Single-cell and spatial transcriptomics reveal alterations in trophoblasts at invasion sites and disturbed myometrial immune microenvironment in placenta accreta spectrum disorders.

BACKGROUND: Placenta accreta spectrum disorders (PAS) are a severe complication characterized by abnormal trophoblast invasion into the myometrium. The underlying mechanisms of PAS involve a complex interplay of various cell types and molecular pathways. Despite its significance, both the characteristics and intricate mechanisms of this condition remain poorly understood. METHODS: Spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq), were performed on the tissue samples from four PAS patients, including invasive tissues (ST, n = 3; scRNA-seq, n = 4), non-invasive normal placenta samples (ST, n = 1; scRNA-seq, n = 2). Three healthy term pregnant women provided normal myometrium samples (ST, n = 1; scRNA-seq, n = 2). ST analysis characterized the spatial expression landscape, and scRNA-seq was used to identify specific cellular components in PAS. Immunofluorescence staining was conducted to validate the findings. RESULTS: ST slices distinctly showed the myometrium in PAS was invaded by three subpopulations of trophoblast cells, extravillous trophoblast cells, cytotrophoblasts, and syncytiotrophoblasts, especially extravillous trophoblast cells. The pathways enriched by genes in trophoblasts, smooth muscle cells (SMC), and immune cells of PAS were mainly associated with immune and inflammation. We identified elevated expression of the angiogenesis-stimulating gene PTK2, alongside the cell proliferation-enhancing gene EGFR, within the trophoblasts of PAS group. Trophoblasts mainly contributed the enhancement of HLA-G and EBI3 signaling, which is crucial in establishing immune escape. Meanwhile, SMC regions in PAS exhibited upregulation of immunomodulatory markers such as CD274, HAVCR2, and IDO1, with CD274 expression experimentally verified to be increased in the invasive SMC areas of the PAS group. CONCLUSIONS: This study provided information of cellular composition and spatial organization in PAS at single-cell and spatial level. The dysregulated expression of genes in PAS revealed a complex interplay between enhanced immune escape in trophoblasts and immune tolerance in SMCs during invasion in PAS. These findings will enhance our understanding of PAS pathogenesis for developing potential therapeutic strategies.

A green, facile, and practical preparation of capsaicin derivatives with thiourea structure.

Capsaicin derivatives with thiourea structure (CDTS) is highly noteworthy owing to its higher analgesic potency in rodent models and higher agonism in vitro. However, the direct synthesis of CDTS remains t one or more shortcomings. In this study, we present reported a green, facile, and practical synthetic method of capsaicin derivatives with thiourea structure is developed by using an automated synthetic system, leading to a series of capsaicin derivatives with various electronic properties and functionalities in good to excellent yields.

A nomogram to predict severe COVID-19 patients with increased pulmonary lesions in early days.

Objectives: This study aimed to predict severe coronavirus disease 2019 (COVID-19) progression in patients with increased pneumonia lesions in the early days. A simplified nomogram was developed utilizing artificial intelligence (AI)-based quantified computed tomography (CT). Methods: From 17 December 2019 to 20 February 2020, a total of 246 patients were confirmed COVID-19 infected in Jingzhou Central Hospital, Hubei Province, China. Of these patients, 93 were mildly ill and had follow-up examinations in 7 days, and 61 of them had enlarged lesions on CT scans. We collected the neutrophil-to-lymphocyte ratio (NLR) and three quantitative CT features from two examinations within 7 days. The three quantitative CT features of pneumonia lesions, including ground-glass opacity volume (GV), semi-consolidation volume (SV), and consolidation volume (CV), were automatically calculated using AI. Additionally, the variation volumes of the lesions were also computed. Finally, a nomogram was developed using a multivariable logistic regression model. To simplify the model, we classified all the lesion volumes based on quartiles and curve fitting results. Results: Among the 93 patients, 61 patients showed enlarged lesions on CT within 7 days, of whom 19 (31.1%) developed any severe illness. The multivariable logistic regression model included age, NLR on the second time, an increase in lesion volume, and changes in SV and CV in 7 days. The personalized prediction nomogram demonstrated strong discrimination in the sample, with an area under curve (AUC) and the receiver operating characteristic curve (ROC) of 0.961 and a 95% confidence interval (CI) of 0.917-1.000. Decision curve analysis illustrated that a nomogram based on quantitative AI was clinically useful. Conclusion: The integration of CT quantitative changes, NLR, and age in this model exhibits promising performance in predicting the progression to severe illness in COVID-19 patients with early-stage pneumonia lesions. This comprehensive approach holds the potential to assist clinical decision-making.

Association of physical activity pattern and risk of Parkinson's disease.

Increasing evidence suggests an association between exercise duration and Parkinson's disease. However, no high-quality prospective evidence exists confirming whether differences exist between the two modes of exercise, weekend warrior and equal distribution of exercise duration, and Parkinson's risk. Hence, this study aimed to explore the association between different exercise patterns and Parkinson's risk using exercise data from the UK Biobank. The study analyzed data from 89,400 UK Biobank participants without Parkinson's disease. Exercise data were collected using the Axivity AX3 wrist-worn triaxial accelerometer. Participants were categorized into three groups: inactive, regularly active, and engaged in the weekend warrior (WW) pattern. The relationship between these exercise patterns and Parkinson's risk was assessed using a multifactorial Cox model. During a mean follow-up of 12.32 years, 329 individuals developed Parkinson's disease. In a multifactorial Cox model, using the World Health Organization-recommended threshold of 150 min of moderate-to-vigorous physical activity per week, both the active WW group [hazard ratio (HR) = 0.58; 95% confidence interval (CI) = 0.43-0.78; P < 0.001] and the active regular group (HR = 0.44; 95% CI = 0.34-0.57; P < 0.001) exhibited a lower risk of developing Parkinson's disease compared with the inactive group. Further, no statistically significant difference was observed between the active WW and the active regular groups (HR = 0.77; 95% CI = 0.56-1.05; P = 0.099). In conclusion, in this cohort study, both the WW exercise pattern and an equal distribution of exercise hours were equally effective in reducing Parkinson's risk.

DDCM: A Computational Strategy for Drug Repositioning Based on Support-Vector Regression Algorithm.

Computational drug-repositioning technology is an effective tool for speeding up drug development. As biological data resources continue to grow, it becomes more important to find effective methods to identify potential therapeutic drugs for diseases. The effective use of valuable data has become a more rational and efficient approach to drug repositioning. The disease-drug correlation method (DDCM) proposed in this study is a novel approach that integrates data from multiple sources and different levels to predict potential treatments for diseases, utilizing support-vector regression (SVR). The DDCM approach resulted in potential therapeutic drugs for neoplasms and cardiovascular diseases by constructing a correlation hybrid matrix containing the respective similarities of drugs and diseases, implementing the SVR algorithm to predict the correlation scores, and undergoing a randomized perturbation and stepwise screening pipeline. Some potential therapeutic drugs were predicted by this approach. The potential therapeutic ability of these drugs has been well-validated in terms of the literature, function, drug target, and survival-essential genes. The method's feasibility was confirmed by comparing the predicted results with the classical method and conducting a co-drug analysis of the sub-branch. Our method challenges the conventional approach to studying disease-drug correlations and presents a fresh perspective for understanding the pathogenesis of diseases.

Development of a machine learning-based prediction model for clinical pregnancy of intrauterine insemination in a large Chinese population.

PURPOSE: This study aimed to evaluate the effectiveness of a random forest (RF) model in predicting clinical pregnancy outcomes from intrauterine insemination (IUI) and identifying significant factors affecting IUI pregnancy in a large Chinese population. METHODS: RESULTS: A total of 11 variables, including eight from female (age, body mass index, duration of infertility, prior miscarriage, and spontaneous abortion), hormone levels (anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone), and three from male (smoking, semen volume, and sperm concentration), were identified as the significant variables associated with IUI clinical pregnancy in our Chinese dataset. The RF-based prediction model presents an area under the receiver operating characteristic curve (AUC) of 0.716 (95% confidence interval, 0.6914-0.7406), an accuracy rate of 0.6081, a sensitivity rate of 0.7113, and a specificity rate of 0.505. Importance analysis indicated that semen volume was the most vital variable in predicting IUI clinical pregnancy. CONCLUSIONS: The machine learning-based IUI clinical pregnancy prediction model showed a promising predictive efficacy that could provide a potent tool to guide selecting targeted infertile couples beneficial from IUI treatment, and also identify which parameters are most relevant in IUI clinical pregnancy.

Can artemisinin and its derivatives treat malaria in a host-directed manner?

Malaria is caused by an apicomplexan protozoan parasite, Plasmodium, and is transmitted through vectors. It remains a substantial health burden, especially in developing countries, leading to significant socioeconomic losses. Although the World Health Organization (WHO) has approved various antimalarial medications in the past two decades, the increasing resistance to these medications has worsened the situation. The development of drug resistance stems from genetic diversity among Plasmodium strains, impeding eradication efforts. Consequently, exploring innovative technologies and strategies for developing effective medications based on the host is crucial. Artemisinin and its derivatives (artemisinins) have been recommended by the WHO for treating malaria owing to their known effectiveness in killing the parasite. However, their potential to target the host for malaria treatment has not been investigated. This article concisely reviews the application of host-directed therapeutics, potential drug candidates targeting the host for treating malaria, and usage of artemisinins in numerous diseases. It underscores the importance of host-directed interventions for individuals susceptible to malaria, suggests the potential utility of artemisinins in host-directed malaria treatments, and posits that the modulation of host proteins with artemisinins may offer a means of intervening in host-parasite interactions. Further studies focusing on the host-targeting perspective of artemisinins can provide new insights into the mechanisms of artemisinin resistance and offer a unique opportunity for new antimalarial drug discovery.

Association between grip strength and albuminuria in the general United States population: NHANES 2011-2014.

Background: Grip strength has been shown to be associated with chronic renal insufficiency, but the relationship between grip strength and albuminuria has not been confirmed. In this study, we used NHANES data to explore the association between grip strength and albuminuria in a US population. Methods: In this analytical study, we utilized data sourced from the National Health and Nutrition Examination Survey (NHANES), specifically spanning the years 2011 to 2014. The dataset included 9,638 participants aged 20 years or older. After adjusting for potential confounders, multiple regression models were developed to infer the interrelationship between grip strength and albumin to creatinine ratio (ACR), and subgroup analyses were conducted. Results: After adjusting for all covariates, ACR by 0.49 mg/g [-0.49 (95% CI: -0.93, -0.04)] for each 1 kg increase in grip strength decreased. Subgroup analysis showed that gender, age, hyperlipidemia, hypertension, diabetes mellitus, smoking, alcohol consumption and body mass index did not influence the negative correlation between grip strength and albuminuria. Conclusion: There is a negative correlation between grip strength and albuminuria in the general U.S. population.

Development and Validation of a Discharge Assessment Scale for Outpatients Undergoing Sedative Anesthesia in the Ambulatory Postanesthesia Care Unit: A Comprehensive Delphi Study.

PURPOSE: The purpose of this study was to develop a discharge assessment scale tailored for outpatients undergoing sedative anesthesia treatment in the ambulatory postanesthesia care unit and validate its agreement with the Post-Anesthetic Discharge Scoring System. DESIGN: The Delphi method. METHODS: A Delphi survey was conducted with 30 experts focusing on the evaluation of outpatient discharges following treatment under ambulatory anesthesia. Subsequently, a cross-sectional observational study employing convenience sampling selected 2,579 outpatients who had undergone painless ambulatory gastrointestinal endoscopy at a tertiary hospital to analyze the level of agreement with the Post-Anesthesia Discharge Scoring System. FINDINGS: The study conducted three rounds of expert consultations to create the ambulatory discharge assessment scale. Twenty-five experts from 12 provinces and municipalities in our country were interviewed. The discharge assessment form encompassed five aspects: consciousness level, vital signs, directional stability, mobility, and adverse reactions. According to the scale, if the total score exceeded 9 points, with none of the items scoring 0 points, the ambulatory patient could be discharged from the hospital with the accompaniment of family members. Patients assessed using this newly constructed scale were able to leave the hospital earlier compared to those assessed using the comparative scale. No significant differences were observed in vital signs at the time of discharge or the occurrence of adverse events within 24 hours after the procedure. CONCLUSIONS: This assessment tool for discharging ambulatory patients after the ambulatory anesthesia from the postanesthesia outpatient care unit can be considered a valuable addition to formalize the discharge process in outpatient services.

Effects of saponins Rb1 and Re in American ginseng combined intervention on immune system of aging model.

Aging is a major risk factor for the development of many pathological processes, such as reduced immunity, cancer, cardiovascular diseases or neurodegenerative diseases, while age-related chronic diseases are the most common causes of death. This paper studies the effects of American ginseng saponin Rb1 and Re alone and combined intervention on the immune system of aging mouse models, by using 30 mg/kg Rb1, 15 mg/kg Re, and Rb1 + Re (30 mg/kg Rb1 and 15 mg/kg Re (co-intervention) was used to intervene in the aging model, and immune indicators such as thymus index, spleen index, interleukin and interferon were detected to evaluate the impact of Rb1 and Re on immune function. The results show that Rb1 and Re intervention alone can increase the spleen index by 7%-12% and the thymus index by 12%-19% in the aging model. After Rb1 or Re alone intervened, the apoptotic cells in the thymus were slightly reduced, and the proportion of apoptotic cells was reduced. The combination of Rb1 + Re can promote the thymus index and spleen index to increase by 23.40% and 25.5% respectively, which is more advantageous than Rb1 or Re alone. In addition, Rb1 and Re intervention can reduce the level of interferon INF to a level comparable to that of young mice. Rb1 + Re can not only reduce the INF content, but also reduce the TNF content. The above results show that American ginseng saponin Rb1 and Re can delay the decline of the immune system in the aging model, and the combined intervention of the two is significantly better than individual intervention in the recovery of the immune system. This paper can provide theoretical basis and data support for the development of American ginseng nutritional supplements and its application in aging groups products to improve immunity.

Physicochemical and antioxidant properties of pectin from Actinidia arguta Sieb.et Zucc (A. arguta) extracted by ultrasonic.

Pectin was extracted from Actinidia arguta Sieb. et Zucc (A.arguta) using the ultrasound-assisted acid method and the single acid method. The physicochemical properties, structure, and antioxidant properties of two different pectins were investigated. The results showed that the extraction yield of the ultrasound-assisted acid method is higher than that of the single acid method. The molecular structure of A. arguta pectin extracted by the ultrasound-assisted acid method belongs to a mixed structure of RG-I and HG-type domains. Through structural feature analysis, the ultrasound-assisted extraction pectin (UAP) has a more branched structure than the single acid-extracted pectin (SAP). The SAP has a higher degree of esterification than the UAP. The physical property results show that the viscosity, solubility, and water-holding capacity of the UAP are better than those of the SAP. The antioxidant test results show that the hydroxyl radical scavenging and reducing powers of the UAP are superior to those of the SAP. This study shows the composition, physicochemical properties, and antioxidant activity of A. arguta pectin extracted by the ultrasonic-assisted extraction method to provide a theoretical basis for its application as an antioxidant and other food additives in the food industry.

Associative role of HLA-DRB1 as a protective factor for susceptibility and progression of Parkinson's disease: a Chinese cross-sectional and longitudinal study.

Background: Previous genome-wide association studies investigating the relationship between the HLA-DRB1 and the risk of Parkinson's disease (PD) have shown limited racial diversity and have not explored clinical heterogeneity extensively. Methods: The study consisted of three parts: a case-control study, a cross-sectional study, and a longitudinal cohort study. The case-control study included 477 PD patients and 477 healthy controls to explore the relationship between rs660895 and PD susceptibility. The cross-sectional study utilized baseline data from 429 PD patients to examine the correlation between rs660895 and PD features. The longitudinal study included 388 PD patients who completed a 3-year follow-up to investigate the effects of rs660895 on PD progression. Results: In the case-control study, HLA-DRB1 rs660895-G allele was associated with a decreased risk of PD in allele model (adjusted OR=0.72, p = 0.003) and dominant model (AG + GG vs. AA: adjusted OR = 0.67, p = 0.003). In the cross-sectional analysis, there was no association between rs660895 and the onset age, motor phenotype, or initial motor symptoms. In the longitudinal analysis, PD patients with the G allele exhibited a slower progression of motor symptoms (MDS-UPDRS-III total score: ß = -5.42, p < 0.001, interaction ptime × genotype < 0.001) and non-motor symptoms (NMSS score: ß = -4.78, p = 0.030, interaction ptime × genotype < 0.001). Conclusion: Our findings support HLA-DRB1 rs660895-G allele is a protective genetic factor for PD risk in Chinese population. Furthermore, we also provide new evidence for the protective effect of rs660895-G allele in PD progression.

Comparison of outcomes between preoperative and postoperative systemic treatment in patients with hepatocellular carcinoma: a SEER database-based study.

Background: Significant advancements in systemic treatment for hepatocellular carcinoma have been made in recent years. However, the optimal timing of systemic treatment before or after surgery remains unknown. This study aims to evaluate the impact of sequencing systemic treatment and surgical intervention on the long-term prognosis of hepatocellular carcinoma patients. Methods: In our study, we analyzed data from patients diagnosed with primary liver cancer (2004-2015) extracted from the SEER database. Patients who underwent both systemic treatment and surgical intervention were selected, divided into preoperative and postoperative systemic therapy groups. The primary endpoint of the study is overall survival(OS), and the secondary endpoint is cancer-specific survival (CSS). Propensity score matching (PSM) reduced the influence of confounding factors, while Kaplan-Meier curves and a multivariable Cox proportional hazards model accounted for variables during survival analysis. Results: A total of 1918 eligible HCC patients were included, with 1406 cases in the preoperative systemic treatment group and 512 cases in the postoperative systemic treatment group. Survival analysis showed that both the preoperative group demonstrated longer median overall survival (OS) and median cancer-specific survival (CSS) before and after PSM. After conducting multivariate COX regression analysis with stepwise adjustment of input variables, the postoperative systemic treatment group continued to exhibit a higher risk of all-cause mortality (HR: 1.84, 95% CI: 1.55-2.1) and cancer-specific mortality (HR: 2.10, 95% CI: 1.73-2.54). Subgroup analysis indicated consistent results for overall survival (OS) across different subgroups. Conclusions: Hepatocellular carcinoma patients from the SEER database who received preoperative systemic therapy had superior OS and CSS compared to those who received postoperative systemic therapy.

Enantioselective Construction of Chiral THIQUINOL and Its Derivatives via Chiral Phosphoric Acid Catalysis.

The first catalytic enantioselective construction of chiral THIQUINOL and its derivatives has been accomplished through a chiral phosphoric-acid-catalyzed direct aza-Friedel-Crafts reaction of 3,4-dihydroisoquinolines with 2-naphthols/anthracen-2-ols/phenanthren-9-ol. This method offers a powerful and straightforward synthetic route toward chiral THIQUINOL derivatives with good to excellent yields and enantioselectivities. These structural motifs are crucial chiral components for further transformations into established or potential chiral ligands and catalysis.

First Detection of Atractylodes Mild Mottle Virus in Atractylodes lancea (Thunb.) DC. in Hubei Province of China.

The cultivated aromatic medicinal herb Atractylodes lancea (Thunb.) DC. is widely used in the pharmaceuticals, nutraceuticals, and cosmetics industries (Na-Bangchang et al. 2014; Zhan et al. 2023). Huanggang in Hubei Province is a major production area for A. lancea (Huang et al. 2022; Wang et al. 2023). In April 2023, more than two-thirds of the surveyed plant leaves in this region exhibited virus-like symptoms, such as curling and mosaic patterns. To identify the underlying cause, 80 symptomatic plant leaf samples were collected from four fields (20 leaves per field) in this region and pooled for virome analysis. Total RNA, including ribosomal RNA, was extracted from the pooled samples using the Plant RNA Extraction Mini Kit (Onrew Biotech, Guangdong, China), for sequencing library construction. The Illumina NovaSeq 6000 platform was used to sequence the library and generate 150 bp paired-end reads. After processing the raw data with Trimmomatic software, a total of 44,354,650 high-quality clean reads were obtained. The clean reads were aligned against ribosomal RNA using BWA software (v0.7.17) to avoid interference and eliminate corresponding sequences. After removing potential contamination, contig assembly of the clean reads was performed using Megahit software (v1.2.9). The resulting contigs were compared with the virus NT database using the BLASTn program. Sequence pairwise comparison revealed 8 contigs (574 nt to 2243 nt) with identities ranging from 81.88% to 90.77% with Atractylodes mild mottle virus (AMMV, NC_027924.1, Lim et al., 2015). Additionally, contigs mapped to Carlavirus, Pelarspovirus, and other plant viruses in our virome dataset had low coverage and pairwise identity (less than 70%), which need to be further investigated. The presence of AMMV was confirmed by aligning the clean reads to the reference sequence (NC_027924.1) using BWA and SAMtools software, resulting in a consensus sequence (8024 nt) with gaps. DNA extraction from the pooled samples was performed using the Rapid Universal Genomic DNA Extraction Kit (Simgen, Zhejiang, China). Two pairs of specific primers, 3399F (5'-AAAGAAGAACCTCCTGATACGG-3')/5924R (5'-TGAACCTGATTCTCTTGGC-3') and 1830F (5'- CTCAGGAAATCCCAATGC -3')/3640R(5'-TTTCCCAATGTTCTTCGGG-3'), were designed to amplify the complete gene sequences of polymerase and coat protein (CP), based on the consensus sequence. The PCR products with the lengths of 2521 bp and 1814 bp were cloned into the pMD18-T vector (Takara Biotech, Dalian, China) for sequencing. The BLASTn analysis showed that the polymerase and CP gene sequences shared an identity of 94.51% (1929/2041 nt) and 88.41% (1419/1605 nt) with the AMMV isolate (NC_027924.1), respectively. The sequences have been deposited in GenBank under the accession numbers OR544810 and OR544811. We collected leaves from 32 A. lancea plants (16 symptomatic and 16 asymptomatic) in the fields. RT-PCR was conducted using CPF (5'-CTGCGAATATGAAAGTGC-3') and CPR (5'-GGTGAGCTTGTCTGTTAGG-3') primers, which were designed targeting a 527bp fragment of the CP gene (OR544811). Amplicons of the expected size (527bp) were detected in 24 plants (11 symptomatic and 13 asymptomatic), three of which were sequenced by Sanger sequencing, showing a 100% match to OR544811. These findings indicate that AMMV is prevalent in the major production area of A. lancea. Further research is needed to better characterize the potential risks of AMMV to A. lancea cultivation in China as well as other countries.

Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: Study protocol for a prospective observational cohort study.

BACKGROUND: To Frailty is associated with postoperative delirium (POD) but is rarely assessed in patients undergoing noncardiac surgery. In this study, the correlation between preoperative frailty and POD, one-year mortality will be investigated in noncardiac Chinese geriatric surgery patients. METHODS: This study is a prospective, observational, cohort study conducted at a single center with Chinese geriatric patients. Patients who undergo noncardiac surgery and are older than 70 years will be included. A total of 536 noncardiac surgery patients will be recruited from the First Affiliated Hospital of Shandong First Medical University for this study. The Barthel Index (BI) rating will be used to assess the patient's ability to carry out everyday activities on the 1st preoperative day. The modified frailty index (mFI) will be used to assess frailty. Patients in the nonfrailty group will have an mFI < 0.21, and patients in the frailty group will have an mFI ≥ 0.21. The primary outcome is the incidence of POD. Three-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM) will be conducted twice daily during the 1st-7th postoperative days, or just before discharge. The secondary outcomes will include one-year mortality, in-hospital cardiopulmonary events, infections, acute renal injury, and cerebrovascular events. DISCUSSION: This study will clarify the correlation of preoperative frailty with POD and one-year all-cause mortality in Chinese geriatric patients undergoing noncardiac surgery. Can preoperative frailty predict POD or one-year mortality? In the face of China's serious aging social problems, this result may have important clinical value for the surgical treatment of geriatric patients. TRIAL REGISTRATION: This protocol has been registered with ClinicalTrials. Gov on 12 January 2022 (https://clinicaltrials.gov/ct2/show/NCT05189678).

Quantum interference enhances the performance of single-molecule transistors.

Quantum effects in nanoscale electronic devices promise to lead to new types of functionality not achievable using classical electronic components. However, quantum behaviour also presents an unresolved challenge facing electronics at the few-nanometre scale: resistive channels start leaking owing to quantum tunnelling. This affects the performance of nanoscale transistors, with direct source-drain tunnelling degrading switching ratios and subthreshold swings, and ultimately limiting operating frequency due to increased static power dissipation. The usual strategy to mitigate quantum effects has been to increase device complexity, but theory shows that if quantum effects can be exploited in molecular-scale electronics, this could provide a route to lower energy consumption and boost device performance. Here we demonstrate these effects experimentally, showing how the performance of molecular transistors is improved when the resistive channel contains two destructively interfering waves. We use a zinc-porphyrin coupled to graphene electrodes in a three-terminal transistor to demonstrate a >104 conductance-switching ratio, a subthreshold swing at the thermionic limit, a >7 kHz operating frequency and stability over >105 cycles. We fully map the anti-resonance interference features in conductance, reproduce the behaviour by density functional theory calculations and trace back the high performance to the coupling between molecular orbitals and graphene edge states. These results demonstrate how the quantum nature of electron transmission at the nanoscale can enhance, rather than degrade, device performance, and highlight directions for future development of miniaturized electronics.

Association between preoperative frailty and myocardial injury after noncardiac surgery in geriatric patients: study protocol for a prospective, multicentre, real-world observational, cohort trial.

INTRODUCTION: Frailty has become a worldwide health burden that has a large influence on public health and clinical practice. The incidence of frailty is anticipated to increase as the ageing population increases. Myocardial injury after noncardiac surgery (MINS) is associated with short-term and long-term mortality. However, the incidence of MINS in frail geriatric patients is unknown. METHODS AND ANALYSIS: This prospective, multicentre, real-world observational cohort study will be conducted at 18 designated centres in China from January 2023 to December 2024, with an anticipated sample size of 856 patients aged 65 years and older who are scheduled to undergo noncardiac surgery. The primary outcome will be the incidence of MINS. MINS is defined as a fourth-generation plasma cardiac troponin T (cTnT) concentration ≥ 0.03 ng/mL exhibited at least once within 30 days after surgery, with or without symptoms of myocardial ischaemia. All data will be collected via electronic data acquisition. DISCUSSION: This study will explore the incidence of MINS in frail patients. The characteristics, predictive factors and 30-day outcomes of MINS in frail patients will be further investigated to lay the foundation for identifying clinical interventions. CLINICAL TRIAL REGISTRATION: https://beta. CLINICALTRIALS: gov/study/NCT05635877 , NCT05635877.

Pyruvate is modified by tea/coffee metabolites and reversely correlated with multiple system atrophy and Parkinson's disease.

Introduction: Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder. Although diverse biomarkers have been established for Parkinson's disease (PD), no widely accepted markers have been identified in MSA. Pyruvate and lactate are the end-product of glycolysis and crucial for brain metabolism. However, their correlation with MSA remains unclear. Moreover, it is elusive how lifestyles modify these metabolites. Methods: To investigate the correlation and diagnostic value of plasma pyruvate and lactate levels in MSA and PD. Moreover, we explored how lifestyle-related metabolites interact with these metabolites in determining the disease risk. We assayed the 3 metabolites in pyruvate/lactate and 6 in the tea/coffee metabolic pathways by targeted mass spectrometry and evaluate their interactions and performance in diagnosis and differentiation between MSA and PD. Results: We found that 7 metabolites were significantly different between MSA, PD and healthy controls (HCs). Particularly, pyruvate was increased in PD while significantly decreased in MSA patients. Moreover, the tea/coffee metabolites were negatively associated with the pyruvate level in HCs, but not in MSA and PD patients. Using machine-learning models, we showed that the combination of pyruvate and tea/coffee metabolites diagnosed MSA (AUC = 0.878) and PD (AUC = 0.833) with good performance. Additionally, pyruvate had good performance in distinguishing MSA from PD (AUC = 0.860), and the differentiation increased (AUC = 0.922) when combined with theanine and 1,3-dimethyluric acid. Conclusions: This study demonstrates that pyruvate correlates reversely with MSA and PD, and may play distinct roles in their pathogenesis, which can be modified by lifestyle-related tea/coffee metabolites.