasound could enhance the detection of US correlates, particularly non-mass-like features. The comprehensive analysis based on clinical and multimodal imaging features could be beneficial in improving the diagnostic and differential efficacy for AD lesions detected on mammography and instrumental in refining clinical management strategies for ADs.

Construction and validation of serum Metabolic Risk Score for early warning of malignancy in esophagus.

Using noninvasive biomarkers to identify high-risk individuals prior to endoscopic examination is crucial for optimization of screening strategies for esophageal squamous cell carcinoma (ESCC). We conducted a nested case-control study based on two community-based screening cohorts to evaluate the warning value of serum metabolites for esophageal malignancy. The serum samples were collected at enrollment when the cases had not been diagnosed. We identified 74 differential metabolites and two prominent perturbed metabolic pathways, and constructed Metabolic Risk Score (MRS) based on 22 selected metabolic predictors. The MRS generated an area under the receiver operating characteristics curve (AUC) of 0.815. The model performed well for the within-1-year interval (AUC: 0.868) and 1-to-5-year interval (AUC: 0.845) from blood draw to diagnosis, but showed limited ability in predicting long-term cases (>5 years). In summary, the MRS could serve as a potential early warning and risk stratification tool for establishing a precision strategy of ESCC screening.

The fungal protease BbAorsin contributes to growth, conidiation, germination, virulence, and antiphytopathogenic activities in Beauveria bassiana (Hypocreales: Cordycipitaceae).

The fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), is one of the most destructive agricultural pests. The entomopathogenic fungus Beauveria bassiana (Hypocreales: Clavicipitaceae) is a biopesticide widely used for biocontrol of various pests. Secreted fungal proteases are critical for insect cuticle destruction and successful infection. We have previously shown that the serine protease BbAorsin in B. bassiana has entomopathogenic and antiphytopathogenic activities. However, the contribution of BbAorsin to fungal growth, conidiation, germination, virulence and antiphytopathogenic activities remains unclear. In this study, the deletion (ΔBbAorsin), complementation (Comp), and overexpression (BbAorsinOE) strains of B. bassiana were generated for comparative studies. The results showed that ΔBbAorsin exhibited slower growth, reduced conidiation, lower germination rate, and longer germination time compared to WT and Comp. In contrast, BbAorsinOE showed higher growth rate, increased conidiation, higher germination rate and shorter germination time. Injection of BbAorsinOE showed the highest virulence against S. frugiperda larvae, while injection of ΔBbAorsin showed the lowest virulence. Feeding BbAorsinOE resulted in lower pupation and adult eclosion rates and malformed adults. 16S rRNA sequencing revealed no changes in the gut microbiota after feeding either WT or BbAorsinOE. However, BbAorsinOE caused a disrupted midgut, leakage of gut microbiota into the hemolymph, and upregulation of apoptosis and immunity-related genes. BbAorsin can disrupt the cell wall of the phytopathogen Fusarium graminearum and alleviate symptoms in wheat seedlings and cherry tomatoes infected with F. graminearum. These results highlight the importance of BbAorsin for B. bassiana and its potential as a multifunctional biopesticide.

Exploring the Molecular Therapeutic Mechanisms of Gemcitabine through Quantitative Proteomics.

Gemcitabine (GEM) is widely employed in the treatment of various cancers, including pancreatic cancer. Despite their clinical success, challenges related to GEM resistance and toxicity persist. Therefore, a deeper understanding of its intracellular mechanisms and potential targets is urgently needed. In this study, through mass spectrometry analysis in data-dependent acquisition mode, we carried out quantitative proteomics (three independent replications) and thermal proteome profiling (TPP, two independent replications) on MIA PaCa-2 cells to explore the effects of GEM. Our proteomic analysis revealed that GEM led to the upregulation of the cell cycle and DNA replication proteins. Notably, we observed the upregulation of S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator. Combining SKP2 inhibition with GEM showed synergistic effects, suggesting SKP2 as a potential target for enhancing the GEM sensitivity. Through TPP, we pinpointed four potential GEM binding targets implicated in tumor development, including in breast and liver cancers, underscoring GEM's broad-spectrum antitumor capabilities. These findings provide valuable insights into GEM's molecular mechanisms and offer potential targets for improving treatment efficacy.

IFN-α/ß/IFN-γ/IL-15 pathways identify GBP1-expressing tumors with an immune-responsive phenotype.

Immunotherapy is widely used in cancer treatment; however, only a subset of patients responds well to it. Significant efforts have been made to identify patients who will benefit from immunotherapy. Successful anti-tumor immunity depends on an intact cancer-immunity cycle, especially long-lasting CD8+ T-cell responses. Interferon (IFN)-α/ß/IFN-γ/interleukin (IL)-15 pathways have been reported to be involved in the development of CD8+ T cells. And these pathways may predict responses to immunotherapy. Herein, we aimed to analyze multiple public databases to investigate whether IFN-α/ß/IFN-γ/IL-15 pathways could be used to predict the response to immunotherapy. Results showed that IFN-α/ß/IFN-γ/IL-15 pathways could efficiently predict immunotherapy response, and guanylate-binding protein 1 (GBP1) could represent the IFN-α/ß/IFN-γ/IL-15 pathways. In public and private cohorts, we further demonstrated that GBP1 could efficiently predict the response to immunotherapy. Functionally, GBP1 was mainly expressed in macrophages and strongly correlated with chemokines involved in T-cell migration. Therefore, our study comprehensively investigated the potential role of GBP1 in immunotherapy, which could serve as a novel biomarker for immunotherapy and a target for drug development.

Development of composite separators by coating hydrochloric acid-treated halloysite nanotubes on polypropylene separators for lithium-ion batteries.

In this study, polypropylene/halloysite nanotube (PP/HNT) composite separators were prepared by coating HNTs treated with hydrochloric acid (HCl) of different concentrations on both sides of a PP separator. The effect of HNTs treated with hydrochloric acid (HCl) of different concentrations on the properties of PP/HNT composite separators was investigated. The results indicate that the PP/HNT composite separator exhibits higher electrolyte uptake and wettability than a commercial PP separator, resulting in a better electrochemical performance in Li/LiFePO4 cells. In particular, the PP/HNTs-1.2 M composite separator with HNTs treated with 1.2 M HCl exhibits the highest electrolyte uptake (384%) and ionic conductivity (1.03 mS cm-1). The cells assembled with a PP/HNTs-1.2 M composite separator deliver discharge capacities of 166 mA h g-1 (0.5 C) and 131 mA h g-1 (3 C) with attractive cycling performance (87.6% capacity retention after 100 cycles). HNTs treated with HCl of appropriate concentrations can significantly improve the properties of PP/HNT composite separators for application in lithium-ion batteries.

Correlation between the triglyceride-glucose index and left ventricular global longitudinal strain in patients with chronic heart failure: a cross-sectional study.

BACKGROUND: Left ventricular global longitudinal strain (GLS) holds greater diagnostic and prognostic value than left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. The triglyceride-glucose (TyG) index serves as a reliable surrogate for insulin resistance (IR) and is strongly associated with several adverse cardiovascular events. However, there remains a research gap concerning the correlation between the TyG index and GLS among patients with chronic heart failure (CHF). METHOD: 427 CHF patients were included in the final analysis. Patient demographic information, along with laboratory tests such as blood glucose, lipids profiles, and echocardiographic data were collected. The TyG index was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. RESULTS: Among CHF patients, GLS was notably lower in the higher TyG index group compared to the lower TyG index group. Following adjustment for confounding factors, GLS demonstrated gradual decrease with increasing TyG index, regardless of the LVEF level and CHF classification. CONCLUSION: Elevated TyG index may be independently associated with more severe clinical left ventricular dysfunction in patients with CHF.

EGCG suppresses PD-1 expression of T cells via inhibiting NF-κB phosphorylation and nuclear translocation.

Epigallocatechin-3-gallate (EGCG) is an important tea polyphenol with anti-tumor potential. Our previous studies revealed that EGCG was a promising immune checkpoint inhibitor (ICI) as it could downregulate expression of programmed cell death 1 ligand 1 (PD-L1) in tumor cells, thereby resulting tumor killing effect. In particular, EGCG can effectively avoid the inflammatory storm caused by anti-tumor therapy, which is a healthy green capacity absent from many ICIs. However, the relationship between EGCG and programmed cell death 1 (PD-1) of T cells remains unclear. In this work, we explored the effect of EGCG on T cells and found that EGCG suppressed PD-1 via inhibiting NF-κB phosphorylation and nuclear translocation. Furtherly, the capability of EGCG was confirmed in tumor-bearing mice to inhibit PD-1 expression in T cells and enhance apoptosis in tumor cells. These results implied that EGCG could inhibit the expression of PD-1 in T cells, thereby promoting anti-tumor effects of T cells. EGCG will be a promising candidate in anti-tumor therapy.

1D hollow tubular/2D nanosheet hybrid dimensional porous carbon prepared by one-step carbonization using natural minerals as templates for supercapacitors.

The reasonable construction of one-dimensional (1D)/two-dimensional (2D) hybrid dimensional porous carbon materials with complementary advantages and disadvantages is an important approach to addressing the structural and performance deficiencies of single carbon materials, while also significantly improving the electrochemical performance of super-capacitors. In this study, 1D hollow tubular/2D nanosheet hybrid dimensional porous carbon was synthesized through one-step carbonization using 1D fibrous brucite and 2D layered magnesium carbonate hydroxide as templates. By adjusting the feed ratio of 1D fibrous and 2D layered templates, the morphology, pore structure and specific surface area (SSA) of the prepared 1D hollow tubular/2D nanosheet hybrid dimensional porous carbon were controlled. The prepared hybrid dimensional porous carbons were characterized using scanning electron microscope (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption-desorption. And their electrochemical performance was also studied by cyclic voltammograms (CV), galvanostatic charge/discharge (GCD) and electrochemical impedance spectroscopy (EIS). The results show that the use of templates with different dimensions significantly influences the morphology, pore structure, SSA and electrochemical performance of the synthesized hybrid dimensional porous carbon. The hybrid dimensional porous carbon (3F) exhibits a high specific capacitance and excellent cycling stability. 3F demonstrates the specific capacitance of 245.3 F g-1 at 1 A g-1. Furthermore, the capacity retention rate remains as high as 93.4% after 8000 cycles at 10 A g-1. This work reveals that hybrid dimensional porous carbon composed of 1D hollow carbon tubes and 2D carbon nanosheets has great potential for use in supercapacitor electrode materials.

LncRNA MIR100HG affects the proliferation and metastasis of lung cancer cells through mediating the microRNA-5590-3p/DCBLD2 axis.

OBJECTIVE: The aim of this paper is to investigate the effect of long noncoding RNA (lncRNA) MIR100HG on the proliferation and metastasis of lung cancer cells by mediating the microRNA (miR)-5590-3p/DCBLD2 axis. METHODS: RNA levels of MIR100HG, miR-5590-3p, and DCBLD2 in lung cancer tissues and cells were detected by quantitative reverse-transcription polymerase chain reaction, and protein level was assessed by Western blot. Effects of MIR100HG or miR-5590-3p on proliferation, migration, and invasion of lung cancer cells were detected by Cell Counting Kit-8, colony formation, and Transwell assays. Luciferase reporter assay and RNA-immunoprecipitation assay confirmed the target relationship between miR-5590-3p and MIR100HG or DCBLD2. RESULTS: MIR100HG and DCBLD2 were highly expressed, while miR-5590-3p was lowly expressed in lung cancer tissues and cells. Silencing MIR100HG or upregulating miR-5590-3p impeded lung cancer cell proliferation, migration, and invasion. MIR100HG could up-regulate DCBLD2 by sponging miR-5590-3p. Downregulation of miR-5590-3p partly overturned the suppressive effect of silencing MIR100HG on lung cancer cell proliferation and metastasis, and overexpression of DCBLD2 also reversed the effect of overexpression of miR-5590-3p on lung cancer cell proliferation and metastasis. CONCLUSION: LncRNA MIR100HG promotes lung cancer progression by targeting and negatively regulating DCBLD2 through binding with miR-5590-3p.

The Effect and Influence of the Responsibility System Rehabilitation Nursing Model in the Nursing of Patients with Ischemic Stroke.

Objective: To explore and evaluate the effect of the accountability rehabilitation nursing model in the care of patients with ischemic stroke and the impact on nursing satisfaction, in order to improve the quality of care for patients with ischemic stroke. Design: This study selected 92 patients with ischemic stroke who met the inclusion criteria as the study objects, and divided them equally into the control group (46 cases) and the research group (46 cases) using a random number table. Data were collected by questionnaire. Interventions: The control group received standard routine rehabilitation nursing care, while the study group underwent an accountable rehabilitation care model. In the accountable rehabilitation care model, distinct nursing practices and strategies were employed to enhance clinical outcomes, limb function, neurological function, quality of life, and nursing satisfaction. Key elements of this model may include personalized care plans, increased emphasis on patient engagement, targeted therapeutic interventions, and a systematic approach to care coordination. A comparative analysis was conducted before and after the intervention to highlight the nuanced differences in outcomes between the two groups, shedding light on the specific benefits and effectiveness of the accountable rehabilitation care model as opposed to routine rehabilitation care. Results: In terms of clinical outcomes, the ESS score of the study group after intervention was significantly higher than that of the control group, indicating a positive impact on overall health (P < .05); limb function assessed by upper and lower limb muscle strength scores improved in both groups after the intervention. There was a significant enhancement, in which the score of the study group was significantly higher than that of the control group (P < .05); the NIHSS score showed that compared with the control group, the neurological function of the study group was significantly improved (P < .05); the SS-QOL score was used The assessed quality of life also improved significantly in the study group, exceeding the scores in the control group (P < .05). In addition, the nursing satisfaction of the study group was significantly higher compared with the control group, which highlighted the positive acceptance of the responsible rehabilitation nursing model by nursing staff (P < .05). Together, these findings highlight the combined benefits of the intervention in enhancing clinical, functional, and subjective outcomes. Discussion: The study underscores the promising clinical benefits of the responsibility system rehabilitation nursing model for patients with ischemic stroke. Marked enhancements in clinical outcomes, limb and nerve function, quality of life, and nursing satisfaction indicate its potential to significantly improve patient care. The personalized and accountable approach, featuring tailored care plans and heightened emphasis on patient engagement, holds promise for fostering positive health outcomes and enhancing overall patient experiences. Integrating this model into routine stroke care protocols emerges as a pivotal strategy for optimizing rehabilitation processes and adopting a patient-centered approach. Despite these advantages, acknowledging study limitations, such as non-randomized participant allocation and the absence of blinding, is crucial to recognizing potential biases. The study's sample size and single-center focus may impact generalizability. Beyond ischemic stroke, the model's broader significance aligns with contemporary healthcare trends, emphasizing accountability, personalized care plans, and enhanced care coordination. Its potential adaptation to various healthcare settings, chronic disease management, and preventive care could contribute to improved patient outcomes and healthcare quality. Future research should explore scalability and sustainability across diverse healthcare settings, investigating applicability to different patient populations and medical conditions. Assessing long-term effects, including healthcare cost-effectiveness and patient adherence, is essential for a comprehensive understanding of impact. Furthermore, delving into the perspectives of healthcare providers and patients can refine and tailor implementation strategies for optimal outcomes. Results: After the intervention, The European Stroke Scale (ESS) score of the study group was higher than that of the control group. After the intervention, the muscle strength scores of the upper and lower limbs of the study group were significantly higher than those of the control group. After intervention, the National Institutes of Health Stroke Scale (NIHSS) score of the study group was lower than that of the control group. After intervention, the stroke-specific quality of life scale (SS-QOL) score of the study group was higher than that of the control group. The nursing satisfaction of the study group was higher than that of the control group after intervention (all P < .05). Conclusion: The results of the study showed that the responsibility system rehabilitation nursing mode showed significant effects in improving the limb function, neurological function and quality of life of patients with ischemic stroke, which could promote the disease outcome of patients, and the nursing satisfaction of patients was high, which was worthy of promotion.

Effectiveness of Endoscopic Screening on Esophageal Cancer Incidence and Mortality: A 9-Year Report of the Endoscopic Screening for Esophageal Cancer in China (ESECC) Randomized Trial.

PURPOSE: To evaluate the effectiveness of endoscopic screening against incidence of and mortality from esophageal squamous cell carcinoma (ESCC). METHODS: From January 2012 to September 2016, we conducted a community-based cluster randomized controlled trial involving permanent residents age 45-69 years in a high-risk region for ESCC in northern China. A total of 668 targeted villages were randomly assigned in a 1:1 ratio to the screening group (offered Lugol's chromoendoscopy) or control group (no screening). Intention-to-treat and per-protocol analyses were performed to compare esophageal cancer (EC) incidence and mortality between the two groups. The per-protocol analysis adjusted for nonadherence to the screening procedure. RESULTS: A total of 33,847 participants were included in the analysis: 17,104 in the screening group, 15,165 (88.7%) of whom underwent screening, and 16,743 in the control group. During a maximum follow-up of 9 years, EC incidence in the screening and control groups were 60.9 and 72.5 per 100,000 person-years, respectively; mortality in the screening and control groups were 29.7 and 32.4 per 100,000 person-years, respectively. Compared with the control group, the incidence and mortality of the screening group reduced by 19% (adjusted hazard ratio [aHR], 0.81 [95% CI, 0.60 to 1.09]) and 18% (aHR, 0.82 [95% CI, 0.53 to 1.26]), respectively, in the intention-to-treat analysis; and by 22% (aHR, 0.78 [95% CI, 0.56 to 1.10]) and 21% (aHR, 0.79 [95% CI, 0.49 to 1.30]), respectively, in the per-protocol analysis. CONCLUSION: With a 9-year follow-up, our trial suggests that chromoendoscopic screening induces modest reductions in EC incidence and mortality. A more efficient strategy for EC screening and subsequent patient management should be established to guarantee the effectiveness of endoscopic screening.

Real-world evidence: Risdiplam in a patient with spinal muscular atrophy type I with a novel splicing mutation and one SMN2 copy.

Spinal muscular atrophy (SMA), which results from the deletion or/and mutation in the SMN1 gene, is an autosomal recessive neuromuscular disorder that leads to weakness and muscle atrophy. SMN2 is a paralogous gene of SMN1. SMN2 copy number affects the severity of SMA, but its role in patients treated with disease modifying therapies is unclear. The most appropriate individualized treatment for SMA has not yet been determined. Here, we reported a case of SMA type I with normal breathing and swallowing function. We genetically confirmed that this patient had a compound heterozygous variant: one deleted SMN1 allele and a novel splice mutation c.628-3T>G in the retained allele, with one SMN2 copy. Patient-derived sequencing of 4 SMN1 cDNA clones showed that this intronic single transversion mutation results in an alternative exon (e)5 3' splice site, which leads to an additional 2 nucleotides (AG) at the 5' end of e5, thereby explaining why the patient with only one copy of SMN2 had a mild clinical phenotype. Additionally, a minigene assay of wild type and mutant SMN1 in HEK293T cells also demonstrated that this transversion mutation induced e5 skipping. Considering treatment cost and goals of avoiding pain caused by injections and starting treatment as early as possible, risdiplam was prescribed for this patient. However, the patient showed remarkable clinical improvements after treatment with risdiplam for 7 months despite carrying only one copy of SMN2. This study is the first report on the treatment of risdiplam in a patient with one SMN2 copy in a real-world setting. These findings expand the mutation spectrum of SMA and provide accurate genetic counseling information, as well as clarify the molecular mechanism of careful genotype-phenotype correlation of the patient.

Characterization of Solitalea canadensis α-mannosidase with specific activity towards α1,3-Mannosidic linkages.

A recombinant exo-α-mannosidase from Solitalea canadensis (Sc3Man) has been characterized to exhibit strict specificity for hydrolyzing α1,3-mannosidic linkages located at the non-reducing end of glycans containing α-mannose. Enzymatic characterization revealed that Sc3Man operates optimally at a pH of 5.0 and at a temperature of 37 °C. The enzymatic activity was notably enhanced twofold in the presence of Ca2+ ions, emphasizing its potential dependency on this metal ion, while Cu2+ and Zn2+ ions notably impaired enzyme function. Sc3Man was able to efficiently cleave the terminal α1,3 mannose residue from various high-mannose N-glycan structures and from the model glycoprotein RNase B. This work not only expands the categorical scope of bacterial α-mannosidases, but also offers new insight into the glycan metabolism of S. canadensis, highlighting the enzyme's utility for glycan analysis and potential biotechnological applications.

Discovery of the potential biomarkers for early diagnosis of endometrial cancer via integrating metabolomics and transcriptomics.

Endometrial cancer (EC) is one of the most common malignant tumors in women, and the increasing incidence and mortality pose a serious threat to the public health. Early diagnosis of EC could prolong the survival period and optimize the survivorship, greatly alleviating patients' suffering and social medical pressure. In this study, we collected urine and serum samples from the recruited patients, analyzed the samples using LC-MS approach, and identified the differential metabolites through metabolomic analysis. Then, the differentially expressed genes were identified through the systematic transcriptomic analysis of EC-related dataset from Gene Expression Omnibus (GEO), followed by network profiling of metabolic-reaction-enzyme-gene. In this experiment, a total of 83 differential metabolites and 19 hub genes were discovered, of which 10 different metabolites and 3 hub genes were further evaluated as more potential biomarkers based on network analysis. According to the KEGG enrichment analysis, the potential biomarkers and gene-encoded proteins were found to be involved in the arginine and proline metabolism, histidine metabolism, and pyrimidine metabolism, which was of significance for the early diagnosis of EC. In particular, the combination of metabolites (histamine, 1-methylhistamine, and methylimidazole acetaldehyde) as well as the combination of RRM2, TYMS and TK1 exerted more accurate discrimination abilities between EC and healthy groups, providing more criteria for the early diagnosis of EC.