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Consumers are attracted to traditional fermented foods due to their unique flavor and nutritional value. However, the traditional fermentation technique can no longer accommodate the requirements of the food industry. Traditional fermented foods produce hazardous compounds, off‐odor, and anti‐nutritional factors, reducing product stability. The microbial system complexity of traditional fermented foods resulting from the open fermentation process has made it challenging to regulate these problems by modifying microbial behaviors. Synthetic microbial communities (SynComs) have been shown to simplify complex microbial communities and allow for the targeted design of microbial communities, which has been applied in processing traditional fermented foods. Herein, we describe the theoretical information of SynComs, particularly microbial physiological processes and their interactions. This paper discusses current approaches to creating SynComs, including designing, building, testing, and learning, with typical applications and fundamental techniques. Based on various traditional fermented food innovation demands, the potential and application of SynComs in enhancing the quality of traditional fermented foods are highlighted. SynComs showed superior performance in regulating the quality of traditional fermented foods using the interaction of core microorganisms to reduce the hazardous compounds of traditional fermented foods and improve flavor. Additionally, we presented the current status and future perspectives of SynComs for improving the quality of traditional fermented foods. [ABSTRACT FROM AUTHOR]

Metabolite profiling has the potential to comprehensively bridge phenotypes and complex heterogeneous physiological and pathological states. We performed a metabolomics study using parallel liquid chromatography–mass spectrometry (LC–MS) combined with multivariate data analysis to screen for biomarkers of primary aldosteronism (PA) from a cohort of 111 PA patients and 218 primary hypertension (PH) patients. Hydrophilic interaction chromatography and reversed‐phase liquid chromatography separations were employed to obtain a global plasma metabolome of endogenous metabolites. The satisfactory classification between PA and PH patients was obtained using the MVDA model. A total of 35 differential metabolites were screened out and identified. A diagnostic biomarker panel was established using the least absolute shrinkage and selection operator (LASSO) binary logistic regression model and receiver operating characteristic analysis. Joint analysis with clinical indicators, including plasma supine aldosterone level, plasma orthostatic aldosterone level, body mass index, and blood potassium, revealed that the combination of metabolite biomarker panel and plasma supine aldosterone has the best clinical diagnostic efficacy. [ABSTRACT FROM AUTHOR]

Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non‐demented adults. We included 1996 non‐demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aβ42 were designated as A+, while those demonstrating high phosphorylated tau (P‐tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aβ42 and P‐tau were categorized as the A−T− group, and those with abnormal levels of both Aβ42 and P‐tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A− subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A−T− subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aβ pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aβ pathology (mediation proportion range 8%–28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aβ pathology. Fibrinogen was associated with both cognition and Aβ pathology. Aβ pathology may be a critical mediator for impacts of fibrinogen on cognition. [ABSTRACT FROM AUTHOR]

The connection between head and neck squamous cell carcinoma (HNSC) and M2 tumour‐associated macrophages is not yet fully understood. We gathered gene expression profiles and clinical data from HNSC patients in the TCGA database. Using Consensus Clustering, we categorized these patients into M2 macrophage‐related clusters. We developed a M2 macrophage‐related signature (MRS) through statistical analyses. Additionally, we assessed gene expression in HNSC cells using single‐cell sequencing data (GSE139324). We identified three distinct M2 macrophage‐related clusters in HNSC, each with different prognostic outcomes and immune characteristics. Patients with different MRS profiles exhibited variations in immune infiltration, genetic mutations and prognosis. FCGR2A may play a role in creating an immunosuppressive tumour microenvironment and could potentially serve as a therapeutic target for HNSC. Our study demonstrated that M2 macrophage‐related genes significantly impact the development and progression of HNSC. The M2 macrophage‐related model offered a more comprehensive assessment of HNSC patient prognosis, genetic mutations and immune features. FCGR2A was implicated in immunosuppressive microenvironments and may hold promise for the development of novel immunotherapeutic strategies for HNSC. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a type of tumour found in the cavity that is characterized by differentiation and metastasis to the lymph nodes. Although diagnosis strategy and clinical treatment have recently improved, the outcomes for OSCC patients remain unsatisfactory. This study verified the characteristics of circPUM1 in OSCC cells, subsequently generating dysregulated circPUM1 cell models, showing that circPUM1 promoted chemoresistance and natural killer (NK) cell toxicity. Furthermore, the transcription factor SP2 regulated the expression of circPUM1 in OSCC cells, circPUM1 acted as a molecular sponge for miR‐770‐5p. Moreover, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) is a downstream target for miR‐770‐5p and essential for circPUM1‐mediated cisplatin resistance and NK cell cytotoxicity in OSCC cells. The network composed of SP2, circPUM1, miR‐770‐5p and NAP1L1 in OSCC appears to be a promising avenue for the development of novel targets for diagnosing or treating OSCC. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high mortality and poor prognosis. Despite intensive research focused on tumor suppression, the 5‐year survival rate of ESCC is lower than 15%. Therefore, investigate fundamental mechanisms involved in ESCC is on‐demand crucial for diagnostics and developing targeted therapeutic drugs. Circular RNAs (circRNAs), as an emerging class of non‐coding RNA, have been elucidated that circRNAs participated in regulating a variety of pathological processes and tumorigenesis. Nevertheless, the functional role of circRNAs in the occurrence and development of ESCC remains unclear. We identify a novel circRNA (hsa_circ_0001707), which was highly expressed in ESCC patients' tissues and cell lines. Furthermore, gain‐ and loss‐of‐function assays were performed and found that overexpression of hsa_circ_0001707 significantly promote tumor proliferation, metastasis, and invasion. By functioning as a competing endogenous RNA (ceRNA), the dual‐luciferase activity assay verified that hsa_circ_0001707 can endogenously bind with miR‐203a‐3p and regulate its downstream gene Snail2. Rescue assay further confirms that hsa_circ_0001707 downregulation could partially attenuate the facilitation effect of miR‐203a‐3p, thereby inhibiting the endothelial‐mesenchymal transition (EMT) process of ESCC. Our results suggested that hsa_circ_0001707 play an oncogenic role in the pathogenesis of ESCC, which might be a potential biomarker for diagnostics and targeting therapy. [ABSTRACT FROM AUTHOR]

Pb‐Sn mixed perovskite has received extensive attention because of its high research value in environmental protection and theoretical prospects. However, the film defects brought on by the quick crystallization of Pb‐Sn mixed perovskites and the facile oxidation of Sn2+ to Sn4+ are detrimental to the performance of Pb‐Sn perovskite solar cells (PSCs). Here, aiming at the interface of Pb‐Sn PSCs, which has been less studied, a reducing agent is first introduced on the top of Pb‐Sn mixed perovskite interface. The results show that in NaBH3CN(SC), B─H can suppress the oxidation of Sn2+ and C≡N can enhance the perovskite crystallinity and passivate the surface defects. Benefitting from this synergistic effect, a champion power conversion efficiency of 21.3% is obtained for Pb‐Sn PSCs. In addition, the encapsulated device can maintain good stability under maximum power point tracking conditions. [ABSTRACT FROM AUTHOR]

Cisplatin (CDDP) chemoresistance is one of the predominant factors in oral squamous cell carcinoma (OSCC) treatment failure. Uncovering the mechanisms underlying CDDP resistance is of great importance in OSCC therapy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs, which are reported to participate in the progression of various diseases, including cancer. However, the function of circRNAs in CDDP resistance in OSCC remains unclear. Quantitative reverse transcription PCR was used to search for different circRNAs between OSCC cell lines and CDDP‐resistant cell lines. The results showed that circ‐ILF2 expression was higher in CDDP‐resistant OSCC cell lines. The stability of circ‐ILF2 was also confirmed using RNase R and actinomycin D assays. Functional experiments, including cytotoxicity, apoptosis and growth rate assays, showed that upregulation of circ‐ILF2 contributes to CDDP resistance. Luciferase reporter‐gene, RNA pull‐down and quantitative real‐time PCR (RT‐qPCR) assays showed that circ‐ILF2 functions as a microRNA sponge for miR‐1252. Luciferase reporter assays, RNA pull‐down, RT‐qPCR and Western blotting showed that miR‐1252 directly targeted and regulated the expression of KLF8. Circ‐ILF2 plays an important role in CDDP resistance in OSCC. Circ‐ILF2 exerts its function through the miR‐1252/KLF8 pathway. In addition, tumour‐associated macrophages (TAM) play important roles in cancer progressions, our results showed that circ‐ILF2 in OSCC cells induced the M2 polarization of macrophages which provided new thoughts on immunotherapy. Our results suggest that circ‐ILF2 may represent a potential therapeutic target in CDDP‐resistant OSCC. [ABSTRACT FROM AUTHOR]

The development of efficient, recyclable and low‐cost heterogeneous catalysts for conversion of carbon dioxide (CO2) into epoxides is highly desired, yet remain a challenge. Herein, we have prepared three two‐dimensional (2D) copper(I) cyclic trinuclear units (Cu(I)‐CTUs) based covalent metal–organic frameworks (CMOFs), namely JNM‐13, JNM‐14, and JNM‐15, via a one‐pot reaction by combination of coordination and dynamic covalent chemistry. Among them, JNM‐15 contained the highest density of copper catalytic sites, and exhibited the highest capacity for adsorption of CO2. More interestingly, JNM‐15 delivered the highest catalytic activity for cycloaddition of CO2 to epoxides with good yields (up to 99 %), good substrate compatibility (11 examples) and reusability (four catalytic cycles) under mild condition. [ABSTRACT FROM AUTHOR]

Objective: Women with rheumatoid arthritis (RA) have higher pain and worse functional outcomes compared to men, even when treated with similar medications. The objective of this study was to identify sex differences in pain intensity, pain interference, and quantitative sensory tests (QST), which are independent of inflammation, in patients with RA. Methods: This study is a post hoc analysis of participants in the Central Pain in Rheumatoid Arthritis cohort. Pain intensity was assessed using a 0–10 numeric rating scale. Pain interference was measured using a Patient‐Reported Outcomes Measurement Information System computerized adaptive test. QST included pressure pain detection thresholds, temporal summation, and conditioned pain modulation. Women and men were compared using multiple linear regression, adjusted for age, education, race, research site, depression, obesity, RA disease duration, swollen joint count, and C‐reactive protein. Results: Mean ± SD pain intensity was 5.32 ± 2.29 among women with RA, compared to 4.60 ± 2.23 among men with RA (adjusted difference 0.83 [95% confidence interval (95% CI) 0.14, 1.53]). Women with RA had lower pressure pain detection thresholds at the trapezius (adjusted difference –1.22 [95% CI –1.73, –0.72]), wrist (adjusted difference –0.57 [95% CI –1.07, –0.06]), and knee (adjusted difference –1.10 [95% CI –2.00, –0.21]). No statistically significant differences in pain interference, temporal summation, and conditioned pain modulation were observed. Conclusion: Women reported higher pain intensity and lower pressure pain detection thresholds (higher pain sensitivity) than men. However, pain interference, temporal summation, and conditioned pain modulation did not differ between men and women. [ABSTRACT FROM AUTHOR]

Objective: To identify modifiable physical and behavioural factors associated with widespread pain (WSP) in older adults with radiographic evidence of knee osteoarthritis (OA). Methods: Cross‐sectional initial visit data of participants with radiographic knee OA (Kellgren‐Lawrence grade of ≥2) from the Osteoarthritis Initiative Study were analysed. WSP was defined as pain on both sides of the body, above and below the waist, and in the axial skeleton. Time (hrs/d) spent participating in sitting and moderate‐strenuous physical activities were calculated from the Physical Activity Scale for the Elderly questionnaire. Physical function was quantified using gait speed and the chair stand test. Restless sleep was assessed using an item on the CES‐D Scale. Logistic regression models were constructed to examine the strength of the associations between primary exposures and WSP in unadjusted and adjusted analyses. Results: Among the 2637 participants (mean age 62.6 years, 58.6% female), 16.8% met the criteria for WSP. All primary measures of interest were related to WSP in unadjusted analyses. In adjusted multivariable analysis, slow gait speed (adjusted odds ratio [aOR] 1.43; 95% CI 1.01, 2.02), lower chair stand rate (aOR 0.98; 95% CI 0.97–0.99), and restless sleep (aOR 1.61; 95% CI 1.25–2.08) maintained significant associations with WSP. Conclusion: Poor sleep behaviours and low physical function capacity are associated with WSP in adults with radiographic knee OA. These findings highlight the importance of assessing sleep, physical function, and pain distribution in this population. Interventions to improve physical function and sleep behaviours should be investigated as potential strategies to mitigate WSP. [ABSTRACT FROM AUTHOR]

SUMMARY: Horticultural plants contribute immensely to the quality of human's life. The rapid development of omics studies on horticultural plants has resulted in large volumes of valuable growth‐ and development‐related data. Genes that are essential for growth and development are highly conserved in evolution. Cross‐species data mining reduces the impact of species heterogeneity and has been extensively used for conserved gene identification. Owing to the lack of a comprehensive database for cross‐species data mining using multi‐omics data from all horticultural plant species, the current resources in this field are far from satisfactory. Here, we introduce GERDH (https://dphdatabase.com), a database platform for cross‐species data mining among horticultural plants, based on 12 961 uniformly processed publicly available omics libraries from more than 150 horticultural plant accessions, including fruits, vegetables and ornamental plants. Important and conserved genes that are essential for a specific biological process can be obtained by cross‐species analysis module with interactive web‐based data analysis and visualization. Moreover, GERDH is equipped with seven online analysis tools, including gene expression, in‐species analysis, epigenetic regulation, gene co‐expression, enrichment/pathway and phylogenetic analysis. By interactive cross‐species analysis, we identified key genes contributing to postharvest storage. By gene expression analysis, we explored new functions of CmEIN3 in flower development, which was validated by transgenic chrysanthemum analysis. We believe that GERDH will be a useful resource for key gene identification and will allow for omics big data to be more available and accessible to horticultural plant community members. Significance Statement: GERDH is a comprehensive, convenient, user‐friendly multi‐omics database that focuses on interactive cross‐species analysis and allows users to quickly and easily obtain gene expression and regulation data generated from horticultural plant species. We believe that GERDH will be a useful resource for efficient data mining and will allow for omics big data to be more available and accessible to horticultural plant community members. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We analyzed relationships among peripheral immunity markers, cognition, Alzheimer's disease (AD)‐related biomarkers, and neuroimaging to understand peripheral immunity involvement in AD. METHODS: Peripheral immunity markers were assessed in AD, non‐AD neurodegenerative disorders, and controls, examining their connections with cognition, AD‐related biomarkers, and neuroimaging using multiple regression models. RESULTS: The study included 1579 participants. Higher levels of white blood cell, neutrophil, monocyte, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), systemic immune‐inflammation index (SII), and lower lymphocyte‐to‐monocyte ratio (LMR) were associated with cognitive decline and more severe anxiety and depression. The impact of lower LMR, lymphocyte count, and higher NLR on cognitive decline is mediated through cerebrospinal fluid amyloid beta (Aβ) levels. Additionally, increased PLR, NLR, and SII were associated with brain atrophy and hippocampal Aβ deposition (amyloid positron emission tomography). DISCUSSION: Peripheral immunity markers offer a non‐invasive and cost‐effective means of studying AD‐related pathophysiological changes, providing valuable insights into its pathogenesis and treatment. Highlights: Peripheral immunity markers linked to cognitive decline and anxiety/depression.Low LMR, LYM, and high NLR linked to reduced CSF Aβ, impacting cognition.High PLR, NLR, SII associated with brain atrophy and hippocampal Aβ deposition [ABSTRACT FROM AUTHOR]

High‐entropy ceramics (HECs) are solid solutions of inorganic compounds with one or more Wyckoff sites shared by equal or near‐equal atomic ratios of multi‐principal elements. Material design and property tailoring possibilities emerge from this new class of materials. Herein, the discovery of superconductivity 2.35 K and topological properties in the (Ti0.2Zr0.2Nb0.2Hf0.2Ta0.2)C high‐entropy carbide ceramic (HECC) is reported, which is not observed before in any of the investigated HECC. Density functional theory calculations show that six type‐II Dirac points exist in (Ti0.2Zr0.2Nb0.2Hf0.2Ta0.2)C, which mainly contributed from the t2g orbitals of transition metals and the p orbitals of C. Due to the stability of the structure, robust superconductivity (SC) under pressure in this HEC superconductor is also observed. This study expands the physical properties of HECs, which may become a new material platform for SC research, especially for studying the coupling between SC and topological physics. [ABSTRACT FROM AUTHOR]

Carbon loading in airway cells has shown to worsen function of antimicrobial peptides, permitting increased survival of pathogens in the respiratory tract; however, data on the impacts of carbon particles on childhood acute respiratory infection (ARI) is limited. We assembled daily health data on outpatient visits for ARI (bronchitis, pneumonia, and total upper respiratory infection [TURI]) in children aged 0–14 years between 2015 and 2019 in Beijing, China. Anthropogenic carbons, including black carbon (BC) and its emission sources, and wood smoke particles (delta carbon, ultra‐violet absorbing particulate matter, and brown carbon) were continuously monitored. Using a time‐stratified case‐crossover approach, conditional logistic regression was performed to derive risk estimates for each outcome. A total of 856,899 children were included, and a wide range of daily carbon particle concentrations was observed, with large variations for BC (0.36–20.44) and delta carbon (0.48–57.66 μg/m3). Exposure to these particles were independently associated with ARI, with nearly linear exposure‐response relationships. Interquartile range increases in concentrations of BC and delta carbon over prior 0–8 days, we observed elevation of the odd ratio of bronchitis by 1.201 (95% confidence interval, 1.180, 1.221) and 1.048 (95% CI, 1.039, 1.057), respectively. Stronger association was observed for BC from traffic sources, which increased the odd ratio of bronchitis by 1.298 (95% CI, 1.273, 1.324). Carbon particles were also associated with elevated risks of pneumonia and TURI, and subgroup analyses indicated greater risks among children older than 6 years. Our findings suggested that anthropogenic carbons in metropolitan areas may pose a significant threat to clinical manifestations of respiratory infections in vulnerable populations. Plain Language Summary: Carbon air pollution has been linked to potential biological mechanisms responsible for respiratory diseases, but its impact on childhood respiratory infection remain sparse. In this study, we examined the associations of carbon particles with childhood hospital visits for acute respiratory infection in the megacity Beijing. The results indicated that recent exposure to ambient black carbon and wood smoke‐related particles (delta carbon, ultra‐violet absorbing particulate matter, and brown carbon) was associated with heightened risks of upper and lower respiratory tract infections in children. Greater detrimental respiratory effects were observed for carbon particles from traffic. Up to date, the global pandemic of pediatric respiratory infection and air pollution episodes occurs frequently under the context of climate crisis, our findings highlighted the importance of discerning adverse respiratory effects caused by source‐specific carbon particles in real‐world settings, particularly at the extreme levels of anthropogenic carbon exposures faced by billions of children living in urban areas worldwide today. Key Points: Extremely high levels of ambient black carbon and wood smoke‐related particles were found during the study periodCarbon particles, particularly from traffic, were associated with increased risks of childhood respiratory infectionsGreater risks were found among children older than 6 years [ABSTRACT FROM AUTHOR]

Objective: Expected outcomes (e.g., expected survivorship after a cancer treatment) have improved decision‐making around treatment options in many clinical fields. Our objective was to evaluate the effect of expected values of 3 widely available total knee arthroplasty (TKA) outcomes (risk of serious complications, time to revision, and improvement in pain and function at 2 years after surgery) on clinical recommendation of TKA. Methods: The RAND/University of California Los Angeles appropriateness criteria method was used to evaluate the role of the 3 expected outcomes in clinical recommendation of TKA. The expected outcomes were added to 5 established preoperative factors from the modified Escobar appropriateness criteria. The 8 indication factors were used to develop 279 clinical scenarios, and a panel of 9 clinicians rated the appropriateness of TKA for each scenario as inappropriate, inconclusive, and appropriate. Classification tree analysis was applied to these ratings to identify the most influential of the 8 factors in discriminating TKA appropriateness classifications. Results: Ratings for the 279 appropriateness scenarios deemed 34.4% of the scenarios as appropriate, 40.1% as inconclusive, and 25.5% as inappropriate. Classification tree analyses showed that expected improvement in pain and function and expected time to revision were the most influential factors that discriminated among the TKA appropriateness classification categories. Conclusion: Our results showed that clinicians would use expected postoperative outcome factors in determining appropriateness for TKA. These results call for further work in this area to incorporate estimates of expected pain/function and revision outcomes into clinical practice to improve decision‐making for TKA. [ABSTRACT FROM AUTHOR]

This study develops a generalised multi‐hazard analysis framework for evaluating the impact of secondary hazard events on structures that have previously been damaged by major hazardous events. More specifically, the present work investigates the effects of thunderstorm downbursts on earthquake‐damaged tall steel buildings giving an emphasis in assessing the revised accumulated earthquake‐wind ductility demands. The novel approach is validated on a 20‐storey steel building. The structure is initially subjected to a ductility‐controlled pushover analysis to simulate the earthquake‐induced damage, and then, a parametric dynamic analysis is performed using damaged structure models under synthetic downburst time‐histories developed for various wind profiles, wind velocities and terrain types. The method accurately controls the damage level induced by the primary hazard and separately assesses secondary hazard effects which enables a direct quantification of the new multi‐hazard design requirements. This can provide effective guidance in the stage of preliminary structural design or post‐hazard assessment of structures identifying new serviceability limits, as well as support repair procedures and decision‐making frameworks for existing structures to prevent collapse. The results demonstrate a significant increase up to three to four times in ductility demands of the structure after the occurrence of the strong downburst winds, compared with the ductility demands that were initially imposed by the varying severity degrees of the earthquake. [ABSTRACT FROM AUTHOR]

Objective: Many patients with rheumatoid arthritis (RA) experience sleep disturbances, commonly attributed to joint pain. Sleep disturbances could also influence pain. One mechanism may be through dysregulated pain processing, manifested by enhanced pain sensitivity. The present study was undertaken to examine the role of pain sensitization, measured by quantitative sensory testing (QST), as a mediator in the pathway of sleep disturbance leading to subsequent pain. Methods: We used longitudinal data from 221 patients with active RA who were followed for 12 weeks after initiating a disease‐modifying antirheumatic drug. Baseline QST included pressure pain thresholds at articular (wrists, knees) and nonarticular (trapezius, thumbnails) sites, temporal summation (TS) at the wrist and forearm, and conditioned pain modulation (CPM). Baseline sleep disturbance and subsequent pain intensity were assessed using the Patient‐Reported Outcomes Measurement Information System (PROMIS). We evaluated correlations between sleep disturbance, QSTs, and subsequent pain intensity. Mediation analyses separately assessed each QST as a mediator, adjusting for baseline confounding factors. Results: Sleep disturbance was correlated with all QST measures except wrist TS and CPM. Sleep disturbance significantly predicted subsequent pain (coefficient for a meaningful increase of 5 units in sleep disturbance = 0.32 (95% confidence interval 0.11, 0.50) in multiple regression. QST mediated 10–19% of this effect. Conclusion: Pain sensitization may be one mechanism through which sleep disturbance contributes to pain. The small magnitude of association indicates that unmeasured pathways may contribute to this relationship. Intervention studies are needed to establish causality and determine whether improving sleep can improve pain in patients with RA. [ABSTRACT FROM AUTHOR]

Objective: Patients with diffuse cutaneous systemic sclerosis (dcSSc) display a complex clinical phenotype. Transcriptional profiling of whole blood or tissue from patients are affected by changes in cellular composition that drive gene expression and an inability to detect minority cell populations. We undertook this study to focus on the 2 main subtypes of circulating monocytes, classical monocytes (CMs) and nonclassical monocytes (NCMs) as a biomarker of SSc disease severity. Methods: SSc patients were recruited from the Prospective Registry for Early Systemic Sclerosis. Clinical data were collected, as well as peripheral blood for isolation of CMs and NCMs. Age‐, sex‐, and race‐matched healthy volunteers were recruited as controls. Bulk macrophages were isolated from the skin in a separate cohort. All samples were assayed by RNA sequencing (RNA‐seq). Results: We used an unbiased approach to cluster patients into 3 groups (groups A–C) based on the transcriptional signatures of CMs relative to controls. Each group maintained their characteristic transcriptional signature in NCMs. Genes up‐regulated in group C demonstrated the highest expression compared to the other groups in SSc skin macrophages, relative to controls. Patients from groups B and C exhibited worse lung function than group A, although there was no difference in SSc skin disease at baseline, relative to controls. We validated our approach by applying our group classifications to published bulk monocyte RNA‐seq data from SSc patients, and we found that patients without skin disease were most likely to be classified as group A. Conclusion: We are the first to show that transcriptional signatures of CMs and NCMs can be used to unbiasedly stratify SSc patients and correlate with disease activity outcome measures. [ABSTRACT FROM AUTHOR]

Objective: To externally validate the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC‐FI) in a prevalent systemic lupus erythematosus (SLE) cohort and to assess the ability of the SLICC‐FI to predict organ damage accrual among individuals with longstanding SLE. Methods: This was a secondary analysis of data from the Study of Lupus Vascular and Bone Long‐Term Endpoints (SOLVABLE) cohort, which consists of adult women from the Chicago Lupus Database who met the 1997 revised American College of Rheumatology (ACR) classification criteria for SLE. There were 185 patients with SLE enrolled, of whom 149 patients were included in a 5‐year follow‐up analysis. The SLICC‐FI and SLICC/ACR Damage Index (SDI) scores were calculated at baseline and 5‐year follow‐up. Unadjusted and adjusted logistic regression models estimated the association of baseline SLICC‐FI scores (per 0.05 increase) with damage accrual at 5‐year follow‐up. Results: At enrollment the mean ± SD age of the 149 patients was 43.30 ± 10.15 years, the mean ± SD disease duration was 11.93 ± 8.46 years, and the mean ± SD SDI score was 1.64 ± 1.83. At baseline, the mean ± SD SLICC‐FI score was 0.18 ± 0.08, and 36% of participants were categorized as frail (SLICC‐FI score >0.21). In a model adjusted for age, race, and disease duration, each 0.05‐unit increase in the baseline SLICC‐FI score was associated with 28% higher odds of subsequent damage accrual (odds ratio 1.28, 95% confidence interval 1.01–1.63). Conclusion: In a prevalent cohort of women with established SLE, higher baseline SLICC‐FI scores were associated with a higher risk of subsequent damage accrual at 5‐year follow‐up. [ABSTRACT FROM AUTHOR]

Although perovskite solar cells have achieved great breakthroughs in photoelectric conversion efficiency (PCE), some challenges still need to be addressed before commercialization. Lead leakage is harmful to the environment and many methods are developed to prevent lead leakage; among them, chemical adsorption has proved to be an effective way. Herein, a simple and low‐cost strategy that can enhance the device performance and mitigate the lead leakage by applying l‐phenylalanine in the interface of NiOx/perovskite is reported. The results show that this strategy can improve the morphology and conductivity of the NiOx film, optimize the NiOx/perovskite interface energy level, resulting in an efficient and stable device with a PCE of 19.0%. Furthermore, the interface modification improves the stability of the perovskite film through strong interaction with the perovskite, inhibits the decomposition of the film in water, slows down the process of lead leakage, and protects the environment from lead pollution. The devices maintain 86% initial efficiency for 200 h maximum power point measurement and 94% for 2100 h under nitrogen. [ABSTRACT FROM AUTHOR]

Objective: Clinical trials for systemic lupus erythematosus ("lupus") under enroll Black individuals despite higher disease prevalence, morbidity, and mortality among Black compared to White individuals. To begin to address this disparity, we leveraged community–academic partnerships in 2 US cities (Boston and Chicago) to train popular opinion leaders (POLs) to disseminate information about clinical trials in predominantly Black communities. Methods: The team of community and academic partners collaboratively developed a 5‐module curriculum about clinical trials, barriers, facilitators, and structural racism in research. We enrolled POLs in Boston and Chicago to participate virtually in the curriculum and assessed knowledge gained by comparing pre‐ and post‐test scores. We described the POLs' ability to disseminate information about clinical trials through their communities. Results: We enrolled 19 POLs in Boston and 16 in Chicago; overall, 71% reported a lupus diagnosis, 94% were female, and 80% self‐identified as Black or African American. The program was adapted to virtual formats due to the COVID‐19 pandemic. POLs demonstrated significant improvement comparing pre/post scores for the conduct of clinical trials and history of racism in clinical research. Fifteen POLs (43%) reported their dissemination of information about clinical trials. Information reached 425 community members in Boston (90% virtually) and 1,887 in Chicago (95% virtually). Conclusion: By leveraging community–academic partnerships, we developed and implemented a curriculum to promote familiarity with clinical trials, leading to information dissemination by POLs in predominantly Black communities that are underrepresented in lupus clinical trials. The program successfully transitioned to a virtual model during the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Sn‐based perovskite material is one of the promising absorption materials due to its low toxicity and narrow bandgap. However, the unsatisfying quality of the perovskite film caused by Sn2+ oxidation and poor crystal growth greatly hinders the device performance. Herein, a layer of tetrapotassium hexacyanoferrate at the PEDOT:PSS/FASnI3 interface is introduced, which can minimize the concentration of Sn4+, thereby suppressing the defect states in the perovskite film, enhancing the conductivity of the PEDOT:PSS film, and forming well‐matched energy alignment in the device. Consequently, the champion device performance of 8.9% is obtained by the modified device, and the unencapsulated device can keep outstanding stability in N2 atmosphere. [ABSTRACT FROM AUTHOR]

Impaired clearance of beta‐amyloid (Aβ) is a primary cause of sporadic Alzheimer's disease (AD). Aβ clearance in the periphery contributes to reducing brain Aβ levels and preventing Alzheimer's disease pathogenesis. We show here that erythropoietin (EPO) increases phagocytic activity, levels of Aβ‐degrading enzymes, and Aβ clearance in peripheral macrophages via PPARγ. Erythropoietin is also shown to suppress Aβ‐induced inflammatory responses. Deletion of EPO receptor in peripheral macrophages leads to increased peripheral and brain Aβ levels and exacerbates Alzheimer's‐associated brain pathologies and behavioral deficits in AD‐model mice. Moreover, erythropoietin signaling is impaired in peripheral macrophages of old AD‐model mice. Exogenous erythropoietin normalizes impaired EPO signaling and dysregulated functions of peripheral macrophages in old AD‐model mice, promotes systemic Aβ clearance, and alleviates disease progression. Erythropoietin treatment may represent a potential therapeutic approach for Alzheimer's disease. Synopsis: How peripheral amyloid‐beta (Aβ) clearance affects Aβ levels in the brain is not clear. Here, it is shown to be promoted by erythropoietin (EPO) signaling in peripheral macrophages and to alleviate disease progression in mouse models of Alzheimer's disease (AD). EPO receptor deletion in peripheral macrophages decreases Aβ clearance, leading to increased peripheral and brain Aβ levels and enhanced AD progression.EPO signaling is impaired in peripheral macrophages of old AD‐model mice.EPO increases peripheral macrophage phagocytic activity and levels of Aβ‐degrading enzymes, and suppresses Aβ‐induced inflammatory response.Exogenous EPO treatment normalizes dysregulated functions of peripheral macrophages to promote systemic Aβ clearance and to alleviate AD progression. [ABSTRACT FROM AUTHOR]

Dating of the Tibetan ice cores is often challenging with great uncertainties. The significant age difference between the Guliya ice core (∼760 ka [thousand years]) and other Tibetan ice cores (Holocene origin) necessitates new approaches to resolve the inconsistency. Here, we present the atmospheric O2δ18O (δ18Oatm) profile of the 216.6 m Chongce ice core. Our data suggest that post depositional alterations significantly changed δ18Oatm. We reject samples with melt layers, and reconstruct the δ18Oatm values with two extreme correction approaches: a minimum isotopic correction based on gas loss fractionation, and a maximum isotopic correction based on respiration fractionation. We consequently estimate the age range of the Chongce ice core to be 2.763–7.192 ka at the depth of 215.14 m, and ∼3–9.799 ka at the depth of 215.61 m. Our work provides an independent line of evidence for the Holocene origin of the Chongce ice core. Plain Language Summary: Dating of the Tibetan ice cores is often challenging with great uncertainties, mainly due to rapid thinning at the ice core bottom sections. There is a significant difference between the published ages of the Tibetan Guliya ice core (∼760,000 yr) and those of other Tibetan ice cores, all of which were confined to the Holocene (∼10,000 yr). The direct distance between the Guliya and Chongce ice core drilling sites is only ∼30 km. Here, we present the gas chronology based on the 18O/16O isotopes of trapped air O2 for the Chongce ice core. We apply corrections to eliminate the isotopic fractionations caused by post depositional alterations. The dating results based on the trapped air 18O/16O constrain the maximum age for the Chongce bottom ice to be within 9.799 ka at 215.61 m, indicating that the Chongce ice core is of Holocene origin. Key Points: We present the profile of δ18O of paleoatmospheric O2 and its implied gas chronology of a Tibetan ice coreThe trapped air δ18O synchronization with the Antarctic Siple Dome ice core yields an upper age limit of 9.799 kaThe age deduced from the trapped air δ18O confirms the Holocene origin of the Chongce ice core [ABSTRACT FROM AUTHOR]

Over the past few years, all‐inorganic perovskite solar cells (PSCs), especially CsPbI2Br PSCs, have received much attention because of their excellent thermal stability and a suitable trade‐off between light absorption and higher phase stability among the family of inorganic perovskites. In this progress report, the realization of highly efficient and stable CsPbI2Br PSCs is summarized through preparation process, additive engineering, interface modification, and transport material selection. Furthermore, the application of CsPbI2Br in tandem solar cells and its large‐area development are highlighted. Finally, the challenges and outlook of CsPbI2Br PSCs are discussed for further performance improvement and future practical deployment. [ABSTRACT FROM AUTHOR]

Background: Endometrial carcinoma (EC) is one of the most common gynecological malignancies with an increasing incidence, and an accurate preoperative diagnosis of deep myometrial invasion (DMI) is crucial for personalized treatment. Objective: To determine the predictive value of a magnetic resonance imaging (MRI)‐based radiomics nomogram for the presence of DMI in the International Federation of Gynecology and Obstetrics (FIGO) stage I EC. Methods: We retrospectively collected 163 patients with pathologically confirmed stage I EC from two centers and divided all samples into a training group (Center 1) and a validation group (Center 2). Clinical and routine imaging indicators were analyzed by logistical regression to construct a conventional diagnostic model (M1). Radiomics features extracted from the axial T2‐weighted and axial contrast‐enhanced T1‐weighted (CE‐T1W) images were treated with the intraclass correlation coefficient, Mann–Whitney U test, least absolute shrinkage and selection operator, and logistic regression analysis with Akaike information criterion to build a combined radiomics signature (M2). A nomogram (M3) was constructed by M1 and M2. Calibration and decision curves were drawn to evaluate the nomogram in the training and validation cohorts. The diagnostic performance of each indicator and model was evaluated by the area under the receiver operating characteristic curve (AUC). Result: The four most significant radiomics features were finally selected from the CE‐T1W MRI. For the diagnosis of DMI, the AUCT/AUCV of M1 was 0.798/0.738, the AUCT/AUCV of M2 was 0.880/0.852, and the AUCT/AUCV of M3 was 0.936/0.871 in the training and validation groups, respectively. The calibration curves showed that M3 was in good agreement with the ideal values. The decision curve analysis suggested potential clinical application values of the nomogram. Conclusion: A nomogram based on MRI radiomics and clinical imaging indicators can improve the diagnosis of DMI in patients with FIGO stage I EC. [ABSTRACT FROM AUTHOR]

The high prevalence of oral squamous cell carcinoma (OSCC) in South Asia is associated with habitual areca nut chewing. Arecoline, a primary active carcinogen within areca nut extract, is known to promote OSCC pathological development. Dysregulation of N6‐methyladenosine (m6A) modification has begun to emerge as a significant contributor to cancer development and progression. However, the biological effects and molecular mechanisms of m6A modification in arecoline‐promoted OSCC malignance remain elusive. We reveal that chronic arecoline exposure substantially induces upregulation of fat mass and obesity‐associated protein (FTO), MYC, and programmed cell death‐ligand 1 (PD‐L1) in OSCC cells. Moreover, upregulation of PD‐L1 is observed in OSCC cell lines and tissues and is associated with areca nut chewing in OSCC patients. We also demonstrate that arecoline‐induced FTO promotes the stability and expression levels of PD‐L1 transcripts through mediating m6A modification and MYC activity, respectively. PD‐L1 upregulation confers superior cell proliferation, migration, and resistance to T‐cell killing to OSCC cells. Blockage of PD‐L1 by administration of anti‐PD‐L1 antibody shrinks tumor size and improves mouse survival by elevating T‐cell‐mediated tumor cell killing. Therefore, targeting PD‐L1 might be a potential therapeutic strategy for treating PD‐L1‐positive OSCC patients, especially those with habitual areca nut chewing. [ABSTRACT FROM AUTHOR]

The microspheres prepared by the microfluidic‐assisted internal gelation process are still challenging to reach the millimeter size due to the large gravity. The gravity would affect the sphericity and size uniformity of microspheres. The improved microfluidic‐assisted internal gelation process is designed and optimized to produce large‐sized monodisperse ceramic microspheres with good sphericity. The movement mechanism of millimeter‐sized sol droplets and gel microspheres in the microchannel is summarized and the state of the dispersed phase entering the measuring cylinder is controlled. The friction between the gel microspheres and the tubing wall is reduced as much as possible, and ZrO2 ceramic microspheres of 500 ± 5 μm with good sphericity are prepared with the broth at room temperature. The mechanism of sol droplets entering the oil surface is explored to demonstrate the superiority of the improved microfluidic‐assisted internal gelation process. The improved microfluidic‐assisted internal gelation process could be directly extended to preparing other millimeter‐sized monodisperse ceramic microspheres. [ABSTRACT FROM AUTHOR]

Background: Oral submucosal fibrosis (OSF) is a precancerous condition that closely related to the habit of chewing betel nut. The OSF patients of 3%–19% may develop cancer, and this probability is increasing year by year. Epigenetics modifications have been reported as part of the pathogenesis of OSF. However, in OSF field, the role and mechanism of arecoline‐induced activation of transforming growth factor β (TGF‐β) signaling on N6‐methyladenosine (m6A) modification remain unclear. In this study, we investigated the effect and mechanism of arecoline on m6A modification. Methods: MeRIP‐Seq and RNA‐seq were performed in arecoline‐stimulated cells. Quantitative polymerase chain reaction and western blot were performed to detect the expression of m6A writers and erasers. CCK‐8 and flow cytometry analyses were performed to measure the cell viability and apoptosis. Results: m6A level was increased in OSF tissues compared to normal tissues; arecoline promoted the m6A methyltransferase Mettl3 and Mettl14 through TGF‐β. MeRIP‐seq and RNA‐seq analyses found that MYC was the target gene of Mettl14. In addition, Mettl14 silence reversed the effects of arecoline on cell proliferation and apoptosis in Hacat cells. Conclusion: TGF‐β‐METTL14‐m6A‐MYC axis was crucially implicated in arecoline‐mediated OSF and may be an effective therapeutic strategy for OSF treatment. [ABSTRACT FROM AUTHOR]

All‐inorganic perovskites have attracted substantial interest due to their outstanding thermal stability. However, the device performance is still inferior to the typical organic–inorganic counterparts because of the unsatisfying phase stability and defects of the inorganic perovskite films. Herein, a multistrategy to optimize CsPbI2Br perovskite solar cells (PSCs) based on dopant‐free poly(3‐hexylthiophene) (P3HT) by applying thienylmethylamine acetate additive to enhance the α phase stability and passivate the bulk defects of CsPbI2Br perovskite is successfully demonstrated, followed by implementing BTCIC‐4Cl interlayer at CsPbI2Br/P3HT interface, which can coordinate with both perovskite and P3HT to suppress the surface defects and promote the hole transport. Benefitting from these, a champion power conversion efficiency (PCE) of 16.3% is achieved, and the unencapsulated optimized device can retain 97% of the initial PCE after aging under N2 atmosphere at 85 °C for 530 h. This work opens up a new era of multistrategy for improving performance and stability of CsPbI2Br PSCs based on dopant‐free hole transport layer. [ABSTRACT FROM AUTHOR]

The nitration of chlorobenzene with concentrated mixed acids is a fast and highly exothermic process, which suffers from considerable mass transfer resistance and poor heat transfer rates. The reaction kinetics has not been thoroughly reported before. In this work, a continuous‐flow microreactor system and a homogeneous reaction condition were proposed to obtain accurate chlorobenzene nitration kinetics parameters at high mixed acid concentrations. A general model for predicting the observed reaction rate constants was established. With a new method for estimating the equilibria associated with HNO3 in aqueous sulfuric acid, the rate constants based on nitronium ion and activation energies were obtained. Compared with batch reactors, the continuous‐flow microreactor system allows for a sufficient heat transfer efficiency and accurate residence time control, making it possible to study the reaction performance more quickly and sensitively. This work may provide a reliable reference for the kinetic study of similar processes. [ABSTRACT FROM AUTHOR]

Summary: The biotrophic fungal pathogen Blumeria graminis f. sp. tritici (Bgt) is a crucial factor causing reduction in global wheat production. Wild wheat relatives, for example Thinopyrum intermedium, is one of the wild‐used parents in wheat disease‐resistant breeding. From T. intermedium line, we identified the aspartic protease gene, TiAP1, which is involved in resistance against Bgt. TiAP1 is a secreted protein that accumulates in large amounts at the infection sites of Bgt and extends to the intercellular space. Yeast two‐hybrid, luciferase complementation imaging and bimolecular florescent complimentary analysis showed that TiAP1 interacted with the chitin deacetylase (BgtCDA1) of Bgt. The yeast expression, purification and in vitro test confirmed the chitin deacetylase activity of BgtCDA1. The bombardment and VIGS‐mediated host‐induced gene silencing showed that BgtCDA1 promotes the invasion of Bgt. Transcriptome analysis showed the cell wall xylan metabolism, lignin biosynthesis‐related and defence genes involved in the signal transduction were up‐regulated in the transgenic TiAP1 wheat induced by Bgt. The TiAP1 in wheat may inactivate the deacetylation function of BgtCDA1, cause chitin oligomers expose to wheat chitin receptor, then trigger the wheat immune response to inhibit the growth and penetration of Bgt, and thereby enhance the resistance of wheat to pathogens. [ABSTRACT FROM AUTHOR]

Background: The benefits of moderate to vigorous physical activity (MVPA) for breast cancer survivors are well established. However, most are insufficiently active. Fit2Thrive used the Multiphase Optimization Strategy methodology to determine the effect of 5 intervention components on MVPA in this population. Methods: Two hundred sixty‐nine participants (mean age, 52.5 years; SD, 9.9 years) received a core intervention (the Fit2Thrive self‐monitoring app and Fitbit) and were randomly assigned to 5 intervention components set to on/off in a full factorial experiment: support calls, deluxe app, buddy, online gym, and text messages. The intervention was delivered over 12 weeks with a 12‐week follow‐up. MVPA was measured via accelerometry at the baseline (T1), at 12 weeks (T2), and at 24 weeks (T3). The main effects and interaction effects at each time point were examined for all components. Results: Trial retention was high: 91.8% had valid accelerometer data at T2 or T3. Across all conditions, there were significant increases in MVPA (+53.6 min/wk; P <.001) and in the proportion of survivors meeting MVPA guidelines (+22.3%; P <.001) at T2 that were maintained but attenuated at T3 (MVPA, +24.6 min/wk; P <.001; meeting guidelines, +12.6%; P <.001). No individual components significantly improved MVPA, although increases were greater for the on level versus the off level for support calls, buddy, and text messages at T2 and T3. Conclusions: The Fit2Thrive core intervention (the self‐monitoring app and Fitbit) is promising for increasing MVPA in breast cancer survivors, but the components provided no additional increases in MVPA. Future research should evaluate the core intervention in a randomized trial and determine what components optimize MVPA behaviors in breast cancer survivors. Systematically testing 5 technology‐supported physical activity promotion intervention components alongside the Fit2Thrive core intervention (Fit2Thrive self‐monitoring app and Fitbit) results in an increase in physical activity after the intervention and at a 12‐week follow‐up in breast cancer survivors. However, increases are not significantly greater with any component turned on versus off. This indicates that the Fit2Thrive core is a promising scalable strategy for increasing moderate to vigorous physical activity. [ABSTRACT FROM AUTHOR]

Information on decadal temperature variations over the northwestern Tibetan Plateau (TP) is still very limited due to a lack of long‐term instrumental data. In this paper, we present a 489‐year (1524–2012 A.D.) reconstruction of annual mean temperature for the northwestern TP using the δ18O record of a 58.82 meter‐long shallow ice core retrieved on the Chongce ice cap in the western Kunlun Mountains. The reconstructed temperature exhibits significant decadal variations, which were mainly driven by the Atlantic Multidecadal Variability. Decadal temperature variation during the Little Ice Age (LIA) is significantly larger than that during the post‐industrial warming period, possibly due to such external forcing as large fluctuations of solar activity and frequent major volcanic eruptions during the LIA. In addition, our reconstruction shows that the recent warming since the 1980s is moderate, comparable to an earlier warm interval in the mid‐20th century, which may partly explain the relatively stable status of glaciers in this region since 1970s. Key Points: The Atlantic Multidecadal Variability plays a critical role in the decadal temperature variations over the northwestern Tibetan PlateauLarge temperature variations before the 1850s were associated with the external forcings, including solar activities and volcanic eruptionsThe weak warming over the northwestern Tibetan Plateau since the 1980s have contributed to the "Karakoram Anomaly" [ABSTRACT FROM AUTHOR]

Herein, a method for improving the direct‐current (DC) breakdown strength of the epoxy resin (ER) was proposed. Nano‐Al2O3 was treated with CF4/Ar plasma and doped into the epoxy resin matrix to obtain epoxy composites with high DC breakdown strength in both extremely uneven and slightly uneven electric fields. The reaction essence of plasma fluoridation was characterized, and the dielectric spectrum, volume conductivity, space charge, and carrier trap characteristics of the modified composites were studied. The plasma fluoridation at the fillers‐matrices interface is an effective pretreatment method to enhance insulation, exhibiting good applicability to ceramic/polymer composites. [ABSTRACT FROM AUTHOR]

ZrO2 microspheres are widely used as a simulant of UO2 in the development of nuclear fuel. However, the cracking of ZrO2 microspheres prepared by internal gelation is still a challenge during drying and sintering processes. To address this issue, we designed and optimized the washing process for obtaining crack‐free ZrO2 microspheres. Through thermogravimetric, infrared, Raman, BET, and SEM analysis, it is shown that the cracking of the microspheres is mainly related to the pores in microspheres. The washing solvent with low surface tension is used to reduce the effect of capillary force on pore shrinkage. Therefore, the optimal washing process was designed as trichloroethylene (TCE)—0.5 M NH3.H2O—Propylene glycol methyl ether (PM) and gel microspheres with a high specific surface area of 315.3 m2/g and pore volume of 0.4125 cm3/g were obtained. The characterizations also further showed that when the microspheres were dried and sintered, the water vapor and the decomposition gas of organic matter were completely released from the pores in the microspheres. Our new washing process could be directly extended for preparing crack‐free ceramic microspheres by internal gelation. [ABSTRACT FROM AUTHOR]

Longevity is a long‐standing concern for organic–inorganic hybrid perovskite solar cells (PSCs). Recently, the use of low dimensional perovskite has been proven to be a promising strategy to improve the stability of PSCs. Herein, it is demonstrated that 1D perovskitoid based on 2‐diethylaminoethylchloride cations can act as a template to induce 1D@3D perovskite structure, leading to smoother surface texture, longer charge‐carrier lifetime, smaller residual tensile strain, and reduced surface‐defect density in the perovskite film. With this strategy, highly efficient and stable 1D@3D PSC with excellent reproducibility, showing a champion power conversion efficiency (PCE) of 22.9% under standard AM 1.5 G one sun illumination is realized. The unencapsulated optimized devices can retain 94.7%, 92.4%, and 90.0% of their initial PCEs for 2100, 2200, and 2200 h under ambient air, 85 °C and illumination conditions, respectively. [ABSTRACT FROM AUTHOR]

Background: Platinum‐based chemotherapy is effective in inducing shrinkage of primary lung cancer lesions; however, it shows finite therapeutic efficacy in patients suffering from brain metastasis (BM). The intrinsic changes of BM cells, which contribute to the poor results remain unknown. Methods: Platinum drug‐sensitivity was assessed by utilizing a preclinical BM model of PC9 lung adenocarcinoma cells in vitro and in vivo. High consumption of glutathione (GSH) and two associated upregulated proteins (GPX4 and GSTM1) in BM were identified by integrated metabolomics and proteomics in cell lines and verified by clinical serum sample. Gain‐of‐function and rescue experiments were implemented to reveal the impact and mechanism of GPX4 and GSTM1 on the chemosensitivity in BM. The interaction between GPX4 and GSTM1 was examined by immunoblotting and immunoprecipitation. The mechanism of upregulation of GPX4 was further uncovered by luciferase reporter assay, immunoprecipitation, and electrophoretic mobility shift assay. Results: The derivative brain metastatic subpopulations (PC9‐BrMs) of parental cells PC9 developed obvious resistance to platinum. Radically altered profiles of BM metabolism and protein expression compared with primary lung cancer cells were described and GPX4 and GSTM1 were identified as being responsible for the high consumption of GSH, leading to decreased chemosensitivity by negatively regulating ferroptosis. Besides, GSTM1 was found regulated by GPX4, which was transcriptionally activated by the Wnt/NR2F2 signaling axis in BM. Conclusions: Collectively, our findings demonstrated that Wnt/NR2F2/GPX4 promoted acquired chemoresistance by suppressing ferroptosis with high consumption of GSH. GPX4 inhibitor was found to augment the anticancer effect of platinum drugs in lung cancer BM, providing novel strategies for lung cancer patients with BM. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of a smartphone application (app) to monitor longitudinal electronic patient‐reported outcomes (ePROs) on patient satisfaction and disease activity in patients with rheumatoid arthritis (RA). Methods: We conducted a 6‐month randomized controlled trial of care coordination along with an app (intervention) versus care coordination alone (control) in 191 RA patients. Participants in the intervention group were prompted to provide information daily using ePROs. In both the intervention and control groups, a care coordinator contacted participants at 6 and 18 weeks to assess for flares. The main outcome measures were the global satisfaction score from the Treatment Satisfaction Questionnaire for Medication (TSQM), the score from the Perceived Efficacy in Patient‐Physician Interactions (PEPPI) Questionnaire, and the Clinical Disease Activity Index (CDAI) score. Results: Groups were similar at baseline. The median TSQM score at 6 months was 83.3 in both groups, and the median PEPPI score at 6 months was 50 in both groups. The median CDAI score at 6 months was 8 in the intervention group versus 10 in the control group. No statistically significant group differences in the medians of TSQM, PEPPI, or CDAI scores at 6 months were detected. Of the 67 intervention participants who completed the exit survey, 90% rated their likelihood of recommending the app as ≥7 of 10. Of the 11 physicians who completed the exit survey, 73% agreed/strongly agreed that they wanted to continue offering the app to patients. Conclusion: A mobile app designed to collect ePRO data on RA symptoms did not significantly improve patient satisfaction or disease activity compared to care coordination alone. However, both patients and physicians reported positive experiences with the app. [ABSTRACT FROM AUTHOR]

Keywords: conjoined twins; embryonic development; fusion theory; marine medaka EN conjoined twins embryonic development fusion theory marine medaka 853 856 4 05/13/21 20210601 NES 210601 Conjoined twins, the manifestation of a structural congenital malformation, are more common in fishes and amphibians than in mammalian embryos. Embryo 2 ultimately formed one embryonic body only in a small portion of the egg, as shown in Figure 2b. However, since the development of the two embryonic bodies was ongoing, the final formation of the tail (i.e. the process of blastopore closure) must involve the meeting and fusion of the two embryos. If secondary union of the double separate blastoderms occurred before this period, the egg would return to normal development and eventually develop into a single embryo; if not, it would develop into one egg with two embryonic bodies. [Extracted from the article]

Objective: To explore how waiting time after failed fresh cycle embryo transfer affects the pregnancy outcomes of the next frozen embryo transfer (FET). Methods: A retrospective analysis was carried out on the data of women who had received at least one FET after a failed fresh embryo transfer between January 2013 to December 2019. The women were grouped based on the "time" of the first FET, referring to the period between a failed fresh embryo transfer and the beginning of the next cycle of FET. This time is divided into two classes: immediate (<90 days after the failed fresh embryo transfer) and delayed (≥90 days after failed fresh embryo transfer). The following parameters were investigated: clinical pregnancy rate; biochemical pregnancy rate; ectopic pregnancy rate; and non‐pregnancy rate. Results: A total of 293 cases of fresh embryo transfer cycles were included. No significant differences in the number of obtained oocytes, total number of FET, and the total amount of gonadotropin were seen between the immediate and delayed fresh embryo transfer groups. The pregnancy outcomes of the two groups were similar. Conclusion: The duration of waiting time between failed fresh embryo transfer and the next FET does not affect pregnancy outcomes. Synopsis: The duration of waiting time between failed fresh embryo transfer and the next frozen embryo transfer does not affect pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objective: Despite the numerous health benefits of physical activity, inactivity is endemic among adults with knee osteoarthritis (OA). Because sleep quality may be a target in order to improve physical activity behavior, we investigated the cross‐sectional relationship between restless sleep and physical activity in participants with or at risk for knee OA. Methods: We analyzed accelerometer‐measured physical activity and clinical data of participants included in the Osteoarthritis Initiative (OAI). We used multiple regression analysis to evaluate physical activity for participants, who were grouped by the reported frequency of restless sleep, and adjusted for demographic and medical confounders. Results: Of the 1,892 OAI participants for whom complete data were available, 300 participants (16%) reported restless sleep ≥3 days in the past week. Participants who reported restless sleep for much of the time (3–4 days/week) and most of the time (5–7 days/week) had 11.9% and 23.7% less weekly minutes of moderately vigorous activity, respectively, compared to participants who reported rarely restless sleep (<1 day/week) (P for trend 0.021). These differences persisted after accounting for age, sex, race, body mass index, medical comorbidity, and knee OA severity and pain (P for trend 0.023). Differences related to restless sleep were largely attenuated by the presence of high depressive symptoms and low energy levels. Conclusion: Poor sleep quality is associated with less physical activity in persons with or at risk for knee OA. Future studies are needed to determine the mechanisms of how poor sleep and physical activity are related, how energy and depression mediate these relationships, and whether interventions that improve sleep quality might result in increased physical activity. [ABSTRACT FROM AUTHOR]

Objective: Little is known regarding what difference in functional performance measures is significant in individuals with chronic medical disease. Our objective was to examine the important differences in gait speed in adults with radiographic knee osteoarthritis. Methods: Functional performance was measured by gait speed using 20‐meter and 400‐meter walk tests performed at a self‐selected usual pace among adults with radiographic knee osteoarthritis participating in the Osteoarthritis Initiative at baseline and 2 years later. Both distribution‐based methods and anchor‐based methods were used to calculate the important differences in gait speed. Anchor‐based methods used the chair stand rate and self‐reported function to estimate gait speed differences related to physical function. Results: We included 2,527 participants with radiographic knee osteoarthritis. Distribution‐based important difference estimates for the 20‐meter walk ranged from 4.1 to 6.4 meters/minute and 400‐meter walk estimates ranged from 2.9 to 6.5 meters/minute. Prevalent (cross‐sectional) anchor‐based estimates for the 20‐meter walk ranged from 5.4 to 6.9 meters/minute and for the 400‐meter walk ranged from 3.0 to 6.9 meters/minute. Longitudinal anchor‐based estimates were deemed unreliable. Combining distribution‐based with prevalent anchor‐based methods showed that an important gait speed difference for the 20‐meter walk is between 4.1 and 6.9 meters/minute and for the 400‐meter walk is between 2.9 and 6.9 meters/minute. Conclusion: Our results found that the important difference in gait speed for the 20‐meter walk and the 400‐meter walk is consistent with important difference estimates for older adult populations. These findings can provide benchmarks for assessing and understanding functional performance outcomes when comparing exposure groups and can be used in designing future studies targeting adults with radiographic knee osteoarthritis. [ABSTRACT FROM AUTHOR]

HLA‐A*31:191 differs from HLA‐A*31:01:02:01 by one single nucleotide substitution at nucleotide 74. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between dysregulated central pain processing and treatment response in rheumatoid arthritis (RA). Methods: One hundred eighty‐two participants with active RA were followed up for 12 weeks after starting a disease‐modifying antirheumatic drug (DMARD). To assess central pain processing, participants underwent quantitative sensory testing (QST), including assessment of pressure pain thresholds (PPTs) at the trapezius muscles, temporal summation, and conditioned pain modulation (CPM). QST measures were categorized as high central dysregulation versus low central dysregulation. The association between baseline central dysregulation and treatment response, as defined by the European League Against Rheumatism (EULAR) response criteria, was assessed using multiple logistic regression adjusted for demographic characteristics, RA‐related variables, and psychosocial variables. Results: A good EULAR response was achieved in fewer participants with high CPM dysregulation than participants with low CPM dysregulation (22.5% versus 40.3%; P = 0.01). A similar trend, though not significant, was noted when central dysregulation was assessed with PPT and temporal summation. The adjusted odds ratios (ORs) for the association between high central dysregulation and good EULAR response were 0.59 for PPTs (95% confidence interval [95% CI] 0.28–1.23), 0.60 for temporal summation (95% CI 0.27–1.34), and 0.40 for CPM (95% CI 0.19–0.83). In a model examining the combined effects of dysregulated temporal summation and CPM, dysregulation of both measures was associated with lower odds of achieving a good EULAR response (OR 0.23 [95% CI 0.07–0.73]). Conclusion: Low CPM was significantly associated with lower odds of achieving a good EULAR response, suggesting that inefficient descending inhibitory mechanisms may be a potential treatment target for further study. [ABSTRACT FROM AUTHOR]