Deciphering the natural and anthropogenic drivers on the fate and risk of antibiotics and antibiotic resistance genes (ARGs) in a typical river-estuary system, China.

This study conducts an in-depth assessment of the spatial distribution, ecological risks, and correlations among 12 antibiotics, antibiotic resistance genes (ARGs), and dominant microorganisms in a representative river-estuary system, classified by land use and hydrodynamic conditions. Sulfonamides and quinolones were identified as the major contaminants in surface waters, with aquaculture and healthcare wastewater responsible for over 80 % of the antibiotic load. Contrasting seasonal patterns were observed between freshwater (wet season: 215 ng/L, dry season: 99.9 ng/L) and tidal estuaries (wet season: 45.9 ng/L, dry season: 121 ng/L), attributed to antibiotic transport from terrestrial sources or coastal aquaculture areas. The estimated annual antibiotic influx into Jiaozhou Bay was 70.4 kg/year, posing a considerable threat to aquatic algae and disrupting the stability of aquatic food chain. BugBase predictions suggested that antibiotics in the environment suppressed bacteria characterized by biofilm formation (FB) and the presence of mobile elements (CME). However, ARG transmission was likely to drive the spread of CME, FB, and stress-tolerant (OST) bacteria within microbial communities. The significant positive correlations observed between sulfamethoxazole and 63 microbial genera indicate a broad distribution of microbial resistance, which exacerbates the potential for ARG accumulation and dissemination across both the bay and the Yellow Sea.

PU.1 regulates osteoarthritis progression via CSF1R in synovial cells.

This study elucidates the molecular mechanisms driving osteoarthritis (OA) by focusing on the transcription factor PU.1's role in synovial cells, specifically macrophages and fibroblast-like synoviocytes (FLS). Analyzing OA-related synovial gene expression from the GEO database highlighted immune regulation pathways in OA. Using protein-protein interaction and the JASPAR database, we pinpointed essential genes in OA development. Synovial tissues from OA patients and controls revealed pronounced PU.1 and its target CSF1R presence. In a surgically induced OA mouse model with PU.1 and CSF1R knockdown, ChIP assays confirmed PU.1's binding to the CSF1R promoter. Dual luciferase reporter assays and immunohistochemistry validated PU.1's regulatory impact on CSF1R transcription. Combined analysis of microarrays GSE55235 and GSE206848 showed heightened PU.1 expression in OA, associated with immune regulation in macrophages. In vitro findings aligned with in vivo results, emphasizing PU.1's influence on macrophage polarization and FLS-induced inflammation. PU.1's direct activation of CSF1R transcription underpins its key role in OA progression. This research offers insights into OA's molecular basis, suggesting potential therapeutic targets.

The role of esmolol in sepsis: a meta-analysis based on randomized controlled trials.

BACKGROUND: Sepsis is associated with a high incidence and mortality and poses a significant challenge to the treatment. Although esmolol has shown promise in sepsis treatment, its efficacy and safety remain contentious. This meta-analysis aims to clarify the role of esmolol in sepsis management. METHODS: PubMed, Embase, Web of Science, Cochrane library, clinicaltrials.gov and the Chinese Clinical Trial Registry were searched and references of relevant reviews and meta-analysis were also screened for appropriate studies. Keywords and free words of 'sepsis', 'esmolol' and 'randomized controlled trials' were used for search. Meta-analysis was performed using RevMan 5.3 software. RESULTS: Fifteen studies involving 1100 patients were included. Compared with the control group, patients receiving esmolol exhibited significantly decreased 28-day mortality (RR, 0.69; 95% CI, 0.60 to 0.81; P < 0.0001), heart rate (HR) (SMD, -1.15; 95% CI, -1.34 to -0.96; P < 0.0001), cardiac troponin I levels (cTnI) (SMD, -0.88; 95% CI, -1.13 to -0.64; P < 0.0001), length of intensive care unit (ICU) stay (SMD, -0.46; 95% CI, -0.62 to -0.3; P < 0.0001) and duration of mechanical ventilation (SMD, -0.28; 95% CI, -0.48 to -0.09; P = 0.004) and significantly increased central venous oxygen saturation (ScvO2) (SMD, 0.66; 95% CI, 0.44 to 0.88; P < 0.0001).While, esmolol had no significant influence on norepinephrine dosage (SMD, 0.08; 95% CI, -0.13 to 0.29; P = 0.46), mean arterial pressure (MAP) (SMD, 0.17; 95% CI, -0.07 to 0.4; P = 0.16), central venous pressure (CVP) (SMD, 0.16; 95% CI, -0.04 to 0.35; P = 0.11) and left ventricular ejection fraction (LVEF) (SMD, 0.21; 95% CI, -2.9 to 0.7; P = 0.41). CONCLUSION: Esmolol reduces 28-day mortality, length of ICU stay and duration of mechanical ventilation in sepsis patients. Furthermore, esmolol improves oxygen metabolism, mitigates myocardial injury and decreases heart rate without significantly affecting hemodynamic parameters. TRIAL REGISTRATION: This study was registered on the PROSPERO website (registration number: CRD42023484884).

Manipulation of Moiré Superlattice in Twisted Monolayer-multilayer Graphene by Moving Nanobubbles.

In the heterostructure of two-dimensional (2D) materials, many novel physics phenomena are strongly dependent on the Moiré superlattice. How to achieve the continuous manipulation of the Moiré superlattice in the same sample is very important to study the evolution of various physical properties. Here, in minimally twisted monolayer-multilayer graphene, we found that bubble-induced strain has a huge impact on the Moiré superlattice. By employing the AFM tip to dynamically and continuously move the nanobubble, we realized the modulation of the Moiré superlattice, like the evolution of regular triangular domains into long strip domain structures with single or double domain walls. We also achieved controllable modulation of the Moiré superlattice by moving multiple nanobubbles and establishing the coupling of nanobubbles. Our work presents a flexible method for continuous and controllable manipulation of Moiré superlattices, which will be widely used to study novel physical properties in 2D heterostructures.

Hierarchical Perceptual Noise Injection for Social Media Fingerprint Privacy Protection.

Billions of people share images from their daily lives on social media every day. However, their biometric information (e.g., fingerprints) could be easily stolen from these images. The threat of fingerprint leakage from social media has created a strong desire to anonymize shared images while maintaining image quality, since fingerprints act as a lifelong individual biometric password. To guard the fingerprint leakage, adversarial attack that involves adding imperceptible perturbations to fingerprint images have emerged as a feasible solution. However, existing works of this kind are either weak in black-box transferability or cause the images to have an unnatural appearance. Motivated by the visual perception hierarchy (i.e., high-level perception exploits model-shared semantics that transfer well across models while low-level perception extracts primitive stimuli that result in high visual sensitivity when a suspicious stimulus is provided), we propose FingerSafe, a hierarchical perceptual protective noise injection framework to address the above mentioned problems. For black-box transferability, we inject protective noises into the fingerprint orientation field to perturb the model-shared high-level semantics (i.e., fingerprint ridges). Considering visual naturalness, we suppress the low-level local contrast stimulus by regularizing the response of the Lateral Geniculate Nucleus. Our proposed FingerSafe is the first to provide feasible fingerprint protection in both digital (up to 94.12%) and realistic scenarios (Twitter and Facebook, up to 68.75%). Our code can be found at https://github.com/nlsde-safety-team/FingerSafe.

A "solo-solvent de novo liquid-phase" method for synthesizing sulfide solid electrolyte Li6PS5Cl.

We report a "solo-solvent de novo liquid-phase" method of synthesizing a highly-favored sulfide electrolyte (Li6PS5Cl) for developing all-solid-state lithium batteries. The key chemistry for such a successful method is that tetrahydropyrrole enables in situ synthesis of the critical precursor Li2S from cheap and air-stable precursors of lithium chloride and sodium sulfide.

TIGIT reverses IFN-α-promoted Th1-like Tregs via in-sequence effects dependent on STAT4.

OBJECTIVES: The induction direction of interferon (IFN)-α in T-cell phenotype and function varies depending on the activation state of the cell and the time of stimulation. To assess the effects of elevated IFN-α on regulatory T cells (Tregs) in systemic lupus erythematosus (SLE) patients, we investigated the differentiation of Th1-like Tregs under in-sequence and out-of-sequence conditions and the reversal effect of activating TIGIT on immune suppression. METHODS: Phenotypes and activation levels of Tregs from SLE patients and healthy controls were analyzed using flow cytometry. In vitro culture conditions based on the sequence of TCR activation and IFN-α stimulation simulated in-sequence or out-of-sequence effects. CD4+T cells and Tregs were cultured under the above conditions with or without TIGIT agonist. Expression of related characteristic markers and phosphorylation levels of AKT, mTOR, and STATs were detected using flow cytometry and ELISA. RESULTS: The frequency of Th1-like Tregs and activation levels of Tregs increased, but TIGIT expression in Tregs decreased in SLE patients. IFN-α promoted the conversation of Tregs to Th1-like Tregs while reducing immunosuppressive function under in-sequence conditions. The STAT4 pathway, but not the STAT1 pathway, was crucial for the IFN-α-mediated in-sequence effects. Reactivation of TIGIT reversed Th1 polarization of Tregs by suppressing AKT/mTOR and STAT4 signaling. CONCLUSIONS: Our findings suggest that IFN-α mediated in-sequence effects on Tregs may be responsible for the expansion of Th1-like Tregs in SLE. TIGIT can restore immune suppression damage in Tregs and represents a potential therapeutic target for SLE.

Invasive alien plants are phylogenetically distinct from other alien species across spatial and taxonomic scales in China.

Introduction: Phylogenetic relatedness is one of the important factors in the community assembly process. Here, we aimed to understand the large-scale phylogenetic relationship between alien plant species at different stages of the invasion process and how these relationships change in response to the environmental filtering process at multiple spatial scales and different phylogenetic extents. Methods: We identified the alien species in three invasion stages, namely invasive, naturalized, and introduced, in China. The occurrence records of the species were used to quantify two abundance-based phylogenetic metrics [the net relatedness index (NRI) and the nearest taxon index (NTI)] from a highly resolved phylogenetic tree. The metrics were compared between the three categories of alien species. Generalized linear models were used to test the effect of climate on the phylogenetic pattern. All analyses were conducted at four spatial scales and for three major angiosperm families. Results: We observed significantly higher NRI and NTI values at finer spatial scales, indicating the formation of more clustered assemblages of phylogenetically closely related species in response to the environmental filtering process. Positive NTI values for the invasive and naturalized aliens suggested that the presence of a close relative in the community may help the successful naturalization and invasion of the introduced alien species. In the two-dimensional phylogenetic space, the invasive species communities significantly differed from the naturalized and introduced species, indicating that established alien species need to be phylogenetically different to become invasive. Positive phylogenetic measures for the invasive aliens across the spatial scales suggested that the presence of invasive aliens could facilitate the establishment of other invasive species. Phylogenetic relatedness was more influenced by temperature than precipitation, especially at a finer spatial scale. With decreased temperature, the invasive species showed a more clustered assemblage, indicating conservatism of their phylogenetic niche. The phylogenetic pattern was different at the family level, although there was a consistent tendency across families to form more clustered assemblages. Discussion: Overall, our study showed that the community assemblage became more clustered with the progression of the invasion process. The phylogenetic measures varied at spatial and taxonomic scales, thereby highlighting the importance of assessing phylogenetic patterns at different gradients of the community assembly process.

Influence of hydrodynamic conditions on the fate of halogenated flame retardants along salinity gradients in a highly polluted micro-tidal estuary.

Halogenated flame retardants (HFRs) have properties similar to those of hydrophobic organic pollutants (HOPs). However, the understanding of their environmental fate in tidal estuaries remains limited. This study aims to bridge knowledge gaps regarding the land-sea transport of HFRs through riverine discharge into coastal waters. HFR levels were significantly influenced by tidal movement, and decabromodiphenyl ethane (DBDPE) was the predominant compound with a median concentration of 3340 pg L-1 in the Xiaoqing River estuary (XRE), whereas BDE209 had a median concentration of 1370 pg L-1. The Mihe River tributary plays a key role in transporting pollution to the downstream estuary of the XRE in summer, and the increasing suspended particulate matter (SPM) by resuspension in winter significantly affects HFR levels. These concentrations were inversely proportional to diurnal tidal oscillations. Tidal asymmetry caused an increase in SPM during an ebb tide, which increased HFR levels in a micro-tidal estuary such as the Xiaoqing River. The location of the point source and flow velocity influences the HFR concentrations during tidal fluctuations. Tidal asymmetry increases the likelihood of some HFRs being adsorbed by particles exported to the adjacent coast, and some settled down in areas with low hydrodynamic conditions, hindering their flow to the ocean.

Diverse Sample Generation: Pushing the Limit of Generative Data-Free Quantization.

Generative data-free quantization emerges as a practical compression approach that quantizes deep neural networks to low bit-width without accessing the real data. This approach generates data utilizing batch normalization (BN) statistics of the full-precision networks to quantize the networks. However, it always faces the serious challenges of accuracy degradation in practice. We first give a theoretical analysis that the diversity of synthetic samples is crucial for the data-free quantization, while in existing approaches, the synthetic data completely constrained by BN statistics experimentally exhibit severe homogenization at distribution and sample levels. This paper presents a generic Diverse Sample Generation (DSG) scheme for the generative data-free quantization, to mitigate detrimental homogenization. We first slack the statistics alignment for features in the BN layer to relax the distribution constraint. Then, we strengthen the loss impact of the specific BN layers for different samples and inhibit the correlation among samples in the generation process, to diversify samples from the statistical and spatial perspectives, respectively. Comprehensive experiments show that for large-scale image classification tasks, our DSG can consistently quantization performance on different neural architectures, especially under ultra-low bit-width. And data diversification caused by our DSG brings a general gain to various quantization-aware training and post-training quantization approaches, demonstrating its generality and effectiveness.

BiFSMNv2: Pushing Binary Neural Networks for Keyword Spotting to Real-Network Performance.

Deep neural networks, such as the deep-FSMN, have been widely studied for keyword spotting (KWS) applications while suffering expensive computation and storage. Therefore, network compression technologies such as binarization are studied to deploy KWS models on edge. In this article, we present a strong yet efficient binary neural network for KWS, namely, BiFSMNv2, pushing it to the real-network accuracy performance. First, we present a dual-scale thinnable 1-bit-architecture (DTA) to recover the representation capability of the binarized computation units by dual-scale activation binarization and liberate the speedup potential from an overall architecture perspective. Second, we also construct a frequency-independent distillation (FID) scheme for KWS binarization-aware training, which distills the high-and low-frequency components independently to mitigate the information mismatch between full-precision and binarized representations. Moreover, we propose the learning propagation binarizer (LPB), a general and efficient binarizer that enables the forward and backward propagation of binary KWS networks to be continuously improved through learning. We implement and deploy BiFSMNv2 on ARMv8 real-world hardware with a novel fast bitwise computation kernel (FBCK), which is proposed to fully use registers and increase instruction throughput. Comprehensive experiments show our BiFSMNv2 outperforms the existing binary networks for KWS by convincing margins across different datasets and achieves comparable accuracy with the full-precision networks (only a tiny 1.51% drop on Speech Commands V1-12). We highlight that benefiting from the compact architecture and optimized hardware kernel, BiFSMNv2 can achieve an impressive 25.1 × speedup and 20.2 × storage-saving on edge hardware.

Implications for biological invasion of non-native plants for sale in the world's largest online market.

Internet trade is increasingly recognized as a dispersal pathway of non-native plant species that is difficult to monitor. We sought to identify non-native flora present in the Chinese online market, the largest e-commerce market globally, and to decipher the effect of existing trade regulations, among other variables, on e-trading patterns and to inform policy. We used a comprehensive list of 811 non-native plant species in China present in 1 of the 3 phases of the invasion continuum (i.e., introduced, naturalized, and invasive). The price, propagule types, and quantities of the species offered for sale were retrieved from 9 online stores, including 2 of the largest platforms. Over 30% of the non-native species were offered for sale in the online marketplaces; invasive non-native species dominated the list (45.53%). No significant price difference was observed across the non-native species of the 3 invasion categories. Among the 5 propagule types, a significantly higher number of non-native species were offered for sale as seeds. The regression models and path analyses consistently revealed a direct positive effect of the number of uses and species' minimum residence time and an indirect effect of biogeography on the pattern of trade in non-native plant species when minimal phylogenetic signal was detected. A review of the existing phytosanitary regulations in China revealed their inadequacy in managing e-trading of non-native plant species. To address the problem, we propose integration of a standardized risk assessment framework that considers perceptions of stakeholders and is adaptable based on continuous surveillance of the trade network. If implemented successfully, the measures could provide a template for other countries to strengthen trading regulations for non-native plant species and take proactive management measures.

La venta de plantas no nativas en el mercado virtual más grande y sus implicaciones para la invasión biológica Resumen El mercado virtual en internet se reconoce cada vez más como una vía de dispersión de especies vegetales no nativas difícil de controlar. Intentamos identificar la flora no nativa presente en el mercado virtual chino, el mayor mercado de comercio electrónico del mundo, para descifrar el efecto de las regulaciones comerciales vigentes, entre otras variables, en los patrones de comercio electrónico e informar a las políticas. Utilizamos una lista integral de 811 especies de plantas no nativas de China presentes en una de las tres fases de invasión (es decir, introducidas, naturalizadas o invasoras). El precio, los tipos de propágulos y las cantidades de las especies puestas a la venta se recuperaron de nueve tiendas en línea, incluidas dos de las mayores plataformas. Más del 30% de las especies no nativas se pusieron a la venta en los mercados en línea; las especies no nativas invasoras dominaron esta lista (45,53%). No se observaron diferencias significativas de precio entre las especies no nativas en las tres categorías de invasión. Entre los cinco tipos de propágulos, se puso a la venta un número significativamente mayor de especies no nativas en forma de semillas. Los modelos de regresión y los análisis de trayectoria revelaron un efecto positivo directo y constante del número de usos y del tiempo mínimo de residencia de las especies y un efecto indirecto de la biogeografía sobre el patrón de comercio de especies vegetales no nativas cuando se detectó una señal filogenética mínima. Una revisión de la normativa fitosanitaria vigente en China reveló su insuficiencia para gestionar el comercio electrónico de las especies vegetales no nativas. Para abordar el problema, proponemos la integración de un marco normalizado de evaluación de riesgos que tenga en cuenta las percepciones de los actores y sea adaptable en función de la vigilancia continua de la red comercial. Si se aplican con éxito, las medidas podrían servir de modelo para que otros países refuercen la normativa sobre comercio de especies vegetales no nativas y adopten medidas proactivas de gestión.

Competitive binding of transcription factors underlies flexibility of T peripheral helper cells and T follicular helper cells in SLE.

OBJECTIVE: Peripheral helper T (Tph) cells interact with B cells and promote immune responses at sites of ectopic lymphoid structures (ELSs). To assess the characteristics of Tph cells, we investigated the phenotype of T helper (Th) cells in patients with SLE and the underlying competitive binding mechanisms using cytokine-mediated signal transducer and activator of transcription (STAT) factors. METHODS: Peripheral blood mononuclear cells from SLE patients and healthy controls were analysed for phenotypic identification. Serum cytokine levels were detected using Luminex assays. In vitro culture was performed to assess cytokine-induced conversion of phenotypes and transcriptional regulation using flow cytometry and PCR. Chromatin immunoprecipitation was used to evaluate STAT binding and histone modifications. RESULTS: CXCR5-PD-1+Tph-like cells were increased in SLE patients and showed strong association with disease activity and renal involvement. Serum IFN-α levels were increased and associated with Tph frequency. IFN-α promoted the differentiation of IL-10-producing CXCR5-PD-1+Tph-like cells, increased the responsiveness of IL-2 and induced the conversion of Tfh-like cells to Tph-like cells. STAT5 gained a competitive advantage and bound to the BCL6 locus at the expense of STAT1, accompanied by suppression of H3K4me3. Finally, anti-IFNAR1 decreased the differentiation of Tph-like cells, thereby suppressing the generation of CD38highCD27highplasmablasts. CONCLUSION: Tph cells might be crucial makers to effectively reflect disease activity level in SLE patients. The finding that synergy of IFN-α and IL-2 increases Tph cells through competitive transcriptional regulation could be one of the mechanisms responsible for pathological formation of ELSs and helpful for selection of individualized therapeutic approaches for SLE.

Universal Adversarial Patch Attack for Automatic Checkout Using Perceptual and Attentional Bias.

Adversarial examples are inputs with imperceptible perturbations that easily mislead deep neural networks (DNNs). Recently, adversarial patch, with noise confined to a small and localized patch, has emerged for its easy feasibility in real-world scenarios. However, existing strategies failed to generate adversarial patches with strong generalization ability due to the ignorance of the inherent biases of models. In other words, the adversarial patches are always input-specific and fail to attack images from all classes or different models, especially unseen classes and black-box models. To address the problem, this paper proposes a bias-based framework to generate universal adversarial patches with strong generalization ability, which exploits the perceptual bias and attentional bias to improve the attacking ability. Regarding the perceptual bias, since DNNs are strongly biased towards textures, we exploit the hard examples which convey strong model uncertainties and extract a textural patch prior from them by adopting the style similarities. The patch prior is closer to decision boundaries and would promote attacks across classes. As for the attentional bias, motivated by the fact that different models share similar attention patterns towards the same image, we exploit this bias by confusing the model-shared similar attention patterns. Thus, the generated adversarial patches can obtain stronger transferability among different models. Taking Automatic Check-out (ACO) as the typical scenario, extensive experiments including white-box/black-box settings in both digital-world (RPC, the largest ACO related dataset) and physical-world scenario (Taobao and JD, the world's largest online shopping platforms) are conducted. Experimental results demonstrate that our proposed framework outperforms state-of-the-art adversarial patch attack methods.

Setting the priorities straight - Species distribution models assist to prioritize conservation targets for the mangroves.

Mangrove forests provide a wide range of ecosystem services, yet they are declining rapidly due to climate change and human activities. Identification of conservation priority targets across spatial and temporal scales may assist in planning and decision making, especially in areas having rich mangrove diversity but with limited response capacity. In this study, we aimed to identify the species and areas which should be prioritized for conservation in the Indo-West Pacific (IWP) region, one of the two global hotspots of mangroves. We used an ensemble species distribution modelling framework to map the potential distribution of ten species, including true mangroves and mangrove associates, in current, past, and future environmental conditions. The priority targets were then identified through a weighted-scoring approach with the current distribution and the modelled outputs. Our study revealed that precipitation and surface elevation could influence the distribution of the true mangroves, while the temperature was the important variable for the mangrove associates. Although suitable habitat for the mangroves is predicted to increase in future, primarily due to the northward range expansion of six species, areas with high species richness would decrease. We found 7.09% and 4.16% areas of the IWP should be prioritized for conservation of the true mangroves and mangrove associates, respectively. The characteristics of these priority sites indicated that the inclusion of the anthropogenic component in the conservation framework and species-targeted management plans in the protected areas are required for the effective implementation of conservation actions. Five of the studied species, namely Acanthus ilicifolius, Dolichandrone spathacea, Heritiera littoralis, Pemphis acidula and Xylocarpus granatum, were found to have the highest priority score for conservation. The glacial refugia of the species, mostly distributed in the Philippines, New Guinea, southern India and Madagascar, should be explored further for species-specific conservation actions.

A systematic review and meta-analysis: effects of glucocorticoids on rheumatoid arthritis and systemic lupus erythematosus.

BACKGROUND: Meta-analysis was performed to explore the efficacy of glucocorticoids in the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), to provide a theoretical basis for the clinical treatment of patients. METHODS: Relevant literatures from the establishment of the database to December 31, 2020, were searched from databases such as PubMed. The literatures with randomized controlled trial of the clinical efficacy of glucocorticoids in the treatment of RA and SLE were screened for meta-analysis. RESULTS: Eleven documents were included, including 1,298 participants. It was found that the cardiovascular system [mean difference (MD) =1.23; 95% confidence interval (CI): 0.64 to 2.34; Z=0.62; P=0.53], respiratory system (MD =1.87; 95% CI: -0.66 to 5.29; Z=1.18; P=0.24), nervous system (MD =1.22; 95% CI: 0.25-5.84; Z=0.25; P=0.8), visual impairment (MD =1.41; 95% CI: 0.79-2.52; Z=1.15; P=0.25), endocrine system (MD =8.53; 95% CI: 2.71-26.88; Z=3.66; P=0.0003), digestive system (MD =1.41; 95% CI: 0.76-2.63; Z=1.09; P=0.28), genitourinary system (MD =1.06; 95% CI: 0.35-3.17; Z=0.1; P=0.92), blood system (MD =2.96; 95% CI: 0.62-14.26; Z=1.35; P=0.18), Z=0.48; P=0.63), infection status (MD =1.36; 95% CI: 0.98-1.87; Z=1.86; P=0.06), clinical efficacy (MD =1.79; 95% CI: 1.27-2.52; Z=3.32; P=0.0009), pain (MD =1.16; 95% CI: 0.76-1.78; Z=0.68; P=0.5), and joint swelling score (MD =0.03; 95% CI: -0.38 to 0.45; Z=0.15; P=0.88) of experimental group after treatment were all superior versus controls. However, the skin and mucous membranes (MD =0.87; 95% CI: 0.55-1.37; Z=0.61; P=0.54), musculoskeletal (MD =0.85; 95% CI: 0.43-1.66; Z=0.48; P=0.63), radiation injury (MD =-1.93; 95% CI: -3.68 to -0.18; Z=2.17; P=0.03), and C-reactive protein (CRP) level (MD =-8.66; 95% CI: -10.16 to -7.16; Z=11.34; P<0.00001) of experimental group were inferior to those of control group. DISCUSSION: Glucocorticoids in the treatment of RA and SLE can improve the clinical efficacy, but it was easy to cause multiple system adverse reactions. Therefore, the clinical treatment should follow the doctor's advice.

Amelioration of Juglanin against LPS-Induced Activation of NLRP3 Inflammasome in Chondrocytes Mediated by SIRT1.

Arthritis is characterized by irreversible joint destruction and presents a global health burden. Natural alternatives to synthetic drugs have been gaining popularity for their safety and effectiveness. Juglanin has demonstrated a range of anti-inflammatory effects in various tissues and cell types. However, the pharmacological function of Juglanin in arthritis and chondrocytes has been little studied. ATDC5 cells were treated with 1 µg/mL lipopolysaccharide (LPS) in the presence or absence of juglanin (2.5, 5 µM) for 24 h. The effects of juglanin on cellular nucleotide-binding domain leucin-rich repeat receptor 3 (NLRP3) inflammasome complex and endproduct interleukin 1ß (IL-1ß) and interleukin (IL-18) were assessed by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot experiments. The oxidative stress was measured by super oxide dismutase (SOD) activity and NADPH oxidase 4 (NOX4) expression. The dependent effect of juglanin on silent information regulator 2 homolog 1 (SIRT1) was evaluated by siRNA knockdown approach. Juglanin significantly reduced cellular oxidative stress by downregulating NOX4 expression production and rescuing the decreased activity of total SOD induced by LPS. Juglanin inhibited the activation of the TxNIP/NLRP3/ASC/caspase-1 axis, and decreased production of IL-1ß and IL-18. Moreover, juglanin rescued the LPS-induced decrease in SIRT1 expression. SIRT1 silencing abolished the anti-NLRP3 inflammasome effect of juglanin, indicating that the effects of juglanin are dependent on its amelioration on SIRT1 expression. Juglanin possesses an anti-inflammatory and anti-ROS capacity in chondrocytes, and this study provides available evidence that juglanin may be of use in the treatment of arthritis.

Serum vascular endothelial growth factor as a biomarker for prognosis of minor ischemic stroke.

Objectives Although vascular endothelial growth factor (VEGF) is a well-known molecule involved with neuronal survival and angiogenesis. there are no prospective studies directed at evaluating a potential association between serum VEGF and minor ischemic stroke. The goal of this study was to investigate the utility of serum VEGF as an index for assessing the 90-day prognosis of minor ischemic stroke patients. Methods Records of acute minor stroke patients (N = 225) and those of age- and gender-matched healthy control subjects (N = 225) were prospectively reviewed. Clinical, laboratory, and imaging data were evaluated. Serum samples collected from these stroke patients immediately after admission were assessed for VEGF levels and compared with those of control subjects. Results Serum VEGF levels were significantly increased in stroke patients (40.01 ±â€¯16.48 pg/mL) as compared with those of controls (32.98 ±â€¯10.35 pg/mL). No statistically significant differences in serum VEGF levels were obtained among the three stroke subtypes analyzed in this study (large-artery atherosclerosis, small-artery occlusion and other types of brain infarction). Multivariate regression analysis revealed that serum VEGF levels and cerebral artery stenosis ≥ 50 % were independently associated with an unfavorable outcome. Unfavorable outcome rates were significantly greater in stroke patients showing VEGF levels in the upper quartiles of the distribution, and these VEGF levels were found to serve as a significant predictor of unfavorable outcomes in these minor ischemic stroke patients. Conclusion Increased serum VEGF may serve as an independent predictor of an unfavorable outcome in minor ischemic stroke.

A gold electrode modified with a gold-graphene oxide nanocomposite for non-enzymatic sensing of glucose at near-neutral pH values.

A nanocomposite was prepared from gold and graphene oxide via one-step electrodeposition and used to modify the surface of a gold electrode (Au-Gr/GE) that was then applied to non-enzymatic determination of glucose. The effects of deposition time and supporting substrate on the morphology, structure, and electrochemical properties of the nanocomposite were optimized. The morphologies and crystal structures were characterized by scanning electron microscopy, transmission electron microscopy, and X-ray diffraction. The results indicate that gold nanoparticles grew on the surface of two-dimensional graphene oxide. The electrocatalytic activity of the modified electrode towards glucose oxidation was evaluated by cyclic voltammetry and amperometric methods at pH 7.4. The Au-Gr/GE, typically operated at a potential of 0.00 V (vs. Ag/AgCl), has a linear response in the 0.05-14 mM and 14-42 mM glucose concentration range, high sensitivity (604 and 267 µA cm-2 mM-1) and a low detection limit (12 µM). The modified GE was applied to quantify glucose in sweat where it exhibited excellent sensitivity and accuracy. Graphical abstract The gold electrode modified with a gold-graphene (Au-Gr/GE) is prepared via a direct electrodeposition. The Au-Gr/GE is used for glucose detection in the neutral solution and it can achieve the effect of non-intrusive detection.

Ultrasound7 versus ultrasound12 in monitoring the response to infliximab in patients with rheumatoid arthritis.

This study aimed to assess the responsiveness of ultrasonography (US)-7 in patients with rheumatoid arthritis (RA). Eighty-two RA patients were recruited and followed up for 22 weeks. The clinical, laboratory, and X-ray assessments, along with grayscale US (GSUS) and power Doppler US (PDUS) examinations were performed at baseline, 6, 14, and 22 weeks after infliximab treatment. GSUS for synovitis and PDUS for synovitis and paratendinitis/tenosynovitis were assessed by a semi-quantitative (0 to 3) score, while GSUS for paratendinitis/tenosynovitis and bone erosion was qualitatively assessed as absent or present (0 or 1). US scores in both 7-joint (US7) and 12-joint (US12) systems were evaluated. After 6, 14, and 22 weeks of treatment with infliximab, indices such as US scores, 28-joint disease activity (DAS28) score, and tender and swelling joint count were all significantly improved compared to baseline. US7 scores were significantly correlated with that of US12. Strong correlations were identified between most US7 scores with DAS28, health assessment questionnaire (HAQ), and C-reactive protein (CRP) levels. When DAS28 was used as a reference, the US7 cutoff for disease remission was less than 35 for GS + PD and also less than 29 for GS and 1 for PD, respectively. Additionally, the positive percent agreement, negative percent agreement, and overall percent agreement for GS + PD were 77.78, 76.19, and 76.67 %, respectively, which were all higher than that of GS or PD. US7 may be a feasible tool to assess the therapeutic response in RA patients.