Screen-printed, biocompatible and ultrasensitive sensor for real-time reactive oxygen species detection in human sweat.

Excessive or burst generation of reactive oxygen species (ROS) can induce oxidative stress, precipitating a range of critical illnesses, including cancers, Parkinson's disease and Ischemia-reperfusion injury. Conventional biological assays for ROS, involving discrete steps of capturing, labelling, and spectrometric detection, are complex and time-intensive. Moreover, their accuracy is substantially compromised by the short lifespan (microseconds to milliseconds) of ROS. Consequently, there is a pressing need for a rapid and efficient method that enables real-time detection. In this study, we have developed a printable, flexible ROS sensor based on a robust nanoenzyme composite by direct deposition of the paste onto a flexible polyethylene terephthalate (PET) substrate. This device demonstrated the fast and real-time responses to the hydrogen peroxide (mimetic agent) in the laboratory and to total ROS in sweat of an individual, exhibiting an outstanding current response to hydrogen peroxide across a broad concentration range of 0.01-10 mM, with a limit of detection (LOD) of 1.85 µM. The device's sensitivity to hydrogen peroxide (136.59 µA mM-1 cm-2), was found to be 1.5 to 10 times higher than that of sensors previously reported. Moreover, the IFRS device successfully identified instantaneous ROS levels in the sweat of adult males in vitro, with amperometric response increased 8 times after half an hour strenuous exercise, thereby exhibiting excellent selectivity, remarkable stability, and confirmed high biosafety. Overall, the IFRS provides a viable and practical solution for simple, expedited, and real-time ROS detection in the near future.

Discovery of Inhibitors Targeting Protein-Protein Interaction between Bacterial RNA Polymerase and NusG as Novel Antimicrobials.

Bacterial RNA polymerase (RNAP), the core enzyme responsible for bacterial transcription, requires the NusG factor for efficient transcription elongation and termination. As the primary binding site for NusG, the RNAP clamp-helix (CH) domain represents a potential protein-protein interaction (PPI) target for novel antimicrobial agent design and discovery. In this study, we designed a pharmacophore model based on the essential amino acids of the CH for binding to NusG, such as R270, R278, and R281 (Escherichia coli numbering), and identified a hit compound with mild antimicrobial activity. Subsequent rational design and synthesis of this hit compound led to improved antimicrobial activity against Streptococcus pneumoniae, with the minimum inhibitory concentration (MIC) reduced from 128 to 1 µg/mL. Additional characterization of the antimicrobial activity, inhibitory activity against RNAP-NusG interaction, and cell-based transcription and fluorescent assays of the optimized compounds demonstrated their potential for further lead optimization.

Secretion of WNT7A by UC-MSCs assist in promoting the endometrial epithelial regeneration.

Stem cell therapy for intrauterine adhesions (IUAs) has been widely used in clinical treatment. However, intravenous injection lacks sufficient targeting capabilities, while in situ injection poses challenges in ensuring the effective survival of stem cells. Furthermore, the mechanism underlying the interaction between stem cells and endometrial cells in vivo remains poorly understood, and there is a lack of suitable in vitro models for studying these problems. Here, we designed an extracellular matrix (ECM)-adhesion mimic hydrogel for intrauterine administration, which was more effective than direct injection in treating IUAs. Additionally, we analyzed the epithelial-mesenchymal transition (EMT) and confirmed that the activation of endometrial epithelial stem cells is pivotal. Our findings demonstrated that umbilical cord mesenchymal stem cells (UC-MSCs) secrete WNT7A to activate endometrial epithelial stem cells, thereby accelerating regeneration of the endometrial epithelium. Concurrently, under transforming growth factor alpha (TGFA) stimulation secreted by the EMT epithelium, UC-MSCs upregulate E-cadherin while partially implanting into the endometrial epithelium.

Zhibai dihuang pill (ZBDH) exhibits therapeutic effects on idiopathic central sexual precocity in rats by modulating the gut microflora.

To reveal the role of gut microbiota (GM) in the occurrence and development of idiopathic central precocious puberty (ICPP) using 16S rDNA sequencing and bioinformatics analysis. The Danazol-induced ICPP model was successfully constructed in this study. ZBDH and GnRHa treatments could effectively inhibit ICPP in rats, as manifested by the delayed vaginal opening time, reduced weight, decreased uterine organ coefficient, and decreased uterine wall thickness and corpus luteum number, as well as remarkably reduced serum hormone (LH, FSH, and E2) levels. According to 16S rDNA sequencing analysis results, there was no significant difference in the GM community diversity across different groups; however, the composition of the microbial community and the abundance of the dominant microbial community were dramatically different among groups. ZBDH and GnRHa treatments could effectively reduce the abundance of Muribaculateae and Lactobacillus and promote Prevotella abundance. ZBDH and GnRHa were effective in treating Danazol-induced ICPP model rats. The therapeutic effects of ZBDH and GnRHa could be related to the changes in GM in rats.

Extension of Japan's Prefectural Emission Accounting and Enrichment of Socioeconomic Data from 1990 to 2020.

With the continuous increase in carbon dioxide emissions due to human activities and the resulting severe climate issues, there is global concern about energy conservation and emission reduction. However, detailed data on energy consumption and emissions at a fine-grained scale, particularly regarding spatial dimensions and sector-specific emissions, remains insufficient and in need of refinement and timely updates. In Japan, following the Fukushima nuclear disaster, there has been a significant shift from nuclear power generation to reliance on fossil fuels across various sectors, highlighting disparities in emissions data across different regions and industries. Our work extends the emissions time series for Japan's 47 prefectures, incorporating their socioeconomic characteristics over a broader time frame and with a more detailed sectoral classification. The emissions inventory, covering the period from 1990 to 2020, is based on the consumption of the three main fossil fuels across 32 sectors, with emissions carefully allocated for regional power generation. This dataset, presented in a unified format, is expanded to include longer time scales and more detailed socioeconomic data. It is anticipated to offer crucial insights for establishing regional emission reduction targets and identifying sectoral priorities for decarbonization.

Mixed diets can meet nutrient requirements with lower carbon footprints.

Achieving sustainable dietary change is essential for safeguarding human and environmental health. However, dietary recommendations based on broad food groups may not accurately reflect real-world realities because individuals select and consume dishes with multiple food items influenced by diverse context-specific factors. Therefore, here we explored the sustainability trade-offs of dietary choices at the dish level through an optimization modeling approach tested in Japan. We estimated the nutritional quality, price, and carbon footprint of major Japanese dishes and examined 16 dietary scenarios to identify options that meet the nutritional requirements and minimize carbon footprint. Overall, mixed diets contain more combinations of dishes that meet nutritional requirements with lower carbon footprints compared to more restrictive dietary scenarios. We argue that the approach developed here enables a better understanding of dietary trade-offs, complements existing methods, and helps identify sustainable diets by offering nuanced information at the national and sub-national levels.

Safety and Survival Outcomes of Liver Resection following Triple Combination Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma.

Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular carcinoma (HCC). However, the safety and long-term survival outcomes of subsequent liver resection after successful conversion still remain to be validated. From February 2019 to February 2023, 726 patients were enrolled in this retrospective study (75 patients received hepatectomy after conversion therapy [CLR group], and 651 patients underwent pure hepatectomy [LR group]). Propensity score matching (PSM) was used to balance the preoperative baseline characteristics. After PSM, 68 patients in the CLR group and 124 patients in the LR group were analyzed, and all the matching variables were well-balanced. Compared with the LR group, the CLR group experienced longer Pringle maneuver time, longer operation time, and longer hospital stays. In addition, the CLR group had significantly higher incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure (PHLF), and Clavien-Dindo grade IIIa complications than the LR group. There were no significant statistical differences in overall survival (OS) (hazard ratio [HR] 0.724; 95% confidence interval [CI] 0.356-1.474; p = 0.374) and recurrence-free survival (RFS) (HR 1.249; 95% CI 0.807-1.934; p = 0.374) between the two groups. Liver resection following triple combination conversion therapy in initially unresectable HCC may achieve favorable survival outcomes with manageable safety profiles; presenting as a promising treatment option for initially unresectable HCC.

Carbon footprint and embodied nutrition evaluation of 388 recipes.

Food consumption, which delivers fundamental energy and essential nutrients to human beings, is crucial for achieving a series of sustainable goals. Alongside rising population growth and living standards, there has been a significant increase in food cultivation demands, supply chain complexities, and waste management. Therefore, to protect human health and the environment, promoting sustainable food systems and the uptake of sustainable dietary habits are vital. Yet, information on the environmental and health impact of dietary choices remains inconsistent across multiple evaluation methods, which fail to deliver essential ideas to consumers. In this study, we formulate an integrated approach using Environmentally Extended Input-Output analysis, covering the food supply chain from production to the distribution phase, complemented with a hybrid Life Cycle Assessment for cooking and disposal processes, to quantify the carbon footprint of specific recipes. Our dataset also includes the distinct nutritional values of each recipe. This dataset not only informs the food industry and recipe platforms, enabling more sustainable choices, but also helps individuals balance nutritional value with environmental impact, leading to more informed and sustainable dietary decisions.

Cluster analysis of antiphospholipid antibodies-associated adverse pregnancy outcome patients: based on a 13-years cohort study.

Antiphospholipid antibodies (aPLs) are the leading causes of adverse pregnancy outcomes (APOs). We conducted cluster analysis to identify distinct phenotypes among aPLs-associated APOs patients. This approach aims to facilitate risk stratification and improve pregnancy outcomes for obstetric APS. This was a retrospective study of persistent aPLs positive women cohort in Peking Union Medical College Hospital. Baseline demographic characteristics, clinical manifestation, previous APOs and antibodies profiles were included for hierarchical cluster analysis. Placentae from portions of patients were collected and performed the histopathologic diagnoses. Four clusters among 209 patients with 477 pregnancies were identified. Cluster 1 comprised patients with triple aPLs positivity and demonstrates a high incidence of gestational hypertension (34.92%, P < 0.05) and preterm delivery (20.63%, P < 0.05). Patients in cluster 2 were characterized by lupus anticoagulant (LA) positivity, with high risk of whole gestational APOs. Cluster 3 included patients with isolated aPLs-IgM isotype combined with early miscarriage (60.92%, P = 0.016). Patients in cluster 4 majorly presented aPLs-IgG isotype combined with placenta insufficiency (22.73%). During the follow-up, the live birth rate in cluster 1 and 2 was only 69.20%. Placenta pathology revealed the most severe impairment within cluster 1, whereas clusters 3 and 4 exhibited relatively milder damage. By cluster analysis, we identified four clinical subtypes of aPLs-associated APOs patients. Patients with triple antibodies or high-risk lupus characteristics were prone to occurred gestational hypertension and premature delivery. Isolated LA or aCL/aß2GPI positivity were found to be more frequently associated with early-stage fetal loss.

Anti-ß2GPI-domain I antibody is associated with extra-criteria manifestations in a large prospective antiphospholipid syndrome cohort in China.

BACKGROUND: Anti-ß2GPI-domain I (ß2GPI-DI) antibody is pathogenic in patients with antiphospholipid syndrome (APS), but its additional clinical associations and diagnostic value are controversial. METHODS: A total of 378 patients were included, of which 119 patients diagnosed with primary APS, 50 with APS secondary to SLE (SAPS group), 209 with SLE without APS (SLE group). Serum anti-ß2GPI-DI IgG was measured using chemiluminescent immunoassay. Extra-criteria manifestations were analysed, including thrombocytopenia, autoimmune haemolytic anaemia, valvular lesions, APS nephropathy and non-vascular neurological manifestations. RESULTS: In 169 patients with APS, 55 (32.5%) were positive for anti-ß2GPI-DI IgG, accounting for 77.5% of those with anti-ß2GPI IgG positivity. It is shown that 96.4% of those with anti-ß2GPI-DI IgG also showed triple positivity in classic antiphospholipid antibodies (aPLs). The positivity of anti-ß2GPI-DI IgG was significantly associated with recurrent thrombosis before APS diagnosis (p=0.015), microvascular thrombosis (p=0.038), but not with pregnancy morbidity (PM). Notably, patients with extra-criteria manifestations showed significantly higher positivity (p=0.001) and titres (p<0.001) in anti-ß2GPI-DI IgG, especially for thrombocytopenia and APS nephropathy. In multivariable analysis, anti-ß2GPI-DI IgG positivity (OR 2.94, 95% CI 1.29 to 6.70), secondary APS, arterial hypertension and Coombs' test positivity independently predicted extra-criteria manifestations (C-index 0.83, 95% CI 0.77 to 0.90). After a median follow-up of 25 months, patients with anti-ß2GPI-DI IgG also showed a tendency of more extra-criteria events, but not thrombotic events. Anti-ß2GPI-DI was positive among 8.1% of the SLE controls, and showed high specificity (91.9%) in diagnosing SAPS among patients with SLE as compared with classic aPLs. CONCLUSION: Anti-ß2GPI-DI IgG was associated with extra-criteria manifestations in patients with APS. Further studies are warranted to validate its predictive values and potential role in daily practice.

Stabilizing Non-Fullerene Organic Photodiodes through Interface Engineering Enabled by a Tin Ion-Chelated Polymer.

The recent emergence of non-fullerene acceptors (NFAs) has energized the field of organic photodiodes (OPDs) and made major breakthroughs in their critical photoelectric characteristics. Yet, stabilizing inverted NF-OPDs remains challenging because of the intrinsic degradation induced by improper interfaces. Herein, a tin ion-chelated polyethyleneimine ethoxylated (denoted as PEIE-Sn) is proposed as a generic cathode interfacial layer (CIL) of NF-OPDs. The chelation between tin ions and nitrogen/oxygen atoms in PEIE-Sn contributes to the interface compatibility with efficient NFAs. The PEIE-Sn can effectively endow the devices with optimized cascade alignment and reduced interface defects. Consequently, the PEIE-Sn-OPD exhibits properties of anti-environmental interference, suppressed dark current, and accelerated interfacial electron extraction and transmission. As a result, the unencapsulated PEIE-Sn-OPD delivers high specific detection and fast response speed and shows only slight attenuation in photoelectric performance after exposure to air, light, and heat. Its superior performance outperforms the incumbent typical counterparts (ZnO, SnO2 , and PEIE as the CILs) from metrics of both stability and photoelectric characteristics. This finding suggests a promising strategy for stabilizing NF-OPDs by designing appropriate interface layers.

Extension and update of multiscale monthly household carbon footprint in Japan from 2011 to 2022.

Household consumption significantly contributes to greenhouse gas emissions as it is the largest component of final demand in the national accounting system. Nevertheless, there is an apparent lack of comprehensive and consistent datasets detailing emissions from household consumption. Here, we expand and update Japan's multiscale monthly household carbon footprint from January 2011 to September 2022, combining data from government statistics and surveys. We constructed a dataset comprising 37,692 direct and 4,852,845 indirect emission records, covering households at the national, regional, and prefectural city levels. The dataset provides critical spatiotemporal information that allows for revealing carbon emission patterns, pinpointing primary sources of emissions, and discerning regional variances. Moreover, the inclusion of micro-scale carbon footprint data enables the identification of specific consumption habits, thereby regulating individual consumption behavior to achieve a low-carbon society.

Japanese urban household carbon footprints during early-stage COVID-19 pandemic were consistent with those over the past decade.

As urbanization accelerates worldwide, substantial energy and services are required to meet the demand from cities, making cities major contributors to adverse environmental consequences. To bridge the knowledge gap in the absence of fine-grained city-level climate protection measures due to data availability and accuracy, this study provides a detailed carbon emission inventory for analyzing the monthly fluctuations based on citizens' daily consumption behaviors. Here, carbon emissions embodied in approximately 500 household consumption items were calculated in 47 prefectural-level cities in Japan from 2011 to June 2021. We analyzed the results considering the regional, seasonal, demand, and emission way-specific aspects, and compared the emission before and during the COVID-19 pandemic. Notably, the carbon footprints during the pandemic were consistent with the previous level despite downtrends in specific categories. This study provides an example of utilizing city-level emission data to improve household green consumption behavior as references for enriching city-level decarbonization paths.

Post-discharge consequences of protein-energy malnutrition, sarcopenia, and frailty in older adults admitted to rehabilitation: A systematic review.

BACKGROUND & AIMS: Malnutrition, sarcopenia, and frailty are three prevalent wasting conditions among older rehabilitation patients that lead to multiple health-related negative outcomes. This systematic review and meta-analysis aimed to determine the post-discharge consequences of malnutrition, sarcopenia, and frailty in older adults admitted to inpatient rehabilitation. METHODS: MEDLINE, Embase, Web of Science, and CINAHL databases were searched on 20 April, 2021 for longitudinal studies in older adults (≥65 years) admitted for inpatient rehabilitation. This systematic review included and synthesised studies that 1) measured malnutrition, sarcopenia, and/or frailty using a validated assessment tool or guideline; and 2) reported the association with post-discharge mortality, physical function, quality of life, or discharge location. The Academy of Nutrition & Dietetics Quality Criteria Checklist and GRADE criteria were used to assess risk of bias and evidence certainty. Where possible, data were pooled using Revman. RESULTS: Twenty-six observational studies (n = 9709 participants in total) with similarly aged populations were included. Eight, seven, and eleven studies assessed malnutrition, sarcopenia, and frailty, respectively. Follow-up periods ranged from immediate to 7 years post-rehabilitation. Malnutrition was associated with discharge to a higher level of care (GRADE: very low), and worse quality of life (GRADE: very low) and physical function (GRADE: very low). Sarcopenia was associated with worse physical function (GRADE: very low) and lower rate of home discharge (OR: 0.14; 95%CI: 0.09-0.20; I2:30%; GRADE: low). Frailty was associated with increased mortality (GRADE: very low), hospital readmission (GRADE: very low), and decreased home discharge (GRADE: very low). CONCLUSION: Wasting conditions in older adults during rehabilitation admission may be associated with poorer quality of life, lower rates of home discharge, and higher rates of health service use, physical dysfunction, and mortality following discharge. Further research is needed to investigate the comparative and combined impacts, as well as the overlap of malnutrition, sarcopenia, and frailty during and after rehabilitation to guide priority screening and intervention.

Use of mouse primary epidermal organoids for USA300 infection modeling and drug screening.

Skin infections caused by drug-resistant Staphylococcus aureus occur at high rates nationwide. Mouse primary epidermal organoids (mPEOs) possess stratified histological and morphological characteristics of epidermis and are highly similar to their derived tissue at the transcriptomic and proteomic levels. Herein, the susceptibility of mPEOs to methicillin-resistant S. aureus USA300 infection was investigated. The results show that mPEOs support USA300 colonization and invasion, exhibiting swollen epithelial squamous cells with nuclear necrosis and secreting inflammatory factors such as IL-1ß. Meanwhile mPEOs beneficial to observe the process of USA300 colonization with increasing infection time, and USA300 induces mPEOs to undergo pyroptosis and autophagy. In addition, we performed a drug screen for the mPEO infection model and showed that vancomycin restores cell viability and inhibits bacterial internalization in a concentration-dependent manner. In conclusion, we establish an in vitro skin infection model that contributes to the examination of drug screening strategies and antimicrobial drug mechanisms.

SERPINA1 and plasminogen as novel biomarkers in obstetric antiphospholipid syndrome patients.

OBJECTIVES: To explore the potential biomarkers and mechanisms in obstetric antiphospholipid syndrome (OAPS) patients by placental proteomics. METHODS: Among 212 follow-up pregnancy patients based on the Chinese Rheumatism Data Center database (CRDC), we continuously recruited 30 pregnancy patients at the late stage of pregnancy for proteomics study. Fresh placental tissues were collected and 4D label-free technologies were used to analyse the placental proteome in patients. Bioinformatic analysis was applied to identify differentially expressed proteins (DEPs) and crucial pathways. Placental tissues were also stained with haematoxylin and eosin (H & E) for histological analysis. RESULTS: We collected 7 OAPS patients (33.85±1.57 years), 4 SAPS patients (34.25 ± 3.86 years), 8 SLE patients (30.38±2.56 years), and 11 healthy controls (31.45±3.01 years). All patients in the SAPS and OAPS group had adverse pregnancy history. A total of 7040 proteins containing at least one unique peptide were identified. There were 214 DEPs between the healthy group and the OAPS group, of which 82 proteins were upregulated and 132 proteins were downregulated in the OAPS group based on fold change ≥1.5 and p-values ≤0.05. We found that the complement and coagulation pathway played a significant role in OAPS patients. Several key proteins (C1Q, C4b, SERPINA1, plasminogen) highly expressed in placental tissues, that may serve as biomarkers for OAPS patients. CONCLUSIONS: The complement and coagulation pathway and related DEPs (SERPINA1 and plasminogen) were of crucial importance in OAPS patients.

Nanostructured polyvinylpyrrolidone-curcumin conjugates allowed for kidney-targeted treatment of cisplatin induced acute kidney injury.

Acute kidney injury (AKI) leads to unacceptably high mortality due to difficulties in timely intervention and less efficient renal delivery of therapeutic drugs. Here, a series of polyvinylpyrrolidone (PVP)-curcumin nanoparticles (PCurNP) are designed to meet the renal excretion threshold (∼45 kDa), presenting a controllable delivery nanosystem for kidney targeting. Renal accumulation of the relatively small nanoparticles, 89Zr-PCurNP M10 with the diameter between 5 and 8 nm, is found to be 1.7 times and 1.8 times higher than the accumulation of 89Zr-PCurNP M29 (20-50 nm) and M40 (20-50 nm) as revealed by PET imaging. Furthermore, serum creatinine analysis, kidney tissues histology, and tubular injury scores revealed that PCurNP M10 efficiently treated cisplatin-induced AKI. Herein, PCurNP offers a novel and simple strategy for precise PET image-guided drug delivery of renal protective materials.

A preliminary study on salivary microbiota of patients with laryngopharyngeal reflux / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the characteristics of salivary microbiota in patients with laryngopharyngeal reflux (LPR). Methods: A case-control study was applied to enroll 60 patients and healthy subjects who were outpatients of the Department of Otorhinolaryngology Head and Neck Surgery of the Eighth Medical Center of the PLA General Hospital from December 2020 to March 2021, including 35 males and 25 females, aged from 21 to 80 (33.75±11.10) years. Thirty patients with suspected laryngopharyngeal reflux were selected as study group and thirty healthy volunteers without pharyngeal symptoms were selected as control group. Their salivary samples were collected, and the salivary microbiota was detected and analyzed by 16S rDNA sequencing. SPSS 18.0 software was used for statistical analysis. Results: There was no significant difference in the diversity of salivary microbiota between the two groups. At the phylum classification level, the relative abundance of Bacteroidetes in the study group was higher than that in the control group[37.86(31.15, 41.54)% vs 30.24(25.51, 34.18)%,Z=-3.46,P<0.01]. And the relative abundance of Proteobacteria in the study group was lower than that in the control group [15.76(11.81, 20.17)% vs 20.63(13.98, 28.82)%, Z=-1.98,P<0.05]. At the genus level, the relative abundance of Prevotella, Lactobacillus, Parascardovia and Sphingobium in the study group was higher than that in the control group(Z values were-2.92, -2.69, -2.05, -2.31, respectively, P<0.05).And the relative abundance of Streptococcus, Cardiobacterium, Klebsiella and Uruburuella of study group was lower than that of control group(Z values were -2.43, -2.32, -2.17, -2.32, respectively, P<0.05). LEfSe difference analysis showed that there were 39 bacteria with significant differences between the two groups, including Bacteroidetes, Prevotellaceae and Prevotella, which were enriched in the study group, and Streptococcaceae, Streptococcus and other taxa, which were enriched in the control group(P<0.05). Conclusion: The changes of the microflora in the saliva between LPR patients and healthy people suggest that the dysbacteriosis might exist in LPR patients, which may play an important role in the pathogenesis and development of LPR.