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Abstract Objective Our aim was to explore the relationship between serum uric acid (UA) levels in early pregnancy and the development of gestational diabetes mellitus (GDM), and to further explore whether there is a causal relationship. Methods 684 pregnant women with GDM and 1162 pregnant women without GDM participated in this study. 311 pregnant women with GDM and 311 matched controls were enrolled in a 1:1 case-control study. We used conditional logistic regression to explore the relationship between UA levels and the risk of developing GDM. The causal relationship between the two was examined by two-sample Mendelian randomization (MR) analysis. Results In the 1:1 matched population, the odds ratio (OR) of developing GDM compared with the extreme tertiles of UA levels was 1.967 (95% confidence interval [CI]: 1.475–2.625; P

Multistage fracturing is a commonly-used method to improve gas production in tight hydrocarbon reservoirs. Stress shadowing effect among multi-fractures is crucial in effectively connecting the pre-existing natural fracture of reservoir and forming a complex fracture network that facilitates gas flow. Challenges remain in accurately characterizing the fracture structure and propogation patterns of naturally fractured reservoirs. In this study, we adopt an adaptive finite-discrete element method to simulate the multistage fracturing of a naturally fractured reservoir by improving the mesh auto-refinement and identification of multiple fracture propagation. The numerical model covers interactions among hydraulic fractures, pre-existing fractures, and microscale pores, while integrates the nonlinear Carter leak-off criterion to describe fluid leak-off and hydromechanical coupling effects during multistage fracturing. We introduce the proppant transport equation for idealised parallel plate flow in fractures, and Darcy's law is adopted to analyse the seepage flow in the fracture network and determine gas recovery. We then compare the fracture network and consequent fluid flow induced by the hydrofracturing of unfractured and naturally fractured models to assess the influence of pre-existing fractures on multistage fracturing behaviour and gas production. This study provides a new approach to determine and optimize fracturing cluster spacing in tight gas reservoirs.

Abstract Keratinocyte proliferation and differentiation in epidermis are well-controlled and essential for reacting to stimuli such as ultraviolet light. Imbalance between proliferation and differentiation is a characteristic feature of major human skin diseases such as psoriasis and squamous cell carcinoma. However, the effect of keratinocyte metabolism on proliferation and differentiation remains largely elusive. We show here that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) promotes differentiation while inhibits proliferation of keratinocyte and suppresses psoriasis development. FBP1 is identified among the most upregulated genes induced by UVB using transcriptome sequencing and is elevated especially in upper epidermis. Fbp1 heterozygous mice exhibit aberrant epidermis phenotypes with local hyperplasia and dedifferentiation. Loss of FBP1 promotes proliferation and inhibits differentiation of keratinocytes in vitro. Mechanistically, FBP1 loss facilitates glycolysis-mediated acetyl-CoA production, which increases histone H3 acetylation at lysine 9, resulting in enhanced transcription of proliferation genes. We further find that the expression of FBP1 is dramatically reduced in human psoriatic lesions and in skin of mouse imiquimod psoriasis model. Fbp1 deficiency in mice facilitates psoriasis-like skin lesions development through glycolysis and acetyl-CoA production. Collectively, our findings reveal a previously unrecognized role of FBP1 in epidermal homeostasis and provide evidence for FBP1 as a metabolic psoriasis suppressor.

Under the influence of information technology and high-speed transportation networks, which compress space and time, the region's population has achieved large-scale fluidity. Examining the temporal heterogeneity of intercity travel networks and its influencing mechanism can help optimize regional spatial organization and provide a scientific basis for regional integrated development. Based on Baidu migration data from January to April 2023, this study uses a PPML(Poisson Pseudo Maximum Likelihood) gravity model and interaction term testing to compare the scale, pattern, and influencing factors of intercity travel networks during weekdays, weekends, and holidays in the Yangtze River Delta region. The results indicate the following: 1) The intercity travel network in the Yangtze River Delta region exhibits temporal heterogeneity characteristics. During weekdays, intercity travel primarily consists of cross-city commuting and business trips, with the lowest daily average scale. This forms a V-shaped intercity travel structure covering Shanghai, southern Jiangsu, Northern Zhejiang, and Southern Anhui. The positive effects of destination city population size and economic status on intercity travel are enhanced. On weekends, intercity travel is dominated by business trips and leisure activities, and residents tend to take shorter trips, which means that intercity distances pose greater hindrances to intercity travel. During holidays, intercity travel is primarily for leisure and entertainment and for visiting friends and relatives, with the highest daily intensity. The promotional effect of destination city population size on intercity travel is weakened, and intercity travel is less hindered by intercity distances. Compared to the effects of geographical distance, economic status, and population size on the scale of intercity travel during weekdays, travel duration, or geographical distance, tends to pose a greater hindrance on weekends and a lesser hindrance during holidays. The promotional effect of economic status is intensified on weekends but diminishes during holidays. Meanwhile, the promotional effect of population size weakens both on weekends and during holidays. 2) Push-pull factors encompass the level of urban development and the incentives that trigger individual travel. In terms of urban development level, indicators such as population size, economic status, and industrial structure reflect the comprehensive strength and development status of a city, influencing its ability to serve as both a starting and destination point for intercity travel. From the perspective of various individual travel incentives, residents pay more attention to various urban resources such as income levels, public service quality, and tourism resources to meet their personal needs for production and living. The primary types of population movements vary across different time periods, shifting between cross-city commuting, business travel, and leisure and entertainment. As a result, the dominant factors among push-pull elements also change, leading to significant variations in the effectiveness of each factor. Intermediate obstacles are the key factors limiting intercity travel. On the one hand, while the level of integration in the Yangtze River Delta region continues to improve, and transportation facilities are gradually improving, geographical distance remains a crucial intermediate obstacle. On the other hand, administrative and cultural differences between different provinces increase residents' adaptation costs, forming "invisible barriers" that hinder cross-province population interactions. The hindrance posed by intermediate obstacles to intercity travel also varies across different travel periods. The effects of push-pull factors exhibit temporal heterogeneity. The small-world characteristics of the intercity travel network during weekdays are more evident, and the central city has a more prominent structural core status. On weekends, the geographical proximity of the intercity travel network improves, with close "center-hinterland" connections and enhanced inter-provincial boundary effects. During holidays, the overall intensity of the intercity travel network increases, with the most significant increase in medium- and long-distance cross-provincial travel. The provincial boundary effect and spatial proximity effect decrease, weakening the structure of the intercity travel network.

Abstract The WRKY transcription factors play essential roles in a variety of plant signaling pathways associated with biotic and abiotic stress response. The transcriptional activity of many WRKY members are regulated by a class of intrinsically disordered VQ proteins. While it is known that VQ proteins interact with the WRKY DNA-binding domains (DBDs), also termed as the WRKY domains, structural information regarding VQ-WRKY interaction is lacking and the regulation mechanism remains unknown. Herein we report a solution NMR study of the interaction between Arabidopsis WRKY33 and its regulatory VQ protein partner SIB1. We uncover a SIB1 minimal sequence neccessary for forming a stable complex with WRKY33 DBD, which comprises not only the consensus “FxxhVQxhTG” VQ motif but also its preceding region. We demonstrate that the βN-strand and the extended βN-β1 loop of WRKY33 DBD form the SIB1 docking site, and build a structural model of the complex based on the NMR paramagnetic relaxation enhancement and mutagenesis data. Based on this model, we further identify a cluster of positively-charged residues in the N-terminal region of SIB1 to be essential for the formation of a SIB1-WRKY33-DNA ternary complex. These results provide a framework for the mechanism of SIB1-enhanced WRKY33 transcriptional activity.

Abstract Background objective This study aimed to understand the basic situation of adults with human immunodeficiency virus (HIV) receiving antiretroviral therapy (ART) in Meigu County, Liangshan Yi Autonomous Prefecture. The information of patients who had been on ART for more than 6 months, the effect of ART, the possible reasons for ART failure, knowledge of drug resistance among patients with ART failure and the possible reasons for the emergence of drug resistance were analyzed. Methods A total of 2753 people living with HIV (PLWH) were collected for HIV-1 RNA virus nucleic acid testing. Plasma specimens with HIV-1 RNA ≥ 1000 copies/mL were sent to the laboratory for nucleic acid extraction, PCR, electrophoresis and sequencing, and the sequencing results were submitted to the HIV drug resistance database of Stanford University for subtyping to determine the drug resistance mutation sites and drug sensitivity levels. Results A total of 2753 patients were enrolled in this study. Antiviral therapy failed in 288 patients and was successfully amplified in 245, of which 111 had resistance genes. The resistance rate to failure of viral suppression was 45.3% (111/245). The highest rates of resistance to NNRTIs were found for efavirenz (EFV) and nevirapine (NVP) (42.9%), and the highest rates of resistance to NRTIs were found for 3TC and emtricitabine (FTC) (15.9%). The most common NNRTI resistance mutation site was K103N (20.8%), followed by V179D (9.4%) and V106M (7.8%); the most common NRTI resistance mutation site was M184V/I/MV (14.3%), followed by K65R (6.9%); three PI-associated resistance mutation sites were identified. The subtype of the resistant strain was CRF07-BC in almost all patients (98.9%). Conclusions Compared with the previous low ART efficacy in the county, this study showed that the overall virological failure (VF) resistance rate in the county is still low, dominated by resistance to EFV, NVP, 3TC, FTC, and didanosine (DDI). Due to economic constraints, the core regimen is still 3TC + TDF, but before initiating ART, testing for HIV-1 subtypes and resistance should be conducted to avoid resistance that can lead to VF, especially for patients with high risk factors for resistance as shown by epidemiologic investigations.

Abstract Functional constipation (FC) has a negative impact on patients' quality of life. We hypothesized that dietary supplementation with xylo‐oligosaccharides (XOS) or fructo‐oligosaccharides (FOS) would improve constipation symptoms by influencing the gut microbiota. A randomized double‐blind controlled trial was conducted in FC patients. Patients were randomly divided into 6 groups and given a dietary supplement containing XOS at doses of 3, 5, or 10 g/day, FOS at doses of 10 and 20 g/day, or placebo at 5 g/day for one month. We compared improvements in gastrointestinal function after the intervention using the Bristol Stool Form Scale (BSFS), Cleveland Clinic Constipation Score (CCCS), and Quality of Life Scale for Patients with Constipation (PAC‐QoL). 16S rRNA sequencing was used to assess changes in the structure of the gut microbiota. Changes in individual bacteria had significant effects in reducing gastrointestinal symptoms during the intervention, even though the flora structure remained unchanged from baseline. Compared to FOS, XOS enriched Bifidobacterium at a lower dose, and patients receiving XOS supplementation showed significant improvements in constipation symptoms without side effects such as diarrhea and flatulence.

The understanding of the link between the gut-bone axis is growing yearly, but the mechanisms involved are not yet clear. Our study analyzed the role of Sestrin2 (SESN2)pathway in the gut-bone axis. We established an osteoarthritis (OA) model in Sprague-Dawley (SD) rats using the anterior cruciate ligament transection (ACLT) procedure, followed by a dietary intervention with varying levels of dietary fiber content for 8 weeks. By 16S rRNA sequencing of the gut microbiota, we found that high dietary fiber (HDF) intake could significantly increase the Bacillota-dominant gut microbiota. Meanwhile, enzyme linked immunosorbent assay (ELISA) and histological analysis showed that intervention with HDF could reduce the degree of bone and joint lesions and inflammation. We hypothesize that HDF increased the dominant flora of Bacillota, up-regulated the expression of SESN2 in knee joint, and reduced gut permeability, thereby reducing systemic inflammatory response and the degree of bone and joint lesions. Therefore, the present study confirms that changes in gut microbiota induced by increased dietary fiber intake delayed the onset of OA by promoting up-regulation of SESN2 expression at the knee joint to maintain chondrocyte activity and reduce synovial inflammation.

Fast and precise identification of microorganisms in the early diagnosis of sepsis is crucial for enhancing patient outcomes. Digital PCR (dPCR) is a highly sensitive approach for absolute quantification that can be utilized as a culture-independent molecular technique for diagnosing sepsis pathogens. We performed a retrospective investigation on 69 ICU patients suspected of sepsis. Our findings showed that a multiplex dPCR diagnostic kit outperformed blood culture in detecting the 15 most frequent bacteria that cause sepsis. Ninety-two bacterial strains were identified using dPCR at concentrations varying from 34 copies/mL to 105,800 copies/mL. The detection rate of dPCR was much greater than that of BC, with 27.53% (19/69) versus 73.91% (51/69). The sensitivity of dPCR was 63.2%. Our research indicated that dPCR outperforms blood culture in the early detection of sepsis-causing microorganisms. The diagnostic kit can detect a greater variety of pathogens with quantitative data, including polymicrobial infections, and has a quicker processing time. DPCR is a valuable technique that could aid in the proper management of sepsis.

Background: In clinical practice, antibiotics and/or inhaled or oral hormone preparations are the first line of treatment for chronic pharyngitis. However, this therapeutic regimen is not satisfactory enough. At present, medicinal plants as dietary supplements or functional foods are widely recognized for the treatment and prevention of different diseases.Purpose: This study aimed to evaluate the efficacy of the botanical lozenge made from several medicinal plant extracts in the treatment of chronic pharyngitis and its effects on patients’ illness perception and adherence to treatment.Methods: Patients with chronic pharyngitis were randomly assigned to the experimental group (n = 52) or the control group (n = 51). Patients were given botanical lozenges prepared from the extracts of medicinal plants such as Siraitia grosvenorii (Swingle) C. Jeffrey ex A.M.Lu and Zhi Y. Zhang [Cucurbitaceae; Siraitiae fructus], Lonicera japonica Thunb [Caprifoliaceae; Lonicerae japonicae flos], Platycodon grandiflorus (Jacq.) A. DC [Campanulaceae; Platycodon radix], and Glycyrrhiza uralensis Fisch. ex DC [Fabaceae; Glycyrrhizae radix et rhizoma] or placebos made of starch for 15 days. The improvement of pharyngeal symptoms and signs, illness perception, and adherence to treatment were evaluated at the end of the intervention.Results: The total score of pharyngeal symptoms of patients in the experimental group (3.33 ± 2.33) was significantly lower than that in the control group (5.20 ± 2.93) (p < 0.01). In comparison to the control group (3.43 ± 1.43), the total pharyngeal signs score of patients in the experimental group (2.69 ± 1.59) was considerably lower (p < 0.01). The improvement rates of pharyngeal itching, dry throat, pharyngeal foreign body sensation, aggravation due to excessive speaking, and congestion of pharyngeal mucosa in the experimental group were 73.81%, 67.50%, 67.57%, 65.22% and 44%, respectively, which were significantly higher than those in the control group (p < 0.05). In addition, patients taking botanical lozenges had better illness perception and adherence to treatment than those taking placebos (p < 0.05). Patients with low adherence to treatment showed less personal control, concerns, and understanding of chronic pharyngitis (p < 0.05).Conclusion: Botanical lozenges not only aided patients in recovering from chronic pharyngitis but also improved their positive perceptions of the disease, which helped them adhere to their treatment regimen.Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR2200062139].

Nitrile-containing insecticides can be converted into their amide derivatives by Pseudaminobacter salicylatoxidans. N-(4-trifluoromethylnicotinoyl) glycinamide (TFNG-AM) is converted to 4-(trifluoromethyl) nicotinoyl glycine (TFNG) using nitrile hydratase/amidase. However, the amidase that catalyzes this bioconversion has not yet been fully elucidated. In this study, it was discovered that flonicamid (FLO) is degraded by P. salicylatoxidans into the acid metabolite TFNG via the intermediate TFNG-AM. A half-life of 18.7 h was observed for P. salicylatoxidans resting cells, which transformed 82.8% of the available FLO in 48 h. The resulting amide metabolite, TFNG-AM, was almost all converted to TFNG within 19 d. A novel amidase-encoding gene was cloned and overexpressed in Escherichia coli. The enzyme, PmsiA, hydrolyzed TFNG-AM to TFNG. Despite being categorized as a member of the amidase signature enzyme superfamily, PsmiA only shares 20–30% identity with the 14 previously identified members of this family, indicating that PsmiA represents a novel class of enzyme. Homology structural modeling and molecular docking analyses suggested that key residues Glu247 and Met242 may significantly impact the catalytic activity of PsmiA. This study contributes to our understanding of the biodegradation process of nitrile-containing insecticides and the relationship between the structure and function of metabolic enzymes.

In order to distinguish terrestrial material sources in the Okinawa Trough (OT), this study analyzed four surface sediment samples from the northern, middle, and southern parts of the OT using detrital zircon U-Pb age analysis. The detrital zircon age distributions in the northern Okinawa Trough (N-OT) predominantly fall into 1,000-2,300 Ma and 100-600 Ma age groups. In contrast, in the middle Okinawa Trough (M-OT) and southern Okinawa Trough (S-OT), the detrital zircon age groups of 100-600 Ma and 600-1,000 Ma increase significantly, while the age groups of 1,000-2,300 Ma and >2,300 Ma decrease. Detrital zircons from the N-OT primarily originate from the Yellow River and mixed with the Old Yellow River, while those from the M-OT come mainly from the Yellow River, Yangtze Rivers, and East China Sea. And Zhuoshui River maybe a potential source for the M-OT. The detrital zircons from the S-OT are mainly influenced by the Yangtze River, with some effects from the Lanyang River. This study utilizes detrital zircon U-Pb age analysis to gain a better understanding of the terrestrial material sources in various regions of the OT. Most of the zircon grain are coarse, with grain sizes of 40-150 µm long and 30-100 µm wide in the N-OT, smaller in the M-OT and S-OT in this study, which are probably not modern deposits, but the products in the low sea level period of last glaciation mixed with modern sediments. The transport and sedimentation processes reflect the comprehensive influence of sea level change, Kuroshio Current, river input, East Asian monsoon and other factors from last glaciation to present. [ABSTRACT FROM AUTHOR]

Understanding preferential flow in porous media holds substantial theoretical significance on the design and optimization of hydrocarbon exploitation in shale reservoir. Previous researches discussed the competition of imbibition front in layered porous media while the underlining mechanism for interfacial dynamics and induced displacement efficiency of multiphase flow remains ambiguous. In this paper, we investigate the spontaneous imbibition in dual permeable media and analyze the flux exchange between the neighboring porous zones with permeability contrast using dynamic pore network model. The impact of fluid viscosity ratio and permeability contrast on the spontaneous imbibition preference have been addressed, and finally a phase diagram for displacement efficiency has been obtained. The results reveal that the dual permeable structure enhances the invasion rate of wetting fluid in the low‐permeable zone and induces unstable displacement patterns, leading to reduction of the long‐term displacement efficiency. The interfacial pattern transition from stable displacement to unstable pattern in dual permeable media could be ascribed into the flux exchange between dual permeable zones, which shows a contrary impact on the fluid flow within the low‐permeable zone under favorable and unfavorable viscosity ratios. The permeability contrast in dual permeable media intensifies this impact during spontaneous imbibition. These results help us to understand the occurrence and mutual interaction of multiphase flow in layered porous media, and provide a theoretical guidance for the hydrocarbon exploitation in shale reservoir. Plain Language Summary: The shale oil reservoir has emerged as a crucial contributor to the global energy supply, primarily attributed to stimulation techniques such as hydraulic fracturing. The geological composition of shale rock encompasses stratified layers characterized by varying permeability, leading to diverse multiphase flow patterns at the pore scale during the shut‐in period. These intricate flow patterns significantly impact shale oil recovery during subsequent exploitations. However, a gap exists in comprehending the optimal design of injection conditions by controlling the multiphase flow pattern for a high‐efficiency exploitation strategy. The elucidation of multiphase displacement mechanisms within the complex porous structure featuring staggered layers are imperative. To address this gap, pore‐scale modeling and analysis were conducted to visualize spontaneous imbibition behaviors across varying fluid viscosity ratios and permeability contrasts. The findings indicate that the imbibition flux in low‐permeable zone is augmented by fluid flow in high‐permeable zone. Furthermore, an escalating permeability contrast intensifies the flux enhancement and reduce the displacement efficiency in dual permeable media by changing the displacement pattern from stable to unstable distribution. These outcomes serve as a theoretical foundation, providing insights for the selection and optimization of an effective exploitation strategy to enhance shale oil recovery under complex engineering conditions. Key Points: A dynamic pore network model for studying spontaneous imbibition in dual permeable media is presentedThe contrary effect of flux exchange on spontaneous imbibition within low‐permeable zone under various viscosity ratios is observedTransition of interface dynamics from stable to unstable pattern is induced by unfavorable viscosity ratio and large permeability contrast [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease caused by autoantibodies. Serum samples from patients with SLE (n = 10) were compared with those from normal controls (NCs, n = 5) using 21K protein chip analysis to identify a biomarker for SLE, revealing 63 SLE-specific autoantibodies. The anti-chaperonin-containing t-complex polypeptide-1 (TCP1) antibody exhibited higher expression in patients with SLE than in NCs. To validate the specificity of the anti-TCP1 antibody in SLE, dot blot analysis was conducted using sera from patients with SLE (n = 100), rheumatoid arthritis (RA; n = 25), Behçet's disease (BD; n = 28), and systemic sclerosis (SSc; n = 30) and NCs (n = 50). The results confirmed the detection of anti-TCP1 antibodies in 79 of 100 patients with SLE, with substantially elevated expression compared to both NCs and patients with other autoimmune diseases. We performed an enzyme-linked immunosorbent assay to determine the relative amounts of anti-TCP1 antibodies; markedly elevated anti-TCP1 antibody levels were detected in the sera of patients with SLE (50.1 ± 17.3 arbitrary unit (AU), n = 251) compared to those in NCs (33.9 ± 9.3 AU), RA (35 ± 8.7 AU), BD (37.5 ± 11.6 AU), and SSc (43 ± 11.9 AU). These data suggest that the anti-TCP1 antibody is a potential diagnostic biomarker for SLE. [ABSTRACT FROM AUTHOR]

Introduction: Percussionists stand out for their expertise in rhythm, with the network for musical rhythm (NMR) serving a vital neurological function in their improvisation, which is deeply rooted in comprehensive musical knowledge. Our research examines the central representations of various improvisation tactics used by percussionists and investigates the interactions between the NMR and other relevant neural networks. Methods: Twenty-five percussionists participated in functional magnetic resonance imaging (fMRI) sessions, which included two cognitive strategies of improvisation. Structural improvisation (SIMP) emphasized rhythmic patterns, while free improvisation (FIMP) focused on musical spontaneity. Sight-reading scenario served as the reference condition. Paired t-tests were utilized for comparative analyses. Results: The findings revealed a dynamic interplay characterized by increased activity in the executive control network and NMR, along with decreased activity in the default mode network during SIMP. During FIMP, heightened activity was observed in the executive control network, NMR, limbic, and memory systems. In both SIMP vs. sight-reading and FIMP vs. sight-reading comparisons, the visual network's activity decreased, a trend also observed in the comparative analysis of FIMP vs. SIMP. Discussion: In SIMP, percussionists leverage external rhythmic signals, resulting in heightened NMR and ECN activity and reduced DMN activity. In contrast, FIMP is characterized by a rise in activity within the NMR, ECN, limbic system, memory system, and reward system, underscoring the vital roles of motivation and memory in the rapid production of spontaneous musical ideas within set frameworks. The diminished activity in the visual network during FIMP compared to SIMP suggests less reliance on visual stimuli in FIMP. These findings suggest that various improvisational tactics may engage different neural pathways. [ABSTRACT FROM AUTHOR]

Microstructural changes in conductive materials induced by electric current treatments, such as electromigration and electroplasticity, are critical in semiconductor and metal processing. However, owing to the inevitable thermal effect (Joule heating), the athermal effect on microstructural modifications remains obscure. This paper presents an approach of utilizing pre-micromachined structures, which obstruct current flow but maintain a thermal history similar to that of the matrix, effectively disentangling the thermal and athermal effects. A duplex stainless-steel material is selected to validate the feasibility of this method. Microstructural characterizations show that the athermal effect, especially the electron wind force (EWF), primarily governs the element diffusion and phase transformation in this study. Moreover, many σ phases (Cr-enriched) are precipitated in the micromachined structures, whereas no precipitation occurred in the matrix, suggesting that the directional EWF disrupts the Cr aggregation caused by Joule heating. Furthermore, we present a critical formula for determining the dimensions of micromachined structures of commonly used metallic materials. The proposed method may serve as an effective and powerful tool for unveiling the athermal effect on microstructural alterations. Understanding the impact of the athermal effect on microstructures is crucial for designing and manufacturing semiconductor and metal materials. Here, the authors propose a method using pre-micromachined structures to decouple thermal and athermal effects and experimentally validate its feasibility. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder primarily targeting joints, significantly impacting patients' quality of life. The introduction of tumor necrosis factor-alpha (TNF-α) inhibitors has markedly improved RA management by reducing inflammation. However, these medications are associated with adverse skin reactions, which can vary greatly among patients due to genetic differences. Objectives: This study aimed to identify risk factors associated with skin adverse events by TNF-α in RA patients. Methods: A cohort study was conducted, encompassing patients with RA who were prescribed TNF-α inhibitors. This study utilized machine learning algorithms to analyze genetic data and identify markers associated with skin-related adverse events. Various machine learning algorithms were employed to predict skin and subcutaneous tissue-related outcomes, leading to the development of a risk-scoring system. Multivariable logistic regression analysis identified independent risk factors for skin and subcutaneous tissue-related complications. Results: After adjusting for covariates, individuals with the TT genotype of rs12551103, A allele carriers of rs13265933, and C allele carriers of rs73210737 exhibited approximately 20-, 14-, and 10-fold higher incidences of skin adverse events, respectively, compared to those with the C allele, GG genotype, and TT genotype. The machine learning algorithms used for risk prediction showed excellent performance. The risk of skin adverse events among patients receiving TNF-α inhibitors varied based on the risk score: 0 points, 0.6%; 2 points, 3.6%; 3 points, 8.5%; 4 points, 18.9%; 5 points, 36.7%; 6 points, 59.2%; 8 points, 90.0%; 9 points, 95.7%; and 10 points, 98.2%. Conclusions: These findings, emerging from this preliminary study, lay the groundwork for personalized intervention strategies to prevent TNF-α inhibitor-associated skin adverse events. This approach has the potential to improve patient outcomes by minimizing the risk of adverse effects while optimizing therapeutic efficacy. [ABSTRACT FROM AUTHOR]

In this study, soy protein isolate (SPI) films incorporating quercetin-grafted dialdehyde starch (DAS-QR) and DAS/QR, respectively, were developed. The structural, physical, and functional properties of the composite films were determined. The results suggested that DAS-QR and DAS/QR formed hydrogen bonding with the SPI matrix, which improved the structural properties of the films. The light-blocking capacity, thermal stability, hydrophobicity, tensile strength, elongation at break, and antioxidant and antibacterial abilities of SPI films were improved by DAS-QR and DAS/QR. Notably, SPI films incorporated with DAS-QR exhibited better performance than those with DAS/QR in terms of antioxidant (SPI/DAS-QR: 79.8% of DPPH and 62.1% of ABTS scavenging activity; SPI/DAS/QR: 71.4% of DPPH and 56.0% of ABTS scavenging activity) and antibacterial abilities against S. aureus (inhibition rate: 92.7% for SPI/DAS-QR, 83.4% for SPI/DAS/QR). The composite coating film SPI/DAS-QR effectively maintained appearance quality, delayed the loss of weight and total soluble solids, postponed malondialdehyde accumulation, and decreased peroxidase activity and microbial contamination in fresh-cut potatoes. These good performances highlight SPI/DAS-QR as a promising active packaging material for fresh-cut product preservation. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to demonstrate the potential of activated leukocyte cell adhesion molecule (ALCAM), hemopexin (HPX), and peroxiredoxin 6 (PRDX6) as urine biomarkers for systemic lupus erythematosus (SLE). Methods: Urine samples were collected from 138 Korean patients with SLE from the Ajou Lupus Cohort and 39 healthy controls (HC). The concentrations of urine biomarkers were analyzed using enzyme-linked immunosorbent assay kits specific for ALCAM, HPX, and PRDX6, respectively. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic utility, and Pearson's correlation analysis was conducted to assess the relationships between the disease activity and urine biomarkers. Results: Patients with SLE and patients with lupus nephritis (LN) showed significantly elevated ALCAM, HPX, and PRDX6 levels compared with HCs. ALCAM, HPX, and PRDX6 showed significant diagnostic values, especially for lupus nephritis (LN), with areas under the receiver operating characteristic curve for LN was 0.850 for ALCAM (95% CI, 0.778-0.921), 0.781 for HPX (95% CI, 0.695-0.867), and 0.714 for PRDX6 (95% CI, 0.617-0.812). Correlation analysis revealed that all proteins were significantly associated with anti-double stranded DNA antibody (ALCAM, r = 0.350, p < 0.001; HPX, r = 0.346, p < 0.001; PRDX6, r = 0.191, p = 0.026) and SLEDAI (ALCAM, r = 0.526, p < 0.001; HPX, r = 0.479, p < 0.001; PRDX6, r = 0.262, p = 0.002). Results from the follow-up of the three biomarker levels in these patients revealed a significant decrease, showing a positive correlation with changes in SLEDAI-2k scores (ALCAM, r = 0.502, p < 0.001; HPX, r = 0.475, p < 0.001; PRDX6, r = 0.245, p = 0.026), indicating their potential as indicators for tracking disease activity. Discussions: Urinary ALCAM, HPX, and PRDX6 levels have diagnostic value and reflect disease activity in Korean patients with SLE, emphasizing their potential for non-invasive monitoring and treatment response evaluation. [ABSTRACT FROM AUTHOR]