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Acute gouty arthritis (AGA) is an acute inflammatory disease, whose occurrence and development mechanism are associated with inflammatory reaction of joint tissue. This study investigated the role of neoisoastilbin (NIA) in the treatment of AGA and explored the underlying mechanisms. C57BL/6 mice underwent intraarticular injection of monosodium urate (MSU) to establish an AGA model in vivo. Enzyme-linked immunosorbent assay, histopathological hematoxylin-eosin staining, western blotting, and other methods were used to observe the therapeutic effects of NIA on AGA and investigate the role of the NF-κB/NLRP3 pathway in the treatment. We found that NIA effectively reduced MSU-induced joint swelling and inflammatory cell infiltration in a concentration-dependent manner. NIA also significantly reduced interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels as compared with the respective values in the model mice group. In addition, administration of NIA significantly mitigated the phosphorylation of NF-κB-related proteins (IKKα, NF-κB, and IκBα) and the expression of NLRP3-related proteins (NLRP3, caspase-1, and ASC) in MSU-induced joint tissues. In conclusion, our research indicated that NIA significantly improved AGA, and its underlying mechanism was achieved by simultaneously inhibiting the NF-κB/NLRP3 pathway and the expression of inflammatory factors. This research preliminarily suggested the potential role of NIA in the treatment of AGA.

The co-occurrence of hyperuricemia and gouty arthritis is common in patients, yet a suitable animal model for this condition is lacking. In present study, a mice model combined hyperuricemia and gouty arthritis was established. Kaempferol, a flavonoid compound with anti-inflammatory and urate-lowering properties, was administered to mice in different dosages (25, 50, and 100 mg/kg). The levels of uric acid, creatinine, blood urea nitrogen and xanthine oxidase activity were measured, then kidney and joint ankle tissues were examined for pathological changes. The expressions of renal transporters, oxidative stress and inflammatory cytokines were detected. Furthermore, the anti-inflammatory mechanism of kaempferol was verified from NOD-like receptor protein 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) pathway. The results of histological analyses showed that kaempferol ameliorated the glomerular and renal tubular lesions and ankle arthritis inflammatory infiltration caused by hyperuricemia combined with gouty arthritis. Additionally, treatment with kaempferol effectively alleviated oxidative stress and decreased the levels of pro-inflammatory cytokines. The research confirmed that kidney and joint inflammation in hyperuricemia combined with gouty arthritis mice were alleviated by kaempferol via suppressing NLRP3 inflammasome and NF-κB pathway.

A bioactive polysaccharide (TS2-2A) with a molecular weight of 15 kDa was isolated from Trametes sanguinea Lloyd, a medicinal food homologous fungus, by water extraction-alcohol precipitation and chromatographic separation. NMR analysis of polysaccharide and MS/MS analysis of its oligosaccharide indicated that TS2-2A featured a novel straight chain with a backbone of 1,3-α-d-glucopyranose and 1,4-β-d-glucopyranose at a molar ratio of 1:4. Moreover, TS2-2A, recognized by Toll-like receptor 4 (TLR4), stimulated RAW 264.7 macrophages to release related cytokines and contributed to immune-enhancing effects. Briefly, with remarkable immune-enhancing activity and noncytotoxicity, TS2-2A was proposed to be a potential immune enhancer for supplementing drugs or functional foods.

To clarify the flow characteristics of the misaligned-phase parallel external gear pump with different phases and rotational speeds, the flow pulsation and cavitation of the misaligned-phase parallel external gear pump under different working conditions were systematically studied by combining theoretical analysis with tridimensional numerical simulation. The flow pulsation characteristics of the misaligned-phase parallel external gear pump are analyzed. Compared with the same-phase gear pump, the flow pulsation of the misaligned-phase parallel external gear pump was reduced. When the phase angle is [Formula: see text], the pressure and flow pulsations of the parallel gear pump are minimum, the flow pulsation is less than 1/4 of the same-phase gear pump. The relationship between cavitation and phase angle of the misaligned-phase parallel external gear pump is verified. When the rotational speed is different, with the increase in the rotational speed, the amplitude of the pressure fluctuation increases, and the effect of pressure pulsation overlapping and counteracting each other in the misaligned phase is more ideal. The flow does not fluctuate with the rotational speed and is only related to the phase angle, the cavitation is aggravated with the increase in the rotational speed.

Endometriosis is an estrogen-dependent chronic inflammatory disease. Hormonal and surgical treatments are the most commonly used clinical therapies, but they have many sides effects or are traumatic to the body. Therefore, specific drugs for endometriosis treatment are urgently needed to develop. In this study, we identified two features of endometriosis, namely the continuous recruitment of neutrophils into the ectopic lesions and the higher uptake of glucose by ectopic cells. For the above features, we designed a glucose oxidase-loaded bovine serum albumin nanoparticle (BSA-GOx-NPs) that is inexpensive and facilitates large-scale production. After injection, BSA-GOx-NPs were high specifically delivered to ectopic lesions in a neutrophil-dependent manner. Furthermore, BSA-GOx-NPs deplete glucose and induce apoptosis in the ectopic lesions. Whereupon BSA-GOx-NPs produced excellent anti-endometriosis effects when administrated in both acute and chronic inflammatory phases. These results reveal for the first time that the neutrophil hitchhiking strategy is effective in chronic inflammatory disease and provide a non-hormonal and easy-to-achieve approach for endometriosis treatment.

2-naphthol is a low-molecular-weight (LMW) polycyclic aromatic hydrocarbon (PAH) and air pollutant associated with childhood obesity. There has been a recent emergence of studies on the consequences of PAHs on human health. Current epidemiological reports suggest LMW-PAHs may contribute to obesity incidences in children, yet most studies focus on high-molecular-weight PAHs. This study explores 2-naphthol’s impact on obesity and obesity-associated metabolic disorders. To investigate 2-naphthol’s effect on lipid metabolism and inflammation, we employed 3T3-L1 and BAT1 cell lines to model white and brown adipocytes, respectively, alongside a murine macrophage cell line (RAW264.7). We found that 2-naphthol increased the expression of key adipogenic and lipogenic genes while decreasing lipolytic gene expression in chronically treated 3T3-L1 and BAT1 adipocytes. In addition, chronic 2-naphthol treatment also suppressed adrenergic-stimulated thermogenic gene expression in BAT1 brown adipocytes. In consistence, an increase in lipid accumulation was demonstrated in BODIPY and Oil Red O-stained adipocytes. Additionally, 3T3-L1 adipocytes and RAW264.7 macrophages chronically exposed to 2-naphthol showed upregulated mRNA expression of major inflammatory cytokines (e.g., tumor necrosis factor α (Tnfα), interleukin-1β (Il-1β), and Il-6). In summary, chronic exposure to 2-naphthol stimulates lipid accumulation in adipocytes and inflammation in adipocytes and macrophages. These findings support previous research that demonstrates 2-naphthol has obesogenic potential.

Aiming at solving the problems of bad imperceptibility and low embedding rate of existing algorithms, a novel large-capacity reversible image watermarking based on improved difference expansion (DE) is proposed. Firstly, the smoothness calculation algorithm is used to calculate and sort the smoothness values of the divided image sub-blocks; then, the scrambled watermark is embedded into the sub-blocks with less smoothness after removing the abrupt point by using the generalized difference expansion (GDE); finally, the absolute difference operation is applied to the generated overflow pixels to make their pixel values within a reasonable range for embedding watermark information. Under the premise of ensuring a certain visual quality, multiple watermark embedding can effectively improve the embedding rate. The simulation results show that this algorithm not only realizes blind extraction, but also recovers the original images without loss. At the same time, this algorithm achieves a high embedding rate (the average embedding rate is as high as 77.91 dB) without decreasing the visual quality.

Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity., Brown adipocytes contribute to energy balance, and adipocyte development and brown adipocyte thermogenesis are in part regulated by epigenetic modifications. Here the authors report that the histone demethylase Utx maintains brown adipocyte identity via demethylation of PRDM16, which in turn represses myogenic remodelling via DNMT1-mediated Myod1 promoter hypermethylation in mice.

Mindfulness-based stress reduction (MBSR) has become an alternative intervention for cancer patients, but its impact on depression and quality of life (QOL) of breast cancer patients remains controversial. The aim of this study was to evaluate the effects of MBSRAccording to the PICOS principles, databases [PubMed, Cochrane Database, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (VIP), and Wanfang Database] were searched for randomized controlled trials (RCTs) on the evaluation of MBSRThe final analysis included 14 studies with a total of 2,224 patients (1,138 in the MBSR group and 1,086 in the control group). The overall results of risk of bias assessment showed that the reporting bias among articles was high, and other bias was relatively moderate. Funnel plots and Egger's tests showed that there was no significant publication bias. Compared with standard or usual care, MBSR effectively relieved the psychological stress [mean difference (MD), -1.72; 95% confidence interval (CI): (-2.53, -0.92); P0.0001] and anxiety [standardized mean difference (SMD), -1.36; 95% CI: (-2.13, -0.60); P=0.0005] of breast cancer patients, and improved depression [SMD, -0.62; 95% CI: (-1.20, -0.03); P=0.04] and sleep status [MD, -0.42; 95% CI: (-0.73, -0.10), P=0.009]. However, it had no significant effect on fatigue [SMD, -0.97; 95% CI: (-2.24, 0.31); P=0.14] or QOL [MD, 1.95; 95% CI: (-3.15, 7.05); P=0.45].MBSR was better than standard or usual care for relieving psychological stress, anxiety, depression, and sleep in patients with breast cancer. Considering the limitations of this article, such as high risk of bias and high heterogeneity of included studies, the interpretation of this conclusion should be cautious.

Homeodomain-leucine zipper (HD-Zip) transcription factors are only present in higher plants and are involved in plant development and stress responses. However, our understanding of their participation in the fruit ripening of economical plants, such as tomato (Solanum lycopersicum), remains largely unclear. Here, we report that VAHOX1, a member of the tomato HD-Zip I subfamily, was expressed in all tissues, was highly expressed in breaker+4 fruits, and could be induced by ethylene. RNAi repression of VAHOX1 (VAHOX1-RNAi) resulted in accelerated fruit ripening, enhanced sensitivity to ethylene, and increased total carotenoid content and ethylene production. Conversely, VAHOX1 overexpression (VAHOX1-OE) in tomato had the opposite effect. RNA-Seq results showed that altering VAHOX1 expression affected the transcript accumulation of a series of genes involved in ethylene biosynthesis and signal transduction and cell wall modification. Additionally, a dual-luciferase reporter assay, histochemical analysis of GUS activity and a yeast one-hybrid (Y1H) assay revealed that VAHOX1 could activate the expression of AP2a. Our findings may expand our knowledge about the physiological functions of HD-Zip transcription factors in tomato and highlight the diversities of transcriptional regulation during the fruit ripening process.

Activation of brown fat thermogenesis increases energy expenditure and alleviates obesity. Sympathetic nervous system (SNS) is important in brown/beige adipocyte thermogenesis. Here we discover a fat-derived “adipokine” neurotrophic factor neurotrophin 3 (NT-3) and its receptor Tropomyosin receptor kinase C (TRKC) as key regulators of SNS growth and innervation in adipose tissue. NT-3 is highly expressed in brown/beige adipocytes, and potently stimulates sympathetic neuron neurite growth. NT-3/TRKC regulates a plethora of pathways in neuronal axonal growth and elongation. Adipose tissue sympathetic innervation is significantly increased in mice with adipocyte-specific NT-3 overexpression, but profoundly reduced in mice with TRKC haploinsufficiency (TRKC +/−). Increasing NT-3 via pharmacological or genetic approach promotes beige adipocyte development, enhances cold-induced thermogenesis and protects against diet-induced obesity (DIO); whereas TRKC + /− or SNS TRKC deficient mice are cold intolerant and prone to DIO. Thus, NT-3 is a fat-derived neurotrophic factor that regulates SNS innervation, energy metabolism and obesity. Activation of brown adipose tissue thermogenesis increases energy expenditure and promotes weight loss in mice. Here the authors identify neurotrophic factor neurotrophin 3 (NT-3) as an adipokine that regulates sympathetic nervous system growth and innervation in adipose tissue and increases white adipose beiging.

Tumor-associated macrophages (TAMs) play an important role in tumor development and progression. In particular, M2 TAMs can promote tumor growth by facilitating tumor progression and malignant behaviors. Selectively targeted elimination of M2 TAMs to inhibit tumor progression is of great significance for cancer treatment. Iron oxide nanoparticles based magnetic hyperthermia therapy (MHT) is a classical approach to destroy tumor tissue with deep penetration depth. In this study, we developed a typical M2 macrophage-targeted peptide (M2pep) functionalized superparamagnetic iron oxide nanoparticle (SPIO) for magnetic resonance imaging (MRI)-guided MHT in an orthotopic breast cancer mouse model. The obtained multifunctional SPIO-M2pep with a hydrodynamic diameter of 20 nm showed efficient targeting capability, high transverse relaxivity (149 mM−1 s−1) and satisfactory magnetic hyperthermia performance in vitro. In vivo studies demonstrated that the SPIO-M2pep based MRI can monitor the distribution of nanoparticles in tumor and indicate the suitable timing for MHT. The M2 macrophage-targeted MHT significantly reduced the tumor volume and the population of pro-tumoral M2 TAMs in tumor. In addition, the SPIO-M2pep based MHT can remodel the tumor immune microenvironment (TIME). The multifunctional SPIO-M2pep with M2 macrophage-targeting ability, high magnetic hyperthermia efficiency, MR imaging capability and effective role in remodeling the TIME hold great potential to improve clinical cancer therapy outcomes.

Although various liver chips have been developed using emerging organ-on-a-chip techniques, it remains an enormous challenge to replicate the liver lobules with self-assembled perfusable hepatic sinusoid networks. Herein we develop a lifelike bionic liver lobule chip (LLC), on which the perfusable hepatic sinusoid networks are achieved using a microflow-guided angiogenesis methodology; additionally, during and after self-assembly, oxygen concentration is regulated to mimic physiologically dissolved levels supplied by actual hepatic arterioles and venules. This liver lobule design thereby produces more bionic liver microstructures, higher metabolic abilities, and longer lasting hepatocyte function than other liver-on-a-chip techniques that are able to deliver. We found that the flow through the unique micropillar design in the cell coculture zone guides the radiating assembly of the hepatic sinusoid, the oxygen concentration affects the morphology of the sinusoid by proliferation, and the oxygen gradient plays a key role in prolonging hepatocyte function. The expected breadth of applications our LLC is suited to is demonstrated by means of preliminarily testing chronic and acute hepatotoxicity of drugs and replicating growth of tumors in situ. This work provides new insights into designing more extensive bionic vascularized liver chips, while achieving longer lasting ex-vivo hepatocyte function.

Our findings indicated that the SlERF.J2-IAA23 module integrates hormonal signals to regulate hypocotyl elongation and plant height in tomato. Light and phytohormones can synergistically regulate photomorphogenesis-related hypocotyl elongation and plant height in tomato. AP2/ERF family genes have been extensively demonstrated to play a role in light signaling and various hormones. In this study, we identified a novel AP2/ERF family gene in tomato, SlERF.J2. Overexpression of SlERF.J2 inhibits hypocotyl elongation and plant height. However, the plant height in the slerf.j2

In the past two decades, significant progress has been made in the past two decades towards the understanding of the basic mechanisms underlying cancer growth and angiogenesis. In this context, receptor tyrosine kinases (RTKs) play a pivotal role in cell proliferation, differentiation, growth, motility, invasion, and angiogenesis, all of which contribute to tumor growth and progression. Mutations in RTKs lead to abnormal signal transductions in several pathways such as Ras-Raf, MEK-MAPK, PI3K-AKT and mTOR pathways, affecting a wide range of biological functions including cell proliferation, survival, migration and vascular permeability. Increasing evidence demonstrates that multiple kinases are involved in angiogenesis including RTKs such as vascular endothelial growth factor, platelet derived growth factor, epidermal growth factor, insulin-like growth factor-1, macrophage colony-stimulating factor, nerve growth factor, fibroblast growth factor, Hepatocyte Growth factor, Tie 1 & 2, Tek, Flt-3, Flt-4 and Eph receptors. Overactivation of RTKs and its downstream regulation is implicated in tumor initiation and angiogenesis, representing one of the hallmarks of cancer. This review discusses the role of RTKs, PI3K, and mTOR, their involvement, and their implication in pro-oncogenic cellular processes and angiogenesis with effective approaches and newly approved drugs to inhibit their unrestrained action.

Tumor microenvironment (TME) is a crucial regulator of tumor progression and cells in the TME release a number of molecules that are responsible for anaplasticity, invasion, metastasis of tumor, establishing stem cell niches, up-regulation and down-regulation of various pathways in cancer cells, interfering with immune surveillance and immune escape. Moreover, they can serve as diagnostic markers, and determine effective therapies. Among them, CircRNAs have gained special attention due to their involvement in mutated pathways in cancers. By functioning as a molecular sponge for miRNAs, binding with proteins, and directing selective splicing. CircRNAs modify the immunological environment of cancers to promote their growth. Besides of critical role in tumor growth, circRNAs are emerging as potential candidates as biomarkers for diagnosis cancer therapy. Also, circRNAs vaccination even offers a novel approach to tumor immunotherapy. Over the recent years, studies are advocating that circRNAs have tissue specific tumor specific expression patterns, which indicates their potential clinical utility. Especially, circRNAs have emerged as potential predictive and prognostic biomarkers. Although, there has been significant progress in deciphering the role of circRNA in cancers, literature lacks comprehensive overview on this topic. Keeping in view of these significant discoveries, this review systematically discusses circRNA and their role in the tumor in different dimensions.

Gouty arthritis (GA) is a frequent inflammatory disease characterized by pain, swelling, and stiffness of joints. Neoastilbin is a flavonoid isolated from the rhizome of Smilax glabra, which possesses various anti-inflammatory effects. However, the mechanism of neoastilbin in treating GA has not yet been clarified. Thus, this study was to investigate the protective effects of neoastilbin in both monosodium urate (MSU) stimulated THP-1-derived macrophages and the animal model of GA by injecting MSU into the ankle joints of mice. The levels of key inflammatory cytokines in MSU stimulated THP-1-derived macrophages were detected by enzyme-linked immunosorbent assay (ELISA) kits. Protein expressions of nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome pathways were further detected by Western blotting. In addition, swelling degree of ankle joints, the levels of inflammatory factors, infiltration of inflammatory cells and the expressions of related proteins were determined. Swelling degree and histopathological injury in ankle joints of MSU-injected mice were significantly decreased after being treated with neoastilbin. Moreover, neoastilbin significantly diminished the secretion of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), suppressing the activation of NF-κB and NLRP3 inflammasome pathways in both MSU stimulated THP-1-derived macrophages and the mouse model of GA. In summary, neoastilbin could alleviate GA by inhibiting the NF-κB and NLRP3 inflammasome pathways, which provided some evidence for neoastilbin as a promising therapeutic agent for GA treatment.

Object detection from remote sensing images serves as an important prerequisite to many applications. However, caused by scale and orientation variations, appearance and distribution diversities, o...

Cross-efficiency in data envelopment analysis is widely used for performance evaluation of decision-making units (DMUs), but it neglects the reference relationship between each pair of DMUs. In order to address the problem, this paper introduces the concept of social network to clearly describe the reference relationship between DMUs and then a fully ranking can be made. A novel cross-efficiency approach is developed by integrating social network analysis in this study. Firstly, we propose a pairwise comparison model based on cross-efficiency evaluation to identify the superiority and inferiority between any pair of DMUs. Secondly, based on pairwise comparison, we build a non-weighted directed social network where a direction generates from one DMU to another DMU if the former one references the latter one. Each edge in the unweighted social network captures the learning procedure from worse-performance DMU to better-performance DMU. Comparing with traditional cross-efficiency approaches, our proposed approach considers the reference relationship among DMUs rather than only cross-efficiency scores. Thus, the importance of each DMU in the network can be measured by its centrality. Finally, the proposed approach is employed to environmental efficiency evaluation of the cities along the Xiangjiang River Basin, then, some beneficial universal policies have been summarized.

Psoriasis is one of the most influential and fastest-growing inflammatory diseases of the skin. Curcumin (CRC) is an effective antipsoriatic drug that is often carried by nanoparticles or liposomes mainly administered via the skin. However, the therapeutic effectiveness and bioavailability of this drug are restricted due to the functions of the skin barrier to liposomes. Herein, we proposed a peptide-modified curcumin-loaded liposome (CRC-TD-Lip) to expedite the transdermal delivery of curcumin and enhance the inhibition of psoriasis. CRC-TD-Lip was prepared and dispersed uniformly with high stability and high curcumin encapsulation efficiency. We confirmed the improved intracellular uptake of CRC-TD-Lip, the increased inhibitory effect of CRC-TD-Lip on HaCaT cells, and the heightened transdermal ability of CRC-TD-Lip. Then, the enhanced antipsoriatic ability of CRC-TD-Lip was evaluated in vivo using an imiquimod-induced psoriasis mouse model. The results indicated that the developed CRC-TD-Lip can effectively improve the delivery of curcumin across the skin and enhance the antipsoriasis efficiency. This work can provide a strategy for enhancing the transdermal delivery efficiency of drugs for various skin diseases.

Super-porous hydrogels are considered a potential drug delivery network for the sedation of gastric mechanisms with retention windows in the abdomen and upper part of the gastrointestinal tract (GIT). In this study, a novel pH-responsive super-porous hybrid hydrogels (SPHHs) was synthesized from pectin, poly 2-hydroxyethyl methacrylate (2HEMA), and N, N methylene-bis-acrylamide (BIS) via the gas-blowing technique, and then loaded with a selected drug (amoxicillin trihydrate, AT) at pH 5 via an aqueous loading method. The drug-loaded SPHHs-AT carrier demonstrated outstanding (in vitro) gastroretentive drug delivery capability. The study attributed excellent swelling and delayed drug release to acidic conditions at pH 1.2. Moreover, in vitro controlled-release drug delivery systems at different pH values, namely, 1.2 (97.99%) and 7.4 (88%), were studied. These exceptional features of SPHHs—improved elasticity, pH responsivity, and high swelling performance—should be investigated for broader drug delivery applications in the future.

Nanozymes that mimic peroxidase (POD) activity can convert H2O2 into bactericidal free radicals, which is referred to as chemodynamic therapy (CDT). High glutathione (GSH) levels in the infectious tissue severely limit the performance of CDT. Herein, we report a near-infrared-controlled antibacterial nanoplatform that is based on encapsulating tungsten sulfide quantum dots (WS2QDs) and the antibiotic vancomycin in a thermal-sensitive liposome. The system exploits the photothermal sensitivity of the WS2QDs to achieve selective liposome rupture for the targeted drug delivery. We determined that WS2QDs show a strong POD-like activity under physiological conditions and the oxidase-like activity, which can oxidate GSH to further improve the CDT efficacy. Moreover, we found that increased temperature promotes multiple enzyme-mimicking activities of WS2QDs. This platform exerts antibacterial effects against Gram-positive Mu50 (a vancomycin-intermediate Staphylococcus aureus reference strain) and Gram-negative Escherichia coli and disrupts biofilms for improved penetration of therapeutic agents inside biofilms. In vivo studies with mice bearing Mu50-caused skin abscess revealed that this platform confers potent antibacterial activity without obvious toxicity. Accordingly, our work illustrates that the photothermal and nanozyme properties of WS2QDs can be deployed alongside a conventional therapeutic to achieve synergistic chemodynamic/photothermal/pharmaco therapy for powerful antibacterial effects.

While the main function of white adipose tissue (WAT) is to store surplus of energy as triacylglycerol, that of brown adipose tissue (BAT) is to burn energy as heat. Epigenetic mechanisms participate prominently in both WAT and BAT energy metabolism. We previously reported that the histone demethylase ubiquitously transcribed tetratricopeptide (Utx) is a positive regulator of brown adipocyte thermogenesis. Here, we aimed to investigate whether Utx also regulates WAT metabolism in vivo. We generated a mouse model with Utx deficiency in adipocytes (AUTXKO). AUTXKO animals fed a chow diet had higher body weight, more fat mass and impaired glucose tolerance. AUTXKO mice also exhibited cold intolerance with an impaired brown fat thermogenic program. When challenged with high-fat diet (HFD), AUTXKO mice displayed adipose dysfunction featured by suppressed lipogenic pathways, exacerbated inflammation and fibrosis with less fat storage in adipose tissues and more lipid storage in the liver; as a result, AUTXKO mice showed a disturbance in whole body glucose homeostasis and hepatic steatosis. Our data demonstrate that Utx deficiency in adipocytes limits adipose tissue expansion under HFD challenge and induces metabolic dysfunction via adipose tissue remodeling. We conclude that adipocyte Utx is a key regulator of systemic metabolic homeostasis.

The understanding about virulence factors (VFs) and the drug resistance of uropathogenic Escherichia coli (UPEC) helps us understand the pathogenesis of urinary tract infections (UTIs) and make better decisions for clinical treatment. This study examined the correlation between the extended-spectrum β-lactamases (ESBLs) phenotype and VFs in UPEC strains. In addition, we validated the therapeutic potential of fosfomycin in acute pyelonephritis mice. From May 2017 to November 2018, 22 nonduplicate E coli. strains were isolated from UTI patients. PCR was utilized to detect the distribution of virulence genes. We also analyzed the ESBL phenotype in E coli. We further evaluated the therapeutic effect of intravenous fosfomycin treatment in the acute pyelonephritis (APN) model. All 22 UPEC strains expressed the type 1 fimbriae (FimH) gene and more than 50% (12/22) of strains produced ESBLs. The detection rates of the iron acquisition-associated genes ChuT and IutA were 77.3% ( n = 17 ) and 50% ( n = 11 ) and those of P fimbria papA and papC genes were 45% ( n = 10 ) and 50% ( n = 11 ), respectively. Though the VFs were closely related with pathologenicity, the relationship between VFs and ESBLs still needs further investigation. Furthermore, intravenous fosfomycin 800 mg/kg significantly reduced the bacterial load and the inflammatory infiltration in the bladder and kidney, maintaining the structural integrity of the kidney. Intravenous fosfomycin administration can be used for the treatment of acute pyelonephritis caused by highly pathogenic and drug-resistant UPEC strains.

ObjectivesTo assess the current status of injury prevention (IP) core competency among medical students majoring in public health in China and to advocate for incorporating IP in the medical curriculum.MethodsThe study used purposive sampling in eight medical universities in China in 2017, including 420 undergraduates and 763 graduates, using self-administered questionnaires based on the core competency instrument for IP with five domains (31 items): A) injury analysis and assessment (8 items), B) IP project planning and implementation (7 items), C) communication (6 items), D) community practice (5 items), and E) leadership and systematic thinking (5 items). The higher score indicated the higher level of proficiency of the ability (scores ranged from 1 to 5). We used linear regression model to test the effect of IP course experience on the core competency mean score after adjusting for potential confounders.ResultsThe total mean score was 2.78 (SD=0.76, median=2.9, range=1–4.55) and 2.68 (SD=0.75, median=2.81, range=1–4.45) for undergraduates and graduates, respectively. There were 60% and 36% of undergraduates and graduates who have ever taken IP course, respectively. IP course class hours were positively associated with core competency level (PConclusionThe core competency level is relatively low among public health students in China. Setting IP courses should be considered as an effective way to improve students’ core competency. It is a step moving towards the IP education promotion, and further boosting the field of public health.

As one of the main groups of marine planktonic protozoa, oligotrich ciliates have shown a high biodiversity. Recently, a new aloricate oligotrich ciliate, Strombidium pseudorapulum sp. n. was isolated from coastal waters of southeast China. The living morphology and infraciliature of this species were studied using live cell observation and protargol impregnation. Strombidium pseudorapulum sp. n. differs from its congeners by having a radish-like body with a bumped anterior end and an elongated tail-like posterior end, possessing a red ‘eyespot’ in apical protrusion of cell, adoral zone of membranelles composed of 12–16 collar and 9–12 buccal membranelles, one spindle-shaped macronucleus, girdle kinety in anterior 2/5 of cell with 45–60 densely spaced dikinetids, and ventral kinety occupying about the posterior 1/3 of the cell with 16–19 dikinetids. Strombidium pseudorapulum sp. n. clusters together with those species having ‘eyespot’ in apical protrusion in the phylogenetic tree based on the small subunit rRNA gene sequence. It is a sister species of S. cuneiforme with 31 unmatched nucleotides between their SSU rRNA gene sequences.

A high gas barrier performance should be ensured in case of biodegradable packing applications. However, the gas barrier properties of the biodegradable poly(lactic acid) (PLA) are not much effective. Nanocomposites can provide innovative solutions to enhance the barrier performance. In this study, different weight percentages of organically modified montmorillonite (OMMT) (0, 2, 4, 6, 8, and 10 wt %)-incorporated PLA/OMMT nanocomposites were prepared by melt mixing. Ethylene glycol diglycidyl ether (EGDE) was used to regulate the interlayer spacing of OMMT and increase the PLA crystallinity to further improve the gas barrier performance of the PLA/OMMT films. The crystallinity of PLA was significantly improved because EGDE-modified OMMT served as an efficient nucleating agent. The PLA/EGDE/OMMT films demonstrated a unique structure such that the adjacent OMMT layers were linked through the PLA crystals that serve as a bridge with respect to the spaces between the OMMT layers. The O2 permeability of the PLA/EGDE4/OMMT-6 film decreased by approximately 79% when compared with that of the neat PLA film. X-ray diffraction and differential scanning calorimetry analyses denoted that the reduced oxygen permeability of the PLA/EGDE4/OMMT-6 film can be primarily attributed to the high crystallinity of the PLA matrix and the bridging effect of the PLA crystals between two adjacent layers. Based on the experimental results, the relation between the relative permeability and vol % OMMT is in good agreement with that of the predicted values obtained using the Bharadwaj model when S = 0. The added EGDE weakened the thermal stability and tensile strength, mainly because of degradation of the hydroxyl groups of EGDE formed by epoxy ring opening, and these hydroxyl groups can promote PLA matrix degradation. However, the practical application temperature of the packaging film is considerably lower than the thermal decomposition temperature; therefore, the reduction of the thermal decomposition temperature does not affect the use of the packaging film.

This study poses the following research questions: What is the prevalence of bullying in vocational schools in China? What are the differences between different genders and professions? How should individuals, families, and schools do to affect school bullying? What can we do to improve and to respond school bullying, to reduce its occurrence and consequences? This cross-sectional study was conducted in 2018 with 95,873 students from 85 vocational schools. The main outcome indicators were self-reported involvement in bullying (perpetrator, victim, perpetrator-victim, or uninvolved). Multinomial logistic regression analyses were conducted, with personal characteristics, relational characteristics, and school climate as predictors. A total of 30.4% of participants reported being bullied, 2.9% reported bullying others, and 21.7% reported being bullied and bullying others. Majors related to primary and secondary industries are more likely to involvement in bullying than majors related to tertiary industries. Boys were more involved in physical or verbal bullying, whereas girls were more involved in relational bullying and cyberbullying. Sex, history of fighting, and emotional/mental state were the strongest individual factors associated with bullying. Having friends was inversely associated with bullying involvement; moreover, a positive relationship with parents and a good parenting style (warmth, democracy, and mutual concern) protected students from bullying others as well as being bullied. School bullying programs, happiness at school, and insecurity at school were strong negative predictors of bullying. Bullying is prevalent among vocational school students in China. An appropriate response to school bullying requires strengthening student capacity to correctly understand and deal with bullying, identifying victims and vulnerable groups, developing school-based interventions, involving parents in prevention programs, and enhancing students’ sense of responsibility in supervision, reporting, and creating a friendly environment.

Tracing magnetically labeled cells with magnetic resonance imaging (MRI) is an emerging and promising approach to uncover in vivo behaviors of cells in cell therapy. Today, existing methods for the magnetic labeling of cells are cumbersome and time-consuming, which has greatly limited the progress of such studies on cell therapy. Thus, in this study, using the flow cytometric loading technology, we develop a sonoporation-based microfluidic chip (i.e., a microfluidic chip integrated with ultrasound; MCU), to achieve the safe, instant, convenient, and continuous magnetic labeling of cells. For the MCU we designed, a suitable group of operating conditions for safely and efficiently loading superparamagnetic iron oxide (SPIO) nanoparticles into DC2.4 cells was identified experimentally. Under the identified operating conditions, the DC2.4 cells could be labeled in approximately 2 min with high viability (94%) and a high labeling quantity of SPIO nanoparticles (19 pg of iron per cell). In addition, the proliferative functions of the cells were also well maintained after labeling. Furthermore, the in vivo imaging ability of the DC2.4 cells labeled using the MCU was verified by injecting the labeled cells into the leg muscle of the C57BL/6 mice. The results show that the excellent imaging outcome can be continuously achieved for 7 days at a density of 106 cells/mL. This work can provide insight for the design of magnetic cell labeling devices and promote the MRI-based study of cell therapies.

Beige adipocytes have become a promising therapeutic target to combat obesity. Our senior author Dr. B. Xue previously discovered a transient but significant induction of beige adipocytes in mice during early postnatal development, which peaked at postnatal day (P) 20 and then disappeared thereafter. However, the physiological mechanism underlying the transient induction of the developmental beige cells remains mystery. Interestingly, there exists a postnatal surge of leptin in mice at P10 before the appearance of the developmental beige adipocytes. Given the neurotropic effect of leptin during neuronal development and its role in activating the sympathetic nervous system (SNS), we tested the hypothesis that postnatal leptin surge is required for the transient induction of developmental beige adipocytes through sympathetic innervation. Unlike wild-type (WT) mice that were able to acquire the developmentally induced beige adipocytes at P20, ob/ob mice had much less uncoupling protein 1 (UCP1)-positive multilocular cells in inguinal white adipose tissue at the same age. This was consistent with reduced expression of UCP1 mRNA and protein levels in white fat of ob/ob mice. In contrast, daily injection of ob/ob mice with leptin between P8 and P16, mimicking the postnatal leptin surge, largely rescued the ability of these mice to acquire the developmentally induced beige adipocytes at P20, which was associated with enhanced sympathetic nerve innervation assessed by whole mount adipose tissue immunostaining of tyrosine hydroxylase. Our data demonstrate that the postnatal leptin surge is essential for the developmentally induced beige adipocyte formation in mice, possibly through increasing sympathetic nerve innervation.

Hole transport layers (HTLs) play a vital role in organic solar cells (OSCs). In this work, a derivative of tetrathiafulvalene with four carboxyl groups TTA was introduced as a novel HTL to fabricate OSC with high performance. Displaying a better energy level match between HTL and active layers, the TTA based devices show a peak power conversion efficiency of 9.09%, which is comparable to the devices based on PEDOT:PSS. The favorable surface morphology recorded via atomic force microscopy, low series loss and charge recombination indicated by electrochemical impedance spectroscopy, synchronously verify the potential of TTA for application in OSCs as a valid kind of HTLs.

As two-dimensional materials with a high specific surface area, strength, and electrical and thermal conductivity, graphene (Gr) and its derivatives have great application prospects in various fields such as structural reinforcement, energy storage, optics, and electrical and thermal conductivity. However, the current preparation method of Gr is complicated and expensive. Its preparation cost can be reduced using Gr composites that include inorganic materials or other polymers. Composite materials comprising Gr and inorganic materials are generally prepared using sinter molding, chemical reduction, or chemical deposition. Gr should be able to mitigate several of the defects resulting from inorganic materials, including their poor toughness, small specific capacity, and low photoelectric conversion rate. The mitigation of these defects should result in the expansion of the applications of Gr composites for use in capacitors, catalysts, and sensors, among other devices. Although solution blending or in situ polymerization produces a relatively good mixing effect, in general, melt blending is used in the large-scale processing of Gr composites with polymer materials. Gr can be used to partially mitigate several weaknesses of polymer materials, including their low strength, poor electrical and thermal conductivities, and poor isolation performance, and expand the applications of Gr composites for use in electrical and thermal conductive materials and functional membrane materials, among other applications. The goal of the present paper is to introduce the structural properties of Gr and a surface modification method for Gr. In addition, the preparation methods and application fields of different Gr composite materials are reviewed. Finally, the development prospects and key issues are discussed.

The emerging threat of multi-drug resistance (MDR) in a wide range of diseases is a major public health problem, which prolongs treatment, imposes disabilities and reduces the expected life...

Over the past four decades, patients with advanced ovarian cancer (OC) has enjoyed greatly improved survival rate considering advances in combined chemotherapy with platinum and paclitaxel. We investigated the association between polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and short- and long-term efficacy of concurrent chemoradiotherapy (CCRT) in advanced OC. Patients with advanced OC and healthy females were selected in our study. Multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) were applied to detect homozygous deletions in GSTM1 and GSTT1, as well as codon 105 genetic polymorphisms in GSTP1 exon 5. All the patients with advanced OC were treated with CCRT. Toxicity of chemotherapy, short-term efficacy, recurrence and metastasis, respectively. Long-term survival outcomes were checked with a further examination and all patients were followed up for three years after CCRT.Compared with healthy females, patients with advanced OC showed higher frequencies of GSTT1 non-null genotype and homozygous mutation type GG of GSTP. GSTP1genetic polymorphisms were relevant to neutropenia resulted from CCRT in patients with advanced OC. Compared with patients with GSTT1non-null genotype, those with GSTT1 null genotype appeared to enjoy a better short-term efficacy, lower recurrence and metastasis rate, higher survival rate and longer mean survival time. Compared with patients with GG genotype, those with GSTP1 AA + AG genotype also enjoyed more positive results. Our results reveal that GSTT1 null genotype and GSTP1AA + AG genotype are associated with short- and long-term efficacy of CCRT in advanced OC.

Autophagy allows cancer cells to respond changes in nutrient status by degrading and recycling non-essential intracellular contents. Inhibition of autophagy combined with nutrient deprivation is an effective strategy to treat cancer. Pain is a primary determinant of poor quality of life in advanced cancer patients, but there is currently no satisfactory treatment. In addition, effective treatment of cancer does not efficiently relieve cancer pain, but may increase pain in many cases. Hence, few studies focus on simultaneous cancer therapy and pain relief, and made this situation even worse. Method: Ropivacaine was loaded into tumor-active targeted liposomes. The cytotoxicity of ropivacaine-based combination therapy in B16 and HeLa cells were tested. Moreover, a mice model of cancer pain which was induced by inoculation of melanoma near the sciatic nerve was constructed to assess the cancer suppression and pain relief effects of ropivacaine-based combination therapy. Results: Ropivacaine and ropivacaine-loaded liposomes (Rop-DPRL) were novelly found to damage autophagic degradation. Replicated administration of Rop-DPRL and calorie restriction (CR) could efficiently repress the development of tumor. In addition, administration of Rop-DPRL could relieve cancer pain with its own analgestic ability in a short duration, while repeated administration of Rop-DPRL and CR resulted in continuous alleviation of cancer pain through reduction of VEGF-A levels in advanced cancer mice. Further, dual inhibition of phosphorylation of STAT3 at Tyr705 and Ser727 by Rop-DPRL and CR contribute to the reduction of VEGF-A. Conclusion: Combination therapy with Rop-DPRL and nutrient deprivation simultaneously suppresses cancer growth and relieves cancer pain.

Background Discs large homolog 5 (Dlg5) is a member of the membrane-associated guanylate kinase (MAGUK) adaptor family of proteins and its deregulation has been implicated in the malignancy of several cancer types. Dlg5 was down-regulated in hepatocellular carcinoma (HCC) and lower Dlg5 expression was associated with poor survival of HCC patients. However, how to regulate Dlg5 remains largely unknown. Methods The co-immunoprecipitation assay was used to determine the interaction between Dlg5 and β-TrCP. The in vivo ubiquitination assay was performed to determine the regulation of Dlg5 by β-TrCP. CCK-8 and colony formation assay were implemented to detect the biological effect of Dlg5 on the growth of HCC cells in vitro. The effect of Dlg5 on HCC tumor growth in vivo was studied in a tumor xenograft model in mice. Results Here we report that Dlg5 is regulated by the ubiquitin proteasome system and depletion of either Cullin 1 or β-TrCP led to increased levels of Dlg5. β-TrCP regulated Dlg5 protein stability by targeting it for ubiquitination and subsequent destruction in a phosphorylation-dependent manner. We further demonstrated a crucial role of Ser730 in the non-canonical phosphodegron of Dlg5 in governing β-TrCP-mediated Dlg5 degradation. Importantly, failure to degrade Dlg5 significantly inhibited HCC cells proliferation both in vitro and in vivo. Conclusion Collectively, our finding provides a novel molecular mechanism for the negative regulation of Dlg5 by β-TRCP in HCC cells. It further suggests that preventing Dlg5 degradation could be a possible novel strategy for clinical treatment of HCC.

Previous studies have proven that polysaccharide obtained from the seeds of Plantago asiatica L. (PLCP) could induce maturation of murine dendritic cells, promote defecation, and possess a...