AbDPP: Target-oriented antibody design with pretraining and prior biological structure knowledge.

Antibodies represent a crucial class of complex protein therapeutics and are essential in the treatment of a wide range of human diseases. Traditional antibody discovery methods, such as hybridoma and phage display technologies, suffer from limitations including inefficiency and a restricted exploration of the immense space of potential antibodies. To overcome these limitations, we propose a novel method for generating antibody sequences using deep learning algorithms called AbDPP (target-oriented antibody design with pretraining and prior biological knowledge). AbDPP integrates a pretrained model for antibodies with biological region information, enabling the effective use of vast antibody sequence data and intricate biological system understanding to generate sequences. To target specific antigens, AbDPP incorporates an antibody property evaluation model, which is further optimized based on evaluation results to generate more focused sequences. The efficacy of AbDPP was assessed through multiple experiments, evaluating its ability to generate amino acids, improve neutralization and binding, maintain sequence consistency, and improve sequence diversity. Results demonstrated that AbDPP outperformed other methods in terms of the performance and quality of generated sequences, showcasing its potential to enhance antibody design and screening efficiency. In summary, this study contributes to the field by offering an innovative deep learning-based method for antibody generation, addressing some limitations of traditional approaches, and underscoring the importance of integrating a specific antibody pretrained model and the biological properties of antibodies in generating novel sequences. The code and documentation underlying this article are freely available at https://github.com/zlfyj/AbDPP.

Association between hypertension and pressure ulcer: A systematic review and meta-analysis.

This review aims to systematically evaluate the association between hypertension and pressure ulcer (PU). PubMed, Embase, Web of Science, and Cochrane Library were searched for studies from their inception until September 12, 2023. Literature search, data extraction, and quality assessment were conducted independently by two researchers. The random-effects model was used to calculate the combined odds ratio (OR) and corresponding 95% confidence interval (CI) of hypertension in patients with PU; subgroup analyses were performed to explore the source of between-study heterogeneity; sensitivity analysis was used to test the robust of the combined result; and funnel plot and Egger's test were used to assess the publication bias. Finally, a total of 19 studies with 564 716 subjects were included; the overall pooled result showed no significant association between hypertension and risk of developing PU (OR = 1.15, 95% CI = 0.90-1.47, p = 0.27); and the sensitivity analysis and publication bias analysis showed robust of the combined result. Subgroup analysis indicated a significant association between hypertension and PU when the primary disease was COVID-19 (OR = 1.73, 95% CI = 1.35-2.22, p < 0.0001). No association between hypertension and PU was seen in subgroup analysis on the patient source and study design. In sum, there is no significantly statistical association between hypertension and the occurrence of PU in most cases, while the risk of PU significantly elevates among COVID-19 patients combined with hypertension regardless of patient source and study design.

Transformational Modulation of Fluorescence to Room Temperature Phosphorescence in Metal-Organic Frameworks with Flexible C-S-C Bonds.

Photoluminescent metal-organic frameworks (MOFs) have been a subject of considerable interest for many years. However, the regulation of excited states of MOFs at the single crystal level remains restricted due to a lack of control methods. The singlet-triplet emissive property can be significantly influenced by crystal conformational distortions. This review introduces an intelligent responsive MOF material, denoted as LIFM-SHL-3a, characterized by flexible C-S-C bonds. LIFM-SHL-3a integrates elastic structural dynamics with fluorescence and room temperature phosphorescence (RTP) modulation under heating conditions. The deformable carbon-sulfur bond essentially propels the distortion of molecular conformation and alters the stacking mode, as illustrated by single-crystal-to-single-crystal transformation detection. The deformation of flexible C-S-C bonds leads to different noncovalent interactions in the crystal system, thereby achieving modulation of the fluorescence (F) and RTP bands. In the final state structure, the ratio of fluorescence is 66.7%, and the ratio of RTP is 32.6%. This stands as a successful demonstration of modulating F/RTP within the dynamic MOF, unlocking potential applications in optical sensing and beyond. Especially, a PL thermometer with a relative sensitivity of 0.096-0.104%·K-1 in the range of 300-380 K and a H2S probe with a remarkably low LOD of 125.80 nM can be obtained using this responsive MOF material of LIFM-SHL-3a.

First Report of Penicillium oxalicum Causing Leaf Blight on 'Hongyang' Kiwifruit in China.

In September 2022, leaf blight symptoms (Fig. 1) were detected on six-year-old kiwi trees (Actinidia chinensis cv. 'Hongyang') in Xuzhou municipality (117.29º E, 34.23º N), Jiangsu Province. Early-stage disease symptoms included light brown necrotic lesions of irregular shape ranging in length from 0.2 to 2.4 cm, which turned into leaf blight after approximately 2 weeks. Those symptoms were similar to those previously reported during a Pestalotiopsis sp. infection on kiwi trees in Turkey (Karakaya 2001). Approximately 20% of the leaves from 300 trees examined in one kiwi orchard, 3000 m2 in size, showed the disease symptoms. Ten leading edges of symptomatic leaves were sterilized with 2% sodium hypochlorite for 1 min, rinsed twice with sterile ddH2O and cultured at 26ºC for 3 days on PDA medium containing 50 µg/ml chloramphenicol. The fungal colonies were collected, and the single spore isolation method was used to obtain four isolates. The obtained isolates showed white aerial mycelia that turned greyish after 2 days of cultivation on PDA medium at 26ºC. ITS (OR054113, OR054153-OR054155), TUB2 (OR060951-OR060953, OR249978), and CMD (OR255947-OR255950) genes were amplified using the ITS1/ITS4, BT2a/BT2b and CMD5/CMD6 primers, respectively (Visagie et al. 2014a). The obtained ITS, TUB2, and CMD sequences shared 99.81%-100%, 96.72%-96.96%, and 90.17%-92.58% homology compared to the ex-type strain P. oxalicum CBS 219.30 (MH855125, KF296462, and KF296367), while the obtained ITS and TUB2 sequences showed 99.62%-99.81%, and 96.46%-96.72% identity compared to the representative strain P. oxalicum DTO 179B9 (KJ775647 and KJ775140) (Visagie et al. 2014b). The sequences obtained also showed high homology compared to P. oxalicum HP7-1 (ITS: 99.81%-100% homology; TUB2: 98.98%-99.38% homology; CMD: 94.71%-95.10% homology) (Li et al. 2022). A molecular phylogenetic tree was constructed using MEGA X with representative Penicillium strains retrieved from GenBank (Fig. 2). Microscope observations revealed the presence of curved septate hyphae. Conidia were colorless, unicellular, and ellipsoidal (5-8 µm in length; > 2000 observations), whereas conidiophores were mainly monoverticillate (approximately 20% of the conidiophores were biverticillate) (50-70 µm in length; 43 observations) and contained cylindrical phialides (13-15 µm in length). These findings are consistent with P. oxalicum morphology (Wu et al. 2022; Zheng et al. 2023). The pathogenicity of the four isolates was screened using healthy non-detached 'Hongyang' kiwi leaves. Fifteen leaves from five different two-month-old trees were used for each isolate, with three repetitions. For inoculation, a 10 mL solution containing 1 × 106 spores/mL was sprayed on the leaves. Sterilized water was used in the control experiment, which was carried out using fifteen leaves from five different two-month-old trees, with three repetitions. Inoculated trees were stored at 26ºC and 60% relative humidity for 2 days. All the infected leaves had necrotic lesions and leaf blight symptoms comparable to those found in the field, but the control leaves had no lesions. The pathogen was recovered, and its identity was confirmed by ITS sequencing and morphology analysis, fulfilling Koch's postulates. P. oxalicum is a common cause of blue mould in postharvest fruits (Tang et al. 2020). P. oxalicum has been recently reported as the causal agent of leaf spot in pineapple (Wu et al. 2022; Zheng et al. 2023), and leaf blight on maize (Han et al. 2023). Although Alternaria sp., Glomerella cingulate, Pestalotiopsis sp., Phomopsis sp., and Phoma sp. were previously isolated from kiwi leaves with blight symptoms (Kim et al. 2017), this is the first report of P. oxalicum causing leaf blight on kiwi trees worldwide. P. oxalicum is a well-known source of mycotoxins, such as secalonic acid (Otero et al. 2020), indicating that its presence in kiwifruit orchards may pose a significant risk to human health. The discovery of this hazardous pathogen in kiwi trees must drive the development of management strategies. Kiwifruit is an important dietary source of vitamins, fiber, folate, and potassium, and China is the major producer of kiwifruit, with more than 1.2 million metric tons harvested in 2021. This report will help to generate a better understanding of the pathogens affecting kiwifruit orchards in China.

Dysregulated lncRNAs regulate human umbilical cord mesenchymal stem cell differentiation into insulin-producing cells by forming a regulatory network with mRNAs.

OBJECTIVE: In recent years, cell therapy has emerged as a new research direction in the treatment of diabetes. However, the underlying molecular mechanisms of mesenchymal stem cell (MSC) differentiation necessary to form such treatment have not been clarified. METHODS: In this study, human umbilical cord mesenchymal stem cells (HUC-MSCs) isolated from newborns were progressively induced into insulin-producing cells (IPCs) using small molecules. HUC-MSC (S0) and four induced stage (S1-S4) samples were prepared. We then performed transcriptome sequencing experiments to obtain the dynamic expression profiles of both mRNAs and long noncoding RNAs (lncRNAs). RESULTS: We found that the number of differentially expressed lncRNAs and mRNAs trended downwards during differentiation. Gene Ontology (GO) analysis showed that the target genes of differentially expressed lncRNAs were associated with translation, cell adhesion, and cell connection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the NF-KB signalling pathway, MAPK signalling pathway, HIPPO signalling pathway, PI3K-Akt signalling pathway, and p53 signalling pathway were enriched in these differentially expressed lncRNA-targeting genes. We also found that the coexpression of the lncRNA CTBP1-AS2 with PROX1 and the lncRNAs AC009014.3 and GS1-72M22.1 with JARID2 mRNA was related to the development of pancreatic beta cells. Moreover, the coexpression of the lncRNAs: XLOC_ 050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14- AS1, RP11-148K1.12, and CTD2020K17.3 with p53, regulated insulin secretion by pancreatic beta cells. CONCLUSION: In this study, HUC-MSCs combined with small molecule compounds were successfully induced into IPCs. Differentially expressed lncRNAs may regulate the insulin secretion of pancreatic beta cells by regulating multiple signalling pathways. The lncRNAs AC009014.3, Gs1-72m21.1, and CTBP1-AS2 may be involved in the development of pancreatic beta cells, and the lncRNAs: XLOC_050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14-AS1, RP11-148K1.12, and CTD2020K17.3 may be involved in regulating the insulin secretion of pancreatic beta cells, thus providing a lncRNA catalogue for future research regarding the mechanism of the transdifferentiation of HUC-MSCs into IPCs. It also provides a new theoretical basis for the transplantation of insulin-producing cells into diabetic patients in the future.

Robust Multiobjective Particle Swarm Optimization With Feedback Compensation Strategy.

Multiobjective particle swarm optimization (MOPSO) has been proven effective in solving multiobjective problems (MOPs), in which the evolutionary parameters and leaders are selected randomly to develop the diversity. However, the randomness would cause the evolutionary process uncertainty, which deteriorates the optimization performance. To address this issue, a robust MOPSO with feedback compensation (RMOPSO-FC) is proposed. RMOPSO-FC provides a novel closed-loop optimization framework to reduce the negative influence of uncertainty. First, Gaussian process (GP) models are established by dynamically updated archives to obtain the posterior distribution of particles. Then, the feedback information of particle evolution can be collected. Second, an intergenerational binary metric is designed based on the feedback information to evaluate the evolutionary potential of particles. Then, the particles with negative evolutionary directions can be identified. Third, a compensation mechanism is presented to correct the negative evolution of particles by modifying the particle update paradigm. Then, the compensated particles can maintain the positive exploration toward the true PF. Finally, the comparative simulation results illustrate that the proposed RMOPSO-FC can provide superior search capability of PFs and algorithmic robustness over multiple runs.

Role of TET1-mediated epigenetic modulation in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder influenced by a complex interplay of environmental, epigenetic, and genetic factors. DNA methylation (5mC) and hydroxymethylation (5hmC) are DNA modifications that serve as tissue-specific and temporal regulators of gene expression. TET family enzymes dynamically regulate these epigenetic modifications in response to environmental conditions, connecting environmental factors with gene expression. Previous epigenetic studies have identified 5mC and 5hmC changes associated with AD. In this study, we performed targeted resequencing of TET1 on a cohort of early-onset AD (EOAD) and control samples. Through gene-wise burden analysis, we observed significant enrichment of rare TET1 variants associated with AD (p = 0.04). We also profiled 5hmC in human postmortem brain tissues from AD and control groups. Our analysis identified differentially hydroxymethylated regions (DhMRs) in key genes responsible for regulating the methylome: TET3, DNMT3L, DNMT3A, and MECP2. To further investigate the role of Tet1 in AD pathogenesis, we used the 5xFAD mouse model with a Tet1 KO allele to examine how Tet1 loss influences AD pathogenesis. We observed significant changes in neuropathology, 5hmC, and RNA expression associated with Tet1 loss, while the behavioral alterations were not significant. The loss of Tet1 significantly increased amyloid plaque burden in the 5xFAD mouse (p = 0.044) and lead to a non-significant trend towards exacerbated AD-associated stress response in 5xFAD mice. At the molecular level, we found significant DhMRs enriched in genes involved in pathways responsible for neuronal projection organization, dendritic spine development and organization, and myelin assembly. RNA-Seq analysis revealed a significant increase in the expression of AD-associated genes such as Mpeg1, Ctsd, and Trem2. In conclusion, our results suggest that TET enzymes, particularly TET1, which regulate the methylome, may contribute to AD pathogenesis, as the loss of TET function increases AD-associated pathology.

Modified LIX®84I-Based Polymer Inclusion Membranes for Facilitating the Transport Flux of Cu(II) and Variations of Their Physical-Chemical Characteristics.

A unique facilitation on the transport flux of Cu(II) was investigated by using modified polymer inclusion membranes (PIMs). LIX®84I-based polymer inclusion membranes (LIX®-based PIMs) using poly(vinyl chloride) (PVC) as support, 2-nitrophenyl octyl ether (NPOE) as plasticizer and Lix84I as carrier were modified by reagents with different polar groups. The modified LIX®-based PIMs showed an increasing transport flux of Cu(II) with the help of ethanol or Versatic acid 10 modifiers. The metal fluxes with the modified LIX®-based PIMs were observed varying with the amount of modifiers, and the transmission time was cut by half for the modified LIX®-based PIM cast with Versatic acid 10. The physical-chemical characteristics of the prepared blank PIMs with different Versatic acid 10 were further characterized by using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), contract angle measurements and electro-chemical impedance spectroscopy (EIS). The characterization results indicated that the modified LIX®-based PIMs cast with Versatic acid 10 appeared to be more hydrophilic with increasing membrane dielectric constant and electrical conductivity that allowed better accessibility of Cu(II) across PIMs. Hence, it was deduced that hydrophilic modification might be a potential method to improve the transport flux of the PIM system.

Injectable Intrinsic Photothermal Hydrogel Bioadhesive with On-Demand Removability for Wound Closure and MRSA-Infected Wound Healing.

Photothermal hydrogel adhesives have yielded promising results for wound closure and infected wound treatment in recent years. However, photothermal hydrogel bioadhesives with on-demand removability without additional nanomaterials-based photothermal agents have rarely been reported in the literature. In this work, an injectable intrinsic photothermal hydrogel bioadhesive with an on-demand removal trait is developed through dynamic cross-linking of gelatin (Gel), tannic acid (TA) quinone, and borax for closing skin incisions and accelerating methicillin-resistant Staphylococcus aureus (MRSA) infected wound healing. The TA quinone containing polyphenol and quinone groups with multifunctional adhesiveness and intrinsic photothermal performance confer the hydrogel adhesive with near-infrared (NIR) responsive antibacterial activity. The cross-linking of pH-sensitive boronic ester (polyphenol-B) and Schiff base bonds endow the hydrogel with great self-healing capacity and on-demand removability. Moreover, the hydrogel possesses good biocompatibility, injectability, and hemostasis. The in vivo experiment in a rat cutaneous incision model and full-thickness MRSA-infected wound model indicate that the smart hydrogel can close wounds efficiently and treat infected ones, demonstrating its superiority in noninvasive treatment of cutaneous incisions and enhancing infected full-thickness wound healing.

Comprehensive 100-bp resolution genome-wide epigenomic profiling data for the hg38 human reference genome.

This manuscript presents a comprehensive collection of diverse epigenomic profiling data for the human genome in 100-bp resolution with full genome-wide coverage. The datasets are processed from raw read count data collected from five types of sequencing-based assays collected by the Encyclopedia of DNA Elements consortium (ENCODE, http://www.encodeproject.org). Data from high-throughput sequencing assays were processed and crystallized into a total of 6,305 genome-wide profiles. To ensure the quality of the features, we filtered out assays with low read depth, inconsistent read counts, and poor data quality. The types of sequencing-based experiment assays include DNase-seq, histone and TF ChIP-seq, ATAC-seq, and Poly(A) RNA-seq. Merging of processed data was done by averaging read counts across technical replicates to obtain signals in about 30 million predefined 100-bp bins that tile the entire genome. We provide an example of fetching read counts using disease-related risk variants from the GWAS Catalog. Additionally, we have created a tabix index enabling fast user retrieval of read counts given coordinates in the human genome. The data processing pipeline is replicable for users' own purposes and for other experimental assays. The processed data can be found on Zenodo at https://zenodo.org/record/7015783. These data can be used as features for statistical and machine learning models to predict or infer a wide range of variables of biological interest. They can also be applied to generate novel insights into gene expression, chromatin accessibility, and epigenetic modifications across the human genome. Finally, the processing pipeline can be easily applied to data from any other genome-wide profiling assays, expanding the amount of available data.

Association Between Weight Change and Increased Likelihood of Abdominal Aortic Calcification Among Men.

Objective: We aimed to explore the effect of weight change on abdominal aortic calcification (AAC) among men. Methods: Data were obtained from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES). Self-reported cardiovascular disease patients were excluded. Lateral spine images were used to quantify AAC score and severe AAC was defined as a AAC score greater than 6. Weight change over a 10-year period was defined as long-term weight change, and weight change over a 1-year period was defined as short-term weight change. The relationship between long-term and short-term weight change with AAC grade was estimated by using multivariable regression analysis and subgroup analysis. Results: After adjusting for covariates, weight gain, especially severe weight gain (> 10 kg), was associated with increased likelihood of AAC and severe AAC both in the short term (1 year) and long term (10 years) among men when compared to stable weight change, while long-term weight loss could also lead to an increased likelihood of AAC and severe AAC. Conclusion: Stable body weight might be a predictor of a lower risk of AAC and severe AAC among men in the long term and short term.

Identification of PSMB5 as a genetic modifier of fragile X-associated tremor/ataxia syndrome.

Fragile X­associated tremor/ataxia syndrome (FXTAS) is a debilitating late-onset neurodegenerative disease in premutation carriers of the expanded CGG repeat in FMR1 that presents with a spectrum of neurological manifestations, such as gait ataxia, intention tremor, and parkinsonism [P. J. Hagerman, R. J. Hagerman, Ann. N. Y. Acad. Sci. 1338, 58­70 (2015); S. Jacquemont et al., JAMA 291, 460­469 (2004)]. Here, we performed whole-genome sequencing (WGS) on male premutation carriers (CGG55­200) and prioritized candidate variants to screen for candidate genetic modifiers using a Drosophila model of FXTAS. We found 18 genes that genetically modulate CGG-associated neurotoxicity in Drosophila, such as Prosbeta5 (PSMB5), pAbp (PABPC1L), e(y)1 (TAF9), and CG14231 (OSGEPL1). Among them, knockdown of Prosbeta5 (PSMB5) suppressed CGG-associated neurodegeneration in the fly as well as in N2A cells. Interestingly, an expression quantitative trait locus variant in PSMB5, PSMB5rs11543947-A, was found to be associated with decreased expression of PSMB5 and delayed onset of FXTAS in human FMR1 premutation carriers. Finally, we demonstrate evidence that PSMB5 knockdown results in suppression of CGG neurotoxicity via both the RAN translation and RNA-mediated toxicity mechanisms, thereby presenting a therapeutic strategy for FXTAS.

Impact of serum uric acid on subclinical myocardial injury in general population.

BACKGROUND AND AIMS: Hyperuricemia is widely thought as a risk factor for myocardial infarction (MI) and all-cause mortality; however, the relation of serum uric acid (sUA) and subclinical myocardial injury (SCeMI) remains unclear. We hypothesize that sUA is associated with subclinical myocardial injury. METHODS AND RESULTS: A total of 5880 adult individuals (57.9 ± 13.0 years, 54.23% women) without known cardiovascular disease from National Health and Nutrition Examination Survey (NHANES) III were included. Determined by Cardiac Infarction Injury Score (CIIS) from 12-lead electrocardiogram, SCeMI was defined by CIIS ≥10 units. The relationship between sUA and SCeMI was analyzed by using logistic regression models and the smooth curve fitting. Subgroup analyses were conducted. After adjusting for potential confounding variables, the smooth curve fitting revealed a non-linear relationship between sUA level and SCeMI. When sUA was above the inflection point 266.5 µmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 15%. In women group, when sUA>340.3 µmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 71%, but no significant correlation was observed in men group. CONCLUSIONS: Our findings confirm that sUA is an independent risk factor for subclinical myocardial injury after adjusting for potential confounding variables, and existence of such an association in women only, which require more random control trials to confirm the strategy of cardiovascular disease prevention based on sUA reduction in female.

Disease category-specific annotation of variants using an ensemble learning framework.

Understanding the impact of non-coding sequence variants on complex diseases is an essential problem. We present a novel ensemble learning framework-CASAVA, to predict genomic loci in terms of disease category-specific risk. Using disease-associated variants identified by GWAS as training data, and diverse sequencing-based genomics and epigenomics profiles as features, CASAVA provides risk prediction of 24 major categories of diseases throughout the human genome. Our studies showed that CASAVA scores at a genomic locus provide a reasonable prediction of the disease-specific and disease category-specific risk prediction for non-coding variants located within the locus. Taking MHC2TA and immune system diseases as an example, we demonstrate the potential of CASAVA in revealing variant-disease associations. A website (http://zhanglabtools.org/CASAVA) has been built to facilitate easily access to CASAVA scores.

Exploring the strategies of online and offline recycling channels in closed-loop supply chain under government subsidy.

The influence of online and offline dual recycling channels in a closed-loop supply chain (CLSC) is investigated in our work. The CLSC models of three recycling modes (single online recycling, single offline recycling, and dual recycling channels of online and offline) are established, respectively, and the impact of government subsidies on the pricing decision-making and recycling mode selection of channel members is therefore researched. The study found that the remanufacturer sets appropriate recycling price and transfer price to coordinate online and offline recycling channels and maximize its profits in the dual recycling modes; collector's offline recycling faces the competitive threat of remanufacturers' online recycling under the dual recycling modes, so the collector prefers a single offline recycling mode; the relationship between the collection quantities of the three modes depends on consumers' preference of the online recycling channel. In the meanwhile, it is illustrated that government subsidy plays a positive role in promoting the recycling and remanufacturing willingness of remanufacturers and collectors. This work provides practical insights for the CLSC system to make recycle decisions.

High uric acid promotes mitophagy through the ROS/CaMKIIδ/Parkin pathway in cardiomyocytes in vitro and in vivo.

BACKGROUND: Increasing evidence has suggested that high uric acid (HUA) is closely related to cardiovascular disease (CVD). Mitophagy abnormalities have been reported to participate in multiple pathogenic processes of CVD. However, the potential molecular mechanisms remain unclear. Herein, we investigated the effect of HUA-induced mitophagy and its potential molecular mechanism in cardiomyocytes. METHODS: We established a model of cardiomyocytes induced by HUA in vitro and in vivo. Mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production and adenosine triphosphate (ATP) content were measured. The mitophagy-related protein expression of LC3B-II, Parkin, Ca2+/calmodulin-dependent protein kinase II δ (CaMKIIδ) and P62 was measured by Western blot. Based on the colocalization of lysosomes and mitochondria, a confocal microscope was used to detect mitophagy. Additionally, we established a mitophagy inhibitor group (3-MA) and CaMKIIδ inhibitor group (KN-93) to verify the pathway. RESULTS: In the HUA stimulation model, ROS production was increased, and mitochondrial injury indexes (MMP and ATP contents) were decreased. Moreover, these indicators were reversed by 3-MA and KN-93. Under HUA stimulation, the expression of LC3B-II, Parkin, CaMKIIδ and P62 increased significantly. Furthermore, these protein levels were reduced by 3-MA and KN-93. CONCLUSION: HUA can promote cardiomyocyte mitophagy activation through the ROS/CaMKIIδ/parkin pathway axis. This study may provide a new target and theoretical basis for the prevention and treatment of HUA-related metabolic heart disease in the future.

The application of a structural nutritional care management model in severe acute pancreatitis patients undergoing early enteral nutrition via nasal jejunal nutrition tubes.

OBJECTIVE: To investigate the advantages of a structural nutritional care management model (hereafter referred to as structural management) in severe acute pancreatitis (SAP) patients undergoing early enteral nutrition via nasal jejunal nutrition tubes. METHODS: A total of 88 patients with SAP diagnosed and treated in our hospital were recruited as the study cohort and underwent enteral nutrition treatment. A random number table was used for the random grouping. The control group was routinely managed, and the study group was also administered structural management. In the study, we observed and compared the differences and changes in the relevant nutritional indexes (albumin (ALB), prealbumin (PA), and transferrin (TRF)) and the gastrointestinal hormone indexes (gastrin (MTL), vasoactive peptide (VIP), and 5-hydroxytryptamine (5-HT)) before and after the treatment. Between the two groups, we also compared the times required for the recovery of the relevant gastrointestinal physiological function indexes, the mechanical ventilation times, the hospitalization durations in the ICU, the complications, the satisfaction indexes and the satisfaction rates. RESULTS: After the treatment, the relevant nutritional indicators, including ALB (35.26±3.35 g/L), PA (25.19±5.64 g/L), and TRF (2.82±0.54 g/L) in the study group were higher than the ALB (28.19±2.74 g/L), PA (21.29±4.32 g/L), and TRF (2.26±0.32 g/L) in the control group (all P<0.05). After the treatment, the relevant gastrointestinal hormone indicators, including MTL (269.72±37.18 pg/mL) and 5-HT (2214.61±432.95 ng/mL) in the study group were higher than the MTL (231.25±32.63 pg/mL) and 5-HT (1914.26±391.53 ng/mL) in the control group (all P<0.05). Moreover, the VIP in the study group was 53.13±6.17 pg/mL, which was significantly lower than the VIP in the control group (65.29±9.35 pg/mL, P<0.05). The time required for the recovery of the gastrointestinal function indexes in the study group was less than it was in the control group (P<0.05). The duration of the mechanical ventilation (8.16±1.93 days) and the hospitalization durations in the ICU (9.24±0.77 days) in the study group were significantly shorter than the duration of the mechanical ventilation (12.24±1.65 days) and the hospitalization durations in the ICU (13.23±0.88 days) in the control group (all P<0.05). The overall complication rate in the study group was significantly lower than it was in the control group (P<0.05), and the satisfaction rate in the study group was significantly higher than it was in the control group (P<0.05). CONCLUSION: The combined use of structural management in SAP patients undergoing enteral nutrition treatment significantly improved the relevant nutritional indicator and gastrointestinal hormone indicator levels. It also contributed to the recovery of the gastrointestinal function indicators in the SAP patients, reduced the durations of their mechanical ventilation, their hospitalization durations in the ICU, and their complications and contributed to a significant increase in their satisfaction with the nursing.

Suspended Membrane Evaporators Integrating Environmental and Solar Evaporation for Oily Wastewater Purification.

Solar-driven evaporation is promising in oily wastewater treatment, in particular for emulsions, but conventional evaporators suffer from pore blocking by residual oil or contamination by volatile oil compounds in the condensed water. In the current research, we develop a suspended membrane evaporator integrating solar evaporation with oil-in-water emulsion separation. The heating and evaporating interface is separated from the rejecting interface to avoid oil escape and improve heat management. A temperature gradient forms on the membrane surface that can promote evaporation performance by combining both solar and environmental evaporation. Such an evaporator achieves a maximum evaporation rate of 1.645 kg/(m2·h) as well as an apparent evaporation efficiency of 111.9%. Moreover, the superhydrophilic and superoleophobic membrane shows excellent oil repellence and emulsion rejection, which can achieve an oil removal efficiency above 98.8% in oil-in-water emulsion separation, and high evaporation rate recovery in cycling tests. A scaled-up membrane evaporator array produces ∼8 kg/(m2·d) of clean water from oily wastewater in outdoor experiments, further demonstrating the strong purification performance of this evaporator in oily wastewater treatment.

A machine learning approach to brain epigenetic analysis reveals kinases associated with Alzheimer's disease.

Alzheimer's disease (AD) is influenced by both genetic and environmental factors; thus, brain epigenomic alterations may provide insights into AD pathogenesis. Multiple array-based Epigenome-Wide Association Studies (EWASs) have identified robust brain methylation changes in AD; however, array-based assays only test about 2% of all CpG sites in the genome. Here, we develop EWASplus, a computational method that uses a supervised machine learning strategy to extend EWAS coverage to the entire genome. Application to six AD-related traits predicts hundreds of new significant brain CpGs associated with AD, some of which are further validated experimentally. EWASplus also performs well on data collected from independent cohorts and different brain regions. Genes found near top EWASplus loci are enriched for kinases and for genes with evidence for physical interactions with known AD genes. In this work, we show that EWASplus implicates additional epigenetic loci for AD that are not found using array-based AD EWASs.