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Purpose: Erectile dysfunction (ED) is associated with several vascular disorders, but the associations between ED and vascular parameters are still unclear. Materials and Methods: We analyzed and synthesized a comprehensive range of studies from PubMed, Web of Science, and Scopus regarding the associations between ED and the following measures: ankle-brachial index (ABI), pulse wave velocity (PWV), intima-media thickness (IMT), nitrate-mediated dilation (NMD), flow-mediated dilation (FMD), augmentation index (AI), endothelial progenitor cells (EPCs) and other vascular parameters. Subgroup analysis was conducted according to specific types of parameters. Study quality was assessed by using the Newcastle–Ottawa Scale. Sensitivity analysis was conducted to confirm the robustness of the pooled results. Results: Fifty-seven studies with 7,312 individuals were included. Twenty-eight studies were considered to be high-quality. ED patients had a 0.11 mm higher IMT (95% confidence interval [CI]: 0.07, 0.15), a 2.86% lower FMD (95% CI: -3.56, -2.17), a 2.34% lower NMD (95% CI: -3.37, -1.31), a 2.83% higher AI (95% CI: 0.02, 5.63), a 1.11 m/s higher PWV (95% CI: 0.01, 2.21), and a 0.72% lower percentage of EPCs (95% CI: -1.19, -0.24) compared to those without ED. However, ABI was similar between ED patients and non-ED individuals. According to sensitivity analysis, the pooled results were robust. Conclusions: Our study confirmed the associations between ED and several vascular parameters and highlighted the importance of prevention and management of vascular and endothelial dysfunction in ED patients.

Abstract The modulation of the chemical microenvironment surrounding metal nanoparticles (NPs) is an effective means to enhance the selectivity and activity of catalytic reactions. Herein, a post‐synthetic modification strategy is developed to modulate the hydrophobic microenvironment of Ru nanoparticles encapsulated in a metal–organic framework (MOF), MIP‐206, namely Ru@MIP‐Fx (where x represents perfluoroalkyl chain lengths of 3, 5, 7, 11, and 15), in order to systematically explore the effect of the hydrophobic microenvironment on the electrocatalytic activity. The increase of perfluoroalkyl chain length can gradually enhance the hydrophobicity of the catalyst, which effectively suppresses the competitive hydrogen evolution reaction (HER). Moreover, the electrocatalytic production rate of ammonia and the corresponding Faraday efficiency display a volcano‐like pattern with increasing hydrophobicity, with Ru@MIP‐F7 showing the highest activity. Theoretical calculations and experiments jointly show that modification of perfluoroalkyl chains of different lengths on MIP‐206 modulates the electronic state of Ru nanoparticles and reduces the rate‐determining step for the formation of the key intermediate of N2H2*, leading to superior electrocatalytic performance.

Background Nonylphenol (NP) is widely recognized as a crucial environmental endocrine-disrupting chemical and persistent toxic substance. The remediation of NP-contaminated sites primarily relies on biological degradation. Compound microbial products, as opposed to pure strains, possess a greater variety of metabolic pathways and can thrive in a wider range of environmental conditions. This characteristic is believed to facilitate the synergistic degradation of pollutants. Limited research has been conducted to thoroughly examine the potential compatibility of compound microbial agents with indigenous microflora, their ability to function effectively in practical environments, their capacity to enhance the dissipation of NP, and their potential to improve soil physicochemical and biological characteristics. Methods In order to efficiently eliminate NP in contaminated soil in an eco-friendly manner, a simulation study was conducted to investigate the impact of bioaugmentation using the functional compound microbial agent NP-M2 at varying concentrations (50 and 200 mg/L) on the dynamics of the soil microbial community. The treatments were set as follows: sterilized soil with 50 mg/kg NP (CK50) or 200 mg/kg NP (CK200); non-sterilized soil with 50 mg/kg NP (TU50) or 200 mg/kg NP (TU200); non-sterilized soil with the compound microbial agent NP-M2 at 50 mg/kg NP (J50) or 200 mg/kg NP (J200). Full-length 16S rRNA analysis was performed using the PacBio Sequel II platform. Results Both the indigenous microbes (TU50 and TU200 treatments) and the application of NP-M2 (J50 and J200 treatments) exhibited rapid NP removal, with removal rates ranging from 93% to 99%. The application of NP-M2 further accelerated the degradation rate of NP for a subtle lag period. Although the different treatments had minimal impacts on the soil bacterial α-diversity, they significantly altered the β-diversity and composition of the bacterial community. The dominant phyla were Proteobacteria (35.54%–44.14%), Acidobacteria (13.55%–17.07%), Planctomycetes (10.78%–11.42%), Bacteroidetes (5.60%–10.74%), and Actinobacteria (6.44%–8.68%). The core species were Luteitalea_pratensis, Pyrinomonas_methylaliphatogenes, Fimbriiglobus_ruber, Longimicrobium_terrae, and Massilia_sp003590855. The bacterial community structure and taxon distribution in polluted soils were significantly influenced by the activities of soil catalase, sucrase, and polyphenol oxidase, which were identified as the major environmental factors. Notably, the concentration of NP and, to a lesser extent, the compound microbial agent NP-M2 were found to cause major shifts in the bacterial community. This study highlights the importance of conducting bioremediation experiments in conjunction with microbiome assessment to better understand the impact of bioaugmentation/biostimulation on the potential functions of complex microbial communities present in contaminated soils, which is essential for bioremediation success.

Abstract Neurosyphilis (NS) is a central nervous system (CNS) infection caused by Treponema pallidum (T. pallidum). NS can occur at any stage of syphilis and manifests as a broad spectrum of clinical symptoms. Often referred to as “the great imitator,” NS can be easily overlooked or misdiagnosed due to the absence of standard diagnostic tests, potentially leading to severe and irreversible organ dysfunction. In this study, proteomic and machine learning model techniques are used to characterize 223 cerebrospinal fluid (CSF) samples to identify diagnostic markers of NS and provide insights into the underlying mechanisms of the associated inflammatory responses. Three biomarkers (SEMA7A, SERPINA3, and ITIH4) are validated as contributors to NS diagnosis through multicenter verification of an additional 115 CSF samples. We anticipate that the identified biomarkers will become effective tools for assisting in diagnosis of NS. Our insights into NS pathogenesis in brain tissue may inform therapeutic strategies and drug discoveries for NS patients.

Abstract Doxorubicin (DOX) has a wide antitumor spectrum, but its adverse cardiotoxicity may lead to heart failure. Urotensin II (UII) is the most potent vasoconstrictor in mammals. It plays a role by activating the UII receptor (UT), the orphan G protein-coupled receptor (GPR14), collectively referred to as the UII/UT system. In the new version of "Chinese expert consensus on cardiac rehabilitation of chronic heart failure," it is pointed out that exercise rehabilitation is the cornerstone of cardiac rehabilitation. In this study, in vitro and in vivo assessments were performed using DOX-treated H9C2 cells and rats. It was found that the UT antagonist Urantide and exercise training improved DOX-induced cardiac insufficiency, reduced DOX-induced cardiomyocyte apoptosis, improved the structural disorder of myocardial fibers, and inhibited DOX-induced myocardial fibrosis. Further studies showed that Urantide alleviated DOX-induced cardiotoxicity by downregulating the expression levels of the p38 mitogen-activated protein kinase signaling pathway.

Here, the authors show that the glycosylceramide synthesis inhibitor and FDA approved drug Eliglustat inhibits autophagic degradation of TRAF3 which is a key step for osteoclast differentiation and thereby improves myeloma bone lesions.

In this paper, a typical teaching building of a university in Urumqi, Xinjiang was taken as the research object. Based on the existing maintenance structure, DesignBuilder software was used to explore the differences in energy consumption and carbon emissions generated by ordinary hot water heating system, ground thermal radiation heating and electric heating under different ventilation times. The effects of intermittent heating and continuous heating on heating energy consumption and carbon emission were studied by software simulation. Conclusion On the condition of ensuring indoor thermal comfort, electric heating is suitable for teaching buildings in Urumqi city, and intermittent heating is not suitable, continuous heating should be used. The heating system with the highest indoor comfort level is the ground heat radiation heating system, and the carbon emission is the ordinary hot water heating system. When the ratio of window and wall area under electric heating increases by 5%, the total heating energy consumption and carbon emission of buildings will increase by 10.8%–16.2% in the heating season, and the heating heat load of buildings will increase by 6.4%–8.2%.

Abstract Investments in the energy networks will significantly influence the outcome of Integrated Energy System (IES) planning. It is difficult to optimally plan the energy stations and energy networks of IES while taking into consideration the energy network investments. Thus, a collaborative planning methodology is proposed for energy stations and energy networks containing multiple energy carriers, which can optimize both the capacity of the energy devices and networks and the topology of the energy networks. The linearization for the energy storage devices and electric air conditioning models, as well as the second‐order relaxation for the power grid and gas network models are implemented, and the optimization model is subsequently transformed into a mixed‐integer second‐order cone programming (MISOCP) form which can be directly solved by the commercial solvers. Numerical analysis is carried out to prove the effectiveness of the proposed model and method and the results show that energy networks with optimal topology can significantly improve the energy utilization efficiency of the system and reduce the total cost. In addition, the investment cost of the energy networks plays a decisive role in the network topology as well as the way how the energy is supplied to energy stations.

Changes in lipid metabolism are associated with aging and age-related diseases, including proteopathies. The endoplasmic reticulum (ER) is uniquely a major hub for protein and lipid synthesis, making its function essential for both protein and lipid homeostasis. However, it is less clear how lipid metabolism and protein quality may impact each other. Here, we identified let-767, a putative hydroxysteroid dehydrogenase in Caenorhabditis elegans, as an essential gene for both lipid and ER protein homeostasis. Knockdown of let-767 reduces lipid stores, alters ER morphology in a lipid-dependent manner, and blocks induction of the Unfolded Protein Response of the ER (UPRER). Interestingly, a global reduction in lipogenic pathways restores UPRER induction in animals with reduced let-767. Specifically, we find that supplementation of 3-oxoacyl, the predicted metabolite directly upstream of let-767, is sufficient to block induction of the UPRER. This study highlights a novel interaction through which changes in lipid metabolism can alter a cell’s response to protein-induced stress.

ABSTRACT Alcohol is an essential drug in human life with multiple medical functions, but excessive alcohol intake, even a single episode of binge drinking, can cause serious damage. Reducing alcohol consumption or absorption is a direct way to alleviate the related harm. Alcohol is decomposed successively by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver. Here, we produced a human ADH1B (hADH1B)-expressing probiotic, a recombinant Lactococcus lactis, that aimed to enhance alcohol degradation in the intestinal tract after oral administration. Our results showed that the oral hADH1B-expressing probiotic reduced alcohol absorption, prolonged the alcohol tolerance time, and shortened the recovery time after acute alcohol challenge. More importantly, the liver and intestine were protected from acute injury caused by alcohol challenge. Therefore, the engineered probiotic has the potential to protect organ damage from alcohol consumption. Furthermore, this engineered probiotic may have beneficial effects on alcohol-related diseases such as alcoholic fatty liver disease. IMPORTANCE Alcohol plays an important role in medical treatment, culture, and social interaction. However, excessive alcohol consumption or improper alcohol intake patterns can lead to serious damage to health. Aiming to reduce the harm of alcohol consumption, we designed a recombinant probiotic expressing hADH1B. Our results showed that this recombinant probiotic can reduce alcohol absorption and protect the body from alcohol damage, including hangover, liver, and intestinal damage. Reducing alcohol damage is helpful to the health of people with difficulty in abstinence. The engineered probiotic may provide new strategies for treatment and prevention of the negative effects of alcohol, and it also has the potential for widespread application.

Abstract Background Wuzhimaotao (Radix Fici Hirtae) originates from the dry root of Ficus hirta (Moraceae), which is widely known as a medical and edible plant distributed in South China. As the increasing demand for Wuzhimaotao, the wild F. hirta has been extremely reduced during the past years. It is urgent to protect and rationally develop the wild resources of F. hirta for its sustainable utilization. However, a lack of genetic background of F. hirta makes it difficult to plan conservation and breeding strategies for this medical plant. In the present study, a total of 414 accessions of F. hirta from 7 provinces in southern China were evaluated for the population genetics using 9 polymorphic SSR markers. Results A mean of 17.1 alleles per locus was observed. The expected heterozygosity (He) varied from 0.142 to 0.861 (mean = 0.706) in nine SSR loci. High genetic diversity (H e = 0.706, ranged from 0.613 to 0.755) and low genetic differentiation among populations (G’ ST = 0.147) were revealed at population level. In addition, analysis of molecular variance (AMOVA) indicated that the principal molecular variance existed within populations (96.2%) was significantly higher than that among populations (3.8%). Meanwhile, the three kinds of clustering methods analysis (STRUCTURE, PCoA and UPGMA) suggested that the sampled populations were clustered into two main genetic groups (K = 2). Mantel test showed a significant correlation between geographic and genetic distance among populations (R 2 = 0.281, P

This paper is devoted to the issue of computationally efficient and robust nonlinear model predictive control (NMPC) for ship dynamic positioning (DP) systems subjected to input constraints and unknown environmental disturbances. The Laguerre functions, typically applied to the linear systems, are introduced to the constrained NMPC design of the nonlinear DP system to reduce the computational burden. The unscented Kalman filter is adopted to estimate the unknown disturbances and states; thus, the disturbance estimates are utilized as the cancellation signal to achieve robust offset-free control. Simulations of the proposed Laguerre function-based NMPC scheme are implemented and compared with the performance of typical Laguerre function-based linear model predictive control (LMPC) for the DP system. Simulation results well demonstrate the effectiveness, robustness and superiority of the proposed controller.

The temporal graph can represent a temporal relationship widely used in compound synthesis analysis, biological gene analysis, etc. However, the temporal graph would embody vertex updates frequently, high time resolution, and not enumerated rules. The construction and update of some temporal graph models are too dependent on the graph operation sequence, which leads to a lack of an effective model. Simultaneously, the temporal subgraph clustering of the temporal graph with frequent updating for the lack of an effective model leads to low accuracy. Therefore, we propose an efficient and frequently updated temporal graph model as vertex driven and corresponding temporal subgraph clustering method. First, we propose a temporal graph construction algorithm and set two thresholds to divide the temporal graph on a timeline to obtain temporal subgraphs. Next, an enhancement strategy based on the sliding window is proposed to accelerate the construction process. Third, we offer a double-standard temporal subgraph clustering method based on community comparison and temporal distance. The temporal subgraph can be effectively distinguished in temporal and structure dimensions. Lastly, experimental results on both real and synthetic datasets show that the temporal graph model proposed in this work can reduce the time overhead of construction compared to other existing models. The cluster method improves the clustering accuracy of temporal subgraphs. The clustering results show through the hierarchical clustering at the same time.

Neoadjuvant chemoradiotherapy (NCRT) plus radical esophagectomy is currently the standard treatment for resectable esophageal or gastroesophageal junction (GEJ) carcinoma. The aim of this study is to evaluate the efficacy and safety of neoadjuvant immunotherapy in resectable esophageal or GEJ carcinoma. Prospective clinical trials investigating efficacy and/or safety of neoadjuvant immunotherapy with immune checkpoint inhibitors (ICIs) followed by radical esophagectomy in patients with newly diagnosed resectable esophageal or GEJ carcinoma were identified through literature search. Quality assessment was performed by using the Newcastle–Ottawa scale. Preliminary treatment outcomes of pathologically complete response (pCR, ypT0N0) and grade 3-4 adverse effects (AEs) were pooled together and then compared with standard NCRT of the historical control CROSS study by Chi-square (χ2) test. A two-sided P value < 0.05 was considered statistically significant. A total of 17 eligible non-randomized trials with 455 participants were included into analysis. The most common primary endpoint was pCR (n = 7, 41%), and the median sample size and follow-up period was 23 patients and 7.9 months, respectively. For patients receiving neoadjuvant immunotherapy, the overall pCR, R0 resection, and grade 3-4 AE rates were 33.2%, 95.5%, and 35.1%, respectively. For esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), neoadjuvant immunochemoradiotherapy showed no significant improvement in pCR rate than NCRT (ESCC, 50% vs 48.7%, P = 0.9; EAC, 32.6% vs 23.1%, P = 0.22). Grade 3-4 AEs were the most common in patients with neoadjuvant immunochemoradiotherapy, significantly higher than immunochemotherapy (46.7% vs 32.8%, P = 0.04) and NCRT (46.7% vs 18.1%, P < 0.0001). In conclusion, for patients with resectable esophageal or GEJ carcinoma, the addition of ICIs to standard NCRT could not improve pCR rate in both ESCC and EAC, but significantly increased the risk of severe AEs. Large-scale phase 3 randomized trials were urgently needed to further confirm the survival benefit and safety profile of neoadjuvant immunotherapy.

IntroductionSoil ammonia oxidation, which acts as the first and rate-limiting step of nitrification, is driven by ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea (AOA) and complete ammonia oxidizer (comammox, amoA gene of clade-A and clade-B). Straw returning, widely used ecological technology in China, is an effective measure for promoting straw decomposition and soil nutrient cycling when combined with earthworm addition. However, the effects of straw returning combined with earthworm addition on soil ammonia oxidizers remain poorly understood.MethodsA 2-year plot experiment was conducted with 5 treatments: no fertilizer (CK); regular fertilization (RT); straw returning (SR); earthworm addition (W); straw returning + earthworm addition (SRW). The AOA, AOB, comammox clade-A and clade-B community microbial diversities and structures were investigated by high-throughput sequencing.ResultsThe results showed that (1) compared to RT treatment, W, SR, and SRW treatments all significantly increased the richness of AOA and comammox clade-A and clade-B (p

PurposeDiabetic heart failure (DHF) or cardiomyopathy is a common complication of diabetes; however, the underlying mechanism is not clear. In the present study, the authors searched for differentially expressed genes associated with DHF and the molecular types of immune cells based on bioinformatics.MethodsThe RNA expression dataset of DHF was obtained from the NCBI Gene Expression Omnibus (GEO) database. After preprocessing the data, the differentially expressed genes (DEGs) between the DHF group and the non-diabetic heart failure (NHF) group were screened and intersected with immune-related genes (IRGs) in the ImmPort database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID tool. The ssGSEA algorithm was used to evaluate immune infiltration of the heart tissue in each group. In addition, the protein-protein interaction (PPI) network and miRNA-mRNA network were constructed using the STRING online website and Cytoscape program. Finally, validation analysis was performed using animal models.ResultsEight immune-related core genes were identified. GO and KEGG showed that core genes were mainly enriched in angiogenesis and cytokine-cytokine receptor interaction. Immune infiltration results showed that activated dendritic cells, central memory CD4 T cells, central memory CD8 T cells, myeloid-derived suppressor cells (MDSCs), neutrophils, and regulatory T cells may be involved in DHF. Neutrophils may play a key role in the pathogenesis of HF in diabetes.ConclusionImmune-related core genes and immune infiltrating cells provide a new perspective on the pathogenesis of DHF.

Neurosyphilis is caused by Treponema pallidum invading the central nervous system, of which the incidence is increasing worldwide. Due to its variable clinical manifestations, diagnosis of neurosyphilis remains challenging, especially the asymptomatic form. This review focuses on recent advances in neurosyphilis, including epidemiology, clinical manifestations, laboratory findings, comorbidities, diagnosis, treatment, prognosis, and basic research. The expansion of men who have sex with men and the infection of human immunodeficiency virus mainly accounted for the increasing incidence of neurosyphilis. The rate of some historically described forms of neurosyphilis in the pre-antibiotic era declined significantly; atypical features are more prevalent. Neurosyphilis, regarded as a great mimicker for neuro-ophthalmic, audio-vestibular, and psychiatric disorders, often presents concomitantly with other diseases, including metabolic disorders. Studies on long non-coding RNAs, miRNAs, chemokines, and metabolites in peripheral blood and cerebrospinal fluid may facilitate exploring the pathogenesis and identifying novel biomarkers of neurosyphilis. The drug resistance of Treponema pallidum to penicillin has not been reported; ceftriaxone was proposed to be more effective than penicillin, whereas few randomized controlled trials supported this view. This study may pave the way for further research, especially the diagnosis and treatment of neurosyphilis.

BackgroundIn recent years, the prevalence of type 2 diabetes mellitus (T2DM) has increased annually. The major complication of T2DM is cardiovascular disease (CVD). CVD is the main cause of death in T2DM patients, particularly those with comorbid acute coronary syndrome (ACS). Although risk prediction models using multivariate logistic regression are available to assess the probability of new-onset ACS development in T2DM patients, none have been established using machine learning (ML).MethodsBetween January 2019 and January 2020, we enrolled 521 T2DM patients with new-onset ACS or no ACS from our institution's medical information recording system and divided them into a training dataset and a testing dataset. Seven ML algorithms were used to establish models to assess the probability of ACS coupled with 5-cross validation.ResultsWe established a nomogram to assess the probability of newly diagnosed ACS in T2DM patients with an area under the curve (AUC) of 0.80 in the testing dataset and identified some key features: family history of CVD, history of smoking and drinking, aspartate aminotransferase level, age, neutrophil count, and Killip grade, which accelerated the development of ACS in patients with T2DM. The AUC values of the seven ML models were 0.70–0.96, and random forest model had the best performance (accuracy, 0.89; AUC, 0.96; recall, 0.83; precision, 0.91; F1 score, 0.87).ConclusionML algorithms, especially random forest model (AUC, 0.961), had higher performance than conventional logistic regression (AUC, 0.801) for assessing new-onset ACS probability in T2DM patients with excellent clinical and diagnostic value.

Chemical fertilizer reduction combined with novel and green agricultural inputs has become an important practice to improve microecological health in agricultural production. Given the close linkages between rhizosphere processes and plant nutrition and productivity, understanding how fertilization impacts this critical zone is highly important for optimizing plant–soil interactions and crop fitness for agricultural sustainability. Here, by using a pot experimental system, we demonstrated that nitrogen fertilizer reduction and microbial agent application promoted plant fitness and altered the microbial community structure in the rhizosphere soil with the following treatments: no fertilization, CK; conventional chemical fertilizer, CF; 30% reduced nitrogen fertilizer, N; 30% reduced nitrogen fertilizer with pure γ-PGA, PGA; 30% reduced nitrogen fertilizer with Bacillus subtilis A-5, A5; 30% reduced nitrogen fertilizer with γ-PGA fermentation broth, FJY. The PGA, A5, and FJY treatments all significantly promoted crop growth, and the FJY treatment showed the strongest positive effect on Chinese cabbage yield (26,385.09 kg/hm2) (P < 0.05). Microbial agents affected the α diversity of the rhizosphere bacterial community; the addition of B. subtilis A-5 (A5 and FJY treatments) significantly affected rhizospheric bacterial community structure. Urease activity and soil pH were the key factors affecting bacterial community structure and composition. The FJY treatment seemed to influence the relative abundances of important bacterial taxa related to metabolite degradation, predation, and nitrogen cycling. This discovery provides insight into the mechanism underlying the effects of microbial agent inputs on rhizosphere microbial community assembly and highlights a promising direction for the manipulation of the rhizosphere microbiome to yield beneficial outcomes.

The intermittent fasting regimen (IFR) has been certified as an effective strategy for improving metabolism. But the underlying mechanism is still obscure. Beige induction in white adipose tissue (WAT) by IFR may account for this. It has been demonstrated that the erupting of pregnancy zone protein (PZP) from the liver coincides with membrane translocation of grp78 in brown adipocytes during IFR to activate brown adipose tissue (BAT), which may partly explain the metabolic benefits of IFR. Liver-derived PZP appears to be responsible for all metabolic regulatory functions; the effect of boosting energy expenditure disappeared in liver-deficient mice. To verify whether any liver-specific modification was essential for functional PZP, we used the PZP adipose tissue-specific overexpression mice model (PZP TG). We found that the metabolic disorders induced by high-fat diet were improved in PZP TG mice under IFR. Additionally, in addition to the activation of BAT, UCP1 protein and angiogenesis were increased in WAT, as well as the expression of genes associated with glucose utilization. These results demonstrate that PZP fat-specific TG increased the energy conversion of WAT, indicating that WAT may be another direct target for PZP during IFR.

Summary: The deleterious potential to generate oxidative stress is a fundamental challenge to metabolism. The oxidative stress response transcription factor, SKN-1/NRF2, can sense and respond to changes in metabolic state, although the mechanism and consequences of this remain unknown. Here, we performed a genetic screen in C. elegans targeting amino acid catabolism and identified multiple metabolic pathways as regulators of SKN-1 activity. We found that knockdown of the conserved amidohydrolase T12A2.1/amdh-1 activates a unique subset of SKN-1 regulated genes. Interestingly, this transcriptional program is independent of canonical P38-MAPK signaling components but requires ELT-3, NHR-49 and MDT-15. This activation of SKN-1 is dependent on upstream histidine catabolism genes HALY-1 and Y51H4A.7/UROC-1 and may occur through accumulation of a catabolite, 4-imidazolone-5-propanoate. Activating SKN-1 results in increased oxidative stress resistance but decreased survival to heat stress. Together, our data suggest that SKN-1 acts downstream of key catabolic pathways to influence physiology and stress resistance.

Abstract The diversity and community structure of soil fungi play an important role in crop production and ecosystem balance, especially in paddy-upland vegetable field systems. High-throughput sequencing was used to study changes in the soil fungal community structure and function in paddy-upland vegetable field systems. The results showed that compared with traditional planting, the diversity and community structure of soil fungi were changed by the combination of flooding and drought, the Shannon index increased by 11.07%, and the proportion of the dominant species, Mortierella, decreased by 22.74%. Soil available nitrogen, total phosphorus, available phosphorus, total nitrogen and organic matter played a leading role in the initial stage of the experiment, while the dominant factor changed to total potassium 3 years later and then to soil pH and water content 6 years later. FUNGuild analysis showed that the proportion of three independent trophic modes of soil fungi were increased by the combined flooded-drought model, and there were multiple interaction factors, For example, nutrient supply, pH and planting pattern. This study showed that soil fertility, crop yield and economic benefits were better than the traditional model after three years of planting and breeding. The longer the time, the better the effect.

In the medical field, with the increasing number of medical images, medical image classification has become a hot spot. The convolutional neural network, a technology that can process more images and extract more accurate features with nonlinear models, has been widely used in this field. However, the classification process with model training with existing medical images needs a large number of samples, and the operation involves complex parameter computations, which puts forward higher requirements for users. Therefore, we propose a scheme for flexible privacy-preserving outsourcing medical image classification based on a convolutional neural network to the cloud. In this paper, three servers on the cloud platform can train the model with images from users, but they cannot obtain complete information on model parameters and user input. In practice, the scheme can not only reduce the computation and storage burdens on the user side but also ensure the security and efficiency of the system, which can be confirmed through the implementation of the experiment.

Skyline query is very useful in decision-making systems, WSN and so on. As a variation of skyline query, skyline-join query can return the results from multiple datasets. However, incomplete datasets are a frequent phenomenon due to the widespread use of automated information extraction and aggregation. Existing methods for dealing with incomplete data, such as probability, data padding can solve the problem, but cannot effectively reflect the real situation and are lack of integrality. Therefore, in this paper, in order to reflect the situation more accuracy and more user-centric, we research the problem of skyline-join query over incomplete datasets with crowdsourcing, named CrowdSJ. The crowdsourcing-based skyline-join query processing problem over incomplete datasets is divided into two situations. One is the skyline-join query only involves the unknown crowdsourcing attribute and the join attribute, named Partial Skyline-Join with Crowdsourcing (PSJCrowd). The other one is the skyline-join query involves all the attributes, named All Skyline-Join with Crowdsourcing (ASJCrowd). For PSJCrowd, first, we filter the known dataset. Then, we present the level-preference-tree-index, and propose the partial skyline-join with crowdsourcing algorithm. For ASJCrowd, first, we filter the known dataset too. Second, we build a level-preference-tree-index based on the known attributes of the incomplete dataset. Third, we propose the skyline-join with crowdsourcing on single dataset algorithm, CrowdSJ-single, to filter the dataset containing unknown attributes. Then, we build a global level-preference-tree-index based on the known attributes of the incomplete dataset and the complete dataset. We propose the skyline-join with crowdsourcing on multiple datasets algorithm, CrowdSJ-multiple. We filter the linked tuples based on the global level-preference-tree-index and the results of each round of crowdsourcing. Numerous experiments on synthetic and real datasets demonstrate that our algorithms are efficient and effective.

Abstract Background Intractable, mechanical hemolytic anemia (IMHA) is a rare catastrophic complication following mitral valve surgery. We analyzed patient characteristics and IMHA management by reoperations after mitral valve surgery. Methods We collected medical records from mitral valve patients requiring reoperation due to IMHA. Inclusion criteria: hemoglobin

Modeling individual and crowd behaviors is the basis for evacuation research, which is essential to reduce casualties under emergency conditions in large venues. This paper focuses on the pedestrian evacuation of large-scale venues with multiple exits, and proposes an improved pedestrian evacuation model which uses a novel dual-strategy adaptive particle swarm optimization algorithm with affinity propagation clustering. Compared with the traditional models, the proposed model is demonstrated to have a better performance in simulating pedestrians' herding behavior in panic situations, especially when not familiar with the environment, as i) individual heterogeneity is considered and affinity propagation clustering is used in population division to simulate the process of people spontaneously gathering into swarms; ii) A dual-strategy updating scheme is designed to balance the cognition difference between the leaders and the agents in the swarm; and iii) Adaptive control of parameters is used to simulate the human-surrounding interaction and psychological fluctuates when the evacuees are moving towards exits. Numerical examples, which simulated the evacuation of a rectangle venue with multiple exits, demonstrate the effectiveness and practicality of the proposed model. Moreover, the influences of pedestrian velocity, characteristics of exits, and leader movement on evacuation are analyzed. Experimental results show that the movement of leaders is different from other evacuees and the parameters of doors, such as width, quantity, and location all have a great influence on evacuation time.

Objective: The main aim of this study was to investigate the prevalence and risk factors of adult self-reported allergic rhinitis and asthma in plain lands and hilly areas of Shenmu City in China, and analyze the differences between regions.Methods: The multi-stage stratified random sampling was applied in a cross-sectional survey of adult residents in Shenmu City, from September to December 2019. The unconditional logistic regression analysis was used to screen the influence factors of allergic rhinitis and asthma.Results: 4,706 adults participated in the survey, and 99% (4,655 in 4,706) completed the questionnaires. The prevalence of allergic rhinitis was 25.4%, and the prevalence of asthma was 9.4%. The prevalence of the allergic rhinitis without asthma, asthma without allergic rhinitis, and the combined allergic rhinitis with asthma were 18.9, 2.9, and 6.5%, respectively. The prevalence of allergic rhinitis and asthma existed regional differences. The prevalence of adult self-reported allergic rhinitis was 41.5% in plain lands areas and 22.1% in hilly areas. The prevalence of adult self-reported asthma was 12.8% in plain lands and 8.8% in hilly areas. The prevalence of allergic rhinitis and asthma existed seasonal differences, with the highest prevalence from July to September. The analysis of risk factors showed that higher education [middle and high school (OR 1.72, 95%CI 1.42–2.07); college and above (OR 2.67, 95%CI 1.99–3.59)], comorbidities of other allergic diseases (OR 3.90, 95%CI 3.23–4.70), family history of allergies (OR 2.89, 95%CI 2.36–3.53), and plain lands areas (OR 2.51, 95%CI 2.06–3.05) were the risk factors for the allergic rhinitis without asthma. Aging [40–49 years old (OR 4.29, 95%CI 1.02–18.13); 50–59 years old (OR 5.89, 95%CI 1.40–24.76); ≥60 years old: (OR 6.14, 95%CI 1.41–26.71)], never-smokers (OR 1.66, 95%CI 0.99–2.80), comorbidities of other allergic disorders (OR 2.17, 95%CI 1.42–3.32), and family history of allergies (OR 2.20, 95%CI 1.40–3.47) were the risk factors for the asthma without allergic rhinitis. Advanced age [30–39 years (OR 2.16, 95%CI 1.23–3.82); 40–49 years (OR 2.86, 95%CI 1.56 to 5.25); 50–59 years (OR 2.95, 95%CI 1.58–5.51); ≥60 years old (OR 2.27, 95%CI 1.09–4.72)], higher education [middle and high school (OR 2.23, 95%CI 1.62–3.07); college and above (OR 4.28, 95%CI 2.72–6.74)], non-agricultural workers (OR 1.70, 95%CI 1.18–2.43),never-smokers (OR 2.26, 95%CI 1.51–3.39), comorbidities of other allergic diseases (OR 4.45, 95%CI 3.37–5.88), family history of allergies (OR 5.27, 95%CI 3.98–6.97), and plain lands areas (OR 2.07, 95%CI 1.51–2.86) were the risk factors for the combined allergic rhinitis with asthma.Conclusions: The prevalence of allergic rhinitis and asthma in Shenmu City was relatively high, with regional differences. Genetic and environmental factors were the important risk factors associated with allergic rhinitis and asthma. Our research would provide data support for preventing and controlling allergic rhinitis and asthma in this region in the future, and appropriate prevention and control programs should be formulated according to the characteristics of different regions.

Background: Clinical amyopathic dermatomyositis (CADM) represents a subtype of 5–20% of patients with dermatomyositis (DM), which can be categorized into amyopathic dermatomyositis (ADM) and hypomyopathic dermatomyositis (HDM). The characteristics of patients with CADM are still limited in English literature.Objective: To investigate clinical features, cutaneous findings, diagnostic accuracy, and treatment regimen of CADM patients.Methods: Sixty-four patients diagnosed with CADM at Peking Union Medical College Hospital by dermatologists were retrospectively analyzed. Data were recorded in the electronic database at each offline clinical consultation and directly extracted from medical records. 2017 EULAR/ACR criteria for idiopathic inflammatory myositis (IIM) classification was used to identify and classify patients with CADM. Published studies were searched to extract relevant data of CADM patients.Results: This cohort included 38 ADM patients and 26 HDM patients. 2017 EULAR/ACR criteria classified 67.2% of patients with CADM into probable or definite DM. Antimalarials were given to a majority of CADM patients (72.6%, n = 45). However, 68.8% (31 out of 45) required at least one aggressive agent combined with hydroxychloroquine due to insufficient response or side effects. The median of systemic treatments in HDM was significantly higher than ADM (p = 0.007). The number of ADM patients using antimalarials as monotherapy was significantly higher than that of HDM patients (p = 0.031), while the number of HDM patients receiving steroids combined with immunosuppressants was significantly higher (p = 0.025). The median of Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) score improvement was 11.5 and 10.5 for ADM and HDM after a median follow-up of 31.5 and 32.5 months, respectively. Six patients with normal muscle strength developed muscle weakness after a median of 10.5 months (IQR 9-13), and elevated inflammatory markers at initial visit might indicate their muscle weakness development.Conclusions: 32.8% of patients may be overlooked using the three skin variables of 2017 EULAR/ACR criteria. The response rate to single hydroxychloroquine in our cohort was 68.8%. Detailed treatment modalities were different among ADM and HDM. Long-term monitoring for the development of myositis in patients with CADM, especially those with elevated inflammatory markers at initial visit, may be warranted.

Removal of lake sediment has been shown to be an effective method for lake restoration. High phosphorus (P) content makes it possible for lake sediment to provide fertility for agricultural production. However, little research has focused on the responses of the soil-phosphorus-related microbial community to the sediment-derived fertilizer enriched in phosphorus content. The phoD-harboring gene, important to the global phosphorus cycle, encodes alkaline phosphatase hydrolyzing organic P in soil. Accordingly, a plot experiment was performed to compare the effects of four different fertilization treatments—no-fertilizer control (CK), 50% chemical fertilization with compressed sediment (CS), 50% chemical fertilization with original lake sediment (S), and conventional chemical fertilization treatment (CT)—on the phoD gene community using QPCR and high-throughput sequencing analysis. Relationships among soil physicochemical properties, phoD-harboring microbial community abundance and composition were also evaluated. Results showed that compared to CT, CS significantly increased soil organic matter (SOM) content by 20.29%, and S enhanced the humus content by 20.75% (p < 0.05). There was no significant influence on phoD gene microbial community richness (Chao1 and Sobs indexes) and diversity (Shannon index) between all treatments. The CS treatment significantly altered the phoD community structure and enhanced the Chinese cabbage yield by 40.19% (p < 0.05). Pearson analysis showed that phoD gene abundance (copy number) had significant and negative relationships with SOM, total nitrogen (TN), total phosphorus (TP), available nitrogen (AN), available phosphorus (AP), and the Chao1 index. Redundancy analysis showed that shifts in the phoD community structure were related to soil physicochemical properties (SOM, TN, TP, AN, AP, and humus) rather than soil pH. In conclusion, the compressed sediment can be used in farmland since it optimizes the phoD-harboring microbial community abundance, composition, and structure, and thus significantly increases the Chinese cabbage yield.

Abstract Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter‐organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant induction during the refeeding stage of IF. Further, loss of function studies and protein therapeutic experiment in mice revealed that PZP promotes diet‐induced thermogenesis through activating brown adipose tissue (BAT). Mechanistically, circulating PZP can bind to cell surface glucose‐regulated protein of 78 kDa (GRP78) to promote uncoupling protein 1 (UCP1) expression via a p38 MAPK‐ATF2 signaling pathway in BAT. These studies illuminate a systemic regulation in which the IF promotes BAT thermogenesis through the endocrinal system and provide a novel potential target for treating obesity and related disorders.

Psoriasis is a chronic and recurrent immune-related skin disease that often causes disfigurement and disability. Due to the visibility of lesions in patients and inadequate understanding of dermatology knowledge in the general public, patients with psoriasis often suffer from stigma in their daily lives, which has adverse effects on their mental health, quality of life, and therapeutic responses. This review summarized the frequently used questionnaires and scales to evaluate stigmatization in patients with psoriasis, and recent advances on this topic. Feelings of Stigmatization Questionnaire, Questionnaire on Experience with Skin Complaints, and 6-item Stigmatization Scale have been commonly used. The relationship between sociodemographic characteristics, disease-related variables, psychiatric disorders, quality of life, and stigmatization in patients with psoriasis has been thoroughly investigated with these questionnaires. Managing the stigmatization in patients with psoriasis needs cooperation among policymakers, dermatologists, psychologists, psychiatrists, researchers, and patients. Further studies can concentrate more on these existing topics, as well as other topics, including predictors of perceived stigmatization, stigmatization from non-patient groups, influence of biologics on stigmatization, and methods of coping with stigmatization.

Polycystic ovary syndrome (PCOS) is a common endocrine disease accompanied by energetic metabolic imbalance. Because the etiology of PCOS is complex and remains unclear, there is no effective and specific treatment for PCOS. It is often accompanied by various metabolic disorders such as obesity, insulin resistances, and others. Activated brown adipose tissue (BAT) consumes excess energy via thermogenesis, which has positive effects on energy metabolism. Our previous research and that of others indicates that BAT activity is decreased in PCOS patients, and exogenous BAT transplantation can improve PCOS rodents. Notably however, it is difficult to apply this therapeutic strategy in clinical practice. Therapeutic strategies of enhancing endogenous BAT activity and restoring whole-body endocrine homeostasis may be more meaningful for PCOS treatment. In the current study, the dehydroepiandrosterone-induced PCOS rat was exposed to low temperature for 20 days. The results show that cold treatment could reverse acyclicity of the estrous cycle and reduce circulating testosterone and luteinizing hormone in PCOS rats by activating endogenous BAT. It also significantly reduced the expression of steroidogenic enzymes as well as inflammatory factors in the ovaries of PCOS rats. Histological investigations revealed that cold treatment could significantly reduce ovary cystic follicles and increase corpus luteum, indicating that ovulation was recovered to a normal level. Concordant with these results, cold treatment also improved fertility in PCOS rats. Collectively, these findings suggest that cold treatment could be a novel therapeutic strategy for PCOS.

Significance: Heart failure, a disease with extremely high incidence, is closely associated with inflammation and oxidative stress. The Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway plays an important role in the occurrence and development of heart failure. Recent advances: Previous studies have shown that TLR4/NF-κB causes heart failure by inducing oxidative stress and inflammation; damaging the endothelia; promoting fibrosis; and inducing myocardial hypertrophy, apoptosis, pyroptosis, and autophagy. Critical issues: Understanding the pathogenesis of heart failure is essential for the treatment of this disease. In this review, we outline the mechanisms underlying TLR4/NF-κB pathway-mediated heart failure and discuss drugs that alleviate heart failure by regulating the TLR4/NF-κB pathway. Future directions: During TLR4/NF-κB overactivation, interventions targeting specific receptor antagonists may effectively alleviate heart failure, thus providing a basis for the development of new anti-heart failure drugs.

Existing preparation methods for microdroplets usually require offline measurements to characterize single microdroplets. Here, we report an optical method used to facilitate the controllable formation and real-time characterization of single microdroplets. The optical tweezer technique was used to capture and form a microdroplet at the center of the trap. The controllable growth and real-time characterization of the microdroplet was realized, respectively, by adjusting experimental parameters and by resolving the Raman spectra by fitting Mie scattering to the spike positions of the spectra during the controllable growth of microdroplets. The proposed method can be potentially applied in optical microlenses and virus detection.

The application of biogas slurry and chemical fertilizer in paddy fields can be a practical method to reduce the environmental risk and utilize the nutrients of biogas slurry. The responses of bacterial and fungal communities to the application of biogas slurry and chemical fertilizer are important reflections of the quality of the ecological environment. In this study, based on a 3-year field experiment with different ratios of biogas slurry and chemical fertilizer (applying the same pure nitrogen amount), the Illumina MiSeq platform was used to investigate the bacterial and fungal community diversity and composition in paddy soil. Our results revealed that compared with the observations under regular chemical fertilization, on the basis of stable paddy yield, the application of biogas slurry combined with chemical fertilizer significantly enhanced the soil nutrient availability and bacterial community diversity and reduced the fungal community diversity. Dissolved organic carbon (DOC), DOC/SOC (soil organic carbon), available nitrogen (AN) and available phosphorus (AP) were positively correlated with the bacterial community diversity, but no soil property was significantly associated with the fungal community. The bacterial community was primarily driven by the application of biogas slurry combined with chemical fertilizer (40.78%), while the fungal community was almost equally affected by the addition of pure biogas slurry, chemical fertilizer and biogas slurry combined with chemical fertilizer (25.65–28.72%). Biogas slurry combined with chemical fertilizer significantly enriched Proteobacteria, Acidobacteria, Planctomycetes, Rokubacteria, and Ascomycota and depleted Chloroflexi, Bacteroidetes, Crenarchaeota, Basidiomycota, and Glomeromycota. The observation of the alteration of some bacteria- and fungus-specific taxa provides insights for the proper application of biogas slurry combined with chemical fertilizer, which has the potential to promote crop growth and inhibit pathogens.

With the recent growth and commercialization of cloud computing, outsourcing computation has become one of the most important cloud services, which allows the resource-constrained clients to efficiently perform large-scale computation in a pay-per-use manner. Meanwhile, outsourcing large scale computing problems and computationally intensive applications to the cloud has become prevalent in the science and engineering computing community. As important fundamental operations, large-scale matrix multiplication computation (MMC), matrix inversion computation (MIC), and matrix determinant computation (MDC) have been frequently used. In this paper, we present three new algorithms to enable secure, verifiable, and efficient outsourcing of MMC, MIC, and MDC operations to a cloud that may be potentially malicious. The main idea behind our algorithms is a novel matrix encryption/decryption method utilizing consecutive and sparse unimodular matrix transformations. Compared to previous works, this versatile technique can be applied to many matrix operations while achieving a good balance between security and efficiency. First, the proposed algorithms provide robust confidentiality by concealing the local information of the entries in the input matrices. Besides, they also protect the statistic information of the original matrix. Moreover, these algorithms are highly efficient. Our theoretical analysis indicates that the proposed algorithms reduce the time overhead on the client side from O(n2.3728639) to O(n2). Finally, the extensive experimental evaluations demonstrate the practical efficiency and effectiveness of our algorithms.

To achieve self-healing in the smart grid, the microgrid can be switched to the islanded state for effective autonomy in the event of disasters or attacks. Based on the data collected by smart meters, the microgrid can support an efficient energy scheduling strategy to guide both energy suppliers and consumers so that electricity can be used efficiently. Significant research efforts have been carried out regarding energy scheduling. Nonetheless, the majority of existing strategies failed to prioritize consumers. In fact, the energy consumption order of different users should be distinguished from each other in islanded microgrids with limited energy supply, meaning that they have different priority. To address this issue, in this paper we propose an energy scheduling strategy with priority within islanded microgrids (E2SP) to ensure that consumers with higher priority can obtain energy supply in an earlier order. To be specific, we solve the problem of deriving the amount of power each energy supplier should supply to each consumer via using the Goal Programming Model with positive and negative deviation variables. To evaluate the validity of E2SP, we conduct comprehensive experiments in five cases. The results show that the E2SP strategy can effectively ensure that energy is supplied to consumers in order of priority. In addition, we introduce the dissatisfaction degree as a metric to measure the effectiveness of our strategy. Simulation results show that our E2SP strategy has a lower dissatisfaction degree compared with the scheduling strategy without considering priority, indicating that our E2SP strategy is more effective.

Neuropeptide Y (NPY) signaling plays an essential role in gating the pruritic afferent information in the spinal cord. Recent studies revealed that the aging process down-regulated the expression of NPY in the central nervous system. We propose that the lack of spinal NPY may be involved in certain types of pruritus in the elderly population. This study was designed to investigate the role of NPY in aging-induced itch using the senile mouse model. The expression of NPY in the spinal dorsal horn was compared between young (2 months old) and aged (24 months old) mice. Western blotting and immunohistochemistry showed that the expression of NPY was significantly reduced in the spinal dorsal horn in aged mice. In addition, a neuronal maker of apoptosis, TUNEL, was detected in the NPY positive neurons only in the aged spinal cord. Behavioral assay indicated that light mechanical stimulus evoked significantly more scratching in the aged than in the young mice, whereas chemical-evoked itch and pain-related behaviors were not altered. Intrathecal injection of either NPY or LP-NPY, a NPY receptor 1 (NPY1R) agonist, significantly alleviated the mechanically evoked itch in aged mice without altering the responses to chemical pruritogens. Our study suggested that downregulation of spinal NPY in the aged mice might play a role in the higher incidence of the mechanically evoked itch than that in the young mice. Therapies targeting the NPY system might serve as a potential strategy for alleviating the pruritic symptoms among the elderly population.

Circular RNAs (circRNAs) are newly discovered RNAs with covalently looped structures. Due to their resistance to RNAase degradation and tissue-specific expression, circRNAs are expected to be potential biomarkers in early diagnosis and target treatment of many diseases. However, the role of circRNAs in melanoma still needs to be systematically reviewed for better understanding and further research. Based on published articles in PubMed, Embase, Cochrane Library, and Web of Science database, we systematically reviewed the implications and recent advances of circRNAs in melanoma, focusing on function, mechanism, and correlation with melanoma progression. According to inclusion and exclusion criteria, a total of 19 articles were finally included in this systematic review. Of the 19 studies, 17 used human samples, including melanoma tissues (n = 16) and blood serum of patients with melanoma (n = 1). The sample size of the study group ranged from 20 to 105 based on the reported data. Several studies explored the association between circRNAs and clinicopathological characteristics. circRNA dysregulation was commonly observed in melanoma patients. circRNAs function in melanoma by miRNA sponging and interaction with RNA binding proteins (RBP), ultimately controlling several important signaling pathways and cancer-related cellular processes, including proliferation, migration, invasion, metastasis, apoptosis, and glucose metabolism. circRNA expression could be associated with prognostic factors and drug responses, consolidating the potential clinical value in melanoma. Herein, we clarified the functional, prognostic, and predictive roles of circRNAs in melanoma in this systematic review, providing future directions for studies on melanoma-associated circRNAs.

With the increasing popularity of renewable energy, energy storage systems (ESSs) have now been used as an essential way to reduce energy bills and mitigate the impact of the uncertainty of renewable generators on the energy network. However, the high investment cost of ESS limits its application. This article proposes the concept of shared ESS (Shared-ESS) for microgrid owner/operator and applies it to the economic optimal dispatch of a microgrid cluster. In addition to the energy storage, the microgrids can achieve the peer-to-peer (P2P) transaction among each other with the use of the Shared-ESS, which significantly improves the energy utilization efficiency. The numerical analysis shows that the Shared-ESS can significantly reduce the energy bills of microgrid owner/operator, shift the usage of energy during peak time, and facilitate the renewable energy consumption.

IntroductionMelanoma is a severe skin cancer that metastasizes quickly. Bibliometric analysis can quantify hotspots of research interest. Google Trends can provide information to address public concerns.MethodsThe top 15 most frequently cited articles on melanoma each year from 2015 to 2019, according to annual citations, were retrieved from the Web of Science database. Original articles, reviews, and research letters were included in this research. For the Google Trends analysis, the topic “Melanoma” was selected as the keyword. Online search data from 2004 to 2019 were collected. Four countries (New Zealand, Australia, the United States and the United Kingdom) were selected for seasonal analysis. Annual trends in relative search volume and seasonal variation were analyzed, and the top related topics and rising related topics were also selected and analyzed.ResultsThe top 15 most frequently cited articles each year were all original articles that focused on immunotherapy (n=8), omics (n=5), and the microbiome (n=2). The average relative search volume remained relatively stable across the years. The seasonal variation analysis revealed that the peak appeared in summer, and the valley appeared in winter. The diseases associated with or manifestations of melanoma, treatment options, risk factors, diagnostic tools, and prognosis were the topics in which the public was most interested. Most of the topics revealed by bibliometric and Google Trends analyses were consistent, with the exception of issues related to the molecular biology of melanoma.ConclusionThis study revealed the trends in research interest and public interest in melanoma, which may pave the way for further research.

IntroductionAcral melanoma (AM) has different biological characteristics from cutaneous melanoma. Although systemic therapeutic strategies for advanced AM resemble those for advanced cutaneous melanoma, the evidence of the clinical use of immune checkpoint inhibitors (ICIs) for AM is still inadequate. We aimed to systematically analyze the therapeutic effects and safety profile of ICI treatments in advanced AM.MethodsThis systematic review was conducted in line with a previously registered protocol. Three electronic databases, conference abstracts, clinical trial registers, and reference lists of included articles were searched for eligible studies. The primary outcomes were therapeutic effects, and the secondary outcomes were the safety profiles.ResultsThis systematic review included six studies investigating anti-CTLA-4 immunotherapy, 12 studies investigating anti-PD-1 immunotherapy, one study investigating the combination therapy of anti-CTLA-4 and anti-PD-1, and one study investigating anti-PD-1 immunotherapy in combination with radiotherapy. In most studies investigating ipilimumab, the anti-CTLA-4 antibody, the objective response rate ranged from 11.4 to 25%, the median progression-free survival ranged from 2.1 to 6.7 months, and the median overall survival was more than 7.16 months. For studies discussing anti-PD-1 immunotherapy with nivolumab, pembrolizumab, or JS001, the objective response rate ranged from 14 to 42.9%, the median progression-free survival ranged from 3.2 to 9.2 months, and the median overall survival was more than 14 months. The combination therapy of anti-CTLA-4 and anti-PD-1 immunotherapy showed better efficacy with an objective response rate of 42.9% than single-agent therapy. The retrospective study investigating the combination therapy of anti-PD-1 immunotherapy and radiation showed no overall response. Few outcomes regarding safety were reported in the included studies.ConclusionsICIs, especially anti-CTLA-4 monoclonal antibodies combined with anti-PD-1 antibodies, are effective systematic treatments in advanced AM. However, there remains a lack of high-level evidence to verify their efficacy and safety and support their clinical application.

Vaccines are powerful tools to develop immune memory to infectious diseases and prevent excess mortality. In older adults, however vaccines are generally less efficacious and the molecular mechanisms that underpin this remain largely unknown. Autophagy, a process known to prevent aging, is critical for the maintenance of immune memory in mice. Here, we show that autophagy is specifically induced in vaccine-induced antigen-specific CD8+ T cells in healthy human volunteers. In addition, reduced IFNγ secretion by RSV-induced T cells in older vaccinees correlates with low autophagy levels. We demonstrate that levels of the endogenous autophagy-inducing metabolite spermidine fall in human T cells with age. Spermidine supplementation in T cells from old donors recovers their autophagy level and function, similar to young donors’ cells, in which spermidine biosynthesis has been inhibited. Finally, our data show that endogenous spermidine maintains autophagy via the translation factor eIF5A and transcription factor TFEB. In summary, we have provided evidence for the importance of autophagy in vaccine immunogenicity in older humans and uncovered two novel drug targets that may increase vaccination efficiency in the aging context.

Gout is an oxidative stress-related disease. Food-derived vanillic acid, a promising xanthine oxidase inhibitor, could potentially be used as a safe, supportive, and therapeutic product for gout. The extraction of vanillic acid from a classic Chinese herbal plant Amomum villosum with ethanol was investigated in the study. The optimum conditions were determined as extraction time of 74 min, extraction temperature of 48.36 °C, and a solid-to-liquid ratio of 1:35 g·mL−1 using the Box–Behnken design (BBD) of response surface methodology (RSM). The experimental extraction yield of 9.276 mg·g−1 matched with the theoretical value of 9.272 ± 0.011 mg·g−1 predicted by the model. The vanillic acid in Amomum villosum was determined to be 0.5450 mg·g−1 by high-performance liquid chromatography–diode array detection (HPLC–DAD) under the optimum extraction conditions and exhibited xanthine oxidase (XO) inhibitory activity, with the half-maximal inhibitory concentration (IC50) of 1.762 mg·mL−1. The nanoemulsion of Amomum villosum extract consists of 49.97% distilled water, 35.09% Smix (mixture of tween 80 and 95% ethanol with 2:1 ratio), and 14.94% n-octanol, with a particle size of 110.3 ± 1.9 nm. The nanoemulsion of Amomum villosum extract exhibited markable XO inhibitory activity, with an inhibition rate of 58.71%. The result demonstrated the potential benefit of Amomum villosum as an important dietary source of xanthine oxidase inhibitors for gout.

Purpose: Cushing's disease (CD) is one of the most severe endocrine disorders and primarily affects women of reproductive age. The peripartum period has been observed to be a common time to develop CD. This study aims to retrospectively analyze the clinical characteristics of CD potentially associated with pregnancy and to evaluate relevant pregnancy outcomes.Methods: Patients who underwent surgery from January 2010 to May 2019 at Peking Union Medical College Hospital (PUMCH) with biochemically and pathologically confirmed CD were retrospectively analyzed. Pregnancy-associated CD was defined as CD onset during gestation or within 12 months after delivery or abortion. Data including demographics, biochemical tests, magnetic resonance imaging (MRI) findings, and disease outcomes were obtained from all patients by reviewing their medical records. Information regarding pregnancy was collected through a supplementary online questionnaire.Results: In a series of female patients (n = 70) of reproductive age with childbearing desire, 27.1% (n = 19) met the criteria for pregnancy-associated CD. The timing of diagnosis of pregnancy-associated CD was 2.7 ± 3.4 years after symptom onset, and the overall remission rate for these women was 89.5%. Three patients with pregnancy-associated CD developed hypertension during pregnancy, two of whom had new-onset hypertension at 16 weeks of gestation and one of whom had a complication of severe diabetes. The rates of spontaneous abortion and preterm birth among the women with pregnancy-associated CD were 26.3 and 28.6%, respectively. The proportions of all low-birth-weight (LBW) newborns (p = 0.002) and term LBW newborns (p = 0.033) were significantly higher in the pregnancy-associated CD group than in the non-pregnancy-associated CD group.Conclusions: In this study, a total of 27.1% of women of reproductive age with CD had pregnancy-associated CD, which might be induced by the hormonal milieu of pregnancy. An increased risk of having a LBW newborn was observed among mothers with pregnancy-associated CD. A high degree of clinical suspicion for CD may be warranted in the peripartum period. Patients with symptoms suspicious for CD throughout pregnancy and after childbirth, such as early-onset hypertension, severe hyperglycemia, and persistent weight gain, should be carefully diagnosed and closely monitored by clinicians.

Phytoremediation is an effective and ecological method used to control soil secondary salinization in greenhouses. However, the plant–soil interactions for phytoremediation have not been studied sufficiently. In this study, three crop species (Astragalus sinicus (CM), Spinacea oleracea (SP) and Lolium perenne (RY)) were compared in a greenhouse experiment. The results showed that all three crops increased the soil microbial biomass, the abundance of beneficial microorganisms, available phosphorus and soil pH, and reduced the soil salt content. The crop nutrient accumulation was positively correlated with the relative abundance of bacterial 16S rRNA sequences in the soil. CM and RY respectively increased the relative abundances of norank_f_Gemmatimonadaceae and norank_f_Anaerolineaceae within the soil bacterial community, while SP increased the relative abundances of Gibellulopsis within the fungal community. Correlation analysis revealed that pH and total dissolved salts were the vital factors affecting soil microbial communities in the secondary salinized soil. Our results suggest that phytoremediation could effectively alleviate secondary salinization by regulating the balance of soil microbial community composition and promoting crop nutrient accumulation.

Searchable encryption can support data user to selectively retrieve the cipher documents over encrypted cloud data by keyword-based search. Most of the existing searchable encryption schemes only focus on the exact keyword search. When data user makes spelling errors, these schemes fail to return the result of interest. In searchable encryption, the cloud server might return the invalid result to data user for saving the computation cost or other reasons. Therefore, these exact keyword search schemes find little practical significance in real-world applications. In order to address these issues, we propose a novel verifiable fuzzy keyword search scheme over encrypted cloud data. For the purpose of introducing this scheme, we first propose a verifiable exact keyword search scheme and then extend this scheme to the fuzzy keyword search scheme. In the fuzzy keyword search scheme, we employ the linked list as our secure index to achieve the efficient storage. We construct a linked list with three nodes for each exact keyword and generate a fuzzy keyword set for it. To reduce the computation cost and the storage space, we generate one index vector for each fuzzy keyword set, rather than each fuzzy keyword. To resist malicious behaviors of the cloud server, we generate an authentication label for each fuzzy keyword to verify the authenticity of the returned ciphertexts. Through security analysis and experiment evaluation, we show that our proposed schemes are secure and efficient.

Deploying electronic health records (EHRs) is now an undisputable trend in healthcare systems. Through affording benefits like flexibility and low cost, the cutting-cloud cloud storage is becoming a popular solution to store a massive amount of EHRs to depress the local storage. Nevertheless, storing sensitive information such as health records on the cloud incurs severe security and privacy risks. In this paper, we propose a novel cloud storage system for EHRs which fully ensures the data privacy by employing the Shamir's secret sharing. In this system, an EHR is divided into multiple segments by a healthcare center, and the segments are distributed to numerous cloud servers. When retrieving the EHR, the healthcare center captures segments from partial cloud servers and reconstructs the EHRs. Meanwhile, in reality, the reconstruction of a shared EHR could be much burdensome for a healthcare center or a patient, we thus propose a practical cloud storage scheme which outsources the reconstruction of a shared EHR to a cloud computing service provider. Such a solution can drastically boost the efficiency of the proposed scheme. As far as we know, our scheme is the first to define reconstruction outsourcing concept in all cloud storage schemes for EHRs based on secret sharing, and the results of outsourcing reconstruction can be verified by healthcare centers or patients in our scheme. The theoretical analysis and experimental results also support that our proposed scheme is secure and efficient.