Nicotinic acetylcholine receptor modulator insecticides act on diverse receptor subtypes with distinct subunit compositions.

Insect nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels mainly expressed in the central nervous system of insects. They are the directed targets of many insecticides, including neonicotinoids, which are the most widely used insecticides in the world. However, the development of resistance in pests and the negative impacts on bee pollinators affect the application of insecticides and have created a demand for alternatives. Thus, it is very important to understand the mode of action of these insecticides, which is not fully understood at the molecular level. In this study, we systematically examined the susceptibility of ten Drosophila melanogaster nAChR subunit mutants to eleven insecticides acting on nAChRs. Our results showed that there are several subtypes of nAChRs with distinct subunit compositions that are responsible for the toxicity of different insecticides. At least three of them are the major molecular targets of seven structurally similar neonicotinoids in vivo. Moreover, spinosyns may act exclusively on the α6 homomeric pentamers but not any other nAChRs. Behavioral assays using thermogenetic tools further confirmed the bioassay results and supported the idea that receptor activation rather than inhibition leads to the insecticidal effects of neonicotinoids. The present findings reveal native nAChR subunit interactions with various insecticides and have important implications for the management of resistance and the development of novel insecticides targeting these important ion channels.

21.83% incident light can circumvent a 6.6 × 6.6 cm2 obstruction by introducing a layer of bubbles into the photovoltaic glass.

Obstruction is inevitable and will significantly impact the actual output performance of photovoltaic modules, even jeopardize their operational safety. We introduced a layer of bubbles into photovoltaic glass. These bubbles can alter the path of incident light, while the internal reflection at the glass/air interface enables the redirected light rays to have longer lateral propagation distance, circumventing the obstructions. The optimized photovoltaic glass with a bubble diameter of 1.8 mm and a surface density of 16 cm-2 enables the light intensity underneath a 6.6 × 6.6 cm2 obstruction to reach 21.83% of the incident light intensity. This enhancement permits a partial shading of the photovoltaic module, increasing its output power by ∼20.8% and decreasing the reverse bias voltage on the shaded cell by ∼1.4 V.

Identifying Hub Genes Related to Vascular Endothelial Cell Permeability Through Bioinformatics and Verification.

BACKGROUND: In this study, we aimed to identify the hub genes responsible for increased vascular endothelial cell permeability. METHODS: We applied the weighted Gene Expression Omnibus (GEO) database to mine dataset GSE178331 and ob-tained the most relevant high-throughput sequenced genes for an increased permeability of vascular endothelial cells due to inflammation. We constructed two weighted gene co-expression network analysis (WGCNA) networks, and the differential expression of high-throughput sequenced genes related to endothelial cell permeability were screened from the GEO database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the differential genes. Their degree values were obtained from the topological properties of protein-protein interaction (PPI) networks of differential genes, and the hub genes associated with an increased endothelial cell permeability were analyzed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting techniques were used to detect the presence of these hub genes in TNF-α induced mRNA and the protein expression in endothelial cells. RESULTS: In total, 1,475 differential genes were mainly enriched in the cell adhesion and TNF-α signaling pathway. With TNF-α inducing an increase in the endothelial cell permeability and significantly increasing mRNA and protein expression levels, we identified three hub genes, namely PTGS2, ICAM1, and SNAI1. There was a significant difference in the high-dose TNF-α group and in the low-dose TNF-α group compared to the control group, in the endothelial cell permeability experiment (p = 0.008 vs. p = 0.02). Measurement of mRNA and protein levels of PTGS2, ICAM1, and SNAI1 by western blotting analysis showed that there was a significant impact on TNF-α and that there was a significant dose-dependent relationship (p < 0.05 vs. p < 0.01). CONCLUSIONS: The three hub genes identified through bioinformatics analyses in the present study may serve as biomarkers of increased vascular endothelial cell permeability. The findings offer valuable insights into the progress and mechanism of vascular endothelial cell permeability.

Navigating Aged Care Services with GIS: Trends, Developments, and Future Directions.

BACKGROUND: With the growing challenge of an aging population, emerging technologies are increasingly being integrated into the production, organization, and delivery of aged care services. Geographic Information System (GIS), a computer-based tool for spatial information analysis and processing, has made significant strides in the allocation of care recources and service delivery for older adults, a notably vulnerable group. Despite its growing importance, cross-disciplinary literature reviews on this theme are scare. This scoping review was conducted to encapsulate the advancements and discern the future trajectory of GIS applications in aged care services. METHODS: A comprehensive search across nine databases yielded 5941 articles. Adhering to specific inclusion and exclusion criteria, 61 articles were selected for a detailed analysis. RESULTS: The 61 articles span from 2003 to 2022, with a notable increase in publications since 2018, comprising 41 articles (67% of the total) published between 2018-2022. Developed countries contributed 66% of the papers, with 45% focusing on accessibility issues. In the domain of aged care services, GIS has been predominantly utilized for model construction, mapping, and site selection, with a growing emphasis on addressing the unique needs of different subgroups of older adults. CONCLUSION: The past two decades have seen substantial growth in the application of GIS in aged care services, reflecting its increasing importance in this field. This scoping review not only charts the historical development of GIS applications in aged care services but also underscores the need for innovative research approaches. Future directions should emphasize the integration of GIS with diverse methodologies to address the heterogeneous needs of older adults and improve the overall delivery of aged care services. Such advancements in GIS applications have the potential to significantly enhance the efficiency, accessibility, and quality of care for the aging population.

A new scale for older resident satisfaction with residential integrated care in China: Development and validation.

The factors that affect resident satisfaction with emerging residential integrated care for older people in China have been unclear due to a lack of validated instruments. Based on psychometric assessment procedures, we developed a new scale for older resident satisfaction with residential integrated care (SORSRIC). The scale was developed using a two-step process and a sample of 16 Chinese institutions and 333 residents. Exploratory and confirmatory factor analysis was used to evaluate reliability and validity. Principal component analysis and maximum variance methods were used to orthogonally rotate the items to extract seven factors. These were: resident expectations, perceived quality (physical care), perceived quality (mental care), perceived value, resident satisfaction, resident complaints, and resident loyalty. The CR value of each dimension of the pre-tested, formal scale was greater than 0.80, and the AVE value was greater than 0.50. This 24-item instrument showed good reliability and structural validity and can be applied to improve the experience and outcomes for older people in residential care.

A review of the signaling pathways of aerobic and anaerobic exercise on atherosclerosis.

Atherosclerosis (AS), a chronic inflammatory vascular disease with lipid metabolism abnormalities, is one of the major pathological bases of coronary heart disease. As people's lifestyles and diets change, the incidence of AS increases yearly. Physical activity and exercise training have recently been identified as effective strategies for lowering cardiovascular disease (CVD) risk. However, the best exercise mode to ameliorate the risk factors related to AS is not clear. The effect of exercise on AS is affected by the type of exercise, intensity, and duration. In particular, aerobic and anaerobic exercise are the two most widely discussed types of exercise. During exercise, the cardiovascular system undergoes physiological changes via various signaling pathways. The review aims to summarize signaling pathways related to AS in two different exercise types and provide new ideas for the prevention and treatment of AS in clinical practice.

Functional changes in fusional vergence-related brain areas and correlation with clinical features in intermittent exotropia using functional magnetic resonance imaging.

To explore the functional changes of the frontal eye field (FEF) and relevant brain regions and its role in the pathogenesis of intermittent exotropia (IXT) children via functional magnetic resonance imaging (fMRI). Twenty-four IXT children (mean age, 11.83 ± 1.93 years) and 28 normal control (NC) subjects (mean age, 11.11 ± 1.50 years) were recruited. During fMRI scans, the IXT children and NCs were provided with static visual stimuli (to evoke sensory fusion) and dynamic visual stimuli (to evoke motor fusion and vergence eye movements) with binocular disparity. Brain activation in the relevant brain regions and clinical characteristics were evaluated. Group differences of brain activation and brain-behavior correlations were investigated. For dynamic and static visual disparity relative to no visual disparity, reduced brain activation in the right FEF and right inferior occipital gyrus (IOG), and increased brain activation in the left middle temporal gyrus complex (MT+) were found in the IXT children compared with NCs. Significant positive correlations between the fusional vergence amplitude and the brain activation values were found in the right FEF, right IPL, and left cerebellum in the NC group. Positive correlations between brain activation values and Newcastle Control Scores (NCS) were found in the left MT+ in the IXT group. For dynamic visual disparity relative to static visual disparity, reduced brain activation in the right middle occipital gyrus, left cerebellum, and bilateral IPL was found in the IXT children compared with NCs. Significant positive correlations between brain activation values and the fusional vergence amplitude were found in the right FEF and right cerebellum in the NC group. Negative correlations between brain activation values and NCS were found in the right middle occipital gyrus, right cerebellum, left IPL, and right FEF in the IXT group. These results suggest that the reduced brain activation in the right FEF, left IPL, and cerebellum may play an important role in the pathogenesis of IXT by influencing fusional vergence function. While the increased brain activation in the left MT+ may compensate for this dysfunction in IXT children.

Inattentional blindness: Attentional set for efficient task success.

Inattentional blindness is the failure to notice an unexpected object in plain sight when attention is otherwise engaged. We investigated what determines observers' attentional set in a dynamic-counting inattentional blindness paradigm, when task instructions and visual distinctiveness of task-relevant objects were either congruent or in opposition. In seven experiments, observers counted bounces by task-relevant objects, with the instruction either to count-by-shape (squares, diamonds, crosses) or count-by-colour (blue, purple). To manipulate visual distinctiveness, we varied the extent to which task-relevant and task-irrelevant objects looked different on two dimensions: shape and colour. When colour better distinguished task-relevant from task-irrelevant objects, observers-even if instructed count-by-shape-reported an unexpected object that matched the colour of task-relevant objects. Crucially, when instructed count-by-colour, but shape better distinguished task-relevant from task-irrelevant objects, observers reported an unexpected object that matched the shape of task-relevant objects. We conclude that observers set their attention to promote efficient task performance.

Is There a Relationship Between Online Health Information Seeking and Health Anxiety? A Systematic Review and Meta-Analysis.

The internet has revolutionized how we live, providing unprecedented convenience and up-to-date information. Consequently, an increasing number of individuals are turning to the internet for health-related information, despite research suggesting a correlation between this behavior and health anxiety. Therefore, drawing on cognitive - behavioral theory, we explore the link between online health information seeking and health anxiety via a systematic review and meta-analysis of cross-sectional studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis, we ran searches in multiple databases, including PubMed, Web of Science, Embase, Elsevier/Science Direct, Cochrane Database, China National Knowledge Infrastructure, VIP Chinese Database, and Wanfang Data. Our searches identified 16 studies eligible for review, involving 4,920 participants across seven countries. The random-effects meta-analysis revealed a significant positive correlation between online health information seeking and health anxiety (r = 0.28, 95% confidence interval [0.16, 0.41], p < .0001), despite considerable heterogeneity. Furthermore, meta-regression analysis demonstrated that the identity characteristics of the sample, female percentage, sample size, and country all contributed to the heterogeneity across studies. Overall, this meta-analysis provides support for the association between online health information seeking and health anxiety, and helps to elucidate the cognitive - behavioral theory underpinning this phenomenon.

Investigations of S-nZVI/AC composites for hexavalent chromium (Cr(VI)) elimination: synthesis and application.

Sulfidated nano zero-valent iron supported by activated carbon (S-nZVI/AC) composites were synthesized via liquid phase reduction method, and then they were used for Cr(VI) elimination. Characterization results showed that Fe0 was the main component, besides, iron oxides and iron sulfides were also detected. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results showed that S-nZVI nanoparticles were homogeneously distributed on the surfaces of AC. The influences of S/Fe ratio, C/Fe ratio, pH value, reaction temperature and co-existed ions (Cl-, SO42-, PO43- and NO3-) on Cr(VI) removal performances were investigated. Furthermore, the corresponding mechanisms were also discussed. The S-nZVI/AC composites exhibited good aging-resistance performances that Cr(VI) removal efficiency still maintained at 83.1% after being sealed in water for seven days, and they also had satisfying cycling stabilities that Cr(VI) removal efficiency only decreased less than 10% after four cycles. The good performances of S-nZVI/AC composites for Cr(VI) removal are attributed to the protection effect of iron sulfides and immobilization effect of AC, making S-nZVI/AC as a promising candidate for Cr(VI) elimination in effluents.

Identification and classification of differentially expressed genes in pyrethroid-resistant Culex pipiens pallens.

Culex pipiens pallens is an important vector that transmits Bancroftian filariasis, Japanese encephalitis and other diseases that pose a serious threat to human health. Extensive and improper use of insecticides has caused insecticide resistance in mosquitoes, which has become an important obstacle to the control of mosquito-borne diseases. It is crucial to investigate the underlying mechanism of insecticide resistance. The aims of this study were to identify genes involved in insecticide resistance based on the resistance phenotype, gene expression profile and single-nucleotide polymorphisms (SNPs) and to screen for major genes controlling insecticide resistance. Using a combination of SNP and transcriptome data, gene expression quantitative trait loci (eQTLs) were studied in deltamethrin-resistant mosquitoes. The most differentially expressed pathway in the resistant group was identified, and a regulatory network was built using these SNPs and the differentially expressed genes (DEGs) in this pathway. The major candidate genes involved in the control of insecticide resistance were analyzed by qPCR, siRNA microinjection and CDC bottle bioassays. A total of 85 DEGs that encoded putative detoxification enzymes (including 61 P450s) were identified in this pathway. The resistance regulatory network was built using SNPs, and these metabolic genes, and a major gene, CYP9AL1, were identified. The functional role of CYP9AL1 in insecticide resistance was confirmed by siRNA microinjection and CDC bottle bioassays. Using the eQTL approach, we identified important genes in pyrethroid resistance that may aid in understanding the mechanism underlying insecticide resistance and in targeting new measures for resistance monitoring and management.

NLRP3 Inflammasome Is Involved in Q-VD-OPH Induced Necroptosis Following Cerebral Ischemia-Reperfusion Injury.

Necroptosis is a manner of caspase-independent cell death,which accounts for delayed ischemic cerebral injury, and can be used as a novel tool to expand the treatment time window in ischemic cerebral injury. Q-VD-OPH, a novel pan caspase inhibitor, has been identified as an inducer of necroptosis. In this study, we determined the optimal dose of Q-VD-OPH, which induces necroptosis in rats by the middle cerebral artery occlusion, followed by reperfusion. Furthermore, we report that the NLRP3 inflammasome is involved in necroptosis, with levels of NLRP3 inflammasome proteins as well as inflammatory cytokines, such as IL-1ß, being elevated. We also demonstrated that NLRP3 was not only expressed in microglia and vascular endothelial cell, but also in neurons when necroptosis is induced with Q-VD-OPH. Inhibition of NLRP3 by glyburide strongly suppressed the expression of NLRP3 inflammasome proteins and IL-1ß, and markedly reduced brain tissue damage. Our findings provide evidence that pretreatment with Q-VD-OPH suppresses apoptosis and induces necroptosis in the cerebral ischemia-reperfusion model. We also identified that the NLRP3 inflammasome plays an important role in neuronal necroptosis, and that NLRP3 inflammasome deficiency reduces brain tissue damage after cerebral ischemia-reperfusion injury in rats.

[Construction of high quality Chrysanthemi Flos pieces standard system based on comprehensive analysis of ancient and modern Chinese and foreign pharmacopoeia].

To study the evolution of Chinese ancient and modern pharmacopoeia standards and compare the domestic and foreign pharmacopoeias, further understand the international requirements on chrysanthemum quality, and establish a more suitable and modern standard system for high quality Chrysanthemi Flos pieces. Newly Revised Materia Medica, Welfare Pharmacy, Collected Essentials of Species of Materia Medica (Bencao Pinhui Jingyao), Chinese Pharmacopoeia and other herbal remedies in various generations were reviewed to summarize the evolution of domestic standards on Chrysanthemi Flos pieces. Then they were compared with those in European Pharmacopoeia, United States Pharmacopoeia, Japanese Pharmacopoeia and other foreign Pharmacopoeias to establish a modern and international high-quality Chrysanthemi Flos pieces standard system with Chinese medicine characteristics and produce more internationally recognized high-quality Chinese medicine pieces.

Repair of hydrogel wearable devices through topological adhesion and cross-shaped sectional enhancement strategy.

Hydrogels, recognized for their biocompatibility, are extensively employed in the realm of wearable devices. Nevertheless, their application is often constrained by their low mechanical robustness, rendering them susceptible to damage during operation. The restoration of their load-bearing and sensory functionalities post-damage represents a captivating yet underexplored domain. Conventional repair techniques, reliant on hydrogen bonding or van der Waals forces, falter in the face of hydrogels' high water content. In this study, a novel composite adhesive gel (SGG), integrating sodium alginate, guar gum, and graphene oxide, was engineered to mend impaired hydrogels. Furthermore, an optimized repair approach, utilizing a cross-shaped sectional (CSS) enhancement strategy, was devised to reinstate the hydrogels' load and sensory capabilities. Investigations revealed that the SGG adhesive infiltrated the hydrogel, establishing an intermediary gel stratum, subsequently solidifying to mend the material through topological adhesion. This process reestablished the continuity of the polymer network and the aqueous phase within the hydrogel. Following the application of the CSS augmentation method, the peak tensile strain of the remediated hydrogel exceeded 200 %, with the uppermost observable adhesive energy touching 2526 J/m2. In addition, the ability to respond to strain was significantly rejuvenated, suggesting an effective methodology for the rehabilitation of wearable technology.

Inference of chromosome selection parameters and missegregation rate in cancer from DNA-sequencing data.

Aneuploidy is frequently observed in cancers and has been linked to poor patient outcome. Analysis of aneuploidy in DNA-sequencing (DNA-seq) data necessitates untangling the effects of the Copy Number Aberration (CNA) occurrence rates and the selection coefficients that act upon the resulting karyotypes. We introduce a parameter inference algorithm that takes advantage of both bulk and single-cell DNA-seq cohorts. The method is based on Approximate Bayesian Computation (ABC) and utilizes CINner, our recently introduced simulation algorithm of chromosomal instability in cancer. We examine three groups of statistics to summarize the data in the ABC routine: (A) Copy Number-based measures, (B) phylogeny tip statistics, and (C) phylogeny balance indices. Using these statistics, our method can recover both the CNA probabilities and selection parameters from ground truth data, and performs well even for data cohorts of relatively small sizes. We find that only statistics in groups A and C are well-suited for identifying CNA probabilities, and only group A carries the signals for estimating selection parameters. Moreover, the low number of CNA events at large scale compared to cell counts in single-cell samples means that statistics in group B cannot be estimated accurately using phylogeny reconstruction algorithms at the chromosome level. As data from both bulk and single-cell DNA-sequencing techniques becomes increasingly available, our inference framework promises to facilitate the analysis of distinct cancer types, differentiation between selection and neutral drift, and prediction of cancer clonal dynamics.

Layer-by-layer self-assembly embedding of nattokinase in chitosan/γ-polyglutamic acid: Preparation, fibrinolytic activity, stability, and in vitro digestion study.

Nattokinase (NK) is a thrombolytic enzyme extracted from natto, which can be used to prevent and treat blood clots. However, it is sensitive to the environment, especially the acidic environment of human stomach acid, and its effect of oral ingestion is minimal. This study aims to increase NK's oral and storage stability by embedding NK in microcapsules prepared with chitosan (CS) and γ-polyglutamic acid (γ-PGA). The paper prepared a double-layer NK oral delivery system by layer self-assembly and characterized its stability and in vitro simulated digestion. According to the research results, the bilayer putamen structure has a protective effect on NK, which not only maintains high activity in various environments (such as acid-base, high temperature) and long-term storage (60 days), but also effectively protects the loaded NK from being destroyed in gastric fluid and achieves its slow release. This work has proved the feasibility of the design of bilayer putamen structure in oral administration and has good fibrolytic activity. Therefore, the novel CS/γ-PGA microcapsules are expected to be used in nutraceutical delivery systems.

[Clinical analysis of breast reconstruction with endoscopic-assisted harvesting of latissimus dorsi muscle flap for breast cancer].

Objective: To investigate the benefits and drawbacks of breast reconstruction with endoscopic-assisted harvesting of the latissimus dorsi muscle flap for breast cancer and treatment experience of postoperative operation-related complications. Methods: A retrospective analysis was performed on clinical data of 26 female patients with breast cancer who met the selection criteria between September 2021 and March 2023 aging 48.7 years (range, 26-69 years). All tumors were unilateral, with 17 on the left side and 9 on the right side. The tumor size ranged from 1.0 to 7.0 cm, with an average of 2.7 cm. The pathological staging included T 1 in 11 cases, T 2 in 14 cases, and T 3 in 1 case; N 0 in 10 cases, N 1 in 11 cases, N 2 in 2 cases, and N 3 in 3 cases; no distant metastasis (M 0) occurred when first diagnosed. Among them, 10 cases underwent breast conserving surgery, and 16 cases underwent nipple-sparing mastectomy. All patients underwent breast reconstruction with endoscopic-assisted harvesting of the latissimus dorsi muscle flap. The operation time, incision length, and postoperative drainage volume in 3 days were recorded. Breast-Q "Satisfaction with back" scale was conducted to evaluate patients' satisfaction with back at 6 months after operation. Results: The operation time was 280-480 minutes (mean, 376.7 minutes), the incision length was 10-15 cm (mean, 12.2 cm), the postoperative drainage volume in 3 days was 500-1 600 mL (mean, 930.2 mL). There were 4 cases of postoperative seroma, 1 case of incision rupture, 1 case of paresthesia of the thoracic wall, and 1 case of edema of the ipsilateral upper limb. All patients were followed up 12-30 months (mean, 20.1 months). No latissimus dorsi muscle flap necrosis, latissimus dorsi muscle atrophy, or shoulder joint dysfunction occurred during follow-up; 2 patients had recurrence of lymph nodes in the ipsilateral axilla after operation, but no distant metastasis occurred. Breast-Q score at 6 months after operation was 64-100 (mean, 79.5). The average score was 78.6 (range, 64-100) in patients underwent nipple-sparing mastectomy and 81.0 (range, 78-100) in patients underwent breast conserving surgery. Conclusion: Breast reconstruction with endoscopic-assisted harvesting of the latissimus dorsi muscle flap for breast cancer is proven to be a surgical approach with safety and cosmetic effects with mild postoperative operation-related complications and considerable patient satisfaction.

Retrospective Analysis of Risk Factors for Urinary Tract Infection after Ureteral Calculi Surgery.

BACKGROUND: Ureteral calculi are a common diagnosis in the field of urology worldwide, and they represent a prevalent subtype of urolithiasis. Ureteroscopic stone surgery is the cornerstone treatment, but postoperative urinary tract infection (UTI) remains a clinical concern. Our study aims to analyse specific risk factors associated with postoperative UTIs following ureteroscopic stone surgery. METHODS: We conducted a case-control study and collected clinical data from 145 patients who underwent ureteroscopic lithotripsy at our hospital from January 2021 to January 2023. Binary logistic regression analysis was used to investigate risk factors for postoperative UTI. Receiver operating characteristic curves were plotted, and area under the curve (AUC) was calculated to evaluate the predictive value of each factor. RESULTS: Forty patients developed UTI after ureteroscopic stone surgery. Compared with the control group, the case group showed significant differences in stone size, history of diabetes mellitus and preoperative urine culture results (p < 0.05). Multivariable binary logistic regression analysis revealed that stone size (Odds Ratio (OR) = 1.952, p = 0.010), history of diabetes mellitus (OR = 2.438, p = 0.038) and preoperative urine culture (OR = 2.914, p = 0.009) were independent risk factors for postoperative UTI. The AUC values of stone size, history of diabetes mellitus and preoperative urine culture were 0.680, 0.627 and 0.630, respectively. The AUC of the combined prediction was 0.756. CONCLUSIONS: This study identified risk factors for postoperative UTI following ureteroscopic stone surgery and emphasised the importance of stone size, history of diabetes mellitus and preoperative urine culture in the diagnosis.

Synergistic enhancement mediated sensitive SERS-based immunoassay of PSA using versatile PDMS@AgNPs@ZIF-67 biomimetic substrates.

Among various biomimetic polymer materials, polydimethylsiloxane (PDMS) stands out as an ideal matrix for surface-enhanced Raman scattering (SERS) due to its unique intrinsic Raman signal and tenacity. In order to realize the precise detection of prostate-specific antigen (PSA), we proposed a sandwich-type SERS-active immunostructure composed of PDMS@silver nanoparticles (Ag NPs)@ZIF-67 biomimetic film as the immunosubstrate and gold nanorods (Au NRs) as immunoprobes. Due to the synergistic effect of electromagnetic enhancement facilitated by biomimetic surfaces and chemical enhancement achieved by ZIF-67, this structure enabled an ultrasensitive and selective detection of PSA across a broad range from 10-3 to 10-9 mg/mL. The achieved limit of detection was as low as 3.0 × 10-10 mg/mL. Particularly, the intrinsic Raman signal of PDMS matrix at 2905 cm-1 was employed as a potential internal standard (IS) in the detection, achieving a high coefficient of determination (R2) value of 0.996. This multifunctional SERS substrate-mediated immunoassay holds vast potential for early diagnosis of prostate cancer, offering promising prospects for clinical applications.

How fragile the positive results of Chinese herbal medicine randomized controlled trials on irritable bowel syndrome are?

OBJECTIVE: The fragility index (FI), which is the minimum number of changes in status from "event" to "non-event" resulting in a loss of statistical significance, serves as a significant supplementary indicator for clinical physicians in interpreting clinical trial results and aids in understanding the outcomes of randomized controlled trials (RCTs). In this systematic literature survey, we evaluated the FI for RCTs evaluating Chinese herbal medicine (CHM) for irritable bowel syndrome (IBS), and explored potential associations between study characteristics and the robustness of RCTs. METHODS: A comprehensive search was conducted in four databases in Chinese and four databases in English from their inception to January 1, 2023. RCTs encompassed 1:1 ratio into two parallel arms and reported at least one binary outcome that demonstrated statistical significance were included. FI was calculated by the iterative reduction of a target outcome event in the treatment group and concomitant subtraction of a non-target event from that group, until positive significance (defined as P < 0.05 by Fisher's exact test) is lost. The lower the FI (minimum 1) of a trial outcome, the more fragile the positive result of the outcome was. Linear regression models were adopted to explore influence factors of the value of FI. RESULTS: A total of 30 trials from 2 4118 potentially relevant citations were finally included. The median FI of total trials included was 1.5 (interquartile range [IQR], 1-5), and half of the trials (n = 15) had a FI equal to 1. In 12 trials (40%), the total number of participants lost to follow-up surpassed the respective FI. The study also identified that increased FI was significantly associated with no TCM syndrome differentiation for inclusion criteria of the patients, larger total sample size, low risk of bias, and larger numbers of events. CONCLUSIONS: The majority of CHM IBS RCTs with positive results were found to be fragile. Ensuring adequate sample size, scientifically rigorous study design, proper control of confounding factors, and a quality control calibration for consistency of TCM diagnostic results among clinicians should be addressed to increase the robustness of the RCTs. We recommend reporting the FI as one of the components of sensitivity analysis in future RCTs to facilitate the assessment of the fragility of trials.