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Abstract Extreme warm water events, known as marine heatwaves, cause a variety of adverse impacts on the marine ecosystem. They are occurring more and more frequently across the global ocean. Yet monitoring marine heatwaves below the sea surface is still challenging due to the sparsity of in situ temperature observations. Here, we propose a statistical learning method guided by ocean dynamics and optimal prediction theory, to detect subsurface marine heatwaves based on the observable sea surface temperature and sea surface height. This dynamics-guided statistical learning method shows good skills in detecting subsurface marine heatwaves in the oceanic epipelagic zone over many parts of the global ocean. It outperforms both the classical ordinary least square regression and popular deep learning methods that do not effectively exploit ocean dynamics, with clear dynamical interpretation for its outperformance. Our study provides a useful statistical learning method for near real-time monitoring of subsurface marine heatwaves at a global scale and highlights the importance of exploiting ocean dynamics for enhancing the efficiency and interpretability of statistical learning.

Background: Neuromyelitis optica spectrum disorders (NMOSD) is characterized by inflammatory demyelinating events in the central nervous system (CNS), primarily affecting the spinal cord and optic nerve, with a significant influence of astrocytes. Longitudinal extensive transverse myelitis (LETM) is a distinct and relatively rare spinal cord syndrome, commonly associated with NMOSD. Case presentation: This report describes a unique case of myelitis in a patient diagnosed with NMOSD. The patient exhibited an uncommon manifestation of ultra- LETM (u-LETM), coexisting with connective tissue disorders including Sjögren's syndrome and autoimmune hepatitis-primary cholestatic cirrhosis. In the acute phase, high-dose methylprednisolone pulse therapy was administered in combination with intravenous human immunoglobulin, while prednisone was gradually tapered and discontinued upon stabilization of the patient's condition. Simultaneously, sequential disease-modifying therapy was initiated, starting with long-term oral administration of mycophenolate mofetil, followed by cyclophosphamide, telitacicept, and Inebilizumab. During follow-up visits conducted every three months, the patient showed gradual improvement, eventually achieving the ability to stand and walk independently. Conclusions: Early and comprehensive evaluation of autoimmune diseases is crucial in patients with NMOSD presenting with u-LETM as the initial symptom. Prompt treatment initiation, followed by disease-modifying therapy, is essential for improving patient prognosis.

Pollen diversity provides insights into our understanding of past plant diversity, a wide variety of diversity indices have been used to characterize plant diversity from sedimentary pollen. However, studies reported inconsistent associations between pollen-plant taxonomic diversity, this could be partly accounted for by biases due to interspecies differences in pollen production, pollen diffusion/deposition, and poorly specified dispersal distance of pollen-source plants. It is therefore crucial to improve the interpretation of the sedimentary pollen diversity by systematic studies of palynological and floristic diversity associations in contemporary landscapes.To test the reliability of pollen assemblages as a proxy of plant diversity, we collected pollen and vegetation from 36 surface sites in southwest Shandong. We detected the correlation between pollen-plant taxonomic and functional diversity indices from different spatial scales.Our results show pollen-plant correlations vary in spatial scales for different indices, the Spearman correlation analysis indicates significant and the strongest correlations between pollen-plant Shannon index around the RSAP (0.399

Background: The elevated long-term cardiovascular disease (CVD) risks associated with pneumonia have been observed among inpatients, yet the risks associated with outpatients are less understood. Methods: We used register-based data and a matched cohort design, including 98,354 pneumonia inpatients and 44,486 outpatients, as well as a 5-fold number of matched healthy controls. Associations between pneumonia presentation (in inpatient and outpatient settings) and long-term CVD risks were measured by rate difference and hazard ratio (HR) using Poisson and Cox regressions in a time-dependent manner. Results: During a maximum follow-up period of 5.7 years of ischemic heart disease (IHD), heart failure (HF), and stroke were documented among pneumonia inpatients.Relative to healthy controls, pneumonia patients showed increased risks of IHD, HF, and stroke. Women and young inpatients demonstrated stronger associations of CVD with pneumonia; inpatients aged 60 years or older showed the highest excessive CVD risks. Conclusions: Pneumonia demanding outpatient and inpatient cares are intermediate-term and long-term risk factors of incident CVDs respectively, underscoring the need to plan setting-specific and time-dependent CVD-preventive cares following pneumonia presentation.

Abstract Background Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital coronary anomaly with the potential to cause adverse cardiac events. However, there is limited data on the association between AAOCA and coronary artery disease (CAD). Therefore, the aim of this study is to determine the prevalence and symptoms of patients with AAOCA, as well as investigate the correlation between AAOCA and CAD in a population referred for coronary computed tomographic angiography (CTA). Methods and results All consecutive patients who underwent CTA from 2010 to 2021 were included. Characteristics, symptoms, coronary related adverse events and CTA information were reviewed by medical records. Separate multivariable cumulative logistic regressions were performed, using the stenosis severity in each of the four coronaries as individual responses and as a combined patient clustered response. Finally, we identified 207 adult patients with AAOCA, the prevalence of AAOCA is 0.23% (207/90,501). Moreover, this study found no significant association between AAOCA and CAD. AAOCA did not contribute to higher rates of hospitalization or adverse cardiac events, including calcification. Conclusion AAOCA is a rare congenital disease that is not associated with increased presence of obstructive CAD in adults.

Background and objectives: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disorder affecting 30% of psoriatic patients. Effective treatment, especially with biologics like IL-17 and TNF inhibitors, is vital for improving patient outcomes. This study aimed to compare the efficacy of secukinumab and adalimumab in PsA patients through clinical and ultrasonographic evaluations.Materials and methods: We enrolled 116 PsA patients, with 58 patients receiving secukinumab and 58 receiving adalimumab. Regular follow-ups were conducted at weeks 4, 12, 24, and 52. The primary outcome was the proportion of patients achieving at least a 20% improvement in the ACR response (ACR20) at week 12, with additional evaluations for axial arthritis, enthesitis, skin involvement, minimal disease activity, health assessment questionnaire, and ultrasound changes.Results: There was no significant difference in ACR20 response between the two groups at week 12 (OR: 0.59, 95% CI: 0.26–1.37, p = 0.22). However, secukinumab demonstrated superior efficacy in achieving Psoriasis Area and Severity Index (PASI)90 (OR: 2.25, 95%CI: 1.07–4.74, p = 0.03), while adalimumab showed better improvement in ultrasound synovitis count (β: 0.94, 95%CI: 0.09–1.79, p = 0.03) and synovitis PD signal (β: 0.20, 95%CI: 0.03–0.36, p = 0.02).Conclusions: In conclusion, both treatments were highly effective for PsA, with secukinumab being more suitable for severe skin involvement and adalimumab for significant ultrasound-confirmed synovitis.

BackgroundFew studies have analysed oxaliplatin-induced adverse events (ADEs) in the immune system and skin and subcutaneous tissues through pharmacovigilance. We used this approach to analyse the risk of such ADEs when oxaliplatin combined with immune checkpoint inhibitors (ICIs).MethodsWe evaluated the association between oxaliplatin and ADEs in the immune system and skin and subcutaneous tissues using the reporting odd ratio (ROR) for mining the ADE report signals in the FDA Adverse Event Reporting System database. Risk factors were analyzed using a binary logistic regression analysis using the sex and age of the patients.ResultsThere were 40,474 reports of oxaliplatin as primary suspect drug or second suspect drug. The signal intensities of ADEs such as type II hypersensitivity, type I hypersensitivity, type III immune complex–mediated reaction, anaphylactoid shock and cytokine release syndrome were high in PTs classified by SOC as immune system disorders; in the PTs classified as skin and subcutaneous tissue disorders by SOC, the signal intensities of ADEs such as skin toxicity, skin reaction, rash maculo-papular and skin fissures were higher. In the risk assessment between the two groups, rash showed an increased risk in the oxaliplatin-ICI group, with an OR of 1.96. Nivolumab in combination with oxaliplatin had an OR of 2.196 and an adjusted OR of 2.231. Combined with pembrolizumab, OR was 2.762 and the adjusted OR was 2.678.ConclusionType II hypersensitivity shows a stronger pharmacovigilance signal. Oxaliplatin in combination with nivolumab or pembrolizumab has been shown to increase the risk of rash.

In crop breeding, genomic selection (GS) serves as a powerful tool for predicting unknown phenotypes by using genome-wide markers, aimed at enhancing genetic gain for quantitative traits. However, in practical applications of GS, predictions are not always made within populations or for individuals that are genetically similar to the training population. Therefore, exploring possibilities and effective strategies for across-population prediction becomes an attractive avenue for applying GS technology in breeding practices. In this study, we used an existing maize population of 5820 hybrids as the training population to predict another population of 523 maize hybrids using the GBLUP and BayesB models. We evaluated the impact of optimizing the training population based on the genetic relationship between the training and breeding populations on the accuracy of across-population predictions. The results showed that the prediction accuracy improved to some extent with varying training population sizes. However, the optimal size of the training population differed for various traits. Additionally, we proposed a population structure-based across-population genomic prediction (PSAPGP) strategy, which integrates population structure as a fixed effect in the GS models. Principal component analysis, clustering, and Q-matrix analysis were used to assess the population structure. Notably, when the Q-matrix was used, the across-population prediction exhibited the best performance, with improvements ranging from 8 to 11% for ear weight, ear grain weight and plant height. This is a promising strategy for reducing phenotyping costs and enhancing maize hybrid breeding efficiency.

The Dashigou deposit is one of the most representative carbonatite-type Mo-REE deposits in the East Qinling metallogenic belt of China, with a molybdenum resource of more than 180 kt and a rare earth resource of 37.8 kt. Recent exploration has revealed a considerable scale of uranium mineralization within this deposit. Therefore, this study conducted detailed mineralogical and EPMA U-Th-Pb chemical dating on the uranium mineralization in the Dashigou deposit. The results indicate that the U-ore body in the Dashigou deposit mainly consists in carbonatite veins, and principally as anhedral, mesh-like uraninite. The mineral assemblage is characterized by uraninite + rutile + bastnasite + parisite or brannerite. The uraninite displays geochemical compositions of high Y and Ce and low Si, Ti, and Mg. The EPMA U-Th-Pb chemical dating is 144 ± 3.1 Ma, representing the Yanshanian uranium mineralization age in the region. The newly discovered uranium mineralization age indicates that the deposit experienced a uranium remobilization event during the Cretaceous and was formed in an intracontinental orogenic and extensional environment post-collision orogeny.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is characterized by a widespread maculopapular rash, lymphadenopathy, fever, and multisystem involvement. Conversely, hemophagocytic lymphohistiocytosis (HLH) is an infrequent yet critical condition presenting with fever, hepatosplenomegaly, cytopenias, coagulation abnormalities, and elevated inflammatory markers. The overlapping clinical and laboratory features between DRESS and HLH poses a significant diagnostic challenge. Secondary HLH (sHLH) typically occurs in adults triggered by viral infections, malignancies, rheumatologic diseases, or immune deficiencies. Recently, COVID-19 has also been identified as one of the triggers for sHLH. Herein, we present a case of Sulfasalazine-induced DRESS coinfected with COVID-19 that subsequently progressed into HLH. Our patient exhibited common hepatorenal and splenic involvement along with rare cholecystitis and appendicitis. However, a significant improvement was observed upon the addition of etoposide and azathioprine. We hypothesize that excessive activation of the immune system and cytokine storm due to DRESS combined with COVID-19 infection led to more extensive systemic damage resulting in HLH development. This highlights the potential for severe consequences when DRESS coincides with HLH during a COVID-19 infection.

Abstract Organ regeneration necessitates precise coordination of accelerators and brakes to restore organ function. However, the mechanisms underlying this intricate molecular crosstalk remain elusive. In this study, the level of proenkephalin-A (PENK-A), expressed by renal proximal tubular epithelial cells, decreases significantly with the loss of renal proximal tubules and increased at the termination phase of zebrafish kidney regeneration. Notably, this change contrasts with the role of hydrogen peroxide (H2O2), which acts as an accelerator in kidney regeneration. Through experiments with penka mutants and pharmaceutical treatments, we demonstrate that PENK-A inhibits H2O2 production in a dose-dependent manner, suggesting its involvement in regulating the rate and termination of regeneration. Furthermore, H2O2 influences the expression of tcf21, a vital factor in the formation of renal progenitor cell aggregates, by remodeling H3K4me3 in renal cells. Overall, our findings highlight the regulatory role of PENK-A as a brake in kidney regeneration.

Natural polyamines, including spermidine (SPD), spermine (SPM) and putrescine (PUT), are evolutionarily conserved endogenous molecules crucially involved in central cellular processes. Their physiological importance may extend to the maintenance of cognitive function during aging. However, limited population-based epidemiological studies have explored the link between dietary polyamines and dementia risk. This study was a prospective analysis of 77,092 UK Biobank participants aged ≥ 60 years without dementia at baseline. We used Cox proportional hazard regression models to explore the associations between dietary polyamines and the risk of dementia, and restricted cubic splines to test the non-linear relationships. During a median follow-up of 12 years, 1087 incidents of all-cause dementia cases occurred, including 450 Alzheimer’s disease (AD) cases and 206 vascular dementia (VD) cases. The fully adjusted hazard ratios (HRs) for the upper fourth quintile of dietary SPD, in comparison with the lowest quintile of intake, were 0.68 (95% confidence interval [95% CI]: 0.66–0.83) for the risk of all-cause dementia, 0.62 (95% CI: 0.45–0.85) for AD and 0.56 (95% CI: 0.36–0.88) for VD, respectively. A 26% reduction in dementia risk [HR: 0.74, (95% CI: 0.61–0.89)] and a 47% reduction in AD [HR: 0.53, (95%CI: 0.39–0.72)] were observed comparing the third with the lowest quintiles of dietary SPM. Dietary PUT was only associated with a reduced risk of all-cause dementia in the fourth quintile [HR (95% CI): 0.82 (0.68–0.99)]. Reduced risk was not found to be significant across all quintiles. There were ‘U’-shaped relationships found between dietary polyamines and all-cause dementia, AD and VD. Stratification by genetic predisposition showed no significant effect modification. Optimal intake of polyamines was linked to a decreased risk of dementia, with no modification by genetic risk. This potentially suggests cognitive benefits of dietary natural polyamines in humans.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with varying clinical presentations. The hereditary susceptibility to IgAN is rather complex. In this report, a Chinese case of IgAN was recruited. Renal biopsy showed the tubular atrophy and dilatation, but the glomerular lesions were rather weak except slight mesangial hyperplasia. Immunological staining of kidney tissue revealed the positive immunological staining of IgA and C3. By using whole-exome sequencing, a heterozygous variant in UMOD gene was found and was confirmed by Sanger sequencing. The variant in UMOD gene might contribute to the disease and this case helps understand the correlation of genotype and phenotypes of UMOD mutations.

The geochemical characteristics and genesis of Paleozoic natural gas in the Ordos Basin are complex, with some disputes on the gas source of Lower Paleozoic. In order to better grasp the overall geochemical characteristics and variation laws of Paleozoic natural gas in the basin, the geochemical data of more than 700 natural gas samples from the whole basin are comprehensively analyzed based on the systematic collection, collation and analysis of previous data, and the genesis of natural gas is explored by combining the analysis of key elements such as natural gas formation, hydrocarbon formation and reservoir formation. The results show that the main body of Upper Paleozoic natural gas is coal-based gas controlled by maturity, with maturity increasing from northeast to southwest, and the southern part of the basin has a mixture of Upper and Lower Paleozoic gas. The Lower Paleozoic gas is dominated by oil-type gas from marine carbonate formations, of which the upper combination is characterized by a two-source composite reservoir of Upper Paleozoic coal-type gas and Lower Paleozoic oil-type gas; the middle-lower combination is a relatively independent oil-type gas reservoir, subject to different degrees of secondary transformation based on geological conditions and the degree of thermal evolution of organic matter, resulting in significant anomalies in its carbon isotope composition. The research has proved that marine hydrocarbon sources including carbonate rocks exist in the Lower Paleozoic of the basin, and the natural gas in the Upper and Lower Paleozoic has mixed to varying degrees in different locations of the basin.

3D printed cement-based structures are subject to fire risk during service, and the study of static and dynamic mechanical properties of 3D printed cement-based materials after high temperature is of great significance for calculating and evaluating the safety performance of their applied structures after fire. Therefore, this paper focuses on the study of the dynamic mechanical properties of splitting tensile of 3D printed cement-based materials after high temperature, setting five temperatures and four strain rates, applying hydraulic servo machine to carry out the experimental study on the static and dynamic mechanical properties of splitting tensile of 3D printed cement-based materials, thus analyzing the influence of high temperature and strain rate on the mechanical properties of splitting and stretching of 3D printed cement-based materials, and mainly obtaining the following conclusions: with the temperature increasing, the 3D printed cement-based materials are more prone to cracking than ordinary concrete, and the structure of 3D printed cement-based materials is more loose. The change of damage pattern of the specimen is influenced by a strain rate lower than that of ordinary concrete. As the temperature increases, the tensile strength of 3D printed cement-based materials decreases gradually, and the tensile strength of specimens under different strain rates is reduced by 85∼90% under the influence of temperature increase. As the strain rate increases, the tensile strength of 3D printed cement-based materials gradually increases, and the increase in temperature leads to a gradual decrease in the tensile strength of specimens affected by the increase in strain rate. Based on the J-criterion, a calculation model of the change in tensile strength of 3D printed cement-based materials by strain rate after considering the effect of temperature is proposed. At the same time, a scanning electron microscope is applied to obtain the microscopic morphology of 3D printed cement-based materials after different high temperature and reveal the mechanical mechanism of the coupling of high temperature and strain rate effects. The results of the study provide a theoretical basis for the calculation and analysis of the dynamics of post-high-temperature 3D printed cement-based structures.

Abstract Background The objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40–45%. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC. Methods The response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Then, a protein‒protein interaction network was constructed to identify key genes. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1β and MMP9. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8+ T cells were performed using flow cytometry. Results Tumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. The objective response rate was 43.48%, and the disease control rate was 69.57%. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8+ T cells. Experiments with both clinical samples and mice indicated that infiltration of IL-1β-driven MDSCs and inactivation of CD8+ T cells contribute to anti-PD-1 resistance in MSI-H/dMMR CRC. Conclusions CD8+ T cells and IL-1β were identified as the cell type and gene, respectively, with the highest correlation with anti-PD-1 resistance. Infiltration of IL-1β-driven MDSCs was a significant factor in anti-PD-1 resistance in CRC. IL-1β antagonists are expected to be developed as a new treatment for anti-PD-1 inhibitor resistance.

This study investigates innovative approaches to improve the quality and aroma characteristics of Muscat Hamburg wine production by substituting the conventional Saccharomyces cerevisiae yeast with an efficient fermentation strain of Schizosaccharomyces pombe. The typical use of S. cerevisiae in Muscat Hamburg wine often leads to uniformity and prolonged processing times, requiring subsequent malolactic fermentation to degrade excessive malic acid. The study advocates for the replacement of S. cerevisiae with a specific S. pombe strain, Sp-410, isolated from the fermented grains of sauce-flavor Baijiu, a Chinese spirit. Muscat Hamburg wine fermented with the S. pombe strain demonstrates decreased malic acid levels, offering a potential alternative to malolactic fermentation. However, exclusive S. pombe fermentation may result in an overproduction of acetic acid metabolites, leading to a monotonous taste. In response, the study proposes a mixed fermentation approach, combining the S. pombe strain with a Saccharomyces uvarum strain and a non-Saccharomyces yeast, Torulaspora delbrueckii. The optimized mixed fermentation strategies (M:SP+TD and M60SP+TD) involve specific proportions and intervals of inoculation, aiming to enhance the quality and aroma complexity of Muscat Hamburg wine. In conclusion, this research contributes to advancing the production of high-quality Muscat Hamburg wines, utilizing S. pombe as the primary yeast strain and implementing mixed fermentation methodologies.

The Landscape Reconstruction Algorithm (LRA) is regarded as the soundest approach for quantifying taxon-specific plant cover from pollen data. The reliability of relative pollen productivity (RPP) estimates is fundamental in the accuracy of quantitative vegetation reconstruction using the LRA approach. Inconsistent RPP estimates produced by different studies can cast doubt on the reliability and applicability of quantitative vegetation reconstruction. Therefore, it is crucial that the RPP estimates are evaluated before being applied for quantitative vegetation reconstruction. We have tested two alternative approaches, namely, a leave-one-out cross-validation (LOO) method and a splitting-by-subregion strategy, using surface pollen assemblages and the REVEALS model—the first step in the LRA—to evaluate the reliability of RPPs estimates of 10 target taxa obtained in the cultural landscape of Shandong. We compared the REVEALS estimates (RVs) with observations of regional vegetation abundance (OBVs) and pollen proportions (PPs). The RVs of all taxa are generally closer to OBVs than PPs, and the degree of similarity depends strongly on the abundance of individual taxa in plant and pollen; taxa dominant in the region show the highest similarity between RVs and OBVs, such as Artemisia, Poaceae, and Humulus. The RVs of all herb taxa except Humulus and Asteraceae SF Cichorioideae are slightly overrepresented, and the RVs of all tree taxa are underrepresented except for Castanea. The comparison of RVs with OBVs collected from different spatial extents shows that the RVs of all herb taxa are more similar to OBVs collected from shorter distances (100 km and 75 km for the entire region and the subregion, respectively), whereas the RVs of all tree taxa are more similar to OBVs collected from longer distances (150 km and 100 km for the entire region and the subregion, respectively). Furthermore, our findings highlight the importance to test different sizes of area for vegetation surveys for evaluation of the RVs given that the appropriate size of vegetation survey may vary between low pollen producers (mainly herbs) and high pollen producers (mainly trees). We consider that the LOO strategy is the best approach in this case study for evaluating the RPP estimates from surface moss polsters. The evaluation confirms the reliability of the obtained RPP estimates for their potential application in quantitative reconstruction of vegetation abundance in temperate China.

Colorectal cancer (CRC) represents 10% of all cancer types, making it the third leading cause of cancer-related deaths globally. Metastasis is the primary factor causing mortality in CRC patients. Approximately 22% of CRC-related deaths have metastasis present at diagnosis, with approximately 70% of these cases recurring. Recently, with the application of novel targeted drugs, targeted therapy has become the first-line option for individualized and comprehensive treatment of CRC. The management of these patients remains a significant medical challenge. The most prevalent targeted therapies for CRC in clinical practice focus on anti-vascular endothelial growth factor and its receptor, epidermal growth factor receptor (EGFR), and multi-target kinase inhibitors. In the wake of advancements in precision diagnosis and widespread adoption of second-generation sequencing (NGS) technology, rare targets such as BRAF V600E mutation, KRAS mutation, HER2 overexpression/amplification, and MSI-H/dMMR in metastatic colorectal cancer (mCRC) are increasingly being discovered. Simultaneously, new therapeutic drugs targeting these mutations are being actively investigated. This article reviews the progress in clinical research for developing targeted therapeutics for CRC, in light of advances in precision medicine and discovery of new molecular target drugs.

The use of human cardiac organoids (hCOs) as 3D in vitro models for cardiovascular research has shown great promise. Human pluripotent stem cells (hPSCs) have proven to be a potent source for engineering hCOs. However, various protocols for generating hCOs from hPSCs result in significant differences in heart development, maturity, complexity, vascularization, and spatial structure, all of which can influence their functional and physiological properties. This protocol review aims to highlight different strategies for generating hCOs using hPSCs while also critically discussing their challenges and limitations.

Abstract Introduction This study aims to describe the demographic, clinical, laboratory, and ultrasonic characteristics of patients with psoriatic arthritis (PsA) in the Psoriatic Arthritis cohort of West China Hospital. Methods In this cross-sectional study, we included patients diagnosed with PsA according to the Classification Criteria for Psoriatic Arthritis, collected their demographic information, medical histories, and treatments, evaluated all domains (skin and nail lesions, tenderness, swelling, enthesitis, dactylitis, and axial arthritis) related to PsA, and then performed descriptive statistical analyses of all data. Results A total of 275 patients with PsA were included in this study. The ratio of male to female patients was 2.16:1. Skin lesions preceded arthritis in 86.5% of these patients with PsA with a mean interval of 10.1 years. The metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints of fingers, and sacroiliac joints are the most commonly involved sites of tenderness, swelling, and the spine, respectively. Among all comorbidities, fatty liver has the highest incidence with 33.1%. Finally, we noted that the mean disease duration of PsA was 4.2 years, suggesting a delay in the diagnosis of PsA. Conclusion Our study proposes that the prevalent population of PsA are male patients with psoriasis over 40 years of age who have a long disease course. For patients with PsA, MCP, PIP joints of fingers, and sacroiliac joints are the most frequently affected anatomical sites. With respect to comorbidities, the association between PsA and fatty liver and the underlying molecular mechanisms are worthy of further exploration.

Abstract With the launch of global decarbonisation, the infiltration of low‐carbon distributed energy resources (DERs) is increasing. The future transaction platforms for those flexibilities are considered to be peer‐to‐peer (P2P) ones conforming to resources' characteristics of small‐scale and independence. This research reviews current flexibility‐related topics and proposes one P2P flexibility market filling in the gaps. The contribution of this research includes: (1) it constructs a flexibility market combining pricing strategy and matching strategy of the mature and successful real‐world P2P business models, accommodating the penetration of DERs. The proposed automatic trading market could mobilise the enthusiasm of market participants and satisfy individuals' needs for a convenient market. (2) it proposes a dynamic pricing strategy where prices fluctuate with the features and portfolios of market participants. More adequate market signals are provided with the promotion of market equity. (3) it discusses the segmentation tendency of the flexibility market when considering energy products as pure commodities following the disintegration from the transmission system operator to the distribution system operator. The feasibility of the proposed market under future energy scenarios is thus explored.

With the increasing penetration of local renewable energy and flexible demand, the system demand is more unpredictable and causes network overloading, resulting in costly system investment. Although the energy storage (ES) helps reduce the system peak power flow, the incentive for ES operation is not sufficient to reflect its value on the system investment deferral resulting from its operation. This paper designs a dynamic pricing signal for ES based on the truncated strategy under robust operation corresponding to the network charge reduction. Firstly, the operation strategy is designed for ES to reduce the total network investment cost considering the uncertainties of flexible load and renewable energy. These nodal uncertainties are converted into branch power flow uncertainties by the cumulant and Gram-Charlier expansion strategy. Then, a time of use (ToU) pricing scheme is designed to guide the ES operation reflecting its impact on network investment based on the long-run investment cost (LRIC) pricing scheme. The proposed ToU LRIC method allocates the investment costs averagely to network users over the potential curtailment periods, which connects the ES operation with network investment. The curtailment amount and the distribution of power flow are assessed by the truncated strategy considering the impact of uncertainties. As demonstrated in a Grid Supply Point (GSP) distribution network in the UK, the network charges at the peak time reduce more than 20% with ES operation. The proposed method is cost-reflective and ensures the fairness and efficiency of the pricing signal for ES.

Abstract Background We investigated the influence of the coronavirus disease 2019 (COVID-19) pandemic on the number of patients with acute ischemic stroke who received intravenous thrombolytic therapy (ITT) in Dalian, China, in 2020. Methods This retrospective descriptive study, conducted from February 1, 2020, to August 31, 2020, examined 13 hospitals in Dalian that participated in the “stroke emergency map”. To use this “stroke emergency map” of China, patients followed the official “Stroke Map” WeChat account and dialed 120 for emergency medical services. We analyzed the number of patients with acute ischemic stroke who underwent ITT. In particular, we examined the onset-to-door time (ODT), door-to-needle time (DNT), onset-to-needle time (ONT), mode of transportation to the hospital, and National Institutes of Health Stroke Scale (NIHSS) scores before and after ITT. Data were collected for the aforementioned period and compared with the 2021 baseline data from the same time of year. The Mann‒Whitney U test was performed for data analysis. Results Compared with the data from 2020, the number of patients with acute ischemic stroke who underwent ITT increased (from 735 to 1719 cases) in 2021, but the DNT decreased (from 59 to 45 min; P = 0.002). Moreover, 83.9% of patients in 2020 presented to the hospital without ambulance transport, compared to 81.1% of patients in the 2021 non-COVID-19 pandemic period. Patients with NIHSS scores of 6–14 were more likely to call an ambulance for transport to the hospital than to transport themselves to the emergency department. Conclusions During the 2020 COVID-19 pandemic, the DNT was prolonged as a result of strengthened fever surveillance. In 2021, the number of patients with acute ischemic stroke who underwent ITT increased compared to the previous year. Notably, the growth in the number of patients with acute ischemic stroke who underwent ITT benefited from both the “stroke emergency map” of China and the “green channel,” a novel treatment approach that focuses on the rational design of the rescue process. Trial registration. Our study was a retrospective descriptive study, not a clinical trial, thus we did not have to register for clinical trials.

Abstract Background Maternal mortality has always been a major medical concern. Recently, the successful application of extracorporeal membrane oxygenation (ECMO) technology in the rescue of near-death patients has been reported. Case presentation This study retrospectively analyzed 5 cases of critically ill pregnant women/parturients treated with ECMO for respiratory and circulatory failure in the Wuxi People’s Hospital from 2018 to 2020. The mean age of the 5 cases was 30.2 years. Among them, Cases 1 and 5 were treated with Venoarterial (VA) ECMO. Case 1 was diagnosed with congenital heart disease, atrial septal defect, and severe pulmonary hypertension. VA ECMO was applied before cesarean section and was successfully removed after double lung transplantation, but the patient died 10 months after delivery from lung infection. While Case 5 was diagnosed with systemic lupus erythematosus, lupus nephritis, thrombotic vascular disease, HELLP syndrome, and cerebral hemorrhage. VA ECMO was applied 39 days after cesarean section, and the patient died 40 days after delivery due to multiple organ failure. Cases 3 and 4 were treated with Venovenous (VV) ECMO. Case 3 was diagnosed with refractory postpartum hemorrhage, and Case 4 was diagnosed with postpartum hypoglycemic coma, aspiration pneumonia, and shock. They were treated with VV ECMO after delivery, and all survived after successful evacuation. Another Case (Case 2) was diagnosed with postpartum pelvic infection, sepsis and septic shock, and was treated with VA ECMO at 15 days after delivery. The patient changed to VV ECMO at 30 days after delivery due to significant improvement in heart function and poor lung function, but eventually died of multiple organ failure. For the 5 cases, the mean duration of ECMO was 8.7 days, the mean duration of intensive care was 22.0 days, and the mean length of hospital stay was 57.6 days. As a result, 3 patients gradually returned to normal with significant improvement in ventilation and oxygenation after ECMO treatment. Conclusions ECMO technology can be used to treat some of the critical obstetric patients with respiratory and circulatory failure that is ineffective to conventional treatment, but it has no therapeutic effect on the primary disease.

Abstract This paper proposes a novel real option (RO)‐based network investment assessment method to quantify the flexibility value of battery energy storage systems (BESS) in distribution network planning (DNP). It applied geometric Brownian motion (GBM) to simulate the long‐term load growth uncertainty. Compared with commonly used stochastic models (e.g. normal probability model) that assume a constant variance, it reflects the fact that from the point of prediction, uncertainty would increase as time elapses. Hence, it avoids the bias of traditional net present value (NPV) frameworks towards lumpy investments that cannot provide strategic flexibility relative to more flexible alternatives. It is for the first time to adopt the option pricing method to evaluate the flexibility value of distribution network planning strategies. To optimize the planning scheme, this paper compares the static NPVs and flexibility values of different investment strategies. A 33‐bus system is used to verify the effectiveness of the formulated model. Results indicate that flexibility values of BESS are of utmost importance to DNP under demand growth uncertainties. It provides an analytical tool to quantify the flexibility of planning measures and evaluate the well‐timed investment of BESS, thus supporting network operators to facilitate flexibility services and hedge risks from the negative impact of long‐term uncertainty.

As an energy industry, the power industry is related to the national economy and the people’s livelihood. It is applied to intensive technology types, and involves all walks of life. Due to the opening of power market and the changes of social economy, such as Internet economy and data economy, the traditional power industry is facing great challenges. Considering the practical problem that the private data anomaly detection model of power network lacks high-quality labeled data set and the anomaly detector is updated in time according to the feedback, an adaptive anomaly detection model of human in the loop is constructed so as to effectively reduce the phenomenon of false positives. This paper proposes an adaptive anomaly detection algorithm based on isolated forest and prediction analysis. The abnormal score is calculated according to the algorithm. The sorting list of abnormal data is given. The samples to be labeled are selected by pal strategy and handed over to the analysts, and then the weight of each side in the database is updated in time according to the labeling feedback. The experimental results show that the detection accuracy of this algorithm is 95% under the low manual annotation budget, which is 5%–10% higher than other algorithms. Besides, about 70% abnormal behaviors were detected from 20000 test data. It realizes the purpose of identifying directional network attacks from multi-source heterogeneous and noisy cyberspace data. This research can help the power department quickly find the abnormal behavior caused by network attack, which aims to solve the problems of low intelligence level and lack of correlation between multi-source heterogeneous data in power network attack detection.

Abstract Adipose-derived stem cells (ADSCs) show potential in skin regeneration research. A previous study reported the failure of full-thickness skin self-repair in an injury area exceeding 4 cm in diameter. Stem cell therapies have shown promise in accelerating skin regeneration; however, the low survival rate of transplanted cells due to the lack of protection during and after transplantation leads to low efficacy. Hence, effective biomaterials for the delivery and retention of ADSCs are urgently needed for skin regeneration purposes. Here, we covalently crosslinked hyaluronic acid with methacrylic anhydride and then covalently crosslinked the product with dopamine to engineer dopamine-methacrylated hyaluronic acid (DA-MeHA). Our experiments suggested that the DA-MeHA hydrogel firmly adhered to the skin wound defect and promoted cell proliferation in vitro and skin defect regeneration in vivo. Mechanistic analyses revealed that the beneficial effect of the DA-MeHA hydrogel combined with ADSCs on skin defect repair may be closely related to the Notch signaling pathway. The ADSCs from the DA-MeHA hydrogel secrete high levels of growth factors and are thus highly efficacious for promoting skin wound healing. This DA-MeHA hydrogel may be used as an effective potential carrier for stem cells as it enhances the efficacy of ADSCs in skin regeneration.

Abstract Background Pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) is recognized as a cancer-like disease with a proliferative and pro-migratory phenotype in pulmonary artery smooth muscle cells (PASMCs). Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP) has been implicated in the progression of various cancers; however, it has not been previously studied in the context of CHD-PAH. Here, we aimed to examine the function of CacyBP/SIP in CHD-PAH and explore its potential as a novel regulatory target for the disease. Methods The expression of CacyBP/SIP in PASMCs was evaluated both in the pulmonary arterioles of patients with CHD-PAH and in high-flow-induced PAH rats. The effects of CacyBP/SIP on pulmonary vascular remodeling and PASMC phenotypic switch, proliferation, and migration were investigated. LY294002 (MedChemExpress, NJ, USA) was used to block the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway to explore changes in PASMC dysfunction induced by low CacyBP/SIP levels. Hemodynamics and pulmonary arterial remodeling were further explored in rats after short-interfering RNA-mediated decrease of CacyBP/SIP expression. Results CacyBP/SIP expression was markedly reduced both in the remodeled pulmonary arterioles of patients with CHD-PAH and in high-flow-induced PAH rats. Low CacyBP/SIP expression promoted hPASMC phenotypic switch, proliferation, and migration via PI3K/AKT pathway activation. Our results indicated that CacyBP/SIP protected against pulmonary vascular remodeling through amelioration of hPASMC dysfunction in CHD-PAH. Moreover, after inhibition of CacyBP/SIP expression in vivo, we observed increased right ventricular hypertrophy index, poor hemodynamics, and severe vascular remodeling. Conclusions CacyBP/SIP regulates hPASMC dysfunction, and its increased expression may ameliorate progression of CHD-PAH.

Abstract Background The biological activity and regenerative medicine of bone marrow mesenchymal stem cells (BMSCs) have been focal topics in the broad fields of diabetic wound repair. However, the molecular mechanisms are still largely elusive for other cellular processes that are regulated during BMSC treatment. Our previous studies have shown that hypoxia is not only a typical pathological phenomenon of wounds but also exerts a vital regulatory effect on cellular bioactivity. In this study, the beneficial effects of hypoxic BMSCs on the cellular behaviors of epidermal cells and diabetic wound healing were investigated. Method The viability and secretion ability of hypoxic BMSCs were detected. The autophagy, proliferation and migration of HaCaT cells cultured with hypoxic BMSCs-derived conditioned medium were assessed by estimating the expression of autophagy-related proteins, MTS, EdU proliferation and scratch assays. And the role of the SMAD signaling pathway during hypoxic BMSC-evoked HaCaT cell autophagy was explored through a series of in vitro gain- and loss-of-function experiments. Finally, the therapeutic effects of hypoxic BMSCs were evaluated using full-thickness cutaneous diabetic wound model. Results First, we demonstrated that hypoxic conditions intensify HIF-1α-mediated TGF-β1 secretion by BMSCs. Then, the further data revealed that BMSC-derived TGF-β1 was responsible for the activation of epidermal cell autophagy, which contributed to the induction of epidermal cell proliferation and migration. Here, the SMAD signaling pathway was identified as downstream of BMSC-derived TGF-β1 to regulate HaCaT cell autophagy. Moreover, the administration of BMSCs to diabetic wounds increased epidermal autophagy and the rate of re-epithelialization, leading to accelerated healing, and these effects were significantly attenuated, accompanied by the downregulation of Smad2 phosphorylation levels due to TGF-β1 interference in BMSCs. Conclusion In this report, we present evidence that uncovers a previously unidentified role of hypoxic BMSCs in regulating epidermal cell autophagy. The findings demonstrate that BMSC-based treatment by restoring epidermal cell autophagy could be an attractive therapeutic strategy for diabetic wounds and that the process is mediated by the HIF-1α/TGF-β1/SMAD pathway.

By analyzing the differences of mineral element contents in dried tangerine peel from different producing areas, combined with multivariate statistical analysis, the effective origin traceability indexes based on mineral element fingerprint analysis technology were selected to construct its discrimination model of different origin identification. In this study, 206 dried tangerine peel samples were collected from three different producing areas as Guangdong, Fujian and Chongqing. The contents of 32 mineral elements were determined by inductively coupled plasma mass spectrometer (ICP-MS) and inductively coupled plasma atomic emission spectrometer (ICP-AES). Combined with analysis of variance, principal component analysis, linear discriminant analysis and orthogonal partial least squares discriminant analysis, a discriminant model of dried tangerine peel producing area was established. The results showed that 26 of the 32 mineral elements in the dried tangerine peel samples had significant differences between Guangdong and other two producing areas, and 11 of them had significant differences between the three different regions. After principal component analysis, four principal components could be extracted from the 32 mineral elements, representing 70.0% of the total index. Based on the principal component analysis, the dried tangerine peel samples could be preliminarily clustered according to their different origin. The main variables of the first two principal components were Dy, Sm, Gd, Pr, Nd, Y, La, Fe, Be, V, Ce, Sc, Co, P, Mo, As, Pb and B. Through linear discriminant analysis, 21 mineral elements K, P, Ca, Co, Cu, Mn, Mo, V, Ni, B, Li, Pb, As, Sr, Ti, Th, Gd, Sc, Nd, Pr and Y were determined as effective traceability indexes of the dried tangerine peel. Additionally, based on the discriminant model established by orthogonal partial least squares discriminant analysis, the importance of 13 elements Sc, B, Y, Co, Nd, La, Pr, Be, Gd, Dy, Sm, Mo and Fe were determined. For the discrimination models established by the two above-mentioned discrimination analysis methods, their overall correct discrimination rates of cross validation and external sample validation were both 100%, which basically achieved the origin discrimination of dried tangerine peel. The research suggested that the mineral element fingerprint analysis technology can be used for the origin traceability discrimination of dried tangerine peel.

Foam drainage gas production is a gas production technology for low-pressure gas well in domestic and abroad industries. In Qinghai Oilfield’s Sebei Gasfield, sand existence often occurs during drainage production. In order to reveal the impacts of formation sands on drainage gas production, a lab test was conducted to make a study on foam performances of different foam drainage agents in case of sand existence. A laboratory test was employed to study the foam performances of different foam drainage agents under varies scenes of sand existence, to reveal the impacts of formation sands during foam drainage gas recovery. In this study, four foam drainage agents, i.e., OP-10, Sodium dodecyl benzene sulfonate, Hexadecyl Trimethyl Ammonium Bromide (CTAB), and Lauramidopropyl Hydroxy Sulfobetaine, were selected to compare with the field compound foam drainage agent QH-X1. Following patterns can be revealed by macroscopic and microscopic experimental results: Foam formed by an ionic-type foam drainage agent is more stable when the hydrophilic sand particles are smaller (which means they have larger specific surface areas and the adsorption energy levels between the sand and bubbles are higher); while foam formed by non-ionic foam drainage agent OP-10 has a short stable period because its polarity is weaker than that of ionic-type agent foam and the adsorbability of the foam on the hydrophilic particles is weak; under different sand conditions, the impacts of different foam drainage agent types on the average bubble area, bubble wall thickness, and Plateau Boundary are markedly different, and appear decreasing tendency with anionic foam drainage agents, is the trend can be more obvious when the sand particles are coarser. The study on QH-X1 shows that the foam parameters are generally lower as the sand particles are smaller, but the changing trends can be different after sand is involved. Particles constitute an adsorption film at the gas-liquid interface and a laminar structure within each interbubble thin liquid film, thus improving bubble coalescence and unloading stability. So, the inflow of the hydrophilic sands increases the stiffness, half-life period, and comprehensive rate of the QH-X1-induced foam.

The quantity and heterogeneity of intelligent energy generation and consumption terminals in the smart grid are increasing drastically over the years. These edge devices have created significant pressures on cloud computing (CC) system and centralised control for data storage and processing in real-time operation and control. The integration of edge computing (EC) can effectively alleviate the pressure and conduct real-time processing while ensuring data security. This paper conducts an extensive review of the EC-CC computing system and its Application to the smart grid, which will integrate a vast number of dispersed devices. It first comprehensively describes the relationship among CC, fog computing (FC), and EC to provide a theoretical basis for the differentiation. It then introduces the architecture of the EC-CC computing system in the smart grid, where the architecture consists of both hardware structure and software platforms, and key technologies are introduced to support functionalities. Thereafter, the application to the smart grid is discussed across the whole supply chain, including energy generation, transportation (transmission and distribution networks)., and consumption. Finally, future research opportunities and challenges of EC-CC while being applied to the smart grid are outlined. This paper can inform future research and industrial exploitations of these new technologies to enable a highly efficient smart grid under decarbonisation, digitalisation, and decentralisation transitions.

The surface turbulent heat flux feedback αT plays an important role in the atmosphere–ocean coupling. However, spatio-temporal variability of αT for sea surface temperature anomaly (SSTA) at oceanic mesoscales in the global ocean remains poorly assessed. In this study, we tackle this issue using an advanced statistical model, i.e., the geographically and temporally weighted regression model. The estimated time-mean αT for mesoscale SSTA generally ranges from 10 to 50 W/(m2 K) within 70°S–70°N, except in the Antarctic coastal region where its value drops to zero. The αT is larger in the tropics than in off-tropical regions and locally enhanced in the equatorial cold tongues, western boundary currents, and their extensions. The spatial structure αT is primarily attributed to the non-linearity in the Clausius–Clapeyron relation and inhomogeneity in the background wind speed, whereas adjustment of surface wind speed, air temperature, or moisture to mesoscale SSTA plays an important role in the regional variability. There is an evident seasonal cycle of αT in the tropics and under the northern hemisphere’s storm tracks. The former is due to the seasonally varying response of surface wind speed to mesoscale SSTA, and the latter results from the seasonality of atmospheric and oceanic background states. Our analysis reveals prominent spatio-temporal variability of αT for mesoscale SSTA governed by complicated dynamics.

The Paleo-Asian Ocean controlled the tectonic evolution of Northeast Asia and formed the Karamaili Orogenic Belt in the eastern Junggar basin. However, the chronological constrain of the evolution of the paleo-Karamaili Ocean remains unclear. In this study, we focused on the sandstones of the Lower Jurassic Badaowan and Sangonghe Formations in the Dongdaohaizi Depression, Junggar basin near the Karamaili orogenic belt. After detailed observations and descriptions of the macroscopic features of the sandstone, we obtained information on petrology and geochronology. The Dickinson diagrams indicate that the provenance area had the characteristics of a transitional and recycling provenance, which is a collisional orogenic belt with a background of oceanic-continental subduction. The detrital zircon ages of the Lower Jurassic sediments in the Dongdaohaizi Depression can be divided into three peaks: ~300 Ma, ~420 Ma, and ~510 Ma for Badaowan Formation and ~310 Ma, ~410 Ma, and ~500 Ma for Sangonghe Formation. The youngest detrital zircon age is 241 ± 2 Ma, representing an Early Permian depositional age. Combined with previous studies, the sediments in the study area represent a provenance from the Karamaili Ocean. During the Early Jurassic, the consistent subduction of the residual East Junggar Ocean induced continuous uplift in the Karamaili region, resulting in an increasing exposure of deep-seated rocks to provide sedimentary material. According to the tectonic background of the Junggar region, the results indicate that the Karamaili Ocean, as part of the Paleo-Asian Ocean, experienced three evolutionary stages: Cambrian-Early Silurian (460–540 Ma), Late Silurian-Early Carboniferous (360–440 Ma), and Late Carboniferous–Triassic (240–340 Ma).

Abstract Tumor-infiltrating T cells are highly expressive of inhibitory receptor/immune checkpoint molecules that bind to ligand expressed by tumor cells and antigen-presenting cells, and eventually lead to T cell dysfunction. It is a hot topic to restore T cell function by targeting immune checkpoint. In recent years, immunotherapy of blocking immune checkpoint and its receptor, such as PD-L1/PD-1 targeted therapy, has made effective progress, which brings hope for patients with advanced malignant tumor. However, only a few patients benefit from directly targeting these checkpoints or their receptors by small compounds or antibodies. Since the complexity of the regulation of immune checkpoints in tumor cells, further research is needed to identify the novel endogenous regulators of immune checkpoints which can help for developing effective drug target to improve the effect of immunotherapy. Here, we verified that microRNA-326 (miR-326) repressed the gene expression of immune checkpoint molecules PD-L1 and B7-H3 in lung adenocarcinoma (LUAD). We detected that the expression of miR-326 in LUAD tissue was negatively correlated with PD-L1/B7-H3. The repression of PD-L1 and B7-H3 expression through miR-326 overexpression leads to the modification the cytokine profile of CD8+ T cells and decreased migration capability of tumor cells. Meanwhile, the downregulation of miR-326 promoted tumor cell migration. Moreover, blocking PD-L1 and B7-H3 attenuated the tumor-promoting effect induced by miR-326 inhibitor. In tumor-bearing mice, the infiltration of CD8+ T cells was significantly increased and the expression of TNF-α, and IFN-γ was significantly enhanced which contributed to tumor progression after miR-326 overexpression. Collectively, miR-326 restrained tumor progression by downregulating PD-L1 and B7-H3 expression and increasing T cell cytotoxic function in LUAD. Our findings revealed a novel perspective on the complex regulation of immune checkpoint molecules. A new strategy of using miR-326 in tumor immunotherapy is proposed.

Abstract Background In order to solve the problem of “expensive medical treatment and difficult medical treatment” for patients and improve the equity of medical services, China started the health-care reform in 2009, and proposed ambitious goals of providing fair and high-quality basic medical and health services to all citizens and reducing economic burden of diseases. This study was to systematically explore the association between population economic status and incidence of catastrophic health expenditures (CHE) in mainland China in the last decade since 2009 health reform. Methods This systematic review was reported according to the standard of preferred reporting items for systematic reviews and meta-analyses (PRISMA). We systematically searched Chinese Electronic literature Database of China Journal Full Text Database, Chinese Biomedical Journal Database, Wan fang Data Resource System, VIP Database, and English literature databases of PubMed, SCI, EMbase and Cochrane Library from January 2000 to June 2020, and references of included studies. Two reviewers independently selected all reports from 2000 to 2020 for empirical studies of CHE in mainland China, extracted data and evaluated the quality of the study. We conducted meta-analysis of the incidence of CHE and subgroup analysis according to the time of the study and the economic characteristics of residents. Results Four thousand eight hundred seventy-four records were retrieved and eventually 47 studies with 151,911 participants were included. The quality scores of most of studies were beyond 4 points (91.49%). The pooled incidence of CHE of Chinese residents in the last two decades was 23.3% (95% CI: 21.1 to 25.6%). The CHE incidence increased from 2000 to 2017, then decreased over time from 2017 to 2020. From 2000 to 2020, the CHE incidence in rural areas was 25.0% (95% CI: 20.9 to 29.1%) compared to urban 20.9% (95% CI: 18.3 to 23.4%); the CHE incidence in eastern, central and western China was 25.0% (95% CI: 19.2 to 30.8%), 25.4% (95% CI: 18.4 to 32.3%), and 23.1% (95% CI: 17.9 to 28.2%), respectively; the CHE incidence was 30.9% (95% CI: 22.4 to 39.5%), 20.3% (95% CI: 17.0 to 23.6%), 19.9% (95% CI: 15.6 to 24.1%), and 23.7% (95% CI: 18.0 to 29.3%) in poverty group, low-income group, middle-income group, and high-income group, respectively. Conclusions In the past two decade, the incidence of CHE in rural areas is higher than that of urban residents; higher in central areas than in eastern, western and other regions; in poverty households than in low-income, middle-income and high-income regions. Further measures should be taken to reduce the incidence of CHE in susceptible people.

Modern pollen–vegetation–climate relationships underpin palaeovegetation and palaeoclimate reconstructions from fossil pollen records. East Siberia is an ideal area for investigating the relationships between modern pollen assemblages and near natural vegetation under cold continental climate conditions. Reliable pollen-based quantitative vegetation and climate reconstructions are still scarce due to the limited number of modern pollen datasets. Furthermore, differences in pollen representation of samples from lake sediments and soils are not well understood. Here, we present a new pollen dataset of 48 moss/soil and 24 lake surface-sediment samples collected in Chukotka and central Yakutia in East Siberia. The pollen–vegetation–climate relationships were investigated by ordination analyses. Generally, tundra and taiga vegetation types can be well distinguished in the surface pollen assemblages. Moss/soil and lake samples contain generally similar pollen assemblages as revealed by a Procrustes comparison with some exceptions. Overall, modern pollen assemblages reflect the temperature and precipitation gradients in the study areas as revealed by constrained ordination analysis. We estimate the relative pollen productivity (RPP) of major taxa and the relevant source area of pollen (RSAP) for moss/soil samples from Chukotka and central Yakutia using Extended R-Value (ERV) analysis. The RSAP of the tundra-forest transition area in Chukotka and taiga area in central Yakutia are ca. 1300 and 360 m, respectively. For Chukotka, RPPs relative to both Poaceae and Ericaceae were estimated while RPPs for central Yakutia were relative only to Ericaceae. Relative to Ericaceae (reference taxon, RPP = 1), Larix, Betula, Picea, and Pinus are overrepresented while Alnus, Cyperaceae, Poaceae, and Salix are underrepresented in the pollen spectra. Our estimates are in general agreement with previously published values and provide the basis for reliable quantitative reconstructions of East Siberian vegetation.

Long-QT syndrome type 2 (LQT2) is a common malignant hereditary arrhythmia. Due to the lack of suitable animal and human models, the pathogenesis of LQT2 caused by human ether-a-go-go-related gene (hERG) deficiency is still unclear. Herein, we have generated a human embryonic stem cell line (WAe009-A-74) carrying a LQTS related mutation in KCNH2. The WAe009-A-74 line maintained stem cell like morphology, pluripotency, normal karyotype and could differentiate into all three germ layers in vivo.

Abstract Background Infections were the primary cause of death (34.3–55.5%) in patients with pemphigus. Skin was usually the origin of infections. The study aimed to explore features and associated factors of bacterial skin infections (BSIs) in inpatients with pemphigus. Methods One hundred and seventy-seven inpatients with pemphigus hospitalizing from November 2014 to April 2019 were continuously recruited through Peking University First Hospital’s inpatient records inpatients with pemphigus hospitalizing from November 2014 to April 2019 were continuously recruited through Peking University First Hospital’s inpatient records. Then, we retrieved the clinical and laboratory data to explore the characteristics and associated factors of BSIs. Results Of patients enrolled, pemphigus vulgaris (PV, n = 142) and pemphigus foliaceus (PF, n = 9) were most common, followed by pemphigus erythematosus (PE, n = 25) and pemphigus vegetans (Pveg, n = 1). Eighty-seven of 177 (49.2%) inpatients developed BSIs, and they had a longer length of stay compared with inpatients without BSIs (median: 18.9 vs. 14.1 days, p = 0.008). Staphylococcus aureus was the most common bacteria (71.3%, 62/87) and highly resistant to penicillin (91.9%, 57/62). Higher levels of anti-Dsg1 autoantibodies (> 124.2 U/mL) (p 169.5 U/mL) (p = 0.03, OR = 2.074, 95% CI: 1.084–3.969) were underlying risk factors of BSIs when analyzed by binary regression analysis. As for Gram’s stain of bacteria, females had a lower rate of Gram-positive infections (p = 0.03). Patients using oral antibiotics (p = 0.05) had a higher rate of Gram-negative infections. Inpatients who were hospitalized in other hospitals within 2 weeks before the current admission had a higher rate of Gram-negative and co-infections (p = 0.03). Conclusions Inpatients with pemphigus had a high incidence of BSIs. Some factors were associated with the susceptibility of BSIs and bacterial species.

Abstract Background Estimating prevalence of Chlamydia trachomatis (CT) worldwide is necessary in designing control programs and allocating health resources. We performed a meta-analysis to calculate the prevalence of CT in the general population. Methods The Pubmed and Embase databases were searched for eligible population-based studies from its inception through June 5, 2019. Q test and I 2 statistic were used to calculate the heterogeneity between studies. Random effects models were used to pool the prevalence of CT. Meta regression was performed to explore the possible sources of heterogeneity. Publication bias was evaluated using a funnel plot and “trim and fill” method. Results Twenty nine studies that reported prevalence of CT infection from 24 countries were identified, including a total population of 89,886 persons. The pooled prevalence of CT among the general population was 2.9% (95% CI, 2.4–3.5%), and females had a higher CT prevalence (3.1, 95% CI, 2.5–3.8%) than males (2.6, 95% CI, 2.0–3.2%) (χ 2 = 10.38, P

Refolding of human interleukin 17A (IL-17A) has been reported; however, the key refolding protocol was not robust enough to deliver consistent results and to be easily scaled up for crystallization. Here we report an optimized refolding method for IL-17A. Although co-crystal structures of IL-17A with ligands have been obtained with a high-affinity peptide and an anti-IL-17A Fab as stabilizers, neither the production yield nor the characterization of the IL-17A/Fab complex was reported. To facilitate co-crystallization of IL-17A with small-molecule compounds derived from our DNA encoded library, we also describe the method for yield enhancement of anti-IL-17A Fab production and characterize the IL-17A/Fab complex for the first time, providing an essential prerequisite for structure-based drug discovery targeting IL-17A.

Background Previous studies have reported that cancer stem cells (CSCs) play a key role in tumorigenesis, metastasis, and recurrence. CSC‐based vaccination confers better protection in tumor cells. However, isolation and cultivation of CSCs are difficult. This study aimed to explore the similarities between CSCs and induced pluripotent stem cells (iPSCs). Methods ALDH1+ cancer stem cells were isolated from lung adenocarcinoma patients and their gene expression patterns compared with human induced pluripotent stem cells (hiPSCs). In addition, a tumor vaccine was developed using hiPSC and unmethylated cytosine‐guanine (CpG). Finally, the antitumor properties of the vaccine were evaluated in a humanized mouse model. Results Preimmunization of iPSC+CpG elicited stronger antigen presentation and cytotoxic T cell response which suppressed the growth of tumors. Adoptive transfer of spleen T cells from the vaccine preimmunized mice inhibited tumor growth in unvaccinated recipients without any side effects. Conclusions This study suggests a universal strategy for tumor therapy which simplifies future clinical procedures. Therefore, the application of hiPSC elicits tumor protective responses.

Abstract Background Nephronophthisis (NPHP) is a rare autosomal recessive inherited disorder with high heterogeneity. The majority of NPHP patients progress to end-stage renal disease (ESRD) within the first three decades of life. As an inherited disorder with highly genetic heterogeneity and clinical presentations, NPHP still poses a challenging task for nephrologists without special training to make a well-judged decision on its precise diagnosis, let alone its mechanism and optimal therapy. Case presentation A Chinese family with NPHP was recruited in current study. The clinical characteristics (including findings from renal biopsy) of NPHP patients were collected from medical records and the potential responsible genes were explored by the whole exome sequencing (WES). A homozygous deletion of NPHP1 (1–20 exons) was found in both affected patients, which was further confirmed by quantitative PCR. Conclusions Homozygous full gene deletion of the NPHP1 gene was identified in a Chinese family with NPHP, which was the molecular pathogenic basis of this disorder. Furthermore, identification of the pathogenic genes for those affected patients can help to have a full knowledge on NPHP’s molecular mechanism and precise treatment.

Developing a reasonable, efficient distributed market transaction mechanism is an important issue in distribution systems. The gaming relation between distributed transaction market entities has yet to be fully elucidated in various trading links, and the impact of distributed transactions on distribution network operations has yet to be comprehensively analyzed. This paper proposes a novel distributed Peer-to-Peer (P2P) day-ahead trading method under multi-microgrid congestion management in active distribution networks. First, a flexible load model for price-based demand response load and an autonomous microgrid economic scheduling model are constructed. Second, under normal operation of the distribution network, a non-cooperative game model and Stackelberg game model are employed to separately and comprehensively analyze gaming relationship among sellers, and between sellers and buyers. Thereafter, a congestion management method based on market capacity is established from the perspective of distribution network control centers. Finally, the impact of end energy consumption characteristics on microgrid economic scheduling and P2P trading is analyzed through a modified IEEE 33-node power distribution system. The economic and technical benefits such as congestion mitigation and network loss reduction that produced by P2P trading to the operation of microgrid systems are analysed with specific indicators.

A study of the kinematic characteristics of a 3UPU_UP coupling parallel platform that has three-degree-of-freedom(3-DOF). In this article, a novel 3UPU_UP parallel platform is presented, which is based on the 5-DOF 3UPU parallel platform by adding a UP followed limb. The DOFs and motion constraints of the platform are analyzed by the screw theory, and the coupling constraint equation of the platform is obtained through coordinate transformation. The inverse kinematics equation of the platform is derived by the closed-loop method, and the forward kinematics equation of the platform is solved by Netwon-Rapson iteration. The trajectory of the platform in space is obtained and the correctness of the coupling constraint equation of the platform in other DOFs is verified. Considering that the motion of a ship on the sea is multi-DOF and complicated, the motion of the cargo on the ship can be compensated by using a coupling characteristic of the platform to improve the safety of marine operations.