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Abstract The thickness of film materials is a critical factor influencing properties such as energy density, optical performance, and mechanical strength. However, the long-standing challenge of the intrinsic thermodynamic limit on maximum thickness often leads to detrimental cracking, compromising these desirable properties. In this study, we present an approach called the stress-eliminated liquid-phase fabrication (SELF) method. The SELF method eliminates the need for substrates to support the precursor solution used for film fabrication. We harness the intrinsic surface tension of the solution by confining it within specifically designed grids in a framework, forming suspended liquid bridges. This technique enables fabrication of crack-free ceramic films within a broad thickness range from 1 to 100 μm. Furthermore, the fabricated PZT films exhibit a high piezoelectric coefficient (d 33) of 229 pC N−1. The customizable grids not only offer design freedom for film topologies but also facilitate the fabrication of diverse film arrays without the need for destructive cutting processes. Moreover, the freestanding nature of these films enhances their adaptability for MEMS processing, and the “capillary bridge” topology allows the PZT films to be used in ultrasound focusing transmitter, providing possibilities in the medical imaging.

A positive-sense (+) single-stranded RNA (ssRNA) virus (e.g. enterovirus A71, EV-A71) depends on viral polypeptide translation for initiation of virus replication after entry. We reported that EV-A71 hijacks Hsp27 to induce hnRNP A1 cytosol redistribution to initiate viral protein translation, but the underlying mechanism is still elusive. Here, we show that phosphorylation-deficient Hsp27-3A (Hsp27S15/78/82A) and Hsp27S78A fail to translocate into the nucleus and induce hnRNP A1 cytosol redistribution, while Hsp27S15A and Hsp27S82A display similar effects to the wild type Hsp27. Furthermore, we demonstrate that the viral 2A protease (2Apro) activity is a key factor in regulating Hsp27/hnRNP A1 relocalization. Hsp27S78A dramatically decreases the IRES activity and viral replication, which are partially reduced by Hsp27S82A. However, Hsp27S15A displays the same activity as the wild-type Hsp27. Peptide S78 potently suppresses EV-A71 protein translation and reproduction through blockage of EV-A71-induced Hsp27 phosphorylation and Hsp27/hnRNP A1 relocalization. A point mutation (S78A) on S78 impairs its inhibitory functions on Hsp27/hnRNP A1 relocalization and viral replication. Taken together, we demonstrate the importance of Ser78 phosphorylation of Hsp27 regulated by virus infection in nuclear translocation, hnRNP A1 cytosol relocation, and viral replication, suggesting a new path (such as peptide S78) for target-based antiviral strategy.

BackgroundArtificial intelligence (AI) chatbots such as ChatGPT are expected to impact vision health care significantly. Their potential to optimize the consultation process and diagnostic capabilities across range of ophthalmic subspecialties have yet to be fully explored. ObjectiveThis study aims to investigate the performance of AI chatbots in recommending ophthalmic outpatient registration and diagnosing eye diseases within clinical case profiles. MethodsThis cross-sectional study used clinical cases from Chinese Standardized Resident Training–Ophthalmology (2nd Edition). For each case, 2 profiles were created: patient with history (Hx) and patient with history and examination (Hx+Ex). These profiles served as independent queries for GPT-3.5 and GPT-4.0 (accessed from March 5 to 18, 2024). Similarly, 3 ophthalmic residents were posed the same profiles in a questionnaire format. The accuracy of recommending ophthalmic subspecialty registration was primarily evaluated using Hx profiles. The accuracy of the top-ranked diagnosis and the accuracy of the diagnosis within the top 3 suggestions (do-not-miss diagnosis) were assessed using Hx+Ex profiles. The gold standard for judgment was the published, official diagnosis. Characteristics of incorrect diagnoses by ChatGPT were also analyzed. ResultsA total of 208 clinical profiles from 12 ophthalmic subspecialties were analyzed (104 Hx and 104 Hx+Ex profiles). For Hx profiles, GPT-3.5, GPT-4.0, and residents showed comparable accuracy in registration suggestions (66/104, 63.5%; 81/104, 77.9%; and 72/104, 69.2%, respectively; P=.07), with ocular trauma, retinal diseases, and strabismus and amblyopia achieving the top 3 accuracies. For Hx+Ex profiles, both GPT-4.0 and residents demonstrated higher diagnostic accuracy than GPT-3.5 (62/104, 59.6% and 63/104, 60.6% vs 41/104, 39.4%; P=.003 and P=.001, respectively). Accuracy for do-not-miss diagnoses also improved (79/104, 76% and 68/104, 65.4% vs 51/104, 49%; P

Abstract In recent years, the incidence of diabetes has been increasing rapidly, posing a serious threat to human health. Diabetic cardiomyopathy (DCM) is characterized by cardiomyocyte hypertrophy, myocardial fibrosis, apoptosis, ventricular remodeling, and cardiac dysfunction in individuals with diabetes, ultimately leading to heart failure and mortality. However, the underlying mechanisms contributing to DCM remain incompletely understood. With advancements in molecular biology technology, accumulating evidence has shown that numerous non-coding RNAs (ncRNAs) crucial roles in the development and progression of DCM. This review aims to summarize recent studies on the involvement of three types of ncRNAs (micro RNA, long ncRNA and circular RNA) in the pathophysiology of DCM, with the goal of providing innovative strategies for the prevention and treatment of DCM.

Abstract Background TikTok is emerging as a vital platform for health information dissemination. Despite myopia being a global public health issue, the high-quality myopia information shared by health educators often fails to go viral. It is imperative to analyze the factors influencing video quality and popularity, especially from diverse perspectives of researchers, health educators, and audiences. Methods TikTok myopia-related videos were retrieved using TikTok’s default comprehensive search (DCS) and most liked search (MLS) strategies. Venn diagrams were employed to illustrate the relationships and commonalities between the two strategies across four sample sizes (top 200, 150, 100, and 50). Video metadata, including details such as creator information, production properties, upload time, video duration, and viewer engagement, were collected. Video quality was assessed using the DISCERN tool. Video content covering six aspects of myopia were evaluated. The impact of search strategies, video sample sizes, production properties, and myopia content on video quality and audience engagement was analyzed through single-factor or multi-factor analysis. Results DCS and MLS retrieval strategies, as well as varying sample sizes, resulted in differences in audience engagement for myopia videos (P 0.221). Videos published by healthcare professionals (HCPs) and non-profit organizations (NPOs) were associated with high-quality (P ≤ 0.014) but comparatively lower popularity (P 60s) exhibited the opposite trend (P

Abstract The rapid-developing soft robots and wearable devices require flexible conductive materials to maintain electric functions over a large range of deformations. Considerable efforts are made to develop stretchable conductive materials; little attention is paid to the frequent failures of integrated circuits caused by the interface mismatch of soft substrates and rigid silicon-based microelectronics. Here, we present a stretchable solder with good weldability that can strongly bond with electronic components, benefiting from the hierarchical assemblies of liquid metal particles, small-molecule modulators, and non-covalently crosslinked polymer matrix. Our self-solder shows high conductivity (>2×105 S m−1), extreme stretchability (~1000%, and >600% with chip-integrated), and high toughness (~20 MJ m−3). Additionally, the dynamic interactions within our solder’s surface and interior enable a range of unique features, including ease of integration, component substitution, and circuit recyclability. With all these features, we demonstrated an application as thermoforming technology for three-dimensional (3D) conformable electronics, showing potential in reducing the complexity of microchip interfacing, as well as scalable fabrication of chip-integrated stretchable circuits and 3D electronics.

Phyllostachys glauca McClure leaves (PML), as economical natural product material, contain abundant phenols, particularly flavonoids, with significant biological activities that contribute to their widespread applications in food, pharmaceutical, and cosmetic industries. To study the significant phenols in PML, an ultrasound-assisted deep eutectic solvent extraction method with high efficiency and low toxicity was established for extracting the phenols from PML and the bamboo leaves of 17 other bamboo species. Using the Ultra Performance Liquid Chromatography (UPLC) method, the content of phenols in the leaves of the 18 bamboo species was determined. PML were found to contain neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoorientin, and orientin at contents of 0.793 ± 00.17 mg/g, 0.491 ± 0.0081 mg/g, 0.485 ± 0.0043 mg/g, 0.465 ± 0.0021 mg/g, and 0.044 ± 0.0005 mg/g, respectively, with a total content of 2.278 mg/g. These contents were significantly higher than those found in the leaves of 17 other bamboo species. Additionally, the significant phenols, neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid were found simultaneously in the leaves of 15 bamboo species, especially in PML. Therefore, PML can be viewed as the natural product material with considerable application values, owing to its abundant phenols, and can exhibit its importance in utilizing neochlorogenic acid, chlorogenic acid, and cryptochlorogenic acid as resources.

BackgroundDry eye disease (DED) is a prevalent ocular surface disease that significantly impacts patients’ quality of life. The association between air pollution and the risk of dry eye disease remains uncertain.MethodsData on outdoor air pollutants, meteorological information, and outpatient visits for DED were collected from July 1, 2014, to December 31, 2019. The relationship between ambient air pollutants and DED outpatient visits was analyzed using a generalized additive model with a Poisson distribution.ResultsAmong the 5,204 DED patients included in the study, 63.76% were female and 36.24% were male. The single-pollutant model revealed a significant association between a 10 μg/m3 increase in concentrations of fine-particulate matter with a median aerometric diameter of less than 10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) and outpatient visits for DED. Fine-particulate matter with a median aerometric diameter of less than 2.5 μm (PM2.5) showed a significant association with DED outpatient visits in males and the 19–59 years age group. The strongest associations between air pollutants and outpatient visits were observed in male patients and during the cold season.ConclusionThe noteworthy correlation between air pollutants and DED outpatient visits can offer evidence for policy makers and underscore the significance of reinforcing environmental protection.

Bamboo vinegar is a liquid biomass with a huge yield and complex chemical composition. At present, the relative quantification of bamboo vinegar has been investigated in most studies. To analyze twelve compounds from bamboo vinegar simultaneously, gas chromatography-mass spectrometry and an external standard method were used to develop an analytical method. In this method, chromatographic separations of all compounds were above 1.5. The linear range was between 0.100 and 10.000 mg/L, and the coefficient of determination (R2) was between 0.9981 and 0.9997, indicating a good linear relationship. The limit of detection (LOD) was between 0.004 and 0.780 mg/L; the limit of quantitation (LOQ) was between 0.016 and 3.120 mg/L; the relative standard deviations (RSDs) of instrument precision and method stability were less than 8%; the recovery rate was between 89.25% and 113.77%, and its RSD was between 0.44% and 5.70%. Using this method, fourteen bamboo vinegars and six wood vinegars were analyzed, and it was found that the content of propionic acid, phenol, and 2-methoxyphenol was higher in most samples. In addition, the differences in physicochemical properties between distilled bamboo vinegar and its original solution after atmospheric distillation were investigated.

The utilization of natural products in food preservation represents a promising strategy for the dual benefits of controlling foodborne pathogens and enhancing the nutritional properties of foods. Among the phytonutrients, flavonoids have been shown to exert antibacterial effects by disrupting bacterial cell membrane functionality; however, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of quercetin on the cell membrane permeability of Staphylococcus aureus ATCC 27217. A combined metabolomic and transcriptomic approach was adopted to examine the regulatory mechanism of quercetin with respect to the fatty acid composition and associated genes. Kinetic analysis and molecular docking simulations were conducted to assess quercetin’s inhibition of β-ketoacyl-acyl carrier protein reductase (FabG), a potential target in the bacterial fatty acid biosynthesis pathway. Metabolomic and transcriptomic results showed that quercetin increased the ratio of unsaturated to saturated fatty acids and the levels of membrane phospholipids. The bacteria reacted to quercetin-induced stress by attempting to enhance fatty acid biosynthesis; however, quercetin directly inhibited FabG activity, thereby disrupting bacterial fatty acid biosynthesis. These findings provide new insights into the mechanism of quercetin’s effects on bacterial cell membranes and suggest potential applications for quercetin in bacterial inhibition.

Pigeon paramyxovirus 1 (PPMV-1) is an antigenic host variant of avian paramyxovirus 1. Sporadic outbreaks of PPMV-1 infection have occurred in pigeons in China; however, few cases of human PPMV-1 infection have been reported. The purpose of this article is to report a case of severe human PPMV-1 infection in an individual with probable post-COVID-19 syndrome (long COVID) who presented with rapidly progressing pulmonary infection. The patient was a 66-year-old man who was admitted to the intensive care unit 11 days after onset of pneumonia and recovered 64 days after onset. PPMV-1 was isolated from the patient’s sputum and in cloacal smear samples from domesticated pigeons belonging to the patient’s neighbour. Residual severe acute respiratory syndrome coronavirus 2 was detected in respiratory and anal swab samples from the patient. Sequencing analyses revealed that the PPMV-1 genome belonged to genotype VI.2.1.1.2.2 and had the 112RRQKRF117 motif in the cleavage site of the fusion protein, which is indicative of high virulence. This case of cross-species transmission of PPMV-1 from a pigeon to a human highlights the risk of severe PPMV-1 infection in immunocompromised patients, especially those with long COVID. Enhanced surveillance for increased risk of severe viral infection is warranted in this population.

Abstract Obesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose tissue are currently lacking and hinder research into this cell type and biotherapy development. Unlike traditional bottom‐up engineering approaches that aim to generate building blocks, here a scalable system is proposed to generate pre‐vascularized and functional human beige adipose tissue organoids using the human stromal vascular fraction of white adipose tissue as a source of adipose and endothelial progenitors. This engineered method uses a defined biomechanical and chemical environment using tumor growth factor β (TGFβ) pathway inhibition and specific gelatin methacryloyl (GelMA) embedding parameters to promote the self‐organization of spheroids in GelMA hydrogel, facilitating beige adipogenesis and vascularization. The resulting vascularized organoids display key features of native beige adipose tissue including inducible Uncoupling Protein‐1 (UCP1) expression, increased uncoupled mitochondrial respiration, and batokines secretion. The controlled assembly of spheroids allows to translate organoid morphogenesis to a macroscopic scale, generating vascularized centimeter‐scale beige adipose micro‐tissues. This approach represents a significant advancement in developing in vitro human beige adipose tissue models and facilitates broad applications ranging from basic research to biotherapies.

Abstract Capillary‐enabled water energy harvesters (WEHs) are capable of generating direct‐current electricity continuously. However, active‐metal electrodes can introduce metal–air batteries in these WEHs. Given the nearly identical device structures and output characteristics of these two technologies, it is essential to distinguish between them. Herein, we present a systematic study of the water‐activated metal–air battery (WMB) through theoretical analyses and experimental verifications. We conclude the general formation rules of the WMB from a material and device‐structure perspective. Furthermore, we provide a comparative summary of various WEHs and WMBs for easy identification. We aim to improve the comprehension of metal–air batteries in the field of WEHs and assist in distinguishing between these technologies.

Dielectric capacitors are receiving increasing attention due to the high-power density and fast charge–discharge speed. However, defects are inevitably induced during the preparation process and then weaken the breakdown strength, thereby limiting their energy density. The phenomenon gives rise to self-healing technology. The discovery of sol–gel-derived aluminum oxide with electrolysis and dielectric dual-characteristic provides a novel, simple and cost-effective self-healing method to heal defects and enhance energy density. In this paper, we systematically reviewed the current self-healing technologies and the important progress of electrolysis and dielectric co-existence dielectrics. Finally, we outlook the electrolysis and dielectric co-existence dielectrics and potential challenge.

Abstract Background The pathological phenotype of perineural invasion (PNI) in squamous cell carcinoma (ESCC) is prevalent but highly heterogeneous. Methods Postoperative specimens from all patients with ESCC at Shaanxi Provincial People’s Hospital were evaluated for PNI using haematoxylin and eosin (H&E) staining and S100 immunohistochemistry (IHC). We determined the correlation between PNI status and clinical outcomes. Results Among 349 ESCC cases, PNI was identified in 127 patients (36.3%), and four subtypes of PNI were identified in our study. Correlation analysis confirmed that PNI was related to tumour invasion depth (pT stage) and lymph node status (pN stage) (P

ObjectiveDuring the COVID-19 pandemic, nurses, especially if females and working in intensive care units or emergencies unit, were much more at risk than other health-workers categories to develop malaise and acute stress symptoms. This study aimed to examine the nurses’ post-traumatic growth and associated influencing factors during the COVID-19 pandemic.MethodsA cross-sectional study using an online survey was conducted at Henan Provincial People’s Hospital to gather data from nurses. A set of questionnaires was used to measure the participants’ professional identity, organizational support, psychological resilience and post-traumatic growth. Univariate, correlation, and multiple linear regression analyses were used to determine significant factors influencing post-traumatic growth. A theoretical framework based on the Bayesian network was constructed to understand post-traumatic growth and its associated factors comprehensively.ResultsIn total, 1,512 nurses participated in the study, and a moderate-to-high level of post-traumatic growth was reported. After screening, the identified variables, including psychological counseling, average daily working hours, average daily sleep duration, professional identity, organizational support, and psychological resilience, were selected to build a Bayesian network model. The results of Bayesian network showed that professional identity and psychological resilience positively affected post-traumatic growth directly, which was particularly pronounced in low- and high-scoring groups. While organizational support positively affected post-traumatic growth indirectly.ConclusionAlthough this study identified a moderate-to-high level of nurses’ post-traumatic growth, proactive measures to improve psychological resilience fostered by professional identity and organizational support should be prioritized by hospitals and nursing managers.

With the growing maritime economy, ensuring the quality of communication for maritime users has become imperative. The maritime communication system based on nearshore base stations enhances the communication rate of maritime users through dynamic resource allocation. A virtual queue-based deep reinforcement learning beam allocation scheme is proposed in this paper, aiming to maximize the communication rate. More particularly, to reduce the complexity of resource management, we employ a grid-based method to discretize the maritime environment. For the combinatorial optimization problem of grid and beam allocation under unknown channel state information, we model it as a sequential decision process of resource allocation. The nearshore base station is modeled as a learning agent, continuously interacting with the environment to optimize beam allocation schemes using deep reinforcement learning techniques. Furthermore, we guarantee that grids with poor channel state information can be serviced through the virtual queue method. Finally, the simulation results provided show that our proposed beam allocation scheme is beneficial in terms of increasing the communication rate.

Abstract Bubbles are pervasive in aqueous media, and on account of numerous advantages of tiny bubbles, efficient bubble splitting is favorable in a wide range of applications. However, underwater bubble splitting faces a lot of challenges because bubbles tend to coalesce during the rising due to the action of buoyancy and surface energy, and the consumption of considerable external energy is needed. Inspired by the bubble bursting phenomenon on the feathers of high‐speed swimming penguins, we proposed a new bubble splitting strategy based on the energy conversion of bubble transportation on superhydrophobic open pathways. A porous superhydrophobic coating was first developed via a bubble‐template assisted fabrication method, which provides hierarchical micro/nanostructures and robust air plastron. Gas bubbles can transport along the superhydrophobic open pathways without perturbation, and split into smaller ones by taking advantage of the potential energy contributed by buoyancy. By controlling the superhydrophobic pathway, the size of the split bubbles can be controlled precisely. We also demonstrated that a bubble splitting device could be applied in underwater reactions where an enhanced gas−liquid mass transfer is desired. This bubble splitting strategy may offer new prospects for underwater bubble manipulation and unfold a potential in many bubble‐involved fields.

Background Postoperative cognitive dysfunction (POCD) is a clinically frequent postoperative complication in the elderly, which is mainly manifested by the occurrence of cognitive dysfunction after anesthetized surgery in patients. To explore the involvement of C/EBPα in microglial polarization in sevoflurane anesthesia induced cognitive impairment in aged rats. Methods Sprague-Dawley (SD) rats were anesthetized by inhalation of 3% sevoflurane for 6 h to establish the POCD model. The histopathological structure of hippocampus was observed by hematoxylin and eosin (HE) staining. Associative learning and memory function and spatial learning and memory function were assessed by conditioned fear test and water maze test. The concentrations of inflammatory factors in the hippocampus were measured by ELISA. The levels of microglial activation marker (Iba1) and microglial M1 (CD86) and M2 (CD206) polarization markers were determined by immunofluorescence staining and RT-qPCR, respectively. The transcriptional regulation of HDAC1 by C/EBPα was confirmed by dual luciferase reporter assay and ChIP assay. Results Sevoflurane-induced pathomorphological damage in the hippocampal tissue of aged rats, accompanied by elevated expression of C/EBPα. Silencing of C/EBPα alleviated hippocampal histopathological injury, inhibited M1 microglial activation and the expression of M1 marker CD86, enhanced the expression of M2 marker CD206. C/EBPα transcriptionally activated HDAC1. Knockdown of C/EBPα downregulated the expression of HDAC1 and STAT3 phosphorylated proteins, which inhibited the pro-inflammatory factors (IL-6 and TNF-α) and accelerated anti-inflammatory factors (IL-10 and TGF-β) secretion. In addition, silencing of C/EBPα caused rats to have a delayed freezing time in contextual conditioned fear, a shorter escape latency, and an increased number of platform crossings. Conclusion Inhibition of C/EBPα promotes the M2 polarization of microglia and reduces the production of pro-inflammatory cytokines to alleviate the cognitive dysfunction of sevoflurane-induced elderly rats by HDAC1/STAT3 pathway.

Abstract This study aims to explore the relationship between abnormal renal- and liver-function and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). A total of 994 T2DM patients who received inpatient treatment in the Endocrinology Department of Henan Province People’s Hospital were included in the study. Logistic regression was performed to identify the relationship between abnormal renal and liver function with DR. Receiver operator characteristic analysis was performed to explore the efficacy of risk factors in predicting DR. Higher urine albumin [OR(95%CI) = 3.344(1.921–5.822), P

Abstract Background Numerous studies have addressed lymphovascular invasion (LVI) in patients with thoracic oesophageal squamous cell carcinoma (ESCC); however, little is known about the individual roles of lymphatic invasion (LI) and vascular invasion (VI). We aimed to analyse the prognostic significance of LI and VI in patients with thoracic ESCC from a single centre. Methods This retrospective study included 396 patients with thoracic ESCC who underwent oesophagectomy and lymphadenectomy in our hospital. The relationship between LI, VI and the other clinical features was analysed, and disease-free survival (DFS) was calculated. Survival analysis was performed by univariate and multivariate statistics. Results Briefly, VI and LI were present in 25.8% (102 of 396) and 23.7% (94 of 396) of ESCC patients, respectively, with 9.15% patients presenting both LI and VI; the remaining patients did not present LI or VI. We found that LI was significantly associated with pN stage (P

The actuation of droplets is necessary for several applications, including the quantitative bioanalysis of viruses. Here, authors show a programmable magnetic actuation method to manipulate droplets of various kinds by making use of the spontaneously formed ferrofluid wetting ridges around each droplet.

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine-related follicular developmental disorder that affects 50 %-70 % of reproductive-aged women diagnosed with ovulation-related infertility. Abnormal proliferation and apoptosis of granulosa cells (GCs) are thought to be the critical factors leading to abnormal maturation of follicles. It has been shown that microRNAs (miRNAs) exert a significant influence in the pathogenesis of PCOS; however, the relationship between miRNA, PCOS, and GC apoptosis is not entirely understood. Methods To clarify the effect of miR-194 in PCOS, CCK-8, Ki67 staining, AO/EB, and flow cytometry assays were used to assess cell growth, proliferation, and apoptosis in KGN cells, which were artificially stimulated to overexpress miR-194. Luciferase reporter assays and rescue experiments were used to elucidate the mechanism underlying miR-194 in PCOS. Results miR-194 expression was significantly up-regulated in rat models of PCOS and the ovarian GCs of PCOS patients. miR-194 suppression promoted KGN cell growth and proliferation. miR-194 overexpression also induced cell apoptosis, while miR-194 downregulation had an opposite effect. Furthermore, up-regulating heparin-binding EGF-like growth factor (HB-EGF) expression rescued the pro-apoptotic effects of miR-194 upregulation on KGN cells. Conclusions miR-194 is increased in PCOS granulosa cell and may function as a novel biomarker and therapeutic target for KGN cells via HB-EGF regulation.

BackgroundMinimal change disease (MCD) has a high recurrence rate, but currently, no biomarker can predict its recurrence. To this end, this study aimed at identifying potential serum cytokines as valuable biomarkers for predicting the risk of MCD recurrence.Materials and methodsRaybiotech 440 cytokine antibody microarray was used to detect the serum samples of eight relapsed, eight non-relapsed MCD patients after glucocorticoid treatment, and eight healthy controls. The differentially expressed cytokines were confirmed by enzyme-linked immunosorbent assay (ELISA) with serum samples from 29 non-relapsed and 35 relapsed MCD patients. The study used the receiver operating characteristic (ROC) curve analysis to investigate the sensitivity and specificity of a serum biomarker for predicting the MCD relapse.ResultsSerum IL-12p40 levels increased significantly in the relapsed group. The Area Under the ROC Curve (AUC) of IL-12p40 was 0.727 (95%CI: 0.597–0.856; P < 0.01). The RNA-sequencing analysis and qPCR assay performed on the IL-12 treated mouse podocytes and the control group showed increased expression of podocyte damage genes, such as connective tissue growth factor (CTGF), matrix metallopeptidase 9 (MMP9), secreted phosphoprotein 1 (SPP1), and cyclooxygenase-2 (COX-2) in the former group.ConclusionIL-12p40 may serve as a new biomarker for predicting the risk of MCD recurrence after glucocorticoid treatment, and it may be involved in the pathogenesis and recurrence of MCD.

Abstract The study aims to explore the distribution characteristics and influencing factors of diabetic retinopathy (DR) in diabetes mellitus (DM) patients and association rules of eye diseases in these patients. Data were obtained from 1284 DM patients at Henan Provincial People’s Hospital. Association rules were employed to calculate the probability of the common occurrence of eye-related diseases in DM patients. A web visualization network diagram was used to display the association rules of the eye-related diseases in DM patients. DR prevalence in people aged

Ionic conductive gels are promising soft conductors for stretchable and flexible electronics. Unfortunately, the basic requirements for an ideal ionic conductive gel, including environmental and chemical stability as well as low toxicity and low cost do not usually coincide in one material. Here we report an ionic conductive gel containing deep eutectic solvents (DES), which are specialized ionic liquids composed of propylene glycol (PG, hydrogen bonding donor) and various salts. In experiments, the DES-gel loses about 10% of the original weight in dry air (5– 9% relative humidity) for 7 days and its conductivity remains unaltered. Comparing to regular salt-containing hydrogels, it exhibits exceptional resistance to metal corrosion. We demonstrate the advantage of DES-gels as the ionic electrode in a flexible and stretchable electroluminescent device, especially in cold environment (−20°C). Through this study, we discover a new candidate for cheap and safe soft ionic conductors with excellent environmental and chemical stability.

Background: Indiolethylamine-N-methyltransferase (INMT) is a methyltransferase responsible for transferring methyl groups from methyl donor SAM to its substrate. S-adenosyl-l-methionine (SAM), obtained from the methionine cycle, is a naturally occurring sulfonium compound that is vital to cellular metabolism. The expression of INMT is down-regulated in many tumorous tissues, and it may contribute to tumor invasion and metastasis. Nevertheless, the expression of INMT and its relationship to methylation and immune infiltrates in head and neck squamous cell carcinoma (HNSC) remains a mystery. Thus, we evaluated expression, clinicopathological features, prognosis, several critical pathways, DNA methylation, and immune cell infiltration for the first time.Methods: Analysis of the clinicopathological characteristics of INMT expression, several tumor-related bioinformatics databases were utilized. In addition, the role of INMT expression was analyzed for prognosis. Several INMT-related pathways were enriched on the LinkedOmics website. In addition, we have analyzed the methylation of INMT in HNSC in detail by using several methylation databases. Lastly, the relationship between INMT gene expression and immune infiltration was analyzed with ssGSEA, Timer, and TISIDB.Results: In HNSC, mRNA and protein levels were significantly lower than in normal tissues. The low expression of INMT was statistically associated with T stage, histological grade, gender, smoking history, and alcohol consumption. HNSC patients with low INMT expression have a poorer OS (overall survival) compared to those with high levels of expression. In addition, the multivariate analysis revealed INMT expression to be a remarkable independent predictor of prognosis in HNSC patients. An analysis of gene enrichment showed that several pathways were enriched in INMT, including the Ras signaling pathway, the cGMP-PKG signaling pathway, and others. Moreover, methylation patterns of INMT detected in a variety of methylation databases are closely associated with mRNA expression and prognosis. Finally, INMT was significantly correlated with immune infiltration levels.Conclusion: HNSC with low levels of INMT exhibits poor survival, hypomethylation, and immune infiltration. For HNSC, this study presented evidence that INMT is both a biomarker of poor prognosis and a target of immunotherapy.

Abstract Demethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers’ expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.

Vaccination is an effective measure to prevent infectious diseases. Protective immunity is induced when the immune system is exposed to a vaccine formulation with appropriate immunogenicity. However, traditional injection vaccination is always accompanied by fear and severe pain. As an emerging vaccine delivery tool, microneedles overcome the problems associated with routine needle vaccination, which can effectively deliver vaccines rich in antigen-presenting cells (APCs) to the epidermis and dermis painlessly, inducing a strong immune response. In addition, microneedles have the advantages of avoiding cold chain storage and have the flexibility of self-operation, which can solve the logistics and delivery obstacles of vaccines, covering the vaccination of the special population more easily and conveniently. Examples include people in rural areas with restricted vaccine storage facilities and medical professionals, elderly and disabled people with limited mobility, infants and young children afraid of pain. Currently, in the late stage of fighting against COVID-19, the main task is to increase the coverage of vaccines, especially for special populations. To address this challenge, microneedle-based vaccines have great potential to increase global vaccination rates and save many lives. This review describes the current progress of microneedles as a vaccine delivery system and its prospects in achieving mass vaccination against SARS-CoV-2.

Abstract Electrochemical CO2 reduction to value‐added chemicals and fuels using renewable energy represents a promising strategy for reducing CO2 emissions and achieving effective energy storage. In this work, nano‐sized CuO catalysts were prepared by using the homogeneous precipitation method for electrochemical CO2 reduction to CO. The CO2 reduction studies combined with the characterization results show that structure‐activity relationships of the CuO catalysts depend on the calcination temperature. The as‐synthesized CuO catalysts calcined at different temperatures are capable of reducing CO2 to generate syngas with tunable CO/H2 ratios of 1 : 2 to 2 : 1. The desired CuO‐400 catalyst exhibits good morphology, small particle size, and enriched oxygen‐vacancy defects and, therefore, shows good performance for electrochemical CO2 reduction to CO. Under the given potential of −0.93 V vs. RHE, CuO‐400 exhibits good reduction activity and selectivity with a great electrochemically active surface area normalized CO partial current density of 1.44 mA/cm2 and a high CO faradaic efficiency of 48.2 %. The deactivation of CuO‐400 in the long‐term test is associated with the increase in particle size, the reduction of CuO to Cu2O and metallic Cu, and the coverage of surface active sites by the formed carbonate species. Our findings indicate that CuO catalysts with tunable physicochemical properties are promising candidates for electrochemical CO2 reduction to produce syngas.

Abstract Background Cancer cells cooperate with cells that compose their environment to promote tumor growth and invasion. Among them, adipocytes provide lipids used as a source of energy by cancer cells and adipokines that contribute to tumor expansion. Mechanisms supporting the dynamic interactions between cancer cells and stromal adipocytes, however, remain unclear. Methods We set-up a co-culture model with breast cancer cells grown in 3D as mammospheres and human adipocytes to accurately recapitulate intrinsic features of tumors, such as hypoxia and cancer cell–adipocytes interactions. Results Herein, we observed that the lipid droplets’ size was reduced in adipocytes adjacent to the mammospheres, mimicking adipocyte morphology on histological sections. We showed that the uncoupling protein UCP1 was expressed in adipocytes close to tumor cells on breast cancer histological sections as well as in adipocytes in contact with the mammospheres. Mammospheres produced adrenomedullin (ADM), a multifactorial hypoxia-inducible peptide while ADM receptors were detected in adipocytes. Stimulation of adipocytes with ADM promoted UCP1 expression and increased HSL phosphorylation, which activated lipolysis. Invalidation of ADM in breast cancer cells dramatically reduced UCP1 expression in adipocytes. Conclusions Breast tumor cells secreted ADM that modified cancer–associated adipocytes through paracrine signaling, leading to metabolic changes and delipidation. Hence, ADM appears to be crucial in controlling the interactions between cancer cells and adipocytes and represents an excellent target to hinder them.

Abstract Background There are conflicting research results about the survival differences between hemodialysis(HD) and peritoneal dialysis (PD). The present study estimated the survival and the relative mortality hazard for incident HD and PD patients with end stage renal disease (ESRD) in eastern China. Methods This study examined a cohort of patients with ESRD who initiated dialysis therapy in Zhejiang province between Jan of 2010 and Dec of 2014, followed up until the end of 2015. PD patients were matched in a 1:1 fashion with HD patients, and Kaplan–Meier analysis was used to explore the survival of them. The Cox proportional hazard regression model was applied to identify the factors that predict survival by treatment modality. Subgroup analyses were conducted by stratifying patients according to gender, age, causes of ESRD and comorbidities. Results Among a total of 22,379 enrolled patients (17,029 HD patients and 5350 PD patients), 5350 matched pairs were identified, and followed for a median of 29 months (3 ~ 72 months). Kaplan-Meier survival curve revealed that overall mortality rate was significantly higher in HD patients than in PD patients (log-rank test, P

Summary: The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) causing high mortality in clinical patients infers the urgent need for developing therapeutic agents. Here, we demonstrated vitamin C (VC) exhibited strong bactericidal, anti-biofilm, and virulence-suppressing effects on CR-hvKP. Our results showed such a bactericidal effect is dose-dependent both in vitro and in the mouse infection model and is associated with induction of reactive oxygen species (ROS) generation. In addition, VC inhibited biofilm formation of CR-hvKP through suppressing the production of exopolysaccharide (EPS). In addition, VC acted as an efflux pump inhibitor at subminimum inhibitory concentration (sub-MIC) to disrupt transportation of EPS and capsular polysaccharide to bacterial cell surface, thereby further inhibiting biofilm and capsule formation. Furthermore, virulence-associated genes in CR-hvKP exposed to sub-MIC of VC were downregulated. Our findings indicated VC could be an effective and safe therapeutic agent to treat CR-hvKP infections in urgent cases when all current treatment options fail.

The early evolutionary history of the armored dinosaurs (Thyreophora) is obscured by their patchily distributed fossil record and by conflicting views on the relationships of Early Jurassic taxa. Here, we describe an early diverging thyreophoran from the Lower Jurassic Fengjiahe Formation of Yunnan Province, China, on the basis of an associated partial skeleton that includes skull, axial, limb, and armor elements. It can be diagnosed as a new taxon based on numerous cranial and postcranial autapomorphies and is further distinguished from all other thyreophorans by a unique combination of character states. Although the robust postcranium is similar to that of more deeply nested ankylosaurs and stegosaurs, phylogenetic analysis recovers it as either the sister taxon of Emausaurus or of the clade Scelidosaurus+ Eurypoda. This new taxon, Yuxisaurus kopchicki, represents the first valid thyreophoran dinosaur to be described from the Early Jurassic of Asia and confirms the rapid geographic spread and diversification of the clade after its first appearance in the Hettangian. Its heavy build and distinctive armor also hint at previously unrealized morphological diversity early in the clade’s history.

Antibiotic pollution has received increasing global and scientific attention in recent years due to its serious impact on ecosystems and human health. As a new advanced oxidation method, Cold Atmospheric Plasmas (CAPs) have been successfully applied to degrade oxytetracycline (OTC) with a large removal rate, high energy efficiency, and environment-friendly requirements; however, the reaction pathways are still unclear. In this study, a reactive Molecular Dynamics (MD) simulation is performed to investigate the mechanisms of OTC degradation induced by Reactive Oxygen Species (ROS) in CAPs. The simulations showed the breaking of chemical bonds upon the impact of ROS, such as C–C, C–N, and C–O. In particular, the removal of important functional groups, including the acylamino at the C2 site, the dimethylamine at the C4 site, and the tertiary alcohol at the C12a site, is observed, and the destruction of these key structures indicates the degradation of OTC by reducing the antibacterial ability. The final products revealed by the computational data agree well with the experimental measurements. The dose effects on OTC degradation are also examined by adjusting the numbers of ROS in the simulation box. This study can further enhance the understanding of OTC degradation induced by CAP according to the reactive MD simulation results, unveiling the key pathways of OTC degradation.

Human induced pluripotent stem cells (hiPSCs) have the potential to be differentiated into any cell type, making them a relevant tool for therapeutic purposes such as cell-based therapies. In particular, they show great promise for obesity treatment as they represent an unlimited source of brown/beige adipose progenitors (hiPSC-BAPs). However, the low brown/beige adipocyte differentiation potential in 2D cultures represents a strong limitation for clinical use. In adipose tissue, besides its cell cycle regulator functions, the cyclin-dependent kinase inhibitor 2A (CDKN2A) locus modulates the commitment of stem cells to the brown-like type fate, mature adipocyte energy metabolism and the browning of adipose tissue. Here, using a new method of hiPSC-BAPs 3D culture, via the formation of an organoid-like structure, we silenced CDKN2A expression during hiPSC-BAP adipogenic differentiation and observed that knocking down CDKN2A potentiates adipogenesis, oxidative metabolism and the browning process, resulting in brown-like adipocytes by promoting UCP1 expression and beiging markers. Our results suggest that modulating CDKN2A levels could be relevant for hiPSC-BAPs cell-based therapies.

Abstract Background Shenxian-Shengmai (SXSM) Oral Liquid is a CFDA-approved patent Chinese Herbal medicine, which has been clinically used for the treatment of bradycardia. However, its active components and action mechanism remain to be established. The present study aimed to evaluate the efficacy of SXSM on bradycardia and to identify the possible active components and their pharmacological targets for this action. Methods A literature-based meta-analysis was performed to evaluate the clinical efficacy of SXSM on bradycardia, which was confirmed by a rat ex vivo cardiac model. Network pharmacology analysis was then conducted to reveal the potential targets of SXSM active components and their anti-arrhythmia mechanisms. Finally, the identified drug-target interaction was confirmed by immunofluorescence assay in cardiomyocyte. Results Meta-analysis of the available clinical study data shows that Shenxian-Shengmai Oral Liquid has a favorable effect for bradycardia. In an ex vivo bradycardia model of rat heart, SXSM restored heart rate by affecting Heart rate variability (HRV) which is associated with autonomic nervous system activity. A drug-target-pathway network analysis connecting SXSM components with arrhythmia suggested that a prominent anti-arrhythmia mechanisms of SXSM was via β1-adrenergic signaling pathway, which was subsequently validated by immunofluorescence assay showing that SXSM indeed increased the expression of ADRB1 in cultured cardiomyocytes. Conclusion By combining approaches of clinical evidence mining, experimental model confirmation, network pharmacology analyses and molecular mechanistic validation, we show that SXSM is an effective treatment for bradycardia and it involves multiple component interacting via multiple pathways, among which is the critical β1-adrenergic receptor upregulation. Our integrative approach could be applied to other multi-component traditional Chinese medicine investigation where ample clinical data are accumulated but advanced mechanistic studies are lacking.

We, the Editor and Publishers of Renal Failure, have retracted the following article: Xi Yao, Shaohua Chen, Wenhua Lei, Nan Shi, Weiqiang Lin, Xiaoying Du, Ping Zhang & Jianghua Chen, The relationship between hemodialysis mortality and the Chinese medical insurance type, Renal Failure, 41:1, 2019, 742–749, https://doi.org/10.1080/0886022X.2019.1652648. The above article has been retracted due to Publisher error as it is an earlier version of an article that was ultimately accepted and published in Renal Failure. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Objectives: In China, there are two major medical insurance models: the Urban Basic Medical Insurance (UBMI) and the New Cooperative Medical Scheme (NCMS). The aim of the present study was to evaluate the association of the medical insurance type of patients undergoing hemodialysis (HD) with their survival. Methods: We retrospectively analyzed the end-stage renal disease adult patients initiating HD between January 2010 and December 2014 in Zhejiang province, followed up through 31 December 2015. Patients who had received HD for over 3 months were separated into two groups, based on different medical insurance type. Demographic, clinical data, and clinical outcomes were analyzed. The survival rates were calculated by using the Kaplan–Meier method. Results: A total of 6779 patients (59 ± 16 years old, 4331 males (63.9%)) with UBMI and 7177 (59 ± 16 years old, 3778 males (52.8%)) with NCMS enrolled from 226 hemodialysis units. Compared with UBMI group, patients with NCMS had a smaller percentage of hypertensive nephropathy, diabetes mellitus and arteriovenous fistula, faced with more problems in anemia, hypoalbuminemia and metabolism of calcium and phosphorous. The 1-, 3- and 5-year survival rates were 95.4, 84.4, and 74.1% in UBMI group, 93.1, 79.7, and 67.7% in NCMS group, respectively. Patients with NCMS showed higher all-cause mortality compared with UBMI (p

Abstract Background Quality of care (QoC) attracts global concerns when unsafe and misuse of healthcare wastes resources and endangers people’s health, especially in low- and middle-income countries. However, little is known about quality of care delivered in China. This study was intended to gauge the quality of care for acute myocardial infarction (AMI) patients in Beijing and identify the quality gaps across tertiary hospitals. Methods One thousand two hundred twenty eight patients, covered by Employee Essential Health Insurance Scheme and diagnosed of AMI, was sampled from 14 large comprehensive hospitals in Beijing, China. Chart review study was conducted through the discharge data and medical records of inpatients to evaluate 6 quality outcomes of interest, including the use of aspirin, beta blocker, and statin at discharge; use of aspirin within 24 h at arrival; angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blocker (ARB) for left ventricular systolic dysfunction (LVSD); percutaneous transluminal coronary intervention (PCI) within 90 min at arrival. Results Of the 1228 subjects, the mean age was 60.8 (11.8 SD) years and 83.0% were male. The overall medication prescribed was highly compliant with the clinical guidelines (97.0% [95% CI 96.8–97.2] for aspirin and 96.3% [95% CI 96.0–96.5] for statin), except for beta-blocker (83.6% [95% CI 83.0–84.1]) and ACEI/ARB use (61.4% [95% CI 60.7–62.2]). More than half of eligible patients did not receive appropriate PCI therapy (44.0% [95% CI 42.5–45.4]). Great variations across hospitals was observed in aspirin within 24 h and beta-blocker at discharge (P

Traditional adhesives or glues such as cyanoacrylates, fibrin glue, polyethylene glycol, and their derivatives have been widely used in biomedical fields. However, they still suffer from numerous limitations, including the mechanical mismatch with biological tissues, weak adhesion on wet surfaces, biological incompatibility, and incapability of integrating desired multifunction. In addition to adaptive mechanical and adhesion properties, adhesive biomaterials should be able to integrate multiple functions such as stimuli-responsiveness, control-releasing of small or macromolecular therapeutic molecules, hosting of various cells, and programmable degradation to fulfill the requirements in the specific biological systems. Therefore, rational molecular engineering and structural designs are required to facilitate the development of functional adhesive materials. This review summarizes and analyzes the current supramolecular design strategies of representative adhesive materials, serving as a general guide for researchers seeking to develop novel adhesive materials for biomedical applications.

Bamboo shoot is a delicious and nutritious forest vegetable. It has been found that bamboo shoots collected from low-light environments have a less bitter taste. The molecular mechanism of light in the regulation of bitter substance accumulation in bamboo shoots is still unclear. In this study, we applied a shading treatment to Pleioblastus amarus bamboo shoots in the preharvesting period. The reduction in the bitterness intensity was confirmed by a sensory test. An integrated metabolomic and transcriptomic analysis was performed on P. amarus bamboo shoots grown under shading treatment and normal growing conditions, and 56 differentially accumulated metabolites and 178 differentially expressed genes were identified. The results showed that the contents of a series of phenolic acids related to the tyrosine metabolism pathway were downregulated under shading treatment, revealing that shading decreased the accumulation of phenolic acids and further mediated the resulting bitter taste of the bamboo shoots. This work will be helpful for understanding the regulatory mechanisms governing the bitter tasting substances in bamboo shoots grown under a shading treatment and provides a reference for the use of shading treatment in cultivation practices to improve the taste of bamboo shoots.

Compared to cell suspensions or monolayers, 3D cell aggregates provide cellular interactions organized in space and heterogeneity that better resume the real organization of native tissues. They represent powerful tools to narrow down the gap between in vitro and in vivo models, thanks to their self-evolving capabilities. Recent strategies have demonstrated their potential as building blocks to generate microtissues. Developing specific methodologies capable of organizing these cell aggregates into 3D architectures and environments has become essential to convert them into functional microtissues adapted for regenerative medicine or pharmaceutical screening purposes. Although the techniques for producing individual cell aggregates have been on the market for over a decade, the methodology for engineering functional tissues starting from them is still a young and quickly evolving field of research. In this review, we first present a panorama of emerging cell aggregates microfabrication and assembly technologies. We further discuss the perspectives opened in the establishment of functional tissues with a specific focus on controlled architecture and heterogeneity to favor cell differentiation and proliferation.

This editorial celebrates the 10th anniversary of Journal of Advanced Dielectrics (JAD) which was launched in January 2011.

Er3+ doped BaxSr0.998-xEr0.002Nb2O6 (SBNx, x = 0.25, 0.40, 0.50, 0.60, 0.75) and Er–Yb co-doped Ba3.75Sr1.24-xEr0.01YbxNb10O30 (SBN75, x = 0, 1:10, 1:20, 1:25, 1:30) ferroelectric ceramics were synthesized by a solid-state reaction method. With the change in stoichiometric x, upconversion (UC) luminescence and temperature sensing properties of the SBN were investigated. The sample (SBN75) at the morphotropic phase boundary is found to obtain the highest emission intensity. For Er–Yb co-doped Ba3.75Sr1.24-xEr0.01YbxNb10O30 ceramics, bright UC green and red emissions originated from a two-photon energy-transfer process were observed under 980 nm laser excitation. The temperature sensing properties were measured by means of a fluorescence intensity ratio technique, and the maximum sensitivity was approximately 0.0074 K−1 at 631 K in the sample SBN75:0.01Er/0.20Yb. From these findings, Er3+ ions doped in SBN ceramic, at the O-T phase boundary, have potential applications for temperature sensors.

Brown and brown-like adipocytes (BAs) are promising cell targets to counteract obesity thanks to their potential to drain and oxidize circulating glucose and triglycerides. However, the scarcity of BAs in human adults is a major limitation for energy expenditure based therapies. Enhanced characterization of BA progenitor cells (BAPs) and identification of critical pathways regulating their generation and differentiation into mature BAs would be an effective way to increase the BA mass. The identification of molecular mechanisms involved in the generation of thermogenic adipocytes is progressing substantially in mice. Much less is known in humans, thus highlighting the need for an in vitro model of human adipocyte development. Pluripotent stem cells (PSCs), i.e., embryonic stem cells and induced pluripotent stem cells, help gain insight into the different phases in the development of multiple cell types. We will discuss the capacity of human PSCs to differentiate into BAs in this review. Several groups, including ours, have reported low spontaneous adipocyte generation from PSCs. However, factors governing the differentiation of induced pluripotent stem cell-derived BA progenitors cells were recently identified, and the TGFβ signaling pathway has a pivotal role. The development of new relevant methods, such as the differentiation of hPSC-BAPs into 3D adipospheres to better mimick the lobular structure of human adipose tissue, will also be discussed. Differentiation of human PSCs into thermogenic adipocytes at high frequency provides an opportunity to characterize new targets for anti-obesity therapy.

Abstract Neem (Azadirachta indica) extract is well-known as a natural pesticide for the control of agricultural pests. Azadirachtin A and its structural analogues are considered as active compounds. However, the amounts of azadirachtins varies in neem extracts, providing a variety of insecticidal activities. In this study, a novel method of automated online solid-phase extraction coupled with liquid chromatography/quadrupole-time-of-flight mass spectrometry (SPE-LC–Q-TOF–MS) was developed and validated for simultaneous quantification of five azadirachtins (azadirachtins A, B, D, H and I) in seed and leaf extracts of A. indica. Different experimental parameters (such as SPE cartridge, injection volume and washing step) were optimized. The optimized SPE-LC–Q-TOF–MS method showed good recovery (82.0–102.8%), linearity (r 2 ≥ 0.9991) and precision (0.83–4.83%). The limit of detections (LODs) for the five analytes ranged from 0.34 to 0.76 ng mL−1. The validated method was successfully applied for determination of the analytes in the neem leaves and seeds from different locations and a neem formulation. The online SPE-LC–Q-TOF–MS method was found to be a simple, precise and accurate and can be used as a powerful tool for quality control of neem extracts or its formulations.

Abstract Background Beginning in 2010, China has endeavoured to expand health coverage and provide residents with fair access to primary health care with the intention of improving health equity. This study aims to measure changes in income-related health inequity in China between 2010 and 2014. Methods Data were extracted from the nationally representative annual survey of the China Family Panel Studies in 2010 and 2014 with a first wave of 31,743 respondents and a second wave of 32,006 respondents over age 15. In both years, subjects were stratified into the following five categories of income: poorest 20%, lower 20%, medium 20%, higher 20% and richest 20%. The concentration curve and index was used to compare the distribution of health status in income quintiles, and a logistic model was used to examine the relationship between health and socioeconomic indicators with self-assessed health as the primary outcome of interest. Results Income was significantly associated with self-assessed health in China. The concentration curve was above the line of equality in both years, while the self-assessed health line in 2014 was closer to the equality line. The concentration index (CIN) displayed the similar result of decreasing inequality, with the CIN in 2014 (− 0.157) closer to zero (the line of equality) than that of 2010 (− 0.167). In 2010, there was a decreasing trend of people reporting poor health from the poorest to the richest, while in 2014, there was no significant difference between the poorest and lower 20% or between the higher 20% and the medium 20%. The odds ratio of the prevalence of self-reporting poor health between the poorest and richest increased from 0.555 (95% CI: 0.484–0.636) in 2010 to 0.598 (95% CI: 0.513–0.696) in 2014. Conclusions From 2010 to 2014, the self-assessed health gap between income groups in China decreased, and health equity improved. However, health differences remain. In order to achieve better health for all, China should further strengthen the role of primary care in reducing health inequity.

Objectives: Genome-wide association studies have reported that DNA polymorphisms at the CDKN2A locus modulate fasting glucose in human and contribute to type 2 diabetes (T2D) risk. Yet the causal relationship between this gene and defective energy homeostasis remains elusive. Here we sought to understand the contribution of Cdkn2a to metabolic homeostasis. Methods: We first analyzed glucose and energy homeostasis from Cdkn2a-deficient mice subjected to normal or high fat diets. Subsequently Cdkn2a-deficient primary adipose cells and human-induced pluripotent stem differentiated into adipocytes were further characterized for their capacity to promote browning of adipose tissue. Finally CDKN2A levels were studied in adipocytes from lean and obese patients. Results: We report that Cdkn2a deficiency protects mice against high fat diet-induced obesity, increases energy expenditure and modulates adaptive thermogenesis, in addition to improving insulin sensitivity. Disruption of Cdkn2a associates with increased expression of brown-like/beige fat markers in inguinal adipose tissue and enhances respiration in primary adipose cells. Kinase activity profiling and RNA-sequencing analysis of primary adipose cells further demonstrate that Cdkn2a modulates gene networks involved in energy production and lipid metabolism, through the activation of the Protein Kinase A (PKA), PKG, PPARGC1A and PRDM16 signaling pathways, key regulators of adipocyte beiging. Importantly, CDKN2A expression is increased in adipocytes from obese compared to lean subjects. Moreover silencing CDKN2A expression during human-induced pluripotent stem cells adipogenic differentiation promoted UCP1 expression. Conclusion: Our results offer novel insight into brown/beige adipocyte functions, which has recently emerged as an attractive therapeutic strategy for obesity and T2D. Modulating Cdkn2a-regulated signaling cascades may be of interest for the treatment of metabolic disorders. Keywords: Obesity, Type 2 diabetes, Insulin sensitivity, Energy expenditure, cdkn2a, Genome-wide association study, Adipose tissue browning