Per- and polyfluoroalkyl substances (PFASs) in bivalve molluscs from Shandong Province, China: Occurrence, distribution, and implications for human consumption.

We examined the occurrence and levels of 19 legacy and emerging per- and polyfluoroalkyl substances (PFASs) in 7 species of marine bivalve molluscs collected from four coastal cities of Shandong Province, China. Perfluorooctanoic acid (PFOA) was the most prevalent component, accounting for 68.1 % of total PFASs. The total PFASs in bivalve molluscs ranged from 0.86 to 6.55 ng/g wet weight, with the highest concentration found in Meretrix meretrix L. The concentration of total PFASs in bivalve molluscs showed the following trend: clams > scallops > oysters > mussels. Estimation on the human intake of PFASs from consumption of bivalve molluscs resulted in hazard ratios (HR) ranging from 0.12 to 6.40. Five of the seven species had HR >1, indicating high exposure risks associated with PFASs. Therefore, the occurrence of PFASs in marine biota is particularly concerning and further investigations on the sources of PFASs in Shandong are warranted.

Measurements of peri-prostatic adipose tissue by MRI predict bone metastasis in patients with newly diagnosed prostate cancer.

Objectives: To investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa). Methods: We performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance. Results: PPAT and normalized PPAT were associated with BM (P<0.001). Normalized PPAT positively correlated with clinical T stage(cT), clinical N stage(cN), and Grading Groups(P<0.05). The results of ROC curves indicated that PPAT and normalized PPAT had promising predictive value for BM with the AUC of 0.684 and 0.775 respectively. Univariate and multivariate analysis revealed that high normalized PPAT, cN, and alkaline phosphatase(ALP) were independently predictors of BM. The nomogram was developed and the concordance index(C-index) was 0.856. Conclusions: Normalized PPAT is an independent predictor for BM among with cN, and ALP. Normalized PPAT may help predict BM in patients with newly diagnosed prostate cancer, thus providing adjunctive information for BM risk stratification and bone scan selection.

Impact of tumour stroma-immune interactions on survival prognosis and response to neoadjuvant chemotherapy in bladder cancer.

BACKGROUND: The tumour stroma is associated with unfavourable prognosis in diverse solid tumours, but its prognostic and predictive value in bladder cancer (BCa) is unclear. METHODS: In this multicentre, retrospective study, we included 830 patients with BCa from six independent cohorts. Differences in overall survival (OS) and cancer-specific survival (CSS) were investigated between high-tumour stroma ratio (TSR) and low-TSR groups. Multi-omics analyses, including RNA sequencing, immunohistochemistry, and single-cell RNA sequencing, were performed to study stroma-immune interactions. TSR prediction models were developed based on pelvic CT scans, and the best performing model was selected based on receiver operator characteristic analysis. FINDINGS: Compared to low-TSR tumours, high-TSR tumours were significantly associated with worse OS (HR = 1.193, 95% CI: 1.046-1.361, P = 0.008) and CSS (HR = 1.337, 95% CI: 1.139-1.569, P < 0.001), and lower rate of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). High-TSR tumours exhibited higher infiltration of immunosuppressive cells, including Tregs and tumour-associated neutrophils, while low-TSR tumours exhibited higher infiltration of immune-activating cells such as CD8+ Teff and XCR1+ dendritic cells. The TSR prediction model was developed by combining the intra-tumour and tumour base radiomics features, and showed good performance to predict high-TSR, as indicted by area under the curve of 0.871 (95% CI: 0.821-0.921), 0.821 (95% CI: 0.731-0.911), and 0.801 (95% CI: 0.737-0.865) in the training, internal validation, and external validation cohorts, respectively. In patients with low predicted TSR, 92.3% (12/13) achieved pCR, while only 35.3% (6/17) of patients with high predicted TSR achieved pCR. INTERPRETATION: The tumour stroma was found to be significantly associated with clinical outcomes in patients with BCa as a result of tumour stroma-immune interactions. The radiomics prediction model provided non-invasive evaluation of TSR and was able to predict pCR in patients receiving NAC for BCa. FUNDING: This work was supported by National Natural Science Foundation of China (Grant No. 82373254 and 81961128027), Guangdong Provincial Natural Science Foundation (Grant No. 2023A1515010258), Science and Technology Planning Project of Guangdong Province (Grant No. 2023B1212060013). Science and Technology Program of Guangzhou (SL2022A04J01754), Sun Yat-Sen Memorial Hospital Clinical Research 5010 Program (Grant No. SYS-5010Z-202401).

Nanofluid Droplet Impact on Rigid and Elastic Superhydrophobic Surfaces.

Ice accumulation on cold surfaces is a common and serious phenomenon that exists in numerous industrial fields, such as power transmission, wind turbines, and aircraft. Despite recent efforts in mitigating ice accumulation on the cold surface, it remains a challenge to achieve robust anti-icing on the cold surface in terms of nanofluid droplet. Here, we report a rigid superhydrophobic Cu surface and an elastic polydimethylsiloxane (PDMS) superhydrophobic surface to enhance water-repellency performance, characterized by a significant reduction in contact time and a decrease in the spreading ratio. As for the rigid superhydrophobic Cu surface, the underlying mechanism is ascribed to the existence of stable air cushions between the micropillar array, which reduce the contact area and further suppress the heat conduction. As for the elastic PDMS superhydrophobic surface, the rapid detachment of the nanofluid droplet relies on superior surface elasticity, which can further suppress the nanofluid droplet splashing at a high impacting velocity. We believe that this work can provide a new view for the improvement of water-repellency for a wide range of applications.

An artificial intelligence model for detecting pathological lymph node metastasis in prostate cancer using whole slide images: a retrospective, multicentre, diagnostic study.

Background: The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. Methods: In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. Findings: In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64-73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953-0.998) to 0.992 (0.982-1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908-1.000]) surpassed that of two junior pathologists (0.862 [0.746-0.939], P = 0.023; 0.879 [0.767-0.950], P = 0.041) by 10-12% and showed no difference to that of two senior pathologists (both 0.983 [0.908-1.000], both P > 0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P = 0.041) to the level of senior pathologists (both P > 0.99), and substantially reduced the four pathologists' slide reviewing time (-31%, P < 0.0001; -34%, P < 0.0001; -29%, P < 0.0001; and -27%, P = 0.00031). Interpretation: ProCaLNMD demonstrated high diagnostic capabilities for identifying LNM in prostate cancer, reducing the likelihood of missed diagnoses by pathologists and decreasing the slide reviewing time, highlighting its potential for clinical application. Funding: National Natural Science Foundation of China, the Science and Technology Planning Project of Guangdong Province, the National Key Research and Development Programme of China, the Guangdong Provincial Clinical Research Centre for Urological Diseases, and the Science and Technology Projects in Guangzhou.

Development and validation of an artificial intelligence-based model for detecting urothelial carcinoma using urine cytology images: a multicentre, diagnostic study with prospective validation.

Background: Urine cytology is an important non-invasive examination for urothelial carcinoma (UC) diagnosis and follow-up. We aimed to explore whether artificial intelligence (AI) can enhance the sensitivity of urine cytology and help avoid unnecessary endoscopy. Methods: In this multicentre diagnostic study, consecutive patients who underwent liquid-based urine cytology examinations at four hospitals in China were included for model development and validation. Patients who declined surgery and lacked associated histopathology results, those diagnosed with rare subtype tumours of the urinary tract, or had low-quality images were excluded from the study. All liquid-based cytology slides were scanned into whole-slide images (WSIs) at 40 × magnification and the WSI-labels were derived from the corresponding histopathology results. The Precision Urine Cytology AI Solution (PUCAS) was composed of three distinct stages (patch extraction, features extraction, and classification diagnosis) and was trained to identify important WSI features associated with UC diagnosis. The diagnostic sensitivity was mainly used to validate the performance of PUCAS in retrospective and prospective validation cohorts. This study is registered with the ChiCTR, ChiCTR2300073192. Findings: Between January 1, 2018 and October 31, 2022, 2641 patients were retrospectively recruited in the training cohort, and 2335 in retrospective validation cohorts; 400 eligible patients were enrolled in the prospective validation cohort between July 7, 2023 and September 15, 2023. The sensitivity of PUCAS ranged from 0.922 (95% CI: 0.811-0.978) to 1.000 (0.782-1.000) in retrospective validation cohorts, and was 0.896 (0.837-0.939) in prospective validation cohort. The PUCAS model also exhibited a good performance in detecting malignancy within atypical urothelial cells cases, with a sensitivity of over 0.84. In the recurrence detection scenario, PUCAS could reduce 57.5% of endoscopy use with a negative predictive value of 96.4%. Interpretation: PUCAS may help to improve the sensitivity of urine cytology, reduce misdiagnoses of UC, avoid unnecessary endoscopy, and reduce the clinical burden in resource-limited areas. The further validation in other countries is needed. Funding: National Natural Science Foundation of China; Key Program of the National Natural Science Foundation of China; the National Science Foundation for Distinguished Young Scholars; the Science and Technology Planning Project of Guangdong Province; the National Key Research and Development Programme of China; Guangdong Provincial Clinical Research Centre for Urological Diseases.

PDCD4-induced oxidative stress through FGR/NF-κB axis in rectal cancer radiotherapy-induced AKI.

This study aimed to investigate the molecular mechanism of the effect of PDCD4 on radiotherapy-induced acute kidney injury (AKI) in rectal cancer through the regulation of FGR/NF-κB signaling. Differentially expressed genes were identified using Gene Expression Omnibus (GEO) datasets (GSE90627 for rectal cancer and GSE145085 for AKI) and R software. The human renal tubular epithelial cell line, HK-2, was used to establish an in vitro model of radiotherapy-induced AKI. RT-qPCR and western blotting were used to detect gene and protein expression levels, respectively. Cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. The malondialdehyde and superoxide dismutase levels in the cell culture supernatants were determined. Additionally, an in vivo AKI model was established using BALB/c mice, and kidney tissue morphology, expression of the renal injury molecule KIM-1, apoptosis of renal tubular cells, and TAS and TOS in serum were evaluated. Bioinformatics analysis revealed the upregulated expression of PDCD4 in AKI. In vitro experiments demonstrated that PDCD4 induced apoptosis in renal tubular cells by promoting FGR expression, which activated the NF-κB signaling pathway and triggered an oxidative stress response. In vivo animal experiments confirmed that PDCD4 promoted oxidative stress response and radiotherapy-induced AKI through the activation of the FGR/NF-κB signaling pathway. Silencing PDCD4 attenuated radiotherapy-induced AKI. Our findings suggest that PDCD4 may induce radiotherapy-induced AKI in rectal cancer by promoting FGR expression, activating the NF-κB signaling pathway, and triggering an oxidative stress response.

A Potential Multitarget Insect Growth Regulator Candidate: Design, Synthesis, and Biological Activity of Novel Acetamido Derivatives Containing Hexacyclic Pyrazole Carboxamides.

Insect growth regulators (IGRs) are important green insecticides that disrupt normal growth and development in insects to reduce the harm caused by pests to crops. The ecdysone receptor (EcR) and three chitinases OfChtI, OfChtII, and OfChi-h are closely associated with the molting stage of insects. Thus, they are considered promising targets for the development of novel insecticides such as IGRs. Our previous work identified a dual-target compound 6j, which could act simultaneously on both EcR and OfChtI. In the present study, 6j was first found to have inhibitory activities against OfChtII and OfChi-h, too. Subsequently, taking 6j as a lead compound, 19 novel acetamido derivatives were rationally designed and synthesized by introducing an acetamido moiety into the amide bridge based on the flexibility of the binding cavities of 6j with EcR and three chitinases. Then, their insecticidal activities against Plutella xylostella (P. xylostella), Ostrinia furnacalis (O. furnacalis), and Spodoptera frugiperda (S. frugiperda) were carried out. The bioassay results revealed that most of these acetamido derivatives possessed moderate to good larvicidal activities against three lepidopteran pests. Especially, compound I-17 displayed excellent insecticidal activities against P. xylostella (LC50, 93.32 mg/L), O. furnacalis (LC50, 114.79 mg/L), and S. frugiperda (86.1% mortality at 500 mg/L), significantly better than that of 6j. In addition, further protein validation and molecular docking demonstrated that I-17 could act simultaneously on EcR (17.7% binding activity at 8 mg/L), OfChtI (69.2% inhibitory rate at 50 µM), OfChtII (71.5% inhibitory rate at 50 µM), and OfChi-h (73.9% inhibitory rate at 50 µM), indicating that I-17 is a potential lead candidate for novel multitarget IGRs. This work provides a promising starting point for the development of novel types of IGRs as pest management agents.

Associations Between Serum Estrogen Levels and Urinary Incontinence in Women: A Cross-sectional Analysis of NHANES 2013 to 2016.

OBJECTIVE: To explore the relationship between serum estrogen levels and urinary incontinence in a nationally representative female population. MATERIALS AND METHODS: We included women who had serum estradiol measurements and self-reported urinary incontinence problems in the 2013-2016 National Health and Nutrition Examination Survey cycles. A weighted multivariable logistic regression model was used to determine the association between urinary incontinence and serum estrogen levels after adjusting for age, race, Body Mass Index, diabetes, venipuncture, hypertension, poverty-to-income ratio, smoking, marital status, alcohol use, education, and menopause. RESULT: A total of 4114 individuals were ultimately included in our study. Of these women, 1200 (29.17%) complained of urge urinary incontinence (UUI), 1674 (40.69%) complained of stress urinary incontinence (SUI), 730 (17.74%) complained of mixed urinary incontinence (MUI). Women in the lowest quartile of serum estrogen were more likely to complain of UUI compared to those in the highest quartile (OR=1.885; 95% CI=1.042-3.412, P = .039). No association was noted between serum estrogen levels and SUI or MUI. CONCLUSION: Our study shows a significant association between low serum estrogen level and the increased likelihood of UUI in women. Further research is required to validate our findings, elucidate the physiological mechanisms that underlie them, and assess potential therapeutic implications.

Evaluating the Effectiveness of a Generative Pretrained Transformer-Based Dietary Recommendation System in Managing Potassium Intake for Hemodialysis Patients.

OBJECTIVE: Despite adequate dialysis, the prevalence of hyperkalemia in Chinese hemodialysis (HD) patients remains elevated. This study aims to evaluate the effectiveness of a dietary recommendation system driven by generative pretrained transformers (GPTs) in managing potassium levels in HD patients. METHODS: We implemented a bespoke dietary guidance tool utilizing GPT technology. Patients undergoing HD at our center were enrolled in the study from October 2023 to November 2023. The intervention comprised of two distinct phases. Initially, patients were provided with conventional dietary education focused on potassium management in HD. Subsequently, in the second phase, they were introduced to a novel GPT-based dietary guidance tool. This artificial intelligence (AI)-powered tool offered real-time insights into the potassium content of various foods and personalized dietary suggestions. The effectiveness of the AI tool was evaluated by assessing the precision of its dietary recommendations. Additionally, we compared predialysis serum potassium levels and the proportion of patients with hyperkalemia among patients before and after the implementation of the GPT-based dietary guidance system. RESULTS: In our analysis of 324 food photographs uploaded by 88 HD patients, the GPTs system evaluated potassium content with an overall accuracy of 65%. Notably, the accuracy was higher for high-potassium foods at 85%, while it stood at 48% for low-potassium foods. Furthermore, the study examined the effect of GPT-based dietary advice on patients' serum potassium levels, revealing a significant reduction in those adhering to GPTs recommendations compared to recipients of traditional dietary guidance (4.57 ± 0.76 mmol/L vs. 4.84 ± 0.94 mmol/L, P = .004). Importantly, compared to traditional dietary education, dietary education based on the GPTs tool reduced the proportion of hyperkalemia in HD patients from 39.8% to 25% (P = .036). CONCLUSION: These results underscore the promising role of AI in improving dietary management for HD patients. Nonetheless, the study also points out the need for enhanced accuracy in identifying low potassium foods. It paves the way for future research, suggesting the incorporation of extensive nutritional databases and the assessment of long-term outcomes. This could potentially lead to more refined and effective dietary management strategies in HD care.

Positron emission tomography guided synergistic treatment of melanoma using multifunctional zirconium-hematoporphyrin nanosonosensitizers.

Sonodynamic therapy (SDT) has emerged as a useful approach for tumor treatment. However, its widespread application is impeded by poor pharmacokinetics of existing sonosensitizers. Here we developed a metal-organic nanoplatform, wherein a small-molecule sonosensitizer (hematoporphyrin monomethyl ether, HMME) was ingeniously coordinated with zirconium, resulting in a multifunctional nanosonosensitizer termed Zr-HMME. Through post-synthetic modifications involving PEGylation and tumor-targeting peptide (F3) linkage, a nanoplatform capable of homing on melanoma was produced, which could elicit robust immune responses to suppress tumor lung metastasis in the host organism. Importantly, after seamless incorporation of positron-emitting 89Zr into this nanosonosensitizer, positron emission tomography (PET) could be used to monitor its in vivo pharmacokinetics. PET imaging studies revealed that this nanoplatform exhibited potent tumor accumulation and strong in vivo stability. Using intrinsic fluorescence from HMME, a dual-modal diagnostic capability (fluorescence and PET) was confirmed for this nanosonosensitizer. In addition, the mechanisms of how this nanoplatform interacted with immune system were also investigated. The collective data proved that the coordination structure between small-molecule drug cargos and metals may enhance the functions of each other while mitigating their weaknesses. This straightforward approach can expand the potential applications of suitable drug molecules.

Design and Experimental Study of an Improved Pressure Core Sampler for Marine Gas Hydrates.

A pressure core sampler (PCS) is considered an effective tool to retrieve marine gas hydrate cores from hydrate-bearing sediments. However, according to the sampling application statistics, the success rate of pressure coring changed from 30% to 85% in different drilling wells. Such severe fluctuation will cause huge uncertainty in the practical application of technology and economic benefits. Herein, we present a new PCS designed to improve pressure-retaining reliability. The work principle, design and calculations, and structure composition were described. Through the laboratory tests and drilling experiments, the maximum holding pressure in the pressure chamber was 32.1 MPa, and the pressure loss rates of holding pressure after 2 h changed from 1.96% to 2.46%. The maximum temperature-rising value in the pressure chamber was 0.96 °C under a temperature of 23.5 °C in 2 h. Furthermore, the success rate of the pressure core reached 87.5% and the core recovery was not less than 80%, which were verified by 8 pressure core runs in three different offshore wells. Therefore, we conclude that this new and improved PCS has great application value in gas hydrate exploration that seeks to recover more accurate cores in situ, especially in the silt and sand layers.

The role and impact of therapeutic counselling on the emotional experience of adults living with dementia: A systematic review.

Introduction There is limited psychological support available to help people living with dementia to deal with the emotional consequences of their condition. Anxiety and depression are commonly experienced in this population, yet the use of counselling and psychotherapeutic interventions is not well documented. Aim This systematic review sought to understand the current knowledge on the role and impact of therapeutic counselling on the emotional experience of adults living with dementia. Methods Qualitative and quantitative research designs were accepted for review. A comprehensive search of the main biomedical, nursing and other specialist databases was performed to access articles published between 2015 and 2022. Trial registers and academic journals were also searched. 43 original studies were included: qualitative (n = 15); RCTs (n = 9); other designs (n = 19); plus eight systematic reviews. Results The majority of studies were conducted in Europe, the United Kingdom in particular, although a range of countries from across the globe were represented. The combined evidence from the different study designs suggest a range of ways that people living with different stages of dementia can participate in, and gain emotional benefit from, therapeutic counselling. Key themes identified: (1) The emotional and well-being benefits of therapeutic counselling; (2) No one size fits all - relational and tailored approaches driven by person-centred values; (3) Training, supervision and building community for counsellors; (4) Involvement of people with dementia in therapeutic interventions. Conclusions Our findings from this systematic review show that different therapeutic approaches have been tested with people at different stages of a dementia diagnosis. The results suggest the value of therapeutic counselling as a supportive medium to help with the processing and coping of difficult emotions and feelings across the trajectory of a dementia illness.

Identification of ALDOB as a novel prognostic biomarker in kidney clear cell renal cell carcinoma.

Kidney clear cell renal cell carcinoma (KIRC) is also the most lethal subtype among all kidney cancer subtypes, posing a severe threat to public health. Therefore, it is crucial to identify new, reliable biomarkers in KIRC. Therefore, it is crucial to identify novel, reliable biomarkers associated with KIRC. We analyzed RNA sequence results from TCGA and several GEO datasets. The commonly deregulated gene, ALDOB, was found in multiple data and confirmed its important prognostic value. Subsequently, we explored the specific mechanism by which ALDOB regulates anti-tumor immunity through in vivo and in vitro experiments. We found that ALDOB may play a role in regulating tumor growth by regulating CD8+ T cell infiltration. This is consistent with the results of our immune infiltration-related analysis. In addition, we have also discovered the effect of ALDOB in previous studies on other cancer types. Finally, we concluded that ALDOB may have potential reference value for immunotherapy and can also be used as an independent predictor of prognosis in KIRC.

An overview of sphingosine-1-phosphate receptor 2: Structure, biological function, and small-molecule modulators.

Over the past decade, there has been a notable increase in research on sphingosine-1-phosphate receptor 2 (S1PR2), which is a type of G-protein-coupled receptor. Upon activation by S1P or other ligands, S1PR2 initiates downstream signaling pathways such as phosphoinositide 3-kinase (PI3K), Mitogen-activated protein kinase (MAPK), Rho/Rho-associated coiled-coil containing kinases (ROCK), and others, contributing to the diverse biological functions of S1PR2 and playing a pivotal role in various physiological processes and disease progressions, such as multiple sclerosis, fibrosis, inflammation, and tumors. Due to the extensive biological functions of S1PR2, many S1PR2 modulators, including agonists and antagonists, have been developed and discovered by pharmaceutical companies (e.g., Novartis and Galapagos NV) and academic medicinal chemists for disease diagnosis and treatment. However, few reviews have been published that comprehensively overview the functions and regulators of S1PR2. Herein, we provide an in-depth review of the advances in the function of S1PR2 and its modulators. We first summarize the structure and biological function of S1PR2 and its pathological role in human diseases. We then focus on the discovery approach, design strategy, development process, and biomedical application of S1PR2 modulators. Additionally, we outline the major challenges and future directions in this field. Our comprehensive review will aid in the discovery and development of more effective and clinically applicable S1PR2 modulators.

Causal effect of sarcopenia-related traits on the occurrence and prognosis of breast cancer - A bidirectional and multivariable Mendelian randomization study.

BACKGROUND AND AIMS: although sarcopenia is associated with several types of cancer, there is limited research regarding its effect on breast cancer. We aimed to explore the causality between sarcopenia-related traits and the incidence and prognosis of breast cancer. METHODS: two-sample bidirectional and multivariate Mendelian randomization (MR) analyses were utilized in this study. Genome-wide association studies were used to genetically identify sarcopenia-related traits, such as appendicular lean mass, grip strength of both hands, and walking pace. Data on the incidence and prognosis of breast cancer were collected from two extensive cohort studies. Multivariate MR analysis was used to adjust for body mass index, waist circumference, and whole-body fat mass. The primary method used for analysis was inverse-variance weighted analysis. RESULTS: a significant association was found between appendicular lean mass and ER- breast cancer (OR = 0.873, 95 % CI: 0.817-0.933, p = 6.570 × 10-5). Increased grip strength of the left hand was associated with a reduced risk of ER- breast cancer (OR = 0.744, 95 % CI: 0.579-0.958, p = 0.022). Stronger grip strength of the right hand was associated with prolonged survival time of ER+ breast cancer patients (OR = 0.463, 95 % CI: 0.242-0.882, p = 0.019). In the multivariable MR analysis, appendicular lean mass, grip strength of both hands, and walking pace were still genetically associated with the development of total breast cancer and ER-/+ breast cancer. CONCLUSIONS: several sarcopenia-related traits were genetically associated with the occurrence and prognosis of breast cancer. It is crucial for elderly women to increase their strength and muscle mass to help prevent breast cancer.

Barriers and facilitators to acceptance and implementation of eMental-health intervention among older adults: A qualitative systematic review.

Objective: Electronic mental health interventions are effective but not well promoted currently among older adults. This study sought to systematically review and summarize the barriers and facilitators of accepting and implementing electronic mental health interventions among older adults. Methods: We comprehensively retrieved six electronic databases from January 2012 to September 2022: PubMed, Web of Science, Embase, Scopus, PsycINFO, and CINAHL. The JBI-QARI was used to assess the quality of the research methodology of each publication. Eligible studies underwent data coding and synthesis aligned to inductive and deductive methods. The Consolidated Framework for Implementation Research 2.0 was used as a deductive framework to guide a more structured analysis. Results: The systematic review screened 4309 articles, 17 of which were included (eight with mixed methods and nine with qualitative methods). We identified and extracted the barriers and facilitators of accepting and implementing electronic mental health interventions among older adults: (1) innovation: technology challenges, optimized functions, and contents, security and privacy; (2) outer setting: community engagement and partnerships, financing; (3) inner setting: leadership engagement, available resources, incompatibility, intergenerational support, training and guidance; (4) individuals: perceptions, capability, motivation of older adults and healthcare providers; and (5) implementation process: recruit, external assistance, and team. Conclusion: These findings are critical to optimizing, promoting, and expanding electronic mental health interventions among older adults. The systematic review also provides a reference for better evidence-based implementation strategies in the future.

Targeted Detoxification of Aflatoxin B1 in Edible Oil by an Enzyme-Metal Nanoreactor.

Mycotoxin contamination is an important issue for food safety and the environment. Removing mycotoxins from food without losing nutrients and flavor components remains a challenge. In this study, a novel strategy was proposed for the targeted removal of aflatoxin B1 (AFB1) from peanut oil using an amphipathic enzyme-metal hybrid nanoreactor (PL-GOx-Fe3O4@COF) constructed with covalent organic frameworks (COFs) which can selectively adsorb AFB1. Due to the confined space provided by COFs and the proximity effect between GOx and Fe3O4, the detoxification of AFB1 is limited in the nanoreactor without affecting the composition and properties of the oil. The detoxification efficiency of AFB1 in the chemoenzymatic cascade reaction catalyzed by PL-GOx-Fe3O4@COF is six times higher than that of the combination of free GOx and Fe3O4. The AFB1 transformation product has nontoxicity to kidney and liver cells. This study provides a powerful tool for the targeted removal of mycotoxins from edible oils.

A nomogram based on clinical characteristics and nutritional indicators for relative and absolute weight loss during radiotherapy in initially inoperable patients with locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: Radiation for locally advanced esophageal squamous cell carcinoma often is accompanied by radiation esophagitis, which interferes with oral intake. We aimed to develop a nomogram model to identify initially inoperable patients with relative and absolute weight loss who need prophylactic nutritional supplementation. METHODS: A total of 365 initially inoperable patients with locally advanced esophageal squamous cell carcinoma receiving radiotherapy between January 2018 and December 2022 were included in the study, which was divided into discovery and validation cohorts. Receiver operating characteristic and Kaplan-Meier curve analyses were performed to compare the areas under the curve and survival benefits. RESULTS: A total of 42.2% (154 of 365) of the patients had been diagnosed with cancer cachexia. The malnourished group had a higher interruption rate of radiotherapy and number of complication diseases (P < 0.05). Meanwhile, patients with malnutrition had lower lymphocytes and prognostic nutritional index (P < 0.05). The combined index showed a higher area under the curve value (0.67; P < 0.001) than number of complication diseases (area under the curve = 0.52) and prognostic nutritional index (area under the curve = 0.49) for relative weight loss (≥ 5%). Similarly, the combined index had a higher area under the curve value (0.79; P < 0.001) than number of complication diseases (area under the curve = 0.56), treatment regimens (area under the curve = 0.56), subcutaneous fat thickness (area under the curve = 0.60), pretreatment body weight (area under the curve = 0.61), neutrophils (area under the curve = 0.56), and prognostic nutritional index (area under the curve = 0.50) for absolute weight loss (≥ 5 kg). Absolute and relative weight loss remained independent prognostic factors, with short overall survival rates compared with the normal group (P < 0.05). Patients with high nomogram scores supported by nutritional intervention had less weight loss, better nutrition scores, and increased plasma CD8+ T cells, and interferon gamma. CONCLUSIONS: We developed a nomogram model that was intended to estimate relative and absolute weight loss in initially inoperable patients with locally advanced esophageal squamous cell carcinoma during radiotherapy, which might help facilitate an objective decision on prophylactic nutritional supplementation.

Evaluation of a new Electrochemiluminescence Immunoassay System for Measuring High-Sensitivity Cardiac Troponin T.

BACKGROUND: The aim of this study was to verify the analytical performance of the UD90DT electrochemiluminescence immunoassay system (the UD90DT system) for measuring high-sensitivity cardiac troponin T (hs-cTnT). METHODS: According to the Clinical and Laboratory Standards Institute guidelines, the imprecision, linearity, reference interval, limit of blank (LoB), limit of detection (LoD), and functional sensitivity (FS) of hs-cTnT using the UD90DT system were verified. The trueness was validated using the Proficiency Testing (PT) materials. RESULTS: The within-run and between-run coefficients of variations (CVs) of two hs-cTnT levels were 7.2% and 1.5%, and 7.1% and 2.6%, respectively. The biases of the PT samples (n = 6) all fell within the allowable total error. The linearity satisfied the requirements, with a slope of 0.9963 and an R12 value of 0.9998. The hs-cTnT levels of the healthy volunteers (n = 20) ranged from 3.0 ng/L to 7.7 ng/L. All blank calibrator measurements (n = 20) fell within the LoD claim, and none of the samples (n = 25) had a LoB value ≤ 3.0 ng/L. The FS was 5.3 ng/L. Furthermore, a good correlation between the UD90DT system and the Cobas e 601 module was observed for hs-cTnT. CONCLUSIONS: The analytical performance of hs-cTnT using the UD90DT system is acceptable and satisfies clinical needs.