Dual electrochemical signal "signal-on-off" sensor based on CHA-Td-HCR and CRISPR-Cas12a for MUC1 detection.

Mucin 1 (MUC1) is frequently overexpressed in various cancers and is essential for early cancer detection. Current methods to detect MUC1 are expensive, time-consuming, and require skilled personnel. Therefore, developing a simple, sensitive, highly selective MUC1 detection sensor is necessary. In this study, we proposed a novel "signal-on-off" strategy that, in the presence of MUC1, synergistically integrates catalytic hairpin assembly (CHA) with DNA tetrahedron (Td)-based nonlinear hybridization chain reaction (HCR) to enhance the immobilization of electrochemically active methylene blue (MB) on magnetic nanoparticles (MNP), marking the MB signal "on". Concurrently, the activation of CRISPR-Cas12a by isothermal amplification products triggers the cleavage of single-stranded DNA (ssDNA) at the electrode surface, resulting in a reduction of MgAl-LDH@Fc-AuFe-MIL-101 (containing ferrocene, Fc) on the electrode, presenting the "signal-off" state. Both MB and MgAl-LDH@Fc-AuFe-MIL-101 electrochemical signals were measured and analyzed. Assay parameters were optimized, and sensitivity, stability, and linear range were assessed. Across a concentration spectrum of MUC1 spanning from 10 fg/mL to 100 ng/mL, the MB and MgAl-LDH@Fc-AuFe-MIL-101 signals were calibrated with each other, demonstrating a "signal-on-off" dual electrochemical signaling pattern. This allows for the precise and quantitative detection of MUC1 in clinical samples, offering significant potential for medical diagnosis.

Electrochemical-Fluorescent Bimodal Biosensor Based on Dual CRISPR-Cas12a Multiple Cascade Amplification for ctDNA Detection.

Circulating tumor DNA (ctDNA) is a critical biomarker for early tumor detection. However, accurately quantifying low-abundance ctDNA in human serum remains a significant challenge. To address this challenge, we introduce a bimodal biosensor tailored for detecting the epidermal growth factor receptor (EGFR) mutation L858R in specific nonsmall cell lung cancer (NSCLC) patients. This biosensor utilizes dual CRISPR-Cas12a systems to quantify the target via fluorescence and electrochemical signals. In our system, the EGFR L858R exhibits resistance to digestion by the restriction enzyme MscI, which activates the first CRISPR-Cas12a protein and inhibits the binding of magnetic beads with fluorescein (FAM)-labeled hybridization chain reaction (HCR) products, thereby reducing the fluorescence signal. This activation also inhibits the cleavage activity of the second CRISPR-Cas12a protein, allowing the electrode to sustain a higher electrochemical signal from nanomaterials. The wild-type EGFR (wt EGFR) produces the opposite effect. Consequently, the concentration of EGFR L858R can be accurately quantified and verified using both fluorescence and electrochemical signals. The biosensor offers a dynamic detection ranging from 10 fM to 1 µM, with a detection limit of 372 aM. It demonstrates excellent specificity, reproducibility, stability, and recovery rates. Moreover, the sensor's enhanced analytical sensitivity highlights its critical role in biosensing applications and early disease diagnosis.

Proportion of confluent B-Lines predicts respiratory support in term infants shortly after birth.

OBJECTIVE: To develop and evaluate the predictive value of a simplified lung ultrasound (LUS) method for forecasting respiratory support in term infants. METHODS: This observational, prospective, diagnostic accuracy study was conducted in a tertiary academic hospital between June and December 2023. A total of 361 neonates underwent LUS examination within 1 h of birth. The proportion of each LUS sign was utilized to predict their respiratory outcomes and compared with the LUS score model. After identifying the best predictive LUS sign, simplified models were created based on different scan regions. The optimal simplified model was selected by comparing its accuracy with both the full model and the LUS score model. RESULTS: After three days of follow-up, 91 infants required respiratory support, while 270 remained healthy. The proportion of confluent B-lines demonstrated high predictive accuracy for respiratory support, with an area under the curve (AUC) of 89.1% (95% confidence interval [CI]: 84.5-93.7%). The optimal simplified model involved scanning the R/L 1-4 region, yielding an AUC of 87.5% (95% CI: 82.6-92.3%). Both the full model and the optimal simplified model exhibited higher predictive accuracy compared to the LUS score model. The optimal cut-off value for the simplified model was determined to be 15.9%, with a sensitivity of 76.9% and specificity of 91.9%. CONCLUSIONS: The proportion of confluent B-lines in LUS can effectively predict the need for respiratory support in term infants shortly after birth and offers greater reliability than the LUS score model.

Long-term noise exposure and cause-specific mortality in chronic respiratory diseases, considering the modifying effect of air pollution.

BACKGROUND: Chronic respiratory diseases (CRDs) are among the top three causes of human mortality. The relationship between modifiable environmental risk factor of noise and risk of mortality in CRDs is unclear. We investigated the longitudinal association between environmental noise exposure and cause-specific mortality in individuals with CRDs, considering the modifying effect of air pollution. METHODS: Residential noise exposure was modelled using Common Noise Assessment Methods in Europe. Information on death causes were acquired from death registry data. Cox proportional-hazards models were used to estimate effect sizes. RESULTS: Among 41,222 participants selected from UK Biobank with CRDs in baseline, a total of 3618 death cases occurred during an average follow-up of 12 years with mortality density of 7.16 per 1000 person years. Exposure with highest noise level (> percentile 90) were associated with 22 % (Hazard ratio [HR] = 1.22, 95 % confidence interval [CI]: 1.05, 1.42), 71 % (HR = 1.71, 95 % CI: 1.14, 2.56), and 84 % (HR = 1.84, 95 % CI: 1.10, 3.07) increased risks for all-cause, respiratory disease (RD)-cause, and COPD-cause mortalities, separately. Both multiplicative and additive interactions was found between air pollution and noise with the risk of RD-cause mortality. Participants with high air pollution and noise exposure were associated with a 101 % (HR = 2.01, 95 % CI: 1.10, 3.66) increased risk of RD-cause mortality. CONCLUSION: It is imperative to mitigate noise exposure as a preventive measure against incident mortality in individuals with CRDs.

YOLOX-SwinT algorithm improves the accuracy of AO/OTA classification of intertrochanteric fractures by orthopedic trauma surgeons.

PURPOSE: Intertrochanteric fracture (ITF) classification is crucial for surgical decision-making. However, orthopedic trauma surgeons have shown lower accuracy in ITF classification than expected. The objective of this study was to utilize an artificial intelligence (AI) method to improve the accuracy of ITF classification. METHODS: We trained a network called YOLOX-SwinT, which is based on the You Only Look Once X (YOLOX) object detection network with Swin Transformer (SwinT) as the backbone architecture, using 762 radiographic ITF examinations as the training set. Subsequently, we recruited 5 senior orthopedic trauma surgeons (SOTS) and 5 junior orthopedic trauma surgeons (JOTS) to classify the 85 original images in the test set, as well as the images with the prediction results of the network model in sequence. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) 20.0 (IBM Corp., Armonk, NY, USA) to compare the differences among the SOTS, JOTS, SOTS + AI, JOTS + AI, SOTS + JOTS, and SOTS + JOTS + AI groups. All images were classified according to the AO/OTA 2018 classification system by 2 experienced trauma surgeons and verified by another expert in this field. Based on the actual clinical needs, after discussion, we integrated 8 subgroups into 5 new subgroups, and the dataset was divided into training, validation, and test sets by the ratio of 8:1:1. RESULTS: The mean average precision at the intersection over union (IoU) of 0.5 (mAP50) for subgroup detection reached 90.29%. The classification accuracy values of SOTS, JOTS, SOTS + AI, and JOTS + AI groups were 56.24% ± 4.02%, 35.29% ± 18.07%, 79.53% ± 7.14%, and 71.53% ± 5.22%, respectively. The paired t-test results showed that the difference between the SOTS and SOTS + AI groups was statistically significant, as well as the difference between the JOTS and JOTS + AI groups, and the SOTS + JOTS and SOTS + JOTS + AI groups. Moreover, the difference between the SOTS + JOTS and SOTS + JOTS + AI groups in each subgroup was statistically significant, with all p < 0.05. The independent samples t-test results showed that the difference between the SOTS and JOTS groups was statistically significant, while the difference between the SOTS + AI and JOTS + AI groups was not statistically significant. With the assistance of AI, the subgroup classification accuracy of both SOTS and JOTS was significantly improved, and JOTS achieved the same level as SOTS. CONCLUSION: In conclusion, the YOLOX-SwinT network algorithm enhances the accuracy of AO/OTA subgroups classification of ITF by orthopedic trauma surgeons.

Electrochemical detection of myoglobin using an ultrasensitive label-free sensor derived from cubic-ZIF67@Au-rGOF-NH2 composite of MOF and GOF.

Markers of myocardial injury, such as myoglobin (Mb), are substances swiftly released into the peripheral bloodstream upon myocardial cell injury or altered cardiac activity. During the onset of acute myocardial infarction, patients experience a significant surge in serum Mb levels. Given this, precise detection of Mb is essential, necessitating the development of innovative assays to optimize detection capabilities. This study introduces the synthesis of a three-dimensional hierarchical nanocomposite, Cubic-ZIF67@Au-rGOF-NH2, utilizing aminated reduced graphene oxide and zeolite imidazolium ester framework-67 (ZIF67) as foundational structures. Notably, this novel material, applied in a label-free electrochemical immunosensor, presents a groundbreaking approach for detecting myocardial injury markers. Experimental outcomes revealed ZIF67 and AuNPs exhibit enhanced affinity and growth on the 3D-rGOF-NH2 matrix, thus amplifying electrical conductivity while preserving the inherent electrochemical attributes of ZIF67. As a result, the Cubic-ZIF67@Au-rGOF-NH2 label-free electrochemical immunosensor exhibited a broad detection range and high sensitivity for Mb. The derived standard curve was ΔIp = 16.67552lgC+275.245 (R = 0.993) with a detection threshold of 3.47 fg/ml. Moreover, recoveries of standards spiked into samples ranged between 96.3% and 108.7%. Importantly, the devised immunosensor retained notable selectivity against non-target proteins, proving its potential clinical utility based on exemplary sample analysis performance.

Role of sugars in the apical hook development of Arabidopsis etiolated seedlings.

KEY MESSAGE: The sugar supply in the medium affects the apical hook development of Arabidopsis etiolated seedlings. In addition, we provided the mechanism insights of this process. Dicotyledonous plants form an apical hook structure to shield their young cotyledons from mechanical damage as they emerge from the rough soil. Our findings indicate that sugar molecules, such as sucrose and glucose, are crucial for apical hook development. The presence of sucrose and glucose allows the apical hooks to be maintained for a longer period compared to those grown in sugar-free conditions, and this effect is dose-dependent. Key roles in apical hook development are played by several sugar metabolism pathways, including oxidative phosphorylation and glycolysis. RNA-seq data revealed an up-regulation of genes involved in starch and sucrose metabolism in plants grown in sugar-free conditions, while genes associated with phenylpropanoid metabolism were down-regulated. This study underscores the significant role of sugar metabolism in the apical hook development of etiolated Arabidopsis seedlings.

Ultrasensitive and label-free electrochemical immunosensor for the detection of the ovarian cancer biomarker CA125 based on CuCo-ONSs@AuNPs nanocomposites.

Cancer antigen 125 (CA125) is pivotal as a tumor marker in early ovarian cancer prevention and diagnosis. In this work, we introduced an ultrasensitive label-free electrochemical immunosensor tailored for CA125 detection, leveraging nanogold-functionalized copper-cobalt oxide nanosheets (CuCo-ONSs@AuNPs) as nanocomposites. For the inaugural application, copper-cobalt oxide nanosheets delivered the requisite DPV electrochemical response for the immunosensors. Their large specific surface area and commendable electrical conductivity amplify electron transfer and enable significant gold nanoparticle loading. Concurrently, AuNPs offer a plethora of active sites, facilitating easy immobilization of biomolecules via the bond between amino groups and AuNPs. We employed scanning electron microscopy, transmission electron microscopy, and x-ray photoelectron spectroscopy to characterize the nanomaterials' surface morphology and elemental composition. The electrochemical sensor response signals were ascertained using differential pulse voltammetry. Under optimal conditions, the immunosensor exhibited a linear detection range from 1×10-7 U/mL to 1×10-3 U/mL and a detection limit of 3.9×10-8 U/mL (S/N=3). The proposed label-free electrochemical immunosensor furnishes a straightforward, dependable, and sensitive approach for CA125 quantification and stands as a promising method for clinical detection of other tumor markers.

Meta-analysis of pulsed-field ablation versus cryoablation for atrial fibrillation.

PURPOSE: The available data on the treatment strategy of pulsed field ablation (PFA) for patients with atrial fibrillation (AF) is limited. This study aims to provide a comparative analysis of the efficacy, safety, and procedural efficiency between PFA and cryoballoon ablation (CBA) for AF. METHODS: We conducted a comprehensive search of the EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov databases to identify trials comparing PFA with CBA for AF from their inception until December 2023. The odds ratio (OR) and mean difference (MD), along with a 95% confidence interval (CI), were utilized as measures of treatment effect. RESULTS: The analysis included 15 eligible trials with a total enrollment of 1880 patients. No significant differences were found in recurrent atrial arrhythmia (OR 0.83, 95% CI 0.64, 1.07) or periprocedural complications (OR 0.78, 95% CI 0.46, 1.30) between the two ablation techniques examined in this study. However, the PFA technique demonstrated a significantly shorter procedure time (MD -7.17, 95% CI -13.60, -0.73), but a longer fluoroscopy time (MD 2.53, 95% CI 0.87, 4.19). Similarly, PFA was found to be significantly associated with a decreased incidence of phrenic nerve palsy (OR 0.20, 95% CI 0.07, 0.59), but an increased incidence of cardiac tamponade (OR 4.07, 95% CI 1.15, 14.39). Moreover, there was a significantly higher release of troponin with PFA compared to CBA (MD 470.28, 95% CI 18.89, 921.67), while the increase in S100 protein and heart rate was significantly lower with PFA than with CBA (MD -64.41, 95% CI -105.46, -17.36), (MD -8.76, 95% CI -15.12, -2.40). CONCLUSION: The utilization of PFA provides a safer, time-saving, and tissue-specific procedure compared to CBA, while maintaining comparable success rates. This has the potential to enhance procedural efficiency and optimize resource utilization in clinical practice. These findings underscore the feasibility and promise of PFA as an alternative technique for PVI in patients with AF.

[Research on fault diagnosis of patient monitor based on text mining].

The conventional fault diagnosis of patient monitors heavily relies on manual experience, resulting in low diagnostic efficiency and ineffective utilization of fault maintenance text data. To address these issues, this paper proposes an intelligent fault diagnosis method for patient monitors based on multi-feature text representation, improved bidirectional gate recurrent unit (BiGRU) and attention mechanism. Firstly, the fault text data was preprocessed, and the word vectors containing multiple linguistic features was generated by linguistically-motivated bidirectional encoder representation from Transformer. Then, the bidirectional fault features were extracted and weighted by the improved BiGRU and attention mechanism respectively. Finally, the weighted loss function is used to reduce the impact of class imbalance on the model. To validate the effectiveness of the proposed method, this paper uses the patient monitor fault dataset for verification, and the macro F1 value has achieved 91.11%. The results show that the model built in this study can realize the automatic classification of fault text, and may provide assistant decision support for the intelligent fault diagnosis of the patient monitor in the future.

Dietary carbohydrate types, genetic predisposition, and risk of adult-onset asthma: A longitudinal cohort study.

We aimed to investigate the longitudinal associations among carbohydrate intake types, genetic predisposition, and risk adult onset asthma (AOA). A dataset of 96,487 participants from UK Biobank was included with 1830 cases of incident AOA during an average follow-up of 9.68 years. Participants with the highest intake of total sugar, free sugar, and fiber intake, as compared to those with the lowest intake of total sugar, free sugar, and fiber intake, showed a 17 % and 22 % increased risk of incident AOA, and a 16 % decreased risk of AOA, respectively. Substitution of 5 % energy from free sugars with 5 % energy from non-free sugars was associated with a significantly lower risk of AOA (Hazard Ratio [HR] = 0.93, 95 % Confidence Interval [CI]: 0.88, 0.99). Participants with high genetic risk and the highest intake of free sugar showed a 112 % (HR = 2.12, 95%CI: 1.68, 2.68) increased risk of incident AOA. Participants with low genetic risk and highest intake of fiber showed a 50 % (HR = 0.50, 95%CI: 0.39, 0.64) reduced risk of AOA. This study highlights the critical role of carbohydrate types in AOA prevention, with an emphasis on reduced free sugar, moderate non-free sugar, and increased fiber intake.

Sandwich-type immunosensor based on aminated 3D-rGOF-NH2 and CMK-3-Fc-MgAl-LDH multilayer nanocomposites for detection of CA125.

Cancer antigen 125 (CA125)1 is the most important biological screening indicator used to monitor epithelial ovarian cancers, and it plays a vital role in distinguishing ovarian cancers from benign diseases. Biosensors show great potential in the analysis and detection of disease markers. In this study, we designed electrochemical sensors based on three-dimensional amino-functionalized reduced graphene oxide (3D-rGOF-NH2),2 MgAl layered double hydroxide nanocomposites containing ordered mesoporous carbon (CMK-3),3 and ferrocene carboxylic acids（Fc-COOH）4for the detection of CA125. 3D-rGOF-NH2 possesses good conductivity, a large surface area, and high porosity, enabling more immobilized nanoparticles to be deposited on its surface with excellent stability. CMK-3@Fc@MgAl-LDH nanocomposite was used as a carrier to enhance the immobilization of antibodies and the loading of Fc, conductors to enhance conductivity, and enhancers to gradually amplify the signal of Fc. The surface morphology, elemental composition, and surface groups of the materials were characterized using scanning electron microscopy (SEM),5 transmission electron microscopy (TEM),6 and X-ray diffraction (XRD)7 techniques. The response signal of the electrochemical sensor was measured by DPV. Under the optimal conditions, the electrochemical sensor obtained a linear detection range of 0.01 U/mL-100 U/mL with a detection limit of 0.00417 U/mL.

Life's Essential 8, genetic predisposition, and risk of incident adult-onset asthma: a prospective cohort study.

BACKGROUND: Adult-onset asthma (AOA) and cardiovascular diseases shared common risk factors and similar pathophysiologic resemblances. The American Heart Association (AHA) unveiled the life's essential 8 (LE8) to promote cardiovascular health (CVH). This study aimed to assess the overall impact of LE8 implementation on AOA prevention. METHODS: According to the guideline of AHA's Construct of CVH in 2022, LE8 score was calculated from 8 health status concerning diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. Cox proportional-hazards models were used to estimate effect sizes of associations between CVH, asthma genetic risk, and risk of incident AOA in participants selected from the UK Biobank study. RESULTS: A total of 6180 incident AOA cases occurred in 249,713 participants during an average of 11.60 y' follow-up. A higher LE8 score was associated with a lower risk of incident AOA with a significant linear trend (P < 0.0001). Every standard deviation increment of LE8 was associated with a 17% (HR: 0.83; 95% CI: 0.81, 0.85) lower risk of incident AOA. Compared with participants with low-CVH score, participants with moderate (HR: 0.72; 95% CI: 0.67, 0.78) and high CVH scores (HR: 0.52; 95% CI: 0.47, 0.58) were associated with a lower risk of incident AOA (P-trend < 0.0001). No significant multiplicative or additive interaction was found between LE8 score and genetic risks. Stratified analysis showed a consistent association between CVH and risk of incident AOA across different asthma polygenic risk score (PRS) levels. Compared with participants with high PRS and low CVH, participants with low PRS and high CVH experienced the lowest risk (HR: 0.28; 95% CI: 0.23, 0.34) of incident AOA. CONCLUSIONS: Our findings suggest that maintaining optimal CVH should be recommended as a preventive strategy for AOA, regardless of their asthma genetic risks.

Identifying interactions among air pollutant emissions on diabetes prevalence in Northeast China using a complex network.

BACKGROUND: Low air quality related to ambient air pollution is the largest environmental risk to health worldwide. Interactions between air pollution emissions may affect associations between air pollution exposure and chronic diseases. Therefore, this study aimed to quantify interactions among air pollution emissions and assess their effects on the association between air pollution and diabetes. METHODS: After constructing long-term emission networks for six air pollutants based on data collected from routine monitoring stations in Northeast China, a mutual information network was used to quantify interactions among air pollution emissions. Multiple linear regression analysis was then used to explore the influence of emission interactions on the association between air pollution exposure and the prevalence of diabetes based on data reported from the Northeast Natural Cohort Study in China. RESULTS: Complex network analysis detected three major emission sources in Northeast China located in Shenyang and Changchun. The effects of particulate matter (PM2.5 and PM10) and ground-level ozone (O3) emissions were limited to certain communities but could spread to other communities through emissions in Inner Mongolia. Emissions of sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) significantly influenced other communities. These results indicated that air pollutants in different geographic areas can interact directly or indirectly. Adjusting for interactions between emissions changed associations between air pollution emissions and diabetes prevalence, especially for PM2.5, NO2, and CO. CONCLUSIONS: Complex network analysis is suitable for quantifying interactions among air pollution emissions and suggests that the effects of PM2.5 and NO2 emissions on health outcomes may have been overestimated in previous population studies while those of CO may have been underestimated. Further studies examining associations between air pollution and chronic diseases should consider controlling for the effects of interactions among pollution emissions.

Precious metal clusters as fundamental agents in bioimaging usability.

Fluorescent nanomaterials (NMs) are widely used in imaging techniques in biomedical research. Especially in bioimaging systems, with the rapid development of imaging nanotechnology, precious metal clusters such as Au, Ag, and Cu NMs have emerged with different functional agents for biomedical applications. Compared with traditional fluorescent molecules, precious metal clusters have the advantages of high optical stability, easy regulation of shape and size, and multifunctionalization. In addition, NMs possess strong photoluminescent properties with good photostability, high release rate, and sub-nanometer size. They could be treated as fundamental agents in bioimaging usability. This review summarizes the recent advances in bioimaging utilization, it conveys that metal clusters refer to Au, Ag, and Cu fluorescent clusters and could provide a generalized overview of their full applications. It includes optical property measurement, precious metal clusters in bioimaging systems, and a rare earth element-doped heterogeneous structure illustrated in biomedical imaging with specific examples, that provide new and innovative ideas for fluorescent NMs in the field of bioimaging usability.

Adherence to healthy lifestyle was associated with an attenuation of the risk of chronic kidney disease from metabolic dysfunction-associated fatty liver disease: Results from two prospective cohorts.

AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) are important risk factors of chronic kidney disease (CKD). Whether adherence to a healthy lifestyle can modify these effects remain unknown. This study aimed to evaluate the modification effects of healthy lifestyle on the associations among NAFLD, MAFLD, and the risk of CKD, with taking into the effect of genetic risk. METHODS: The Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study (TCLSIH), the UK Biobank Study (UKB). The outcome was incident CKD. The exposures including NAFLD, MAFLD, healthy lifestyle, and a genetic risk score (GRS) for CKD. RESULTS: After 1,135,334 person-year follow-up, we documented 2975 incident CKD cases in the two cohorts. MAFLD and NAFLD were associated with a higher risk of CKD, particularly in patients with MAFLD. In the TCLSIH and UKB, the hazard ratios (95% confidence intervals) of incident CKD for MAFLD were 1.47 (1.30, 1.66) and 1.73 (1.57, 1.91), respectively. Adherence to a healthier lifestyle decreased the risk of CKD from MAFLD with significant interaction effects (TCLSIH: Pinteraction = 0.02; UKB: Pinteraction = 0.04). Participants with a lower CKD-GRS experienced a higher risk of CKD from MAFLD, but achieved two healthy lifestyles can significantly decreased the risk of CKD in patients with MAFLD. CONCLUSIONS: MAFLD and NAFLD are associated with a higher CKD risk, particularly MAFLD. Adherence to a healthier lifestyle was associated with a lower risk of CKD from MAFLD. These results highlight the important role of following a healthy lifestyle to prevent CKD.

Dietary patterns, uric acid levels, and hyperuricemia: a systematic review and meta-analysis.

Background: Studies investigating the effects of dietary intake on serum uric acid (SUA) and hyperuricemia have yielded inconsistent results. Therefore, we conducted a meta-analysis to assess the associations between various dietary patterns and SUA levels as well as hyperuricemia. Methods: We searched PubMed, Web of Science, and EMBASE databases for relevant articles examining the association between dietary intake and SUA levels and/or hyperuricemia published until March 2023. Dietary intake patterns were classified into plant-based, animal-based, and mixed dietary patterns based on predominant foods. The pooled effect sizes of eligible studies and their corresponding 95% confidence intervals (CIs) were estimated using random-effects models. Publication bias was assessed using Egger's test. Results: We included 41 studies, comprising 359 317 participants, that investigated the effects of dietary patterns on SUA levels (n = 25) and hyperuricemia (n = 19). Our findings suggested that a plant-based dietary pattern was associated with decreased SUA levels in both interventional (standard mean difference: -0.24 mg dL-1, 95% CI: -0.42, -0.06; I2 = 61.4%) and observational studies (odds ratio (OR): 0.92, 95% CI: 0.89, 0.95, I2 = 91.1%); this association was stronger in men (OR: 0.45, 95% CI: 0.35, 0.58; I2 = 0). We observed that plant- and animal-based dietary patterns were associated with a reduced risk (OR: 0.75; 95% CI: 0.67, 0.83, I2 = 93.3%) and an increased risk (OR: 1.38; 95% CI: 1.20, 1.59, I2 = 88.4%) of hyperuricemia, respectively. Conclusions: Collectively, a plant-based dietary pattern is negatively associated with SUA levels and hyperuricemia. Therefore, a plant-based dietary pattern should be recommended for the management of SUA levels and the prevention of hyperuricemia.

Internet accessibility and incident depressive symptoms in middle aged and older adults in China: A national longitudinal cohort study.

BACKGROUND: With the rapid development of the Internet over the past ten years, its widespread applications and accessibility may cause dynamic changes in the association between internet use and depressive symptoms. OBJECTIVE: We aim to explore the association between internet accessibility (including broadband connection, internet use, frequency, and devices for internet use), as well as its changes, and the risk of incident depressive symptoms for middle aged and older adults based on a cohort study. METHODS: 8772 participants with three repeat waves of follow-up (average 6.04 years) were included. Cox proportional hazards regressions were used to explore risk effects. Hazard ratios (HRs) and 95 % Confidence Intervals [CI] were presented. RESULTS: Incidence density for depressive symptoms was 53.89 for every 1000 person-years. The rate of internet usage by middle aged and older adults in China increased evidently from 2012 to 2018 (16.39 % vs 77.41 %). Broadband internet connection (BIC) (HR = 0.80, 95%CI: 0.71, 0.90) and moderate frequency of internet use (IU) (HR = 0.30, 95%CI: 0.10, 0.92) were associated with decreased risk of depressive symptoms. Participants who changed from no internet accessibility to internet accessibility were associated with a lower risk of depressive symptoms (BIC: HR = 0.46, 95%CI: 0.41, 0.51; IU: HR = 0.42, 95%CI: 0.34, 0.51). Using large screen devices (HR = 0.64, 95%CI: 0.45, 0.91) for internet access, instead of phones, was associated with lower risk of depressive symptoms. CONCLUSIONS: Older adults should be encouraged to use the Internet; online time, frequency, and devices for internet use should be considered simultaneously.

Dietary intake patterns during pregnancy and excessive gestational weight gain: a systematic review and meta-analysis.

Excessive gestational weight gain (EGWG) is associated with gestational complications and adverse birth outcomes. Dietary intake is closely related to EGWG; however, evidence of the association between different dietary patterns and EGWG is inconsistent. We conducted a meta-analysis to systematically evaluate this association using articles from PubMed, Embase, and Web of Science databases published up to March 1st 2023 and included observational studies revealing an association between EGWG and dietary patterns during pregnancy. Dietary patterns were categorized into three groups: healthy, unhealthy, and mixed. Summary odds ratio (OR) and 95% confidence interval (CI) were calculated using the fixed-effects (I2 < 50%) or random-effects model (I2 ≥ 50%). Fourteen studies from eleven countries, including a total of 77,550 participants, met the inclusion criteria. The overall effect of healthy dietary patterns on EGWG was non-significant. After excluding one result in overweight participants, a significant negative association between healthy dietary patterns and EGWG was found in studies with a priori defined healthy dietary patterns (OR = 0.97, 95% CI: 0.94-1.00, P = 0.047), with sample size <1000 (OR = 0.68, 95% CI: 0.48-0.97, P = 0.031), and cohort studies (OR = 0.97, 95% CI: 0.95-1.00, P = 0.043). Overall analysis revealed a significant association between unhealthy dietary patterns and EGWG (OR = 1.22, 95% CI: 1.02-1.45, P = 0.031), and the results were similar in sub-groups of cohort studies (OR = 1.23, 95% CI: 1.02-1.49, P = 0.009) and those with a sample size < 1000 (OR = 1.31, 95% CI: 1.07-1.61, P = 0.03). A healthy dietary pattern instead of an unhealthy dietary pattern is recommended for pregnant women to prevent EGWG. This meta-analysis was registered in PROSPERO as CRD42023404179.

Overcoming Multidrug Resistance by Base-Editing-Induced Codon Mutation.

Multidrug resistance (MDR) is the main obstacle in cancer chemotherapy. ATP binding cassette (ABC) transporters on the MDR cell membrane can transport a wide range of antitumor drugs out of cells, which is one of the main causes of MDR. Therefore, disturbing ABC transporters becomes the key to reversing MDR. In this study, we implement a cytosine base editor (CBE) system to knock out the gene encoding ABC transporters by base editing. When the CBE system works in MDR cells, the MDR cells are manipulated, and the genes encoding ABC transporters can be inactivated by precisely changing single in-frame nucleotides to induce stop (iSTOP) codons. In this way, the expression of ABC efflux transporters is reduced and intracellular drug retention is significantly increased in MDR cells. Ultimately, the drug shows considerable cytotoxicity to the MDR cancer cells. Moreover, the substantial downregulation of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) implies the successful application of the CBE system in the knockout of different ABC efflux transporters. The recovery of chemosensitivity of MDR cancer cells to the chemotherapeutic drugs revealed that the system has a satisfactory universality and applicability. We believe that the CBE system will provide valuable clues for the use of CRISPR technology to defeat the MDR of cancer cells.