Causal Association of Rheumatoid Arthritis With Adverse Pregnancy Outcomes: Genetic Evidence From Mendelian Randomization.

OBJECTIVE: Although the association of rheumatoid arthritis (RA) to multiple adverse pregnancy outcomes has been well-studied, the association between serum antibody levels in patients with RA and multiple adverse pregnancy outcomes has not been conclusively demonstrated. Here, we comprehensively assessed the causal impact of RA, serologic antibody-positive RA (pRA), and serologic antibody-negative RA (nRA) on the risk of 14 adverse pregnancy outcomes. METHODS: The causal impact of RA, pRA, and nRA on 14 adverse pregnancy outcomes was comprehensively assessed using two-sample Mendelian randomization (MR). Evidence maps based on the results of these two-sample MR analyses were developed. Data from the UK Biobank and FinnGen databases were utilized for this analysis. The inverse variance weighted (IVW) test was employed as the primary method to estimate causality. "TwoSampleMR" and "MR-PRESSO" packages were used for data analysis in this study. RESULTS: Using two-sample MR analysis, we found a significant positive causal association between RA and increased risk of cesarean section (p = 0.003), gestational hypertension (p < 0.001), number of spontaneous miscarriages (p = 0.041), preeclampsia (p = 0.008), premature rupture of membranes (p = 0.030), and preterm (p = 0.010). pRA had a significant positive causal association with an increased risk of cesarean section (p = 0.012), gestational hypertension (p < 0.001), preeclampsia (p = 0.002), and preterm (p = 0.007). A significant positive causal association was also established between nRA and gestational hypertension (p = 0.010), the number of spontaneous miscarriages (p = 0.024), and placental abruption (p = 0.027). In addition, we found a causal association between nRA and birth weight (p = 0.007), but not between RA and pRA and birth weight. CONCLUSION: The results of this study have important implications for the individualized treatment of RA patients, especially those with positive serum antibody levels.

Effects of a novel sawdust-modified carrier on performance, bioaccumulation and microbial community of sequencing batch reactor.

The impact of a novel sawdust-modified carrier on the performance of aerobic sequencing batch reactor (SBR) was examined. Compared with the conventional polyethylene (PE) carrier, the sawdust-modified carrier had coarse surface and porous side wall, which was beneficial for the rapid formation of biofilm. The biomass of sawdust-modified carrier was 3.4 ± 0.7 times more than those of PE carrier at the end of this study. The biofilm gotten from suspended carrier had higher extracellular polymeric substances (EPS) concentrations than activated sludge (AS). The EPS from biofilm contained higher proportions of polysaccharides compared to those from AS. The SBR with addition of sawdust-modified carrier exhibited higher ammonia nitrogen removal efficiency (84.8%) than the one with addition of conventional PE carrier (73.1%) in a typical cycle at 12 h. The volumetric nitrification rates of modified carrier were higher than those of conventional PE carrier. High throughput sequencing revealed that sawdust-modified carriers exhibited greater microbial richness and diversity compared with traditional PE carriers. Saccharimonadales was the most predominant genus that removed organic matter under aerobic condition, whereas Nitrospira was the dominant nitrifying genus. The present study verifies the advantage of sawdust-modified carrier, which has the potential for the full-scale application in the future.

Comparative study on the effects of anionic, cationic, and nonionic polyacrylamide surface modified magnetic micro-particles (MMP) for anaerobic digestion treatment of vegetable waste water (VWW).

Anaerobic digestion provides a solution for the treatment of vegetable waste water (VWW), but there are currently limited targeted treatment methods available. Building upon previous studies, this research investigated the effects of polyacrylamide-modified magnetic micro-particles (MMP) on anaerobic digestion (AD) of VWW. Three variations of these particles were created by grafting anionic, cationic, and non-ionic polyacrylamide (PAM) onto the MMPs' surfaces, resulting in aPAM-MMP, cPAM-MMP, and nPAM-MMP, respectively. In AD experiments, the addition of aPAM-MMP notably enhanced the degradation of chemical oxygen demand (COD) in VWW. COD decreased to 1290 mg/L in the reactor with aPAM-MMP by day 12 and remained low, while the other reactors had COD concentrations of 4137.5, 5510, and 3010 mg/L on the same day, decreasing thereafter. This modification also improved the production and utilization of hydrogen gas and volatile fatty acids (VFAs), along with the conversion of methane. When tested for bioaffinity using fluorescent GFP-E.coli bacteria, the aPAM-MMP, cPAM-MMP, and nPAM-MMP demonstrated increases in fluorescence intensity by 51.66%, 36.13%, and 37.02%, respectively, compared to unmodified MMP when attached with GFP-E.coli. Further analyses of microbial community revealed that the reactor with aPAM-MMP had the highest microbial richness and enriched bacteria capable of organic matter degradation, such as Bacteroidota, Synergistota, Chloroflexi, Halobacterota phyla, and Parabacteroides, Muribaculaceae, and Azotobacter genera. In conclusion, our experiment verifies that APAM-MMP promotes anaerobic treatment of VWW and provides a novel reference point for enhancing VWW degradation.

Intrinsically Elastic Semiconductors through Aldehyde-Amine Polycondensation and Its Application on Stretchable Transistor.

With the increasing demand for elastic electronics, as a crucial component, elastic semiconductors have been widely studied. However, there are some issues for the current preparation of elastic semiconductors, such as harsh reaction conditions, low atomic economic utilization, and complicated product separation and purification. Aldehyde-amine polycondensation is an important chemical reaction with the advantages of mild reaction conditions, high atomic-economic efficiency, and easy separation and purification. Herein, intrinsically elastic semiconductors are developed via aldehyde-amine polycondensation, including a semiconducting segment and an elastic segment. The resulting polymer containing 42.62 wt % soft segments exhibits excellent stretchability and mechanical reversibility, especially with a lower modulus. Interestingly, the carrier mobility displays up to 0.04 cm2·V-1·s-1, in the range of the fully conjugated reference polymer (0.1 cm2·V-1·s-1). In brief, this strategy provides important guiding principles for the development of intrinsically elastic polymer semiconductors.

Ovatodiolide inhibited hepatocellular carcinoma stemness through SP1/MTDH/STAT3 signaling pathway.

Hepatocellular carcinoma (HCC) is characterized with high recurrence and mortality, and the clinical treatments for HCC are very limited. Hepatocellular carcinoma stem cells are the root of HCC progress, recurrence, and multidrug resistance. Ovatodiolide (OVA) is a bioactive diterpenoid served as an inflammatory and immunotherapeutic responses modulator. In this research, we found OVA inhibited HCC stemness through inhibiting MTDH gene transcription. Moreover, we firstly discovered transcription factor SP1 bound to the promoter region of MTDH to transcriptionally regulate MTDH level. Mechanically, we demonstrated OVA decreased SP1 protein stability to transcriptionally inhibit MTDH gene, and inhibited the nuclear translocation of p65, and then diminished IL-6 level to suppress JAK/STAT3 signaling pathway, eventually decreases CD133 level and the stemness of HCC. Furthermore, we demonstrated ACT004, OVA derivative with high metabolic stability towards cytochrome P450 enzymes, showed no genotoxicity and no accumulative or delayed toxicities after long-term administration in rats. And the in vivo efficacy experiments indicated ACT004 inhibited tumor growth of hepatocellular carcinoma. In conclusion, we revealed the mechanism of OVA in regulating HCC stemness, detected the toxicity of OVA derivative and evaluated the in vivo efficacy which lays a foundation for further discovery of anti-HCC stem cell agents and provide a new strategy for the application of OVA in clinical treatment.

Circular RNA circLIFR suppresses papillary thyroid cancer progression by modulating the miR-429/TIMP2 axis.

PURPOSE: Circular RNAs (circRNAs) are increasingly recognized for their important roles in various cancers, including papillary thyroid cancer (PTC). The specific mechanisms by which the circLIF receptor subunit alpha (circLIFR, hsa_circ_0072309) influences PTC progression remain largely unknown. METHODS: In our study, CircLIFR, miR-429, and TIMP2 levels were assessed using reverse transcription-quantitative PCR. The roles of circLIFR and miR-429 in PTC cells were determined using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. Western blotting was utilized to examine the levels of TIMP2. The direct interaction between circLIFR, TIMP2, and miR-429 was confirmed using dual-luciferase reporter, RNA immunoprecipitation, and fluorescence in situ hybridization assays. RESULTS: In PTC tissues and cells, a decrease in circLIFR and TIMP2 levels, accompanied by an increase in miR-429 levels, was observed. Overexpression of circLIFR or downregulation of miR-429 effectively suppressed the proliferation and migration of PTC cells. Conversely, the knockdown of circLIFR or overexpression of miR-429 had the opposite effect. Furthermore, circLIFR overexpression suppressed tumor growth in vivo. Mechanistically, circLIFR modulated TIMP2 expression by serving as a sponge for miR-429. Rescue experiments indicated that the antitumor effect of circLIFR could be reversed by miR-429. CONCLUSION: This study confirmed circLIFR as a novel tumor suppressor delayed PTC progression through the miR-429/TIMP2 axis. These findings suggested that circLIFR held promise as a potential therapeutic target for PTC.

Exploring the enigma: history, present, and future of long non-coding RNAs in cancer.

Long noncoding RNAs (lncRNAs), which are more than 200 nucleotides in length and do not encode proteins, play crucial roles in governing gene expression at both the transcriptional and posttranscriptional levels. These molecules demonstrate specific expression patterns in various tissues and developmental stages, suggesting their involvement in numerous developmental processes and diseases, notably cancer. Despite their widespread acknowledgment and the growing enthusiasm surrounding their potential as diagnostic and prognostic biomarkers, the precise mechanisms through which lncRNAs function remain inadequately understood. A few lncRNAs have been studied in depth, providing valuable insights into their biological activities and suggesting emerging functional themes and mechanistic models. However, the extent to which the mammalian genome is transcribed into functional noncoding transcripts is still a matter of debate. This review synthesizes our current understanding of lncRNA biogenesis, their genomic contexts, and their multifaceted roles in tumorigenesis, highlighting their potential in cancer-targeted therapy. By exploring historical perspectives alongside recent breakthroughs, we aim to illuminate the diverse roles of lncRNA and reflect on the broader implications of their study for understanding genome evolution and function, as well as for advancing clinical applications.

Increased Deep Trap Density in Interfacial Engineered Nanocomposite Revealed by Sequential Kelvin Probe Force Microscopy for High Dielectric Energy Storage.

Nanocomposites combining inorganic nanoparticles with high dielectric constant and polymers with high breakdown strength are promising for the high energy density storage of electricity, and carrier traps can significantly affect the dielectric breakdown process. Nevertheless, there still lacks direct experimental evidence on how nanoparticles affect the trap characteristics of nanocomposites, especially in a spatially resolved manner. Here, a technique is developed to image the trap distribution based on sequential Kelvin probe force microscopy (KPFM) in combination with the isothermal surface potential decay (ISPD) technique, wherein both shallow and deep trap densities and the corresponding energy levels can be mapped with nanoscale resolution. The technique is first validated using the widely-used commercial biaxially oriented polypropylene, yielding consistent results with macroscopic ISPD. The technique is then applied to investigate polyvinylidene fluoride-based nanocomposites filled with barium titanate nanoparticles, revealing higher deep trap density around surface-modified nanoparticles, which correlates well with its increased breakdown strength. This technique thus provides a powerful spatially resolved tool for understanding the microscopic mechanism of dielectric breakdown of nanocomposites.

Strong Acceptors Based on Derivatives of Benzothiadiazoloimidazole.

Despite the rapid progression of organic semiconductors, developing high-air-stability n-type organic semiconductors are still challenging. Herein, novel strong acceptors based on benzothiadiazoloimidazole units are reported. The results reveal that the strong acceptor BTI-NDI-BTI-a has good solubility and high electron affinity (3.94 eV), accompanied by 1D slipped-stacking crystals. Notably, the material presents promising potential for developing into air-stable n-type organic semiconductor materials.

Rapid Separation and API Grades Identification of Base Oil in Low Viscosity Gasoline Engine Oil SN 0W-16.

Using low viscosity engine oil is one of the most economical and easily achievable ways to improve fuel economy. Base oil is a main component in low viscosity engine oils, and therefore, the separation and identification of its are of great significance for oil product developers to prepare high-performance lubricants. However, the extraction methods reported for base oils mainly adopt membrane dialysis, which not only fails to completely separate the base oil but also wastes a large amount of solvent. The reason for this result is that the concentration of substances inside and outside the membrane cannot always be in an imbalanced state of permeation resulting from manual operation. Additionally, most studies primarily focus on the characterization of base oil components, while there are few reports on grade identification. For the above reasons, an economically effective separation technique of base oil from low viscosity gasoline engine oil SN 0W-16 is successfully established by combining improved Soxhlet extraction and a column chromatography separation method. By applying this method, the yield of extracting base oil generally exceeds 96%, and the solvent can also save more than 3 times. Besides, an exclusion method is built through several simple characterization steps including viscosity index (VI), FT-IR, size-exclusion chromatography (SEC), and hydrocarbon composition, which can quickly identify the American Petroleum Institute (API) grade and brand of the base oils.

Synthesis of Structure-Adjustable R-Au/Pt-CdS Nanohybrids with Strong Plasmon Coupling and Improved Photothermal Conversion Performance.

Noble metal nanomaterials with a localized surface plasmon resonance effect exhibit outstanding advantages in areas such as photothermal therapy and photocatalysis. As a unique plasmonic metal nanostructure, gold nanobipyramids have been attracting much interest due to their strong specific local electric field intensity, large optical cross sections, and high refractive index sensitivity. In this study, we propose a novel three-component hetero-nanostructure composed of rough gold nanobipyramids (R-Au NBPs), Pt, and CdS. Initially, purified gold nanobipyramids are regrown to form R-Au NBPs that have a certain degree of roughness. These R-Au NBP substrates with a rough surface provide more hotspots and strengthen the intensity of localized electric fields. Subsequently, Pt and CdS nanoparticles are selectively deposited onto the surface of R-Au NBPs. Pt nanoparticles can provide more active sites. Each component of this hetero-nanostructure directly contacts others, creating multiple electron transfer channels. This novel design allows for tunable localized plasmon resonance wavelengths ranging from the visible to near-infrared regions. These factors contribute to the final superior photothermal conversion performance of the R-Au/Pt-CdS nanohybrids. Under the irradiation of near-infrared light (1064 nm), the photothermal conversion efficiency of R-Au/Pt-CdS reached 38.88%, which is 4.49, 1.5, and 1.22 times higher than that of Au NBPs, R-Au NBPs, and R-Au NBPs/Pt, respectively.

Highly controlled synthesis of symmetrically branched tripod and pentapod nanocrystals with enhanced photocatalytic performance.

Anisotropic nanostructures with tunable optical properties induced by controllable size and symmetry have attracted much attention in many applications. Herein, we report a controlled synthesis of symmetrically branched AuCu alloyed nanocrystals. By varying Au:Cu atom ratio in precursor, Y-shaped tripods with three-fold symmetry and star-shaped pentapods with five-fold symmetry are synthesized, respectively. The growth mechanism of AuCu tripods from icosahedral seeds and AuCu pentapods from decahedral seeds is revealed. Aiming to excellent photocatalytic performance, CdS nanocrystals are controlled grown onto the sharp tips of AuCu tripods and pentapods. In addition, a carrier-selective blocking layer of Ag2S is introduced between AuCu and CdS, for achieving effective charge separation in AuCu-Ag2S-CdS nanohybrids. Through evaluating the photocatalytic performance by hydrogen generation experiments, the AuCu-Ag2S-CdS tripod nanocrystals exhibit an optimized hydrogen evolution rate of 2182 µmol·g-1·h-1. These findings will contribute greatly to the understanding of complex nanoparticle growth mechanism and provide a strategy for the design of anisotropic nanoalloys for widely photocatalytic applications.

Amorphous Iridium Oxide-Integrated Anode Electrodes with Ultrahigh Material Utilization for Hydrogen Production at Industrial Current Densities.

Herein, ionomer-free amorphous iridium oxide (IrOx) thin electrodes are first developed as highly active anodes for proton exchange membrane electrolyzer cells (PEMECs) via low-cost, environmentally friendly, and easily scalable electrodeposition at room temperature. Combined with a Nafion 117 membrane, the IrOx-integrated electrode with an ultralow loading of 0.075 mg cm-2 delivers a high cell efficiency of about 90%, achieving more than 96% catalyst savings and 42-fold higher catalyst utilization compared to commercial catalyst-coated membrane (2 mg cm-2). Additionally, the IrOx electrode demonstrates superior performance, higher catalyst utilization and significantly simplified fabrication with easy scalability compared with the most previously reported anodes. Notably, the remarkable performance could be mainly due to the amorphous phase property, sufficient Ir3+ content, and rich surface hydroxide groups in catalysts. Overall, due to the high activity, high cell efficiency, an economical, greatly simplified and easily scalable fabrication process, and ultrahigh material utilization, the IrOx electrode shows great potential to be applied in industry and accelerates the commercialization of PEMECs and renewable energy evolution.

Identification of RACK1 as a novel regulator of non-structural protein 4 of chikungunya virus.

Chikungunya virus (CHIKV) is a neglected arthropod-borne and anthropogenic alphavirus. Over the past two decades, the CHIKV distribution has undergone significant changes worldwide, from the original tropics and subtropics regions to temperate regions, which has attracted global attention. However, the interactions between CHIKV and its host remain insufficiently understood, which dampens the need for the development of an anti-CHIKV strategy. In this study, on the basis of the optimal overexpression of non-structural protein 4 (nsP4), we explore host interactions of CHIKV nsP4 using mass spectrometry-based protein-protein interaction approaches. The results reveal that some cellular proteins that interact with nsP4 are enriched in the ubiquitin-proteasome pathway. Specifically, the scaffold protein receptor for activated C kinase 1 (RACK1) is identified as a novel host interactor and regulator of CHIKV nsP4. The inhibition of the interaction between RACK1 and nsP4 by harringtonolide results in the reduction of nsP4, which is caused by the promotion of degradation but not the inhibition of nsP4 translation. Furthermore, the decrease in nsP4 triggered by the RACK1 inhibitor can be reversed by the proteasome inhibitor MG132, suggesting that RACK1 can protect nsP4 from degradation through the ubiquitin-proteasome pathway. This study reveals a novel mechanism by which the host factor RACK1 regulates CHIKV nsP4, which could be a potential target for developing drugs against CHIKV.

U-shaped stereoscopic design strategy toward N-doped nanographene segment.

There have been scarce reports about stereoscopic design of N-heteroacenes (NHAs), especially for the electron-deficient π-building blocks. Herein, we report the design and synthesis of a U-shaped bis(pyrene-quinoxaline) (BPQ). Single crystal X-ray diffraction reveals the herringbone stacking pattern and the presence of regular and incompletely closed pores.

Macrophage pyroptosis induced by Candida albicans.

Candida albicans (C. albicans) is a prevalent opportunistic pathogen that causes mucocutaneous and systemic infections, particularly in immunocompromised individuals. Macrophages play a crucial role in eliminating C. albicans in local and bloodstream contexts, while also regulating antifungal immune responses. However, C. albicans can induce macrophage lysis through pyroptosis, a type of regulated cell death. This process can enable C. albicans to escape from immune cells and trigger the release of IL-1ß and IL-18, which can impact both the host and the pathogen. Nevertheless, the mechanisms by which C. albicans triggers pyroptosis in macrophages and the key factors involved in this process remain unclear. In this review, we will explore various factors that may influence or trigger pyroptosis in macrophages induced by C. albicans, such as hypha, ergosterol, cell wall remodeling, and other virulence factors. We will also examine the possible immune response following macrophage pyroptosis.

Novel flocking materials as biocarriers in moving bed biofilm reactor for improving simultaneous nitrification and denitrification performance.

Biocarrier is the key factor for the stable operation of moving bed biofilm reactor (MBBR). To achieve efficient simultaneous nitrification and denitrification (SND), this study provided novel flocking materials as biocarriers. The biofilm formation experiment showed that longer flocking carrier was more conducive to biomass accumulation, resulting in greater oxygen uptake rate. The continuous operation results showed that the total nitrogen removal and SND performance of the MBBR with the addition of 5.0 mm flocking carriers reached 52.0 % and 70.5 %, respectively, which were 29.1 % and 33.3 % greater than those of the control. Compared with those in suspended sludge, the extracellular polymeric substances and protein components in the biocarrier were more abundant. Furthermore, the relative abundance of genera related to denitrification and the nitrogen metabolic sequence improved with the addition of the novel flocking biocarriers. This study demonstrated the effectiveness of novel flocking fillers in improving the performance of MBBR.

Simultaneous denitrification enhancement and sludge reduction based on novel suspended carrier modified using activated carbon and magnetite at low carbon/nitrogen ratio.

A novel suspended carrier was prepared by sticking activated carbon (AC) and magnetite (Fe3O4) onto polypropylene slices. Although this carrier could not reverse the decreased denitrification capacity trends under anoxic conditions at an influent carbon/nitrogen (C/N) ratio of 2, it enhanced denitrification by stimulating sludge reduction and accelerating electron transfer to certain extent. The carrier stuck by mixed AC/Fe3O4 exhibited better performance in terms of sludge reduction, extracellular polymeric substances (EPS) secretion, and denitrification than that merely stuck by AC and Fe3O4 at an influent C/N ratio of 2. The carrier stuck by mixed AC/Fe3O4 increased the total nitrogen removal efficiency by 24.6 % ± 12.5 % in a 72-h denitrification batch experiment compared to the common polypropylene carrier. Moreover, the carrier improved EPS secretion and nitrogen metabolism and promoted the growth of Trichococcus and some denitrifying genera. This study provides a reference for the treatment of low C/N ratio sewage.

Effect of the Structure of Epoxy Monomers and Curing Agents: Toward Making Intrinsically Highly Thermally Conductive and Low-Dielectric Epoxy Resins.

The low intrinsic thermal conduction and high dielectric properties of epoxy resins have significantly limited their applications in electrical and electronic devices with high integration, high frequency, high power, and miniaturization. Herein, a liquid crystalline epoxy (LCE) monomer with a biphenyl mesogenic unit was first synthesized through an efficient one-step reaction. Subsequently, bisphenol AF (BPAF) containing low-polarizable -CF3 groups and 4,4'-diaminodiphenylmethane (DDM) were applied to cure the LCE and commercial diglycidyl ether of bisphenol A-type epoxy (E-51), respectively, to afford four kinds of epoxy resins with various intrinsic thermal conductivity and dielectricity values. Owing to the dual effect of microscopically stacking of mesogens and the contribution of fluorine to the formation of liquid crystallinity, ordered microstructures of the nematic liquid crystal phase were formed within the cross-linking network of LCE as confirmed by polarized optical microscopy and X-ray diffraction. Consequently, phonon scattering was suppressed, and the intrinsic thermal conductivity was improved considerably to 0.38 W/(m·K), nearly twice as high as that of E-51 cured with DDM (0.20 W/(m·K)). Additionally, the ordered microstructure and ultralow polar -CF3 groups within LCE cured with BPAF enabled the epoxy resin to exhibit a remarkably lower and stable dielectric constant (ε) and dielectric loss tangent (tan δ) over both low and high frequencies compared to E-51 cured with DDM. The ε decreased from 3.40 to 2.72 while the tan δ decreased from 0.044 to 0.038 at 10 GHz. This work presents a scalable and facile strategy for breaking the bottleneck of making epoxy resins simultaneously with high inherent thermal conduction and low dielectric performance.