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Objective The objective of this study was to analyze the impact of the Area Deprivation Index (ADI) on disease activity and cardiovascular comorbidity in rheumatoid arthritis (RA). Methods A retrospective analysis of adult patients with RA was conducted to highlight differences in academic and safety net hospital clinics. Demographics, RA medication history, patient portal engagement, primary care presence, emergency or inpatient visits, RA disease activity and functional scores, Charlson Comorbidity Index (CCI), and cardiovascular disease (CVD) presence were captured. The ADI rank was assigned using nine‐digit zip codes. Patients were stratified by the upper versus lower ADI decile group and matched by age, sex, race, ethnicity, insurance, and CCI using propensity score analysis. Results Patients with RA from the academic practice (n = 542) and the safety net hospital (n = 496) were assessed. In the academic cohort, those with high ADI scores (>8, more deprivation) had higher RA disease activity scores (Routine Assessment of Patient Index Data 3 mean ± SD: high 13.83 ± 6.94 vs low 11.17 ± 7.37, P < 0.0001; Clinical Disease Activity Index mean ± SD: high 11.97 ± 11.74 vs low 9.40 ± 7.97, P < 0.05), more functional impairment (Multidimensional Health Assessment Questionnaire mean ± SD: high 2.99 ± 2.29 vs low 2.34 ± 2.23, P < 0.01), lower MyChart use (P < 0.001), and different smoking history (P < 0.01) compared to those with low ADI scores (

Abstract Background The atherogenic index of plasma (AIP) is considered an independent risk factor for coronary artery disease (CAD). The present study investigated whether AIP correlates with the formation of coronary collateral circulation (CCC) in CAD patients with chronic total occlusion (CTO). Methods This retrospective study included 1093 CAD patients with CTO confirmed by coronary angiography from January 2020 to December 2020 at Beijing Anzhen Hospital. Based on the Rentrop scoring system, the patients were divided into the good CCC group and the poor CCC group. AIP was calculated by log (triglyceride/high-density lipoprotein cholesterol). Meanwhile, the study population was further divided into four groups according to the quartiles of AIP. Results Patients in the poor CCC group exhibited significantly higher AIP compared to those in the good CCC group (0.31 ± 0.27 vs. 0.14 ± 0.24, p

This study employed optical microscopy (OM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) to investigate the impact of vanadium (V) on the microstructure and mechanical properties of gray cast iron (GCI) HT250. Additionally, Thermo-Calc software was employed to explore the influence of V on the solidification process. The results indicate that adding trace amounts of V in GCI forms a face-centered cubic VC phase, with the precipitation temperature of the VC phase gradually increasing. When the V content reaches 0.28 wt%, the VC phase begins to precipitate during the eutectic reaction. The incorporation of V consumes carbon, reducing the graphite content and promoting the formation of type D graphite. As the V content increases, there is an enlargement in the pearlite area ratio, a decrease in the pearlite layer spacing, and a reduction in the size of eutectic cells. These microstructural alterations lead to enhanced mechanical properties. The tensile strength peaks at 336 MPa with a V content of 0.77 wt%, representing a 29% increase compared to samples without added V. Similarly, the Vickers hardness increases with increasing V content, reaching a peak of 373 HV at 0.92 wt% V, a 27% increase compared to samples without V addition. However, at this point, the tensile strength decreases to 322 MPa.

Chitosan is a naturally-occurring alkaline polysaccharide with excellent biocompatibility, biodegradability, low toxicity, and easy preparation. It has been widely used in the construction of delivery systems for various nutrients and bioactive substances. The chitosan-based nutrient delivery systems are mainly constructed by cross-linking, drying, layer-by-layer self-assembly, coalescence, covalent grafting, microfluidics and biosynthesis. Chitosan can be combined with carbohydrates, proteins and liposomes to form a composite carrier that can obtain more excellent performance and broaden its application in food packaging materials, slow release of bioactive substances and probiotic embedding. In addition, this paper further analyzes the obstacles and limitations of the actual application of chitosan-based nutrient delivery systems in the food industry, to provide important references for the application of chitosan-based delivery carriers in imparting new functional properties to foods, developing new food ingredients, and nutrient fortification.

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

Flexible pressure sensors are lightweight and highly sensitive, making them suitable for use in small portable devices to achieve precise measurements of tiny forces. This article introduces a low-cost and easy-fabrication strategy for piezoresistive flexible pressure sensors. By embedding silver nanowires into a polydimethylsiloxane layer with micro-pyramids on its surface, a flexible pressure sensor is created that can detect low pressure (17.3 Pa) with fast response (

Abstract Defense-associated sirtuin 2 (DSR2) systems are widely distributed across prokaryotic genomes, providing robust protection against phage infection. DSR2 recognizes phage tail tube proteins and induces abortive infection by depleting intracellular NAD+, a process that is counteracted by another phage-encoded protein, DSR Anti Defense 1 (DSAD1). Here, we present cryo-EM structures of Bacillus subtilis DSR2 in its apo, Tube-bound, and DSAD1-bound states. DSR2 assembles into an elongated tetramer, with four NADase catalytic modules clustered in the center and the regulatory-sensing modules distributed at four distal corners. Interestingly, monomeric Tube protein, rather than its oligomeric states, docks at each corner of the DSR2 tetramer to form a 4:4 DSR2-Tube assembly, which is essential for DSR2 NADase activity. DSAD1 competes with Tube for binding to DSR2 by occupying an overlapping region, thereby inhibiting DSR2 immunity. Thus, our results provide important insights into the assembly, activation and inhibition of the DSR2 anti-phage defense system.

ABSTRACT Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial β-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The β-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF.IMPORTANCENeuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.

Purpose: Invasive micropapillary carcinoma (IMPC) of the breast has a high propensity for lymphovascular invasion and axillary lymph node metastasis and displays an ‘inside-out’ growth pattern, but the molecular mechanism of invasion, metastasis and cell polarity reversal in IMPC is unclear. Methods: and Patients: Cell growth curves, tumor sphere formation assays, transwell assays, mouse xenograft model and immunofluorescence were evaluated to investigate the effects of miR-30c and MTDH. Dual luciferase reporter assays was performed to confirm that the MTDH (metadherin) 3′UTR bound to miR-30c. MiRNA in situ hybridization (ISH) and immunohistochemistry (IHC) were carried out on IMPC patient tissues for miR-30c and MTDH expression, respectively. Results: We found miR-30c as a tumor suppressor gene in cell proliferation, metastasis and polarity reversal of IMPC. Overexpression of miR-30c inhibited cell growth and metastasis in vitro and in vivo. MiR-30c could directly target the MTDH 3′UTR. MiR-30c overexpression inhibited breast cancer cell proliferation, invasion and metastasis by targeting MTDH. Moreover, miR-30c/MTDH axis could also regulate cell polarity reversal of IMPC. By ISH and IHC analyses, miR-30c and MTDH were significantly correlated with tumor size, lymph nodule status and tumor grade, the ‘inside-out’ growth pattern, overall survival (OS) and disease-free survival (DFS) in IMPC patients. Conclusions: Overall, miR-30c/MTDH axis was responsible for tumor proliferation, metastasis and polarity reversal. It may provide promising therapeutic targets and prognostic biomarkers for patients with IMPC.

We propose a distributed multi-objective optimization (DMO) method for designing chiral plasmonic metasurface that satisfies multiple objectives simultaneously. We aim to improve the refractive index sensitivity of the archetypical Born-Kuhn type chiral plasmonic metasurface while ensuring that circular dichroism (CD) is as pronounced as possible at a designated resonance wavelength. By leveraging distributed technology, the proposed method significantly improves the time efficiency of the optimization process. The simulation results demonstrate approximately 33% enhancement in sensitivity by DMO, as well as greater than 100% boost in time efficiency compared to stand-alone optimization approaches. These findings highlight the potential of the proposed method to guide the design of chiral plasmonic metasurface sensors, enabling the simultaneous optimization of multiple objectives and facilitating advancements in chiral optics and sensing applications.

To address the issues of high attenuation, weak reception signal, and channel blockage in the current electric field communication of underwater robots, research on autonomous underwater vehicle (AUV) multi-node networking communication based on underwater electric field Carrier Sense Multiple Access with Collision Avoidance (CSMA/CA) channel was conducted. This article, first through simulation, finds that the Optimized Link State Routing (OLSR) protocol has a smaller routing packet delay time and higher reliability compared to the Ad Hoc On-Demand Distance Vector (AODV) protocol on underwater electric field CSMA/CA channels. Then, a 2FSK underwater electric field communication system was established, and dynamic communication experiments were carried out between two AUV nodes. The experimental results showed that within a range of 0 to 3.5 m, this system can achieve underwater dynamic electric field communication with a bit error rate of 0 to 0.628%. Finally, to avoid channel blockage during underwater AUV multi-node communication, this article proposes a dynamic backoff method for AUV multi-node communication based on CSMA/CA. This system can achieve dynamic multi-node communication of underwater electric fields with an error rate ranging from 0 to 0.96%. The research results have engineering application prospects for underwater cluster operations.

Montmorillonite (MMT) was used to improve the performance of starch and nano-ZnO was added to act as antibacterial agent for developing a starch-based active packaging material via solution mixing and casting methods. The effect of MMT and ZnO on the performance of starch films was investigated, and then the composite films were used for cherry preservation. The results indicated that the addition of MMT could improve the mechanical and water-vapor barrier properties of starch films, but it had only a slight impact on optical properties. However, the addition of nano-ZnO could reduce the optical, mechanical, and water vapor barrier properties of composite films. In preservation applications, compared to the other films, the composite films containing nano-ZnO could be beneficial to maintain quality and nutritional value of cherries by slowing down the growth of bacteria and thereby delaying weight loss, decreasing hardness, and decreasing pH and soluble solid content, resulting in a better preservation effect. Therefore, a starch-based active packaging film with good properties and preservation effect was developed with nano-ZnO and MMT, which could be applied in the field of preservation.

Abstract The co‐occurrence of plasmid‐mediated multidrug resistance and hypervirulence in epidemic carbapenem‐resistant Klebsiella pneumoniae has emerged as a global public health issue. In this study, an ST23 carbapenem‐resistant hypervirulent K. pneumoniae (CR‐HvKP) strain VH1‐2 was identified from cucumber in China and harbored a novel hybrid plasmid pVH1‐2‐VIR. The plasmid pVH1‐2‐VIR carrying both virulence and multidrug‐resistance (MDR) genes was likely generated through the recombination of a virulence plasmid and an IncFIIK conjugative MDR plasmid in clinical ST23 18622 isolated from a sputum sample. The plasmid pVH1‐2‐VIR exhibited the capacity for transfer to the clinical ST11 carbapenem‐resistant K. pneumoniae (CRKP) strain via conjugation assay. Acquisition of pVH1‐2‐VIR plasmid directly converted a CRKP into CR‐HvKP strain characterized by hypermucoviscosity, heightened virulence for Galleria mellonella larvae, and increased colonization ability in the mouse intestine. The emergence of such a hybrid plasmid may expedite the spread of CR‐HvKP strains, posing a significant risk to human health.