An in-situ-tag-generation proximity labeling technology for recording cellular interactions.

Obtaining information about cellular interactions is fundamental to the elucidation of physiological and pathological processes. Proximity labeling technologies have been widely used to report cellular interactions in situ; however, the reliance on addition of tag molecules typically restricts their application to regions where tags can readily diffuse, while the application in, for example, solid tissues, is susceptible. Here, we propose an "in-situ-tag-generation mechanism" and develop the GalTag technology based on galactose oxidase (GAO) for recording cellular interactions within three-dimensional biological solid regions. GAO mounted on bait cells can in situ generate bio-orthogonal aldehyde tags as interaction reporters on prey cells. Using GalTag, we monitored the dynamics of cellular interactions and assessed the targeting ability of engineered cells. In particular, we recorded, for the first time, the footprints of Bacillus Calmette-Guérin (BCG) invasion into the bladder tissue of living mice, providing a valuable perspective to elucidate the anti-tumor mechanism of BCG.

Validation of the Barthel Index in Chinese nursing home residents: an item response theory analysis.

Background: The Barthel Index (BI) is used to standardize the grading of assessments for clinical needs, insurance support, and long-term care resource allocation in China. However, its psychometric properties among nursing home residents remain unclear. Therefore, this study aims to assess and modify the psychometric properties of BI in nursing home residents. Methods: A total of 1,402 individuals undergoing evaluation in a nursing home facility in China were included in this study from November 2021 to November 2022. Correlations between items were examined to identify the potential multicollinearity concerns. The unidimensional item response theory (IRT) was used to validate and modify the single structure of BI. Furthermore, the logistic regression/IRT hybrid DIF detection method was conducted to assess differential item functioning (DIF) between the dementia group and the normal group. Results: The pairing of items 5 ("bowl control") and 6 ("bladder control") revealed a local dependence issue, leading to their consolidation. Items 56 (bowel and bladder control) and 9 (mobility) both displayed poor fit indices and underwent category collapsing. Through the application of the generalized partial credit model, the adjusted scale displayed better fit indices, demonstrating a robust discriminative power (DC >1.5) and orderly thresholds. Furthermore, non-uniform DIF was identified in item 2 (bathing) between the dementia group and the normal group. Conclusion: The modified BI demonstrated favorable psychometric properties and proved to be suitable for evaluating nursing home residents experiencing moderate functional impairment, which may provide a precise evaluation for long-term care resource allocation. Future studies could explore integrating supplementary measurements, such as objective indices, to assess a broader spectrum of functional statuses to potentially enhance the limited precision width observed in BI.

Sentinel and networked symptoms in patients with breast cancer undergoing chemotherapy.

PURPOSE: It was designed to identify the symptom clusters and sentinel symptoms among patients with breast cancer receiving chemotherapy at the community level, and to explore core and bridge symptoms at the global level. METHODS: A cross-sectional survey was conducted using the MD Anderson Symptom Inventory. Patients with breast cancer receiving chemotherapy, recruited from the "Be Resilient to Breast Cancer" project between January 2023 and December 2023, were included in the study. Symptom clusters and their sentinel symptoms were identified using exploratory factor analysis and Apriori algorithm. Core and bridge symptoms were identified using network analysis. RESULTS: A total of 468 patients with breast cancer participated in the current study. At the community level, three symptom clusters and their corresponding sentinel symptoms were identified: a gastrointestinal symptom cluster (with nausea as the sentinel symptom), a psycho-sleep-related symptom cluster (with distress as the sentinel symptom), and a neurocognition symptom cluster (with dry mouth as the sentinel symptom). At the global level, fatigue emerged as the core symptom, while disturbed sleep and lack of appetite as bridge symptoms. CONCLUSION: Addressing nausea, distress, and dry mouth are imperative for alleviating specific symptom clusters at the community level. Furthermore, targeting fatigue, disturbed sleep, and lack of appetite are crucial to break the interactions among diverse symptoms at the global level.

Aglycone sterics-selective enzymatic glycan remodeling.

Precision remodeling of glycans in their native environments is pivotal for understanding glycan-mediated biological events and has important biotechnological implications in fields of clinical diagnosis, glyco-immune checkpoint therapy, and so forth. However, the influence of aglycone-steric diversity on the selectivity of glycan remodeling has been largely overlooked, limiting the application in complex biological scenarios. Here, we report the achievement of aglycone sterics-selective enzymatic glycan remodeling by controlled grafting of functional polymers from glycoenzyme. Through tuning polymer length, a series of enzyme-polymer composites with varying substrate permeability are prepared, which afford an activity pattern-based differentiation strategy for aglycone sterics. This leads to the implementation of glycolipid's partner screening, and aglycone sterics-selective glycan remodeling in a complex biological environment. We further orchestrate the polymer length adjustment with external cues to regulate aglycone-steric selectivity in a multi-faceted fashion, resulting in an unexpected enhancement of glycolipid remodeling, and temporal control of glycan remodeling on live cells.

Effects of aerobic, resistance, and combined exercise on metabolic syndrome parameters and cardiovascular risk factors: a systematic review and network meta-analysis.

This study examines the effects of aerobic, resistance, and combined exercise on metabolic syndrome parameters and cardiovascular risk factors, to identify the most effective way of improving metabolic syndrome and preventing cardiovascular disease. We searched EMBASE, the Cochrane Library, PubMed, MEDLINE, Ovid, the Chinese Biological Medicine Database (CBM), the Wanfang Database, the China National Knowledge Infrastructure (CNKI) database, and the Chinese Scientific Journal Database (VIP), for randomized controlled trials (RCTs), identifying 15 comparing the effects of aerobic, resistance, and combined exercise on metabolic syndrome parameters and cardiovascular risk factors (e.g., glucose, triglyceride, blood pressure, body mass index, etc.). We assessed the quality of the articles and performed a network meta-analysis with a Bayesian random effects model to synthesize direct and indirect evidence. Combined exercise was most effective at controlling glucose and total triglyceride (TG) levels. Aerobic, resistance, and combined exercise groups achieved significant effects regarding body fat. Aerobic exercise was superior to resistance exercise regarding body mass index (BMI). There was no statistically significant difference in weight, waist circumference (WC), levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), insulin, systolic blood pressure (SBP), and diastolic blood pressure (DBP) among the exercise groups. Combined exercise was the best exercise scheme for improving weight, WC, DBP, TG, TC, glucose, and insulin levels. Resistance exercise was most effective at ameliorating body fat, LDL-C levels, and SBP. Aerobic exercise was the optimal way of improving BMI and HDL-C levels. This network meta-analysis suggests combined exercise is the most effective choice in improving the metabolic syndrome and cardiovascular risk parameters, whereas aerobic exercise reveals the minimum effect. Further studies should certify the role resistance exercises play in metabolic syndrome and cardiac rehabilitation.

Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium.

The serine/arginine-rich (SR) family of splicing factors plays important roles in mRNA splicing activation, repression, export, stabilization, and translation. SR-splicing factor 5 (SRSF5) is a glucose-inducible protein that promotes tumor cell growth. However, the functional role of SRSF5 in tissue development and disease remains unknown. Here, Srsf5 knockout (Srsf5 -/- ) mice were generated using CRISPR-Cas9. Mutant mice were perinatally lethal and exhibited cardiac dysfunction with noncompaction of the ventricular myocardium. The left ventricular internal diameter and volume were increased in Srsf5 -/- mice during systole. Null mice had abnormal electrocardiogram patterns, indicative of a light atrioventricular block. Mechanistically, Srsf5 promoted the alternative splicing of Myom1 (myomesin-1), a protein that crosslinks myosin filaments to the sarcomeric M-line. The switch between embryonic and adult isoforms of Myom1 could not be completed in Srsf5-deficient heart. These findings indicate that Srsf5-regulated alternative splicing plays a critical role during heart development.

Silica sol-gel amperometric immunosensor for Schistosoma japonicum antibody assay.

An amperometric immunosensor was constructed by dispersing graphite, schistosoma-japonicum antigen (SjAg) and silica sol-gel at low temperature. The performance characteristics of the prepared immunosensor were examined in the buffered solution of o-aminophenol (o-AP) used as a substrate. It exhibited excellent physical and electrochemical stability with a renewable external surface. A competitive binding assay was employed to determine schistosoma-japonicum antibody (SjAb) with the aid of horseradish peroxidase labeled SjAb (HRP-SjAb). The experimental parameters for SjAb assay were optimized, including the amount of labeled SjAb in incubation solution, incubation time, temperature and the pH of solution. The use of o-AP substrate and amperometric detection at -250 mV (vs. SCE) results in a determination limit of 0.32 microg/ml and a linear range extending up to 0.18 microg/ml. The results of SjAb assay in serum samples demonstrate the feasibility of using the proposed immunosensor for clinical analysis.

Primary cutaneous CD30-positive anaplastic large cell lymphoma analysis.

OBJECTIVE: To examine 10 cases with primary cutaneous CD30-positive anaplastic large cell lymphoma (ALCL), analyze their clinical manifestations and pathological and immunohistochemical features, and improve early diagnosis of this disease. METHODS: We studied the morphological characteristics of primary cutaneous CD30-positive ALCL using histopathological methods. Leukocyte common antigen (LCA), CD20, CD30, CD45RO, CD68, epithelial membrane antigen (EMA), cytokeratin (CK) and HMB45 antibodies were used to determine the expression of their respective antigens from routine paraffin samples of the patients. RESULTS: Ten patients (7 men and 3 women, aged 31 to 84 years) complained of subcutaneous masses or papular eruptions over their lower trunks and extremities. Histopathologically, the lesions were composed of numerous large round or oval pleomorphic cells. The cytoplasm was usually abundant, amphophilic or basophilic, and finely vacuolated. Nuclei were commonly eccentrically localized and lobated or horseshoed in shape, and multinucleated giant cells and Reed-Sternberg-like cells were seen. Nucleoli were generally multiple and large. Of the 10 patients, tumor cells displayed positive antigen expression of CD30 in all cases, positive CD45RO in 6 cases, positive CD20 in only 1 case, but negative CD45RO and CD20 expressions in 3 cases. Two patients died at 7 weeks and 3.4 years of follow-up, respectively. CONCLUSION: Our study highlights the importance of histopathologic features and positive CD30 staining for differentiation of this disease from other malignant skin tumors.