A Peritrophin-44 gene in Litopenaeus vannamei is involved in disease resistance.

Peritrophic membrane (PM) is a pellicle structure present in the midgut of some invertebrates, such as insects and crustaceans. It could isolate harmful components and pathogens in food from intestinal epithelial cells; and it also plays a role in improving digestion and absorption efficiency. So PM is important for survival of its owner. In current study, 44 PM proteins were identified in Litopenaeus vannamei by PM proteome analysis. Among these PM proteins, the Peritrophin-44 homologous protein (LvPT44) was further studied. Chitin-binding assay indicated that LvPT44 could bind to colloidal chitin, and immunoeletron microscopy analysis shown that it was located to PM of L. vannamei. Furthermore, LvPT44 promoter was found to be activated by L. vannamei STAT and c-Jun. Besides, LvPT44 was induced by ER-stress as well as white spot syndrome virus infection. Knocked-down expression of LvPT44 by RNA inference increased the cumulative mortality of shrimp that caused by ER-stress or white spot syndrome virus. These results suggested that LvPT44 has an important role in disease resistance.

Factors associated with burnout among frontline nurses in the post-COVID-19 epidemic era: a multicenter cross-sectional study.

BACKGROUND: The COVID-19 pandemic has significantly increased the risk of burnout among frontline nurses. However, the prevalence of burnout and its associated factors in the post-pandemic era remain unclear. This research aims to investigate burnout prevalence among frontline nurses in the post-pandemic period and pinpoint associated determinants in China. METHODS: From April to July 2023, a cross-sectional study was carried out across multiple centers, focusing on frontline nurses who had been actively involved in the COVID-19 pandemic. The data collection was done via an online platform. The Maslach Burnout Inventory-Human Services Survey was utilized to evaluate symptoms of burnout. A multivariable logistic regression analysis was used to pinpoint factors associated with burnout. RESULTS: Of the 2210 frontline nurses who participated, 75.38% scored over the cut-off for burnout. Multivariable logistic regression revealed that factors like being female [odds ratio (OR) = 0.41, 95%CI = 0.29-0.58] and exercising 1-2 times weekly[OR = 0.53, 95%CI = 0.42-0.67] were protective factors against burnout. Conversely, having 10 or more night shifts per month[OR = 1.99, 95%CI = 1.39-2.84], holding a master's degree or higher[OR = 2.86, 95% CI = 1.59-5.15], poor health status[OR = 2.43, 95% CI = 1.93-3.08] and [OR = 2.82, 95%CI = 1.80-4.43], under virus infection[OR = 7.12, 95%CI = 2.10-24.17], and elevated work-related stress[OR = 1.53, 95% CI = 1.17-2.00] were all associated with an elevated risk of burnout. CONCLUSION: Our findings indicate that post-pandemic burnout among frontline nurses is influenced by several factors, including gender, monthly night shift frequency, academic qualifications, weekly exercise frequency, health condition, and viral infection history. These insights can inform interventions aimed at safeguarding the mental well-being of frontline nurses in the post-pandemic period.

Identification of potential crucial genes and therapeutic targets for epilepsy.

BACKGROUND: Epilepsy, a central neurological disorder, has a complex genetic architecture. There is some evidence suggesting that genetic factors play a role in both the occurrence of epilepsy and its treatment. However, the genetic determinants of epilepsy are largely unknown. This study aimed to identify potential therapeutic targets for epilepsy. METHODS: Differentially expressed genes (DEGs) were extracted from the expression profiles of GSE44031 and GSE1834. Gene co-expression analysis was used to confirm the regulatory relationship between newly discovered epilepsy candidate genes and known epilepsy genes. Expression quantitative trait loci analysis was conducted to determine if epilepsy risk single-nucleotide polymorphisms regulate DEGs' expression in human brain tissue. Finally, protein-protein interaction analysis and drug-gene interaction analysis were performed to assess the role of DEGs in epilepsy treatment. RESULTS: The study found that the protein tyrosine phosphatase receptor-type O gene (PTPRO) and the growth arrest and DNA damage inducible alpha gene (GADD45A) were significantly upregulated in epileptic rats compared to controls in both datasets. Gene co-expression analysis revealed that PTPRO was co-expressed with RBP4, NDN, PAK3, FOXG1, IDS, and IDS, and GADD45A was co-expressed with LRRK2 in human brain tissue. Expression quantitative trait loci analysis suggested that epilepsy risk single-nucleotide polymorphisms could be responsible for the altered PTPRO and GADD45A expression in human brain tissue. Moreover, the protein encoded by GADD45A had a direct interaction with approved antiepileptic drug targets, and GADD45A interacts with genistein and cisplatin. CONCLUSIONS: The results of this study highlight PTPRO and GADD45A as potential genes for the diagnosis and treatment of epilepsy.

Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications.

Background: Previous studies have shown that the rs717620 polymorphism in ABCC2, the gene encoding multidrug resistance protein 2, influences the therapeutic response to anti-seizure medications (ASMs). However, this result is not consistent, and the mechanism by which rs717620 influences ASM responses is unclear. Aims: The present study evaluated the association between rs717620 genotype and ASM efficacy, and examined the potential mechanisms. Main: methods: We conducted a literature search of five electronic databases, Embase, Medline, Web of Science, China National Knowledge Infrastructure, and Wanfang, to identify relevant studies on response to ASM therapy among rs717620 genotypes. Expression quantitative trait loci analysis and drug-gene interaction analysis were also performed to assess the underlying mechanisms. Key findings: The pooled results for 18 studies revealed a significant association between rs717620 genotype and ASM resistance under the recessive model (TT vs. CT + CC: OR = 1.68, 95 % CI = 1.27-2.21, I2 = 3.1 %). A significant association was also found in the Asian population under the recessive model (TT vs. CT + CC: OR = 1.70, 95 % CI = 1.26-2.29, I2 = 29.3 %). Further analysis revealed that rs717620 regulates the expression of ABCC2 in human brain, while drug-gene interaction analysis suggested that ABCC2 interacts with oxcarbazepine and carbamazepine. Significance: The rs717620 polymorphism influences ASM therapeutic responses by altering brain expression levels of ABCC2.

Functional Characterization of A Deformed Epidermal Autoregulatory Factor 1 Gene in Litopenaeus vannamei.

Innate immunity is crucial for invertebrate defense against pathogenic infections. Numerous studies have indicated that the Toll-NF-κB pathway plays an important role in this process, particularly in anti-bacterial and anti-fungal immunity. Although the function of this pathway has been studied extensively, there are still uncertainties regarding its role in shrimp. In this study, we investigated the functions of Deformed Epidermal Autoregulatory Factor 1 (LvDEAF1) in Litopenaeus vannamei, a member of the Toll-NF-κB pathway. Our findings revealed that LvDEAF1 interacts with L. vannamei Pellino1 (LvPellino1). LvDEAF1 enhances the promoter activity of certain antimicrobial peptide genes, such as Metchnikowin and Drosomycin, in Drosophila Schneider 2 (S2) cells by binding to the NF-κB binding site. LvDEAF1 and LvPellino1 exhibit positive and synergistic effects. Additionally, the expression of LvDEAF1 is induced by Vibrio parahaemolyticus infection and lipopolysaccharides or zymosan treatment. Knockdown LvDEAF1 expression resulted in a decrease in Penaeidins 4 expression and an increase in the cumulative mortality of shrimp infected with V. parahaemolyticus. These findings indicate that LvDEAF1 plays an important role in the Toll-NF-κB pathway of L. vannamei and is essential for its immune response against pathogens.

Comprehensive analyses identify potential biomarkers for encephalitis in HIV infection.

Human immunodeficiency virus encephalitis (HIVE) is a severe neurological complication after HIV infection. Evidence shows that genetic factors play an important role in HIVE. The aim of the present study was to identify new potential therapeutic targets for HIVE. Differentially expressed gene (DEG), functional annotation and pathway, and protein-protein interaction analyses were performed to identify the hub genes associated with HIVE. Gene co-expression analysis was carried out to confirm the association between the hub genes and HIVE. Finally, the role of the hub genes in HIVE therapy was evaluated by conducting drug-gene interaction analysis. A total of 20 overlapping DEGs closely related to HIVE were identified. Functional annotation and pathway enrichment analysis indicated that the markedly enriched DEG terms included ion transport, type II interferon signaling, and synaptic signaling. Moreover, protein-protein interaction analysis revealed that 10 key HIVE-related genes were hub genes, including SCN8A, CDK5R2, GRM5, SCN2B, IFI44L, STAT1, SLC17A7, ISG15, FGF12, and FGF13. Furthermore, six hub genes were co-expressed with HIVE-associated host genes in human brain tissue. Finally, three hub genes (STAT1, ISG15, and SCN2B) interacted with several inflammation-associated drugs. These findings suggested that SCN8A, CDK5R2, GRM5, SCN2B, IFI44L, STAT1, SLC17A7, ISG15, FGF12, and FGF13 may be new targets for diagnosis and therapy of HIVE.

A Study on the Structural Relationships between COVID-19 Coping Strategies, Positive Expectations, and the Behavioral Intentions of Various Tourism-Related Behaviors.

The purpose of this study was to investigate the impact of coping strategies, attitudes, and positive anticipated emotions on the positive expectations and behavioral intentions of Korean tourists during the COVID-19 pandemic. An integrated model was proposed and tested, and the results indicate that effective coping strategies, attitudes, and positive anticipated emotions have a positive effect on the positive expectations of tourism during the pandemic, which in turn positively influences behavioral intentions. Practical suggestions were also provided based on the findings. This research has implications for understanding the ways in which individuals cope with and adapt to travel during times of crisis, and for identifying strategies that may facilitate positive expectations and behavioral intentions in the tourism industry.

Polyphenylene Sulfide Ultrafine Viscous Fibrous Membrane Modified by ZIF-8 for Highly Effective Oil/Water Separation under High Salt or Alkaline Conditions.

The oil/water separation in harsh environments has always been a challenging topic all over the world. In this study, the ZIF-8/PPS fiber membranes were fabricated via the combination of hot pressing and in situ growth. The distribution of ZIF-8 in the membranes was adjusted by changing the ZIF-8 in situ growth time, which could control the oil/water separation effect. Due to the hydrophilic nature of the ZIF-8/PPS fiber membranes, the water molecules in the oil-in-water emulsion could quickly penetrate into the fiber membrane under the drive of pressure, gravity, and capillary force, forming a water layer on the surface of the fiber membranes. The coupling of the water layer and the fiber structure prevented direct contact between the oil molecules and the fiber membrane, thereby realizing the separation of the emulsion. The results show that when the ZIF-8 in situ growth time was 10 h, the contact angle, the porosity, and the pure water flux of the ZIF-8/PPS fiber membranes were 72.5°, 52.3%, and 12,351 L/h·m2, respectively. More importantly, the separation efficiency of M10 was 97%, and the oil/water separation efficiency reached 95% after 14 cycles. This study provides a novel strategy for preparing MOFs/fiber materials for oil/water separation in harsh environments.

Integrative Analyses Identify KCNJ15 as a Candidate Gene in Patients with Epilepsy.

INTRODUCTION: Although there is accumulating evidence that genetic factors play a vital role in the pathogenesis of epilepsy, few epilepsy-associated genes have been identified. Additionally, the role of KCNJ15 in epilepsy has not been evaluated so far. METHODS: Here, we performed differentially expressed gene analysis, expression quantitative trait loci analysis, gene co-expression analysis, and protein-protein interaction analysis to evaluate the role of KCNJ15 in epilepsy. RESULTS: Analysis of gene expression and expression quantitative trait loci data revealed that KCNJ15 was significantly downregulated in patients with epilepsy (adjusted P = 0.0146 and log2 Fold change = - 1.0025), and an epilepsy-associated polymorphism (rs2833098) was linked to altered KCNJ15 expression level in human temporal lobe brain tissue (P = 0.0036). Gene co-expression analysis revealed that KCNJ15 was co-expressed with genes that have been reported to be associated with epilepsy in human brain tissue. Furthermore, protein-protein interaction analysis revealed strong supportive evidence for the role of KCNJ15 in epilepsy. CONCLUSION: Our results show that KCNJ15 may be a candidate target for epilepsy. Functional analysis of KCNJ15 may provide novel insights for epilepsy treatment.

Cerebral infarction caused by systemic sclerosis: a case report.

Systemic sclerosis, also known as scleroderma, is a rare multisystem autoimmune disease characterized by vascular lesions caused by collagen deposition in the skin and viscera and damage to the endothelium. Endothelial injury and microvascular occlusion result in Raynaud's phenomenon, finger ischemia, pulmonary hypertension, and scleroderma renal crisis. Scleroderma itself is a rare disease with an incidence ranging from 0.1 to 14 per 100,000 people in the general population. Cerebral involvement is not considered a common manifestation of systemic sclerosis, although studies have shown that the brain can be involved. Therefore, to deepen the understanding of this disease, we herein report a case of cerebral infarction associated with systemic sclerosis.

Oxygen-releasing polycaprolactone/calcium peroxide composite microspheres.

Oxygen-releasing polycaprolactone/calcium peroxide (PCL/CaO2 ) composite microspheres were fabricated via homogenization, electrospray with a single nozzle, and electrospray with a co-axial nozzle, resulting in homogenized, single-walled, and double-walled microspheres, respectively. Scanning electron microscopy revealed that homogenized microspheres had pores, while electrosprayed microspheres did not. Alizarin Red S staining showed a core-shell structure for double-walled microspheres. In a hypoxia incubator, single-walled, double-walled, and homogenized microspheres could maintain oxygen tension in PBS at or above 10% for approximately 5, 4, and 3 days, respectively. All the PCL/CaO2 microspheres could support viability of pancreatic ß-cell line MIN6 cells in 2D cultures in a hypoxia incubator for 1 week, with the cells supported by double-walled and homogenized microspheres exhibiting the highest and the lowest metabolic activity, respectively. For 3D MIN6 cell cultures in a hypoxia incubator, single-walled and homogenized PCL/CaO2 microspheres led to the highest and the lowest live cell densities, respectively. Double-walled and single-walled microspheres provided the best support for 2D and 3D cultures, respectively, suggesting that they are suitable for different applications.

Efficient release of immunocaptured cells using coiled-coils in a microfluidic device.

Label-free and affinity-based cell separation allows highly specific cell capture through simple procedures, but it remains a major challenge to efficiently release the captured cells without changing their structure, phenotype, and function. We report a microfluidic platform for label-free immunocapture of target cells and efficient release of the cells with minimal biochemical and biophysical perturbations. The method capitalizes on self-assembly of a pair of heterodimerizing coiled-coils, A and B. Target cells are captured in microchannels functionalized with an antibody and A and efficiently released by a liquid flow containing B-PEG (a conjugate of B and polyethylene glycol) at a controlled, low shear stress. The released cells have no antibodies attached or endogenous surface molecules cleaved. In a model system, human umbilical vein endothelial cells (HUVECs) were isolated from a mixture of HUVECs and human ovarian carcinoma cells. The capture selectivity, capture capacity, and release efficiency were 96.3% ± 1.8%, 10 735 ± 1897 cells per cm2, and 92.5% ± 3.8%, respectively, when the flow was operated at a shear stress of 1 dyn cm-2. The method can be readily adapted for isolation of any cells that are recognizable by a commercially available antibody, and B-PEG is a universal cell-releasing trigger.

Skeletal Muscle Constructs Engineered from Human Embryonic Stem Cell Derived Myogenic Progenitors Exhibit Enhanced Contractile Forces When Differentiated in a Medium Containing EGM-2 Supplements.

Three-dimensional (3D) skeletal muscle constructs engineered from myogenic progenitors derived from human pluripotent stem cells (hPSCs) have a wide range of applications, but to date, such constructs generate lower specific tetanic force than adult human muscles. Methods enhancing functional muscle differentiation and force generation of these constructs are highly desirable. The finding of this study is that addition of the supplements in the endothelial cell growth medium-2 (EGM-2) to the myogenic differentiation medium can substantially enhance contractile force generation. For constructs differentiated for 4 weeks, addition of the EGM-2 supplements in the first 2 weeks leads to tenfold and sevenfold increases in twitch and tetanic forces, respectively. The specific tetanic force generated by these constructs is 33 mN mm-2 , which is significantly higher than previously reported. These constructs show wider myotubes and higher gene expression levels for all skeletal muscle-specific myosin heavy chain isoforms, suggesting that a more mature differentiation stage of the cells underlies the greater contractile force generation. The constructs exposed to these supplements for 4 weeks do not generate as high contractile forces, suggesting that prolonged treatment is not beneficial. These results suggest that temporal conditioning with the EGM-2 supplements assists functional development of hPSC-derived skeletal muscle constructs.

Doxorubicin-Conjugated PAMAM Dendrimers for pH-Responsive Drug Release and Folic Acid-Targeted Cancer Therapy.

We present here the development of multifunctional doxorubicin (DOX)-conjugated poly(amidoamine) (PAMAM) dendrimers as a unique platform for pH-responsive drug release and targeted chemotherapy of cancer cells. In this work, we covalently conjugated DOX onto the periphery of partially acetylated and folic acid (FA)-modified generation 5 (G5) PAMAM dendrimers through a pH-sensitive cis-aconityl linkage to form the G5.NHAc-FA-DOX conjugates. The formed dendrimer conjugates were well characterized using different methods. We show that DOX release from the G5.NHAc-FA-DOX conjugates follows an acid-triggered manner with a higher release rate under an acidic pH condition (pH = 5 or 6, close to the acidic pH of tumor microenvironment) than under a physiological pH condition. Both in vitro cytotoxicity evaluation and cell morphological observation demonstrate that the therapeutic activity of dendrimer-DOX conjugates against cancer cells is absolutely related to the DOX drug released. More importantly, the FA conjugation onto the dendrimers allowed a specific targeting to cancer cells overexpressing FA receptors (FAR), and allowed targeted inhibition of cancer cells. The developed G5.NHAc-FA-DOX conjugates may be used as a promising nanodevice for targeted cancer chemotherapy.

Efficient Release of Affinity-Captured Cells Using a Coiled-Coil-Based Molecular Trigger.

Affinity-based cell separation is label-free and highly specific, but it is difficult to efficiently and gently release affinity-captured cells due to the multivalent nature of cell-material interactions. To address this challenge, we have developed a platform composed of a capture substrate and a cell-releasing molecular trigger. The capture substrate is functionalized with a cell-capture antibody and a coiled-coil A. The cell-releasing molecular trigger B-PEG (polyethylene glycol), a conjugate of a coiled-coil B and polyethylene glycol, can drive efficient and gentle release of the captured cells, because A/B heterodimerization brings B-PEG to the substrate and PEG chains adopt extended conformations and break nearby multivalent antibody-biomarker interactions. No enzymes or excessive shear stress are involved, and the released cells have neither external molecules attached nor endogenous cell-surface molecules cleaved, which is critical for the viability, phenotype, and function of sensitive cells.

Impact of dendrimer surface functional groups on the release of doxorubicin from dendrimer carriers.

Generation 5 (G5) poly(amidoamine) dendrimers with acetyl (G5.NHAc), glycidol hydroxyl (G5.NGlyOH), and succinamic acid (G5.SAH) terminal groups were used to physically encapsulate an anticancer drug doxorubicin (DOX). Both UV-vis spectroscopy and multiple NMR techniques including one-dimensional NMR and two-dimensional NMR were applied to investigate the interactions between different dendrimers and DOX. The influence of the surface functional groups of G5 dendrimers on the DOX encapsulation, release kinetics, and cancer cell inhibition effect was investigated. We show that all three types of dendrimers are able to effectively encapsulate DOX and display therapeutic inhibition effect to cancer cells, which is solely associated with the loaded DOX. The relatively stronger interactions of G5.NHAc or G5.NGlyOH dendrimers with DOX than that of G5.SAH dendrimers with DOX demonstrated by NMR techniques correlate well with the slow release rate of DOX from G5.NHAc/DOX or G5.NGlyOH/DOX complexes. In contrast, the demonstrated weak interaction between G5.SAH and DOX causes a fast release of DOX, suggesting that the G5.SAH/DOX complex may not be a proper option for further in vivo research. Our findings suggest that the dendrimer surface functional groups are crucial for further design of multifunctional dendrimer-based drug delivery systems for various biomedical applications.

Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy.

BACKGROUND: We report here a unique approach to using multifunctional dendrimer/combretastatin A4 (CA4) inclusion complexes for targeted cancer therapeutics. METHODS: Amine-terminated generation 5 polyamidoamine dendrimers were first partially acetylated to neutralize a significant portion of the terminal amines, and then the remaining dendrimer terminal amines were sequentially modified with fluorescein isothiocyanate as an imaging agent and folic acid as a targeting ligand. The multifunctional dendrimers formed (G5.NHAc-FI-FA) were utilized to encapsulate the anticancer drug, CA4, for targeted delivery into cancer cells overexpressing folic acid receptors. RESULTS: The inclusion complexes of G5.NHAc-FI-FA/CA4 formed were stable and are able to significantly improve the water solubility of CA4 from 11.8 to 240 µg/mL. In vitro release studies showed that the multifunctional dendrimers complexed with CA4 could be released in a sustained manner. Both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and morphological cell observation showed that the inhibitory effect of the G5.NHAc-FI-FA/CA4 complexes was similar to that of free CA4 at the same selected drug concentration. More importantly, the complexes were able to target selectively and display specific therapeutic efficacy to cancer cells overexpressing high-affinity folic acid receptors. CONCLUSION: Multifunctional dendrimers may serve as a valuable carrier to form stable inclusion complexes with various hydrophobic anticancer drugs with improved water solubility, for targeting chemotherapy to different types of cancer.