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Protein solubility is a critical parameter that determines the stability, activity, and functionality of proteins, with broad and far-reaching implications in biotechnology and biochemistry. Accurate prediction and control of protein solubility are essential for successful protein expression and purification in research and industrial settings. This study gathered information on soluble and insoluble proteins. In characterizing the proteins, they were mapped to STRING and characterized by functional and structural features. All functional/structural features were integrated to create a 5768-dimensional binary vector to encode proteins. Seven feature-ranking algorithms were employed to analyze the functional/structural features, yielding seven feature lists. These lists were subjected to the incremental feature selection, incorporating four classification algorithms, one by one to build effective classification models and identify functional/structural features with classification-related importance. Some essential functional/structural features used to differentiate between soluble and insoluble proteins were identified, including GO:0009987 (intercellular communication) and GO:0022613 (ribonucleoprotein complex biogenesis). The best classification model using support vector machine as the classification algorithm and 295 optimized functional/structural features generated the F1 score of 0.825, which can be a powerful tool to differentiate soluble proteins from insoluble proteins.

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As a substitute for brominated flame retardants, organophosphate flame retardants (OPFRs) have become a global concern due to their high toxicity and bioaccumulation. To paint an overall picture of OPFRs in the global environment, the present study develops a gridded global emission inventory of OPFRs on a spatial resolution of 1 × 1° from 2010 to 2020. Revealing a 3.31% average annual increase in emissions, totaling 21,324.42 tons. The production process is the primary source, accounting for 55.43% of emissions, with consumption processes making up the rest. Major sources are in Asia, North America, and Europe. The inventory is verified by implementing emission data into a global atmospheric transport model to predict OPFR concentrations in the global environment and comparing modeled concentrations with field sampled data. The results indicate that the inventory is reliable except for the pristine polar region, where the emission inventory and modeled concentrations underestimate OPFR levels in the atmosphere, likely resulting from ignorance of chemical reactions and the secondary derivative of parent OPFRs during their global long-distance atmospheric transport in the model. This comprehensive data set aids in formulating OPFR emission control policies and assessing health risks.

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The purpose of this study was to investigate the effect of whole-body cryotherapy (WBC) on acute recovery after a single high-intensity training day. Twelve elite professional male rowers from the national aquatic training base. They were randomly divided into a WBC group (n = 6) and a control group (CON group, n = 6). They performed a high-intensity training program, with a single session immediately followed by WBC (-110°C, 3 min) or recovered naturally for 3 min (CON group). Rowing performance, skin temperature, heart rate, blood pressure, and blood lactate concentrations were recorded before training, immediately, 5 min, and 15 min after the intervention. Blood samples were collected early in the morning of the day of intervention and that of the following day. The results indicated that 1) the blood lactate concentrations after WBC were significantly lower than pre-training (p < 0.05); 2) the maximum power significantly decreased immediately after WBC compared to pre-training (p < 0.05); 3) a significant main effect of time was observed for average speed, which significantly decreased after WBC (p < 0.05); 4) a significant main effect of time for blood parameters was observed. Specifically, hematocrit, cortisol, and hemoglobin were significantly lower after WBC than pre-intervention, whereas testosterone/cortisol was significantly higher than pre-intervention (p < 0.05). The results of this study showed that a single session of WBC had a positive effect on accelerating the elimination of blood lactate after HIT, but did not significantly change rowing performance and physiological parameters. A single session of WBC was not an effective strategy for elite rowers for acute recovery after HIT.

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HNRNPA2B1 is a member of the HNRNP family, which is associated with telomere function, mRNA translation, and splicing, and plays an important role in tumor development. To date, there have been no pan-cancer studies of HNRNPA2B1, particularly within the TME. Therefore, we conducted a pan-cancer analysis of HNRNPA2B1 using TCGA data. Based on datasets from TCGA, TARGET, Genotype-Tissue Expression, and Human Protein Atlas, we employed a range of bioinformatics approaches to explore the potential oncogenic role of HNRNPA2B1. This included analyzing the association of HNRNPA2B1 expression with prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), immune response, and immune cell infiltration of individual tumors. We further validated the bioinformatic findings using immunohistochemistry techniques. HNRNPA2B1 was found to be differentially expressed across most tumor types in TCGA's pan-cancer database and was predictive of poorer clinical staging and survival status. HNRNPA2B1 expression was also closely linked to TMB, MSI, tumor stemness, and chemotherapy response. HNRNPA2B1 plays a significant role in the TME and is involved in the regulation of novel immunotherapies. Its expression is significantly associated with the infiltration of macrophages, dendritic cells, NK cells, and T cells. Furthermore, HNRNPA2B1 is closely associated with immune checkpoints, immune-stimulatory genes, immune-inhibitory genes, MHC genes, chemokines, and chemokine receptors. We performed a comprehensive evaluation of HNRNPA2B1, revealing its potential role as a prognostic indicator for patients and its immunomodulatory functions.

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Understanding the differences in ubiquitination-modified proteins between Duroc pigs and Tibetan fragrant pigs is crucial for comprehending the growth and development of their skeletal muscles. In this study, skeletal muscle samples from 30-day-old Duroc pigs and Tibetan fragrant pigs were collected. Using ubiquitination 4D-Label free quantitative proteomics, we analyzed and identified ubiquitination-modified peptides, screening out 109 differentially expressed ubiquitination-modified peptides. Further enrichment analysis was conducted on the proteins associated with these differential peptides. GO analysis results indicated that the differential genes were primarily enriched in processes such as regulation of protein transport, motor activity, myosin complex, and actin cytoskeleton. KEGG pathway analysis revealed significant enrichment in pathways such as Glycolysis/Gluconeogenesis and Hippo signaling pathway. The differentially expressed key ubiquitinated proteins, including MYL1, MYH3, TNNC2, TNNI1, MYLPF, MYH1, MYH7, TNNT2, TTN, and TNNC1, were further identified. Our analysis demonstrates that these genes play significant roles in skeletal muscle protein synthesis and degradation, providing new insights into the molecular mechanisms of muscle development in Duroc pigs and Tibetan fragrant pigs, and offering theoretical support for breeding improvements in the swine industry.

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Diabetic foot ulcers (DFUs) are chronic wounds and one of the most common complications of diabetes, imposing significant physical and mental burdens on patients due to their poor prognosis and treatment efficacy. Adipose-derived stem cells (ADSCs) have been proven to promote wound healing, with studies increasingly attributing these beneficial effects to their paracrine actions. Consequently, research on ADSC secretome as a novel and promising alternative for DFU treatment has been extensively conducted. This article provides a comprehensive review of the mechanisms underlying refractory DFU wounds, the secretome of ADSCs, and its role in promoting wound healing in diabetes foot ulcers. And the review aims to provide reliable evidence for the clinical application of ADSC secretome in the treatment of refractory DFU wounds.

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In this study, in order to solve the application problems of poor water solubility and low bioavailability of quercetin, we prepared a nano-delivery system with core-shell structure by anti-solvent method, including a hydrophilic shell composed of tea saponin and a hydrophobic core composed of Zein, which was used to improve the delivery efficiency and biological activity of quercetin. Through the optimal experiments, the loading rate and encapsulation rate of nanoparticles reached 89.41 % and 7.94 % respectively. And the water solubility of quercetin is improved by 30.16 times. At the same time, the quercetin acted with Zein through non-covalent interaction and destroyed its spatial network through structural characterization, while tea saponin covered the surface of Zein through electrostatic interaction, making it change into amorphous state. In addition, the addition of tea saponin makes the nanoparticles remain stable under the changes of external environment. During simulating gastrointestinal digestion procedure, ZQTNPs has higher release rate and bioavailability than free quercetin. Importantly, ZQTNPs can overcome the limitations of a single substance through synergy. These results will promote the innovative development of quercetin precision nutrition delivery system.

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Hepatocellular carcinoma (HCC) exhibits a low response to immunotherapy due to the dense extracellular matrix (ECM) filled with immunosuppressive cells including dendritic cells (DCs) of blocked maturation. Herein, we develop a nanoprodrug self-assembled from polyethylene glycol-poly-4-borono-l-phenylalanine (mPEG-PBPA) conjugating with quercetin (QUE) via boronic ester bonds. In addition, an immune adjuvant of imiquimod (R837) is incorporated. The nanodrug (denoted as Q&R@NPs) is prepared from a simple mixing means with a high loading content of QUE reaching more than 30%. Owing to the acid and reactive oxygen species (ROS) sensitivities of boronic ester bonds, Q&R@NPs can respond to the tumor microenvironment (TME) and release QUE and R837 to synchronously exert multicellular regulation functions. Specifically, QUE inhibits the activation state of hepatic stellate cells and reduces highly expressed programmed death receptor ligand 1 (PD-L1) on tumor cells, meanwhile R837 exposes calreticulin on tumor cell surface as an "eat me" signal and leads to a large number of DCs maturing for enhanced antigen presentation. Consequently, the cooperative immune regulation results in a remodeled TME with high infiltration of cytotoxic T lymphocytes for enhanced HCC immunotherapy, which demonstrates an effective immunotherapy paradigm for dense ECM characterized solid tumors with high PD-L1 expression.

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Herbal extracts are rich sources of active compounds that can be used for drug screening due to their diverse and unique chemical structures. However, traditional methods for screening these compounds are notably laborious and time-consuming. In this manuscript, we introduce a new high-throughput approach that combines nuclear magnetic resonance (NMR) spectroscopy with a tailored database and algorithm to rapidly identify bioactive components in herbal extracts. This method distinguishes characteristic signals and structural motifs of active constituents in the raw extracts through a relaxation-weighted technique, particularly utilizing the perfect echo Carr-Purcell-Meiboom-Gill (peCPMG) sequence, complemented by precise 2D spectroscopic strategies. The cornerstone of our approach is a customized database designed to filter potential compounds based on defined parameters, such as the presence of CHn segments and unique chemical shifts, thereby expediting the identification of promising compounds. This innovative technique was applied to identifying substances interacting with choline kinase α (ChoKα1), resulting in the discovery of four new inhibitors. Our findings demonstrate a powerful tool for unraveling the complex chemical landscape of herbal extracts, considerably facilitating the search for new pharmaceutical candidates. This approach offers an efficient alternative to traditional methods in the quest for drug discovery from natural sources.

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BACKGROUND AND AIMS: Poor cardiovascular-kidney-metabolic (CKM) health is a major determinant of all-cause mortality, which poses a significant burden on global public health systems and socio-economics. However, the association between different stages of CKM syndrome and the risk of all-cause mortality remains unclear. This study aimed to evaluate the association between different stages of CKM syndrome and risk of all-cause mortality. METHODS: A total of 97,777 adults from the Kailuan Study were included. Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) of all-cause mortality according to different stages of CKM syndrome. RESULTS: Over a median follow-up of 15.0 (14.7-15.2) years, we identified 14,805 all-cause mortality cases. The stage of CKM syndrome was positively associated with the risk of all-cause mortality (p-trend <0.001). Compared with Stage 0, the multivariable-adjusted HRs (95 % CIs) of all-cause mortality were 1.24 (1.06-1.45) for Stage 1, 1.72 (1.48-2.00) for Stage 2, 2.58 (2.22-3.01) for Stage 3 and 3.73 (3.19-4.37) for Stage 4. Moreover, the observed associations were more pronounced in younger adults (aged <60 years) compared with older adults (p for interaction <0.001). CONCLUSIONS: Our data showed that a higher stage of CKM syndrome was associated with a higher risk of all-cause mortality, with a particularly pronounced association observed in younger adults. The study emphasized the need for targeted public health strategies and clinical management tailored to the stages of CKM syndrome, aiming to alleviate its burden on individuals and healthcare systems.

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African swine fever virus (ASFV), a highly contagious pathogen characterized by a complex structure and a variety of immunosuppression proteins, causes hemorrhagic, acute, and aggressive infectious disease that severely injures the pork products and industry. However, there is no effective vaccine or treatment. The main reasons are not only the complex mechanisms that lead to immunosuppression but also the unknown functions of various proteins. This review summarizes the interaction between ASFV and the host immune system, along with the involvement of virulence-related genes and proteins, as well as the corresponding molecular mechanism of immunosuppression of ASFV, encompassing pathways such as cGAS-STING, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Janus Kinase (JAK) and JAK Signal Transducers and Activators of Transcription (STAT), apoptosis, and other modulation. The aim is to summarize the dynamic process during ASFV infection and entry into the host cell, provide a rational insight into development of a vaccine, and provide a better clear knowledge of how ASFV impacts the host.

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In order to improve the service life of extrusion taps and reduce their wear, this paper adopted the coating-simulation technology to investigate the influence laws of tool coating type and coating thickness on extrusion torque, extrusion temperature and wear amount. The validity of the numerical simulation results is confirmed through internal thread extrusion experiments. The results showed that the extrusion torque and extrusion temperature of single-layer coating and composite coating showed a tendency of decreasing and then increasing with the increase of the coating thickness; the extrusion torque and extrusion temperature of the double-layer coating increased with the increase of the coating thickness; the wear amount of the three types of coatings increased with the increase of the coating thickness. The TiAlN single coating demonstrates the most pronounced impact on decreasing extrusion torque and temperature (3.82 N·m and 88.4 °C), resulting in a smooth extrusion process. The TiAlN-TiAlN double coating exhibits the lowest wear amount of 0.076 mm. The utilization of numerical simulation proves to be a dependable approach for evaluating the efficacy of tool coatings, and reasonable selection of coating type and thickness can effectively reduce the extrusion torque, extrusion temperature and wear amount.

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Importance: Hyperkalemia is a common complication in people with type 2 diabetes (T2D) that may limit the use of guideline-recommended renin-angiotensin system inhibitors (RASis). Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase urinary potassium excretion, which may translate into reduced hyperkalemia risk. Objective: To compare rates of hyperkalemia and RASi persistence among new users of GLP-1RAs vs dipeptidyl peptidase-4 inhibitors (DPP-4is). Design, Setting, and Participants: This cohort study included all adults with T2D in the region of Stockholm, Sweden, who initiated GLP-1RA or DPP-4i treatment between January 1, 2008, and December 31, 2021. Analyses were conducted between October 1, 2023, and April 29, 2024. Exposures: GLP-1RAs or DPP-4is. Main Outcomes and Measures: The primary study outcome was time to any hyperkalemia (potassium level >5.0 mEq/L) and moderate to severe (potassium level >5.5 mEq/L) hyperkalemia. Time to discontinuation of RASi use among individuals using RASis at baseline was assessed. Inverse probability of treatment weights served to balance more than 70 identified confounders. Marginal structure models were used to estimate per-protocol hazard ratios (HRs). Results: A total of 33 280 individuals (13 633 using GLP-1RAs and 19 647 using DPP-4is; mean [SD] age, 63.7 [12.6] years; 19 853 [59.7%] male) were included. The median (IQR) time receiving treatment was 3.9 (1.0-10.9) months. Compared with DPP-4i use, GLP-1RA use was associated with a lower rate of any hyperkalemia (HR, 0.61; 95% CI, 0.50-0.76) and moderate to severe (HR, 0.52; 95% CI, 0.28-0.84) hyperkalemia. Of 21 751 participants who were using RASis, 1381 discontinued this therapy. The use of GLP-1RAs vs DPP-4is was associated with a lower rate of RASi discontinuation (HR, 0.89; 95% CI, 0.82-0.97). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function. Conclusions: In this study of patients with T2D managed in routine clinical care, the use of GLP-1RAs was associated with lower rates of hyperkalemia and sustained RASi use compared with DPP-4i use. These findings suggest that GLP-1RA treatment may enable wider use of guideline-recommended medications and contribute to clinical outcomes in this population.

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Air pollution has been recognized as a global issue, through adverse effects on environment and health. While vertical atmospheric processes substantially affect urban air pollution, traditional epidemiological research using Land-use regression (LUR) modeling usually focused on ground-level attributes without considering upper-level atmospheric conditions. This study aimed to integrate Doppler LiDAR and machine learning techniques into LUR models (LURF-LiDAR) to comprehensively evaluate urban air pollution in Hong Kong, and to assess complex interactions between vertical atmospheric processes and urban air pollution from long-term (i.e., annual) and short-term (i.e., two air pollution episodes) views in 2021. The results demonstrated significant improvements in model performance, achieving CV R2 values of 0.81 (95 % CI: 0.75-0.86) for the long-term PM2.5 prediction model and 0.90 (95 % CI: 0.87-0.91) for the short-term models. Approximately 69 % of ground-level air pollution arose from the mixing of ground- and lower-level (105 m-225 m) particles, while 21 % was associated with upper-level (825 m-945 m) atmospheric processes. The identified transboundary air pollution (TAP) layer was located at ~900 m above the ground. The identified Episode one (E1: 7 Jan-22 Jan) was induced by the accumulation of local emissions under stable atmospheric conditions, whereas Episode two (E2: 13 Dec-24 Dec) was regulated by TAP under instable and turbulent conditions. Our improved air quality prediction model is accurate and comprehensive with high interpretability for supporting urban planning and air quality policies.

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Motion artifacts compromise the quality of magnetic resonance imaging (MRI) and pose challenges to achieving diagnostic outcomes and image-guided therapies. In recent years, supervised deep learning approaches have emerged as successful solutions for motion artifact reduction (MAR). One disadvantage of these methods is their dependency on acquiring paired sets of motion artifact-corrupted (MA-corrupted) and motion artifact-free (MA-free) MR images for training purposes. Obtaining such image pairs is difficult and therefore limits the application of supervised training. In this paper, we propose a novel UNsupervised Abnormality Extraction Network (UNAEN) to alleviate this problem. Our network is capable of working with unpaired MA-corrupted and MA-free images. It converts the MA-corrupted images to MA-reduced images by extracting abnormalities from the MA-corrupted images using a proposed artifact extractor, which intercepts the residual artifact maps from the MA-corrupted MR images explicitly, and a reconstructor to restore the original input from the MA-reduced images. The performance of UNAEN was assessed by experimenting with various publicly available MRI datasets and comparing them with state-of-the-art methods. The quantitative evaluation demonstrates the superiority of UNAEN over alternative MAR methods and visually exhibits fewer residual artifacts. Our results substantiate the potential of UNAEN as a promising solution applicable in real-world clinical environments, with the capability to enhance diagnostic accuracy and facilitate image-guided therapies. Our codes are publicly available at https://github.com/YuSheng-Zhou/UNAEN.

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BACKGROUND AND AIMS: The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and the risk of MASLD and its severity. APPROACH AND RESULTS: This prospective multicohort study included 15,263 adults from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort, 1137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort, and 175,078 adults from the UK Biobank. In addition, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included. An EAT-Lancet diet index was created to reflect adherence to the EAT-Lancet reference diet. The TCLSIH cohort recorded 3010 MASLD cases during 53,575 person-years of follow-up, the GNHS cohort documented 624 MASLD cases during 6454 person-years of follow-up, and the UK Biobank developed 1350 MASLD cases during 1,745,432 person-years of follow-up. In multivariable models, participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles (TCLSIH: HR = 0.87, 95% CI: 0.78, 0.96; GNHS: HR = 0.79, 95% CI: 0.64, 0.98; UK Biobank: HR = 0.73, 95% CI: 0.63, 0.85). Moreover, liver-controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (ß = -5.895; 95% CI: -10.014, -1.775). CONCLUSIONS: Adherence to the EAT-Lancet reference diet was inversely associated with the risk of MASLD as well as its severity.

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The bioavailability and degradation of riverine dissolved organic matter (DOM) play crucial roles in greenhouse gas emissions; however, studies on the kinetic decomposition of fluvial DOM remain scarce. In this study, the decomposition kinetics of dissolved organic carbon (DOC) were characterized using the reactivity continuum model through 28-day bio-incubation experiments with water samples from the Yangtze River. The relationship between DOM composition and decomposition kinetics was analyzed using optical and molecular characterization combined with apparent decay coefficients. Our results revealed that DOM compounds rich in nitrogen and sulfur were predominantly removed, exhibiting a transition from an unsaturated to a saturated state following microbial degradation. These heteroatomic compounds, which constituted 75.61 % of the DOM compounds positively correlated with the decay coefficient k0, underwent preferential degradation in the early stages of bio-incubation due to their higher bioavailability. Additionally, we observed that S-containing fractions with high molecular weight values (MW > 400 Da) may be associated with larger reactivity grades. This study underscored the complex interplay between DOM composition and its kinetic decomposition in river ecosystems, providing further support for the significance of molecular composition in large river DOM as crucial factors affecting decomposition.

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In this study, ovalbumin (OV) and sodium alginate (SA), two macromolecular complexes, were coagulated into the emulsifier (OV/SA), which stabilized soybean oil by electrostatic interaction, hydrophobic interactions, and hydrogen bonding. The structure of OV/SA and properties of OV/SA Pickering emulsion were investigated. Additionally, the effect of emulsions on the gel and protein properties of hairtail surimi was studied. The results revealed that with the increasing concentration of OV/SA, the particle size and zeta potential value (negative value) of the emulsion initially decreased and then increased, while the rheological properties gradually improved. Compared with the surimi gel directly supplemented with soybean oil, the addition of emulsion enhanced gel strength, whiteness, water holding capacity, and hydrophobic interactions, resulting in a more stable gel network structure. In summary, incorporating emulsion into surimi at the same lipid content not only maintained its gel properties but also improved its color and compensated for lipid loss.

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Usher syndrome (USH) is a recessive genetic disorder manifested by congenital sensorineural hearing loss and progressive retinitis pigmentosa, which leads to audiovisual impairment. We report a patient with Usher syndrome type 1 with new compound heterozygous MYO7A variants. A total of four members from the USH family were included. Medical history and retinal examinations were taken and genomic DNA from peripheral blood was extracted in the proband and other members. 381 retinal disease-associated genes were screened using targeted sequence capture array technology and Sanger sequencing was used to confirm the screening results. Scanning laser ophthalmoscope showed bone spicule pigmentary deposits in the mid-peripheral retina and whitish and thin retinal blood vessels especially in the arterioles. Optical coherence tomography showed that the centrality of the macular ellipsoid band disappeared in both eyes, and only remained near the fovea. Visual field examination showed a progressive loss of the visual field in a concentric pattern in both eyes. The electroretinography showed a significant decrease in the amplitudes of a- and b-waves in the scotopic and photopic condition. DNA sequencing identified the compound heterozygous variants including c.1003+1G > A: p. (?) and c.5957_5958del: p.G1987Lfs*50 of MYO7A, with the latter being novel. In this study, we found a novel compound heterozygous variant in MYO7A, which enriched the mutation spectrum and expanded our understanding of the heterogeneity of phenotype and genotype of Usher syndrome type 1.

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