Comparative proteomics reveals that fatty acid metabolism is involved in myocardial adaptation to chronic hypoxic injury.

Congenital heart disease (CHD) is the most serious form of heart disease, and chronic hypoxia is the basic physiological process underlying CHD. Some patients with CHD do not undergo surgery, and thus, they remain susceptible to chronic hypoxia, suggesting that some protective mechanism might exist in CHD patients. However, the mechanism underlying myocardial adaptation to chronic hypoxia remains unclear. Proteomics was used to identify the differentially expressed proteins in cardiomyocytes cultured under hypoxia for different durations. Western blotting assays were used to verify protein expression. A Real-Time Cell Analyzer (RTCA) was used to analyze cell growth. In this study, 3881 proteins were identified by proteomics. Subsequent bioinformatics analysis revealed that proteins were enriched in regulating oxidoreductase activity. Functional similarity cluster analyses showed that chronic hypoxia resulted in proteins enrichment in the mitochondrial metabolic pathway. Further KEGG analyses found that the proteins involved in fatty acid metabolism, the TCA cycle and oxidative phosphorylation were markedly upregulated. Moreover, knockdown of CPT1A or ECI1, which is critical for fatty acid degradation, suppressed the growth of cardiomyocytes under chronic hypoxia. The results of our study revealed that chronic hypoxia activates fatty acid metabolism to maintain the growth of cardiomyocytes.

Exploration of surface tension measurement methods for pharmaceutical excipients.

Surface tension is a crucial functional indicator for various classes of pharmaceutical excipients, as highlighted in both the Pharmacopoeia of the People's Republic of China (ChP) < 9601 Guidelines for Functionality-related Characteristics of Pharmaceutical Excipients > and the United States Pharmacopoeia (USP) < 1059 Excipient Performance >. However, there are few systematic studies on surface tension measurement of pharmaceutical excipients, resulting in a lack of stable parameter support in practical applications. In this study, we aim to fill this gap by exploring three different methods for measuring surface tension. These methods were carefully developed taking into account the actual measurement process and statistical theory, thus ensuring their applicability and reliability. Through comparative analyses, we have identified the most suitable measurement methods for different classes of pharmaceutical excipients. In addition, this paper describes the surface adsorption behavior of various excipients. Therefore, this study provides valuable guidance for the determination of surface tension and the study of surface adsorption behavior, which lays the foundation for further comprehensive research in the field of surface tension of pharmaceutical excipients and the improvement of general pharmacopoeia specification.

Compositing effects for high thermoelectric performance of Cu2Se-based materials.

Thermoelectric materials can realize direct conversion between heat and electricity, showing excellent potential for waste heat recovery. Cu2Se is a typical superionic conductor thermoelectric material having extraordinary ZT values, but its superionic feature causes poor service stability and low mobility. Here, we reported a fast preparation method of self-propagating high-temperature synthesis to realize in situ compositing of BiCuSeO and Cu2Se to optimize the service stability. Additionally, using the interface design by introducing graphene in these composites, the carrier mobility could be obviously enhanced, and the strong phonon scatterings could lead to lower lattice thermal conductivity. Ultimately, the Cu2Se-BiCuSeO-graphene composites presented excellent thermoelectric properties with a ZTmax value of ~2.82 at 1000 K and a ZTave value of ~1.73 from 473 K to 1000 K. This work provides a facile and effective strategy to largely improve the performance of Cu2Se-based thermoelectric materials, which could be further adopted in other thermoelectric systems.

LINC01123 acts as an oncogenic driver in lung adenocarcinoma by regulating the miR-4766-5p/PYCR1 axis.

BACKGROUND: Lung adenocarcinoma remains one of the most significant threats to human life as it involves multiple etiologies, including alteration of oncogenes or tumor-inhibitory genes. Long non-coding RNAs (lncRNAs) have been reported to have both cancer promoting and cancer inhibiting effects. In this work, we investigated the function and mechanism of lncRNA LINC01123 in lung adenocarcinoma. METHODS: The expression of LINC01123, miR-4766-5p, and PYCR1 (pyrroline-5-carboxylate reductase 1) mRNA was analyzed by RT-qPCR. The protein expression levels of PYCR1 and the apoptosis-related proteins (Bax and Bcl-2) were determined by western blotting. Cell proliferation and migration were determined by CCK-8 and wound-healing assays, respectively. Tumor growth in nude mice and Ki67 immunohistochemical staining were used to determine the in vivo role of LINC01123. The putative binding relationships miR-4766-5p has with LINC01123 and PYCR1, which had been identified by analysis of public databases, were validated through RIP and dual-luciferase reporter assays. RESULTS: LINC01123 and PYCR1 overexpression and miR-4766-5p downregulation were shown to occur in lung adenocarcinoma samples. LINC01123 depletion repressed lung adenocarcinoma cell growth and migration and blocked the development of solid tumors in an animal model. Moreover, LINC01123 bound directly to miR-4766-5p, the downregulation of which attenuated the anticancer effects of LINC01123 depletion in lung adenocarcinoma cells. MiR-4766-5p directly targeted downstream PYCR1 to suppress PYCR1 expression. The repressive effects of PYCR1 knockdown on the migration and proliferation of lung adenocarcinoma cells were also partly abolished by miR-4766-5p downregulation. CONCLUSION: Downregulation of LINC01123 represses lung adenocarcinoma progression. This suggests that LINC01123 functions as an oncogenic driver in lung adenocarcinoma by controlling the miR-4766-5p/PYCR1 axis.

Trading-Off Transit and Non-Transit Physical Activity among Older People: Evidence from Longitudinal Accelerometer Data of a Natural Experiment Study.

This study used a natural experiment of a new metro line in Hong Kong to examine trade-offs between transit-related and non-transit-related physical activity (PA) among 104 older people (aged ≥ 65 years) based on longitudinal accelerometer data that distinguished transit-related and non-transit-related PA. Difference-in-difference (DID) analysis compared PA changes between treatment and control groups. We found that new metro stations have trade-off effects between transit and non-transit PA. After opening metro stations, transit-related PA increased by 12 min per day on average, but non-transit-related PA decreased by 18 min per day. In addition, the proportion of time spent in transit-related PA increased by 6%. The results suggested that new metro stations could generate transit-related PA, but it might shift from non-transit-related PA among older people. Our findings revealed trade-off effects of public transit interventions and have significant implications for transport and healthy ageing studies.

LncRNA BBOX1-AS1 Contributes to the Progression of Esophageal Carcinoma by Targeting the miR-361-3p/COL5A1 Axis.

Long noncoding RNAs (lncRNAs) are known to participate in the progression of several cancers, including esophageal carcinoma (EC), a common malignancy of the digestive system. Although the role of the lncRNA-miRNA-mRNA regulatory network is crucial for the growth and progression of EC, the regulation of lncRNA BBOX1-AS1 (BBOX1 antisense RNA1) remains unclear. We performed reverse transcription-quantitative PCR (RT-qPCR) and western blotting to evaluate miR-361-3p, collagen type V alpha 1 chain (COL5A1), and BBOX1-AS1 expression levels in EC cells and tissues. The colony formation assay (CFA) and Cell Counting Kit-8 (CCK-8) were employed to identify EC cell proliferation, while western blotting was used to examine EC cell apoptosis and Bax and Bcl-2 expression levels. The effect of BBOX1-AS1 on EC proliferation was determined using an in vivo carcinogenesis assay. Correlation between COL5A1, BBOX1-AS1, and miR-361-3p was examined using the luciferase reporter system and RNA immunoprecipitation assay (RIP). Herein, we observed that BBOX1-AS1 expression levels were upregulated in EC cells and tissues. BBOX1-AS1 knockdown inhibited EC cell proliferation and conferred a pro-apoptotic effect. These results indicated a positive interaction between BBOX1-AS1 and miR-361-3p in EC and a negative association with miR-361-3p. COL5A1 was recognized as a downstream miR-361-3p target and was inversely related to miR-361-3p in EC. Therefore, BBOX1-AS1 expression suppressed cell apoptosis and promoted cell proliferation via the downregulation of miR-361-3p and upregulation of COL5A1 expression. Overall, BBOX1-AS1 facilitates EC progression via the miR-361-3p or COL5A1 axis, indicating that BBOX1-AS1 might be a potential therapeutic target for EC therapy.

Pregabalin supplementation for the pain relief of septorhinoplasty: a meta-analysis study.

BACKGROUND: Pregabalin supplementation may have some potential in improving pain relief in patients with septorhinoplasty, and this meta-analysis aims to explore the impact of pregabalin supplementation on pain control for septorhinoplasty. METHODS: PubMed, EMbase, Web of science, EBSCO and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of pregabalin supplementation on pain control for septorhinoplasty. RESULTS: Six RCTs were finally included in the meta-analysis. Overall, when compared with control intervention for septorhinoplasty, pregabalin intervention showed significantly reduced pain scores at 1 h (SMD - 1.05; 95% CI - 1.85 to - 0.24; P = 0.01), 2 h (SMD - 1.01; 95% CI - 1.83 to - 0.20; P = 0.02), 6 h (SMD - 1.00; 95% CI - 1.47 to - 0.54; P < 0.0001) and 12 h (SMD - 0.69; 95% CI - 1.35 to - 0.02; P = 0.04), as well as rescue analgesics (OR 0.17; 95% CI 0.07 to 0.44; P = 0.0002), but had no notable influence on nausea and vomiting (OR 0.67; 95% CI 0.30 to 1.46; P = 0.31), or drowsiness (OR 1.22; 95% CI 0.64 to 2.35; P = 0.54). CONCLUSIONS: Pregabalin supplementation benefits to pain control after septorhinoplasty.

The effects of metro interventions on physical activity and walking among older adults: A natural experiment in Hong Kong.

This paper provides causal inference on how transport intervention affects moderate-to-vigorous physical activity (MVPA) and walking among older adults using a natural experiment of a new metro line in Hong Kong. A longitudinal survey of 449 cohort participants was collected before and after the metro operation. Treatment groups live within a 400m walking buffer of the new metro stations, while control groups are located around comparable stations on existing metro lines. These metro lines were planned at the same time using similar principles, but the intervention line was built later due to different financial models. Our difference-in-difference (DID) models found that the new metro line significantly decreased older adults' weekly MVPA (-129.33 min, p < 0.05) in treatment groups, while the effect on change in walking time did not significantly differ between the treatment and control groups. We also found heterogeneous treatment effects among gender and age subgroups. Furthermore, our time effect tests suggested that older adults' physical activity and walking levels may stabilise, based on participants living around a metro station operated four years ago with another comparable station operated three decades ago. This practice-based evidence suggests that new metro developments might not promote physical activity and walking levels among older adults in the high-density city of Hong Kong.

Development of a multiplex RT-PCR method for the detection of four porcine enteric coronaviruses.

Porcine enteric coronaviruses are pathogens that cause viral diarrhea in pigs and are widely prevalent worldwide. Moreover, studies have shown that some porcine enteric coronaviruses can infect humans and poultry. In order to effectively monitor these viruses, it is necessary to establish a multiple detection method to understand their prevalence and conduct in-depth research. Common porcine enteric coronaviruses include Porcine epidemic diarrhea virus (PEDV), Porcine transmissible gastroenteritis virus (TGEV), Porcine delta coronavirus (PDCoV), and Swine acute diarrhea syndrome coronavirus (SADS-CoV). Pigs infected with these viruses have the common clinical symptoms that are difficult to distinguish. A quadruplex RT-PCR (reverse transcription-polymerase chain reaction) method for the simultaneous detection of PEDV, PDCoV, TGEV and SADS-CoV was developed. Four pairs of specific primers were designed for the PEDV M gene, PDCoV N gene, TGEV S gene and SADS-CoV RdRp gene. Multiplex RT-PCR results showed that the target fragments of PDCoV, SADS-CoV, PEDV and TGEV could be amplified by this method. and the specific fragments with sizes of 250 bp, 368 bp, 616 bp and 801 bp were amplified, respectively. This method cannot amplify any fragment of nucleic acids of Seneca Valley virus (SVV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Atypical Porcine Pestivirus (APPV), and has good specificity. The lowest detection limits of PDCoV, PEDV, TGEV and SADS-CoV were 5.66 × 105 copies/µL, 6.48 × 105 copies/µL, 8.54 × 105 copies/µL and 7.79 × 106 copies/µL, respectively. A total of 94 samples were collected from pig farms were analyzed using this method. There were 15 positive samples for PEDV, 3 positive samples for mixed infection of PEDV and PDCoV, 2 positive samples for mixed infection of PEDV and TGEV, and 1 positive sample for mixed infection of PEDV, TGEV, and PDCoV. Multiplex RT-PCR method could detect four intestinal coronaviruses (PEDV, PDCoV, TGEV, and SADS-CoV) in pigs efficiently, cheaply and accurately, which can be used for clinical large-scale epidemiological investigation and diagnosis.

The Effect of miR-505-5p on Inhibition of Serum Uromodulin Ameliorates Myocardial Inflammation and Apoptosis Induced by Ischemia-Reperfusion.

Background: It has been found that miR-505-5p is closely related to cardiovascular metabolic risk factors. Nonetheless, there is little research analyzing miR-505-5p for its role as well as molecular mechanism in myocardial injury caused by ischemia-reperfusion (I/R). Methods: This work utilized quantitative reverse transcriptase PCR (qRT-PCR) for detecting miR-505-5p and serum uromodulin (sUmod) levels. sUmod, interleukin-1beta (IL-1ß), IL-6, IL-10, caspase7, caspase9, tumor necrosis factor-alpha (TNF-α), Bax, and Bcl-xL expression was detected by western blot. Bioinformatics database was used for target prediction and miR-505-5's target was determined by luciferase reporter gene assay. Results: Relative to sham group, sUmod was highly expressed within myocardial I/R injury (MIRI), whereas sUmod silencing significantly decreased the heart weight/body weight ratio, reduced serum myocardial enzymes expression, ameliorated I/R-mediated myocardial apoptosis, and inflammation. TargetScan bioinformatics database and luciferase reporter genes confirmed that sUmod was miR-505-5p's direct target gene, besides, miR-505-5p overexpression significantly improved the myocardial injury score, increased IL-10, decreased TNF-α, IL-1ß, IL-6 expression, decreased caspase7, caspase9, Bax expression, and increased Bcl-xL expression. More importantly, overexpression of sUmod abolished miR-505-5p overexpression's role in I/R-mediated myocardial apoptosis and inflammation. Conclusion: miR-505-5p can improve I/R-mediated myocardial apoptosis and inflammation by targeting sUmod. In this study, miR-505-5p is related to MIRI pathogenesis, which provides the new possible targeted therapy in patients with MIRI.

Dietary Stevia Residue Extract Supplementation Improves Antioxidant Capacity and Intestinal Microbial Composition of Weaned Piglets.

This study aimed to investigate the effects of diet supplementation with stevia residue extract (SRE) on growth performance, intestinal health, and antioxidant capacity of weaned piglets. A total of 144 weaned piglets (body weight 6.8 ± 0.5 kg) were randomly selected and allocated into four treatment groups with six replicates of six pigs/pen. The treatments consisted of a basal diet without SRE or basal diet supplemented with 100, 200, or 400 mg/kg SRE. The results showed that the addition of 200 mg/kg SRE to the diet significantly reduced (p < 0.05) the diarrhea rate of piglets compared with the control group. The supplementation of 400 mg/kg SRE in the diet significantly reduced the piglets' serum MDA content and significantly increased (p < 0.05) the T-AOC, T-SOD, and GSH-PX activity in the serum. The dietary supplementation with 400 mg/kg SRE significantly increased (p < 0.05) the CAT and GSH-PX activity in the liver. Moreover, the supplementation of 400 mg/kg SRE in the diet significantly increased (p < 0.05) the relative abundance of Prevotellaceae (genus) and Roseburia (genus) beneficial bacteria compared to the control group. Spearman's correlation analysis showed that Prevotella (genus) abundance was positively correlated with liver GSH-PX activity and acetic acid content of colon contents. In conclusion, the supplementation of 400 mg/kg SRE to the diet can improve piglet health by regulating antioxidant reduction homeostasis, which may also be associated with an increase in the relative numbers of potentially beneficial bacteria.

Prevalence and clinical characteristics of Crooke's cell adenomas in 101 patients with T-PIT-positive pituitary adenomas: Case series and literature review.

Purpose: We aimed to perform a retrospective analysis of a rare subtype of corticotroph adenoma, Crooke's cell adenoma, to better understand its clinical features. Methods: We collected T-PIT-positive pituitary adenomas and screened Crooke's cell adenomas from January 2020 to December 2021 in our center. Case reports of such tumors were also collected through a literature search. Clinical data such as biochemical tests, imaging examinations, and pathological data of the above cases were analyzed. Results: A total of 101 T-PIT-positive patients were treated in our center in the last 2 years, and 4 were finally pathologically diagnosed with Crooke's cell adenomas. All of these patients were male with elevated adrenocorticotropic hormone levels, and 50.0% presented with hypercortisolemia, Cushing's syndrome, visual impairment, and headache. The tumor diameter was significantly larger in these 4 patients (37.0 mm) than in the other patients (26.0 mm), and their tumor invasive behavior was more pronounced. Cases reported in the literature were mainly female (72.8%), and the clinical presentation was also dominated by Cushing's syndrome (65.1%) and hormonal dysfunction. Tumors were more common as macroadenomas (33.2 mm) and suprasellar growths (63.8%). The tumor recurrence rate was as high as 55.6%, with 6 cases progressing to pituitary carcinomas and 7.7% of tumor-related deaths. Our further integrated analysis of our center and reported cases revealed that gender, Cushing's syndrome, visual dysfunction, hormonal disorders, and tumor growth characteristics were statistically different in different tumor categories. Conclusion: Crooke's cell adenoma is a tumor subtype with obvious clinical aggressive behavior, and an in-depth analysis of its clinical characteristics may assist in developing a comprehensive treatment plan.

Preventive use of beta-blockers for anthracycline-induced cardiotoxicity: A network meta-analysis.

Background: Anthracyclines are commonly used chemotherapeutic agents to treat malignant tumors. However, cardiotoxicity is a potentially serious adverse effect of anthracyclines. Beta-blockers may be effective in preventing anthracycline-induced cardiotoxicity (AIC). However, the lack of direct comparisons of various beta-blockers interferes with clinical decision-making. Network meta-analysis (NMA) was performed to assess the effectiveness of beta-blockers for AIC. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Clinical Trials. The last update was in May 2022. Randomized controlled trials (RCT) of beta-blockers for AIC were included. Four beta-blockers were selected for comparison based on the number of studies. NMA was conducted with STATA 14.0 software. Results: A total of 10 RCTs (875 patients) met the selection criteria. NMA results showed that carvedilol was superior to bisoprolol [SMD = -0.50, 95% CI (-0.91, -0.10)] and nebivolol [SMD = -1.46, 95%CI (-2.82, -0.11)] in a delay of LVEF. The results of the cumulative probability ordering are as follows: carvedilol (83.8%) > metoprolol (71.8%) > bisoprolol (43.9%) > placebo (40.9%) > nebivolol (9.5%). Conclusion: Based on the available evidence, carvedilol is the best beta-blocker for AIC, followed by metoprolol. However, additional studies with large samples should be conducted to confirm our findings.

Effects of niacin on intestinal epithelial Barrier, intestinal Immunity, and microbial community in weaned piglets challenged by PDCoV.

The objective was to evaluate effects of niacin on the intestinal epithelial barrier, intestinal immunity, and microbial community in weaned piglets challenged by Porcine Deltacoronavirus (PDCoV). In this study, fifteen weaned piglets were randomly assigned to 1 of 3 groups, (1) control group, normal diet; (2) PDCoV group, infected with 1 × 107 TCID50 of the PDCoV CHN-HN-17 strain by oral administration; (3) NA + PDCoV group, infected with 1 × 107 TCID50 of the PDCoV CHN-HN-17 strain by oral administration following administration of 40 mg of niacin for three days. The results showed that PDCoV infection induced diarrhea and other clinical symptoms with intestinal villi shedding and atrophy in weaned piglets. Niacin alleviated the symptoms of diarrhea and intestinal damage of PDCoV-infected weaned piglets. Additionally, PDCoV increased (P < 0.05) the mRNA expression of tight junction proteins [zonula occludens-1 (ZO-1) and Claudin] and antimicrobial peptides [porcine ß defensin 1 (pBD1), pBD2, proline-arginine rich 39-amino acid peptide (PR39) and protegrin 1-5 (PG1-5) in the jejunum and ileum of weaned piglets, while niacin increased (P < 0.05) the expression of PG1-5 compared with PDCoV. PDCoV increased (P < 0.05) the contents of serum interleukin-1ß (IL-1ß), IL-8 and intestinal IL-8, and up-regulated the mRNA expression of tumor necrosis factor-α (TNF-α), IL-1ß, IL-6, IL-10, IL-12, and IL-18 in ileum of weaned piglets compared with control. However, niacin decreased (P < 0.05) the contents of serum IL-1ß, IL-6 and intestinal IL-10 and IL-8, and also reduced (P < 0.05) the mRNA expression of ileal TNF-α, IL-10 and IL-12 in the PDCoV-infected piglets. Compared with control, PDCoV up-regulated (P < 0.05) the mRNA expression of key genes related to innate immune and antiviral molecules [toll-like receptor 4 (TLR4), NOD1, NOD2, DDX58, CCL2, STAT2, Mx1, IFN-γ, and protein kinase R (PKR) in the ileum of weaned piglets. Niacin decreased (P < 0.05) the mRNA expression of NOD1, NOD2, STAT2, IFN-γ, and PKR in PDCoV-infected weaned piglets. Moreover, the mRNA expression of IL-6 decreased (P < 0.05) and 2'-5'-oligoadenylate synthetase (OAS), IFN-α, and PKR increased (P < 0.05) in PDCoV-infected IPEC-J2 cells treated with niacin in vitro. Furthermore, niacin decreased (P < 0.05) the elevation of protein expression including inducible NOS (iNOS), nuclear factor-κB (NF-κB p65), inhibitor kappa B (IKKß), histone deacetylase [Sirtuin 1 (SIRT1) and histone deacetylase 7 (HDAC7) and phosphorylation of histone H3 at serine s10 (pH3s10) in the ileum of PDCoV-infected piglets, and increased (P < 0.05) the expression of G protein-coupled receptor (GPR109A). PDCoV disrupted the composition and structure of microflora in the colon of weaned piglets, and reduced the relative abundance of the beneficial bacteria Spirobacterium, but niacin could improve the intestinal microbial flora of the PDCoV-infected piglets associated with increasing the relative abundance of Lactobacillus. Overall, niacin could alleviate diarrhea, intestinal barrier damages, intestinal immune response and colonic microflora disfunction in PDCoV-infected weaned piglets.

FAT10 Combined with Miltefosine Inhibits Mitochondrial Apoptosis and Energy Metabolism in Hypoxia-Induced H9C2 Cells by Regulating the PI3K/AKT Signaling Pathway.

Hypoxia-induced cardiomyocyte apoptosis is the main contributor to heart diseases. Human leukocyte antigen F-associated transcript 10 (FAT10), the small ubiquitin-like protein family subtype involved in apoptosis, is expressed in the heart and exhibits cardioprotective functions. This study explored the impact of FAT10 on hypoxia-induced cardiomyocyte apoptosis and the involved mechanisms. The cardiomyocyte cell line H9C2 was cultivated in hypoxia-inducing conditions (94% N2, 5% CO2, and 1% O2) and the expression of FAT10 in hypoxia-stimulated H9C2 cells was identified. For this, FAT10 overexpression/interference vectors were exposed to transfection into H9C2 cells with/without the PI3K/AKT inhibitor, miltefosine. The results indicated that hypoxia exposure decreased the FAT10 expression, suppressed H9C2 cell growth, disrupted mitochondrial metabolism, and promoted H9C2 cell apoptosis and oxidative stress. However, these impacts were reversed by the FAT10 overexpression. In addition, the inhibition of PI3K/AKT in FAT10-overexpressing cells suppressed cell proliferation, impaired mitochondrial metabolism, and promoted apoptosis and oxidative stress response. The findings demonstrated that FAT10 inhibited mitochondrial apoptosis and energy metabolism in hypoxia-stimulated H9C2 cells through the PI3K/AKT pathway. This finding can be utilized for developing therapeutic targets for treating heart disorders associated with hypoxia-induced apoptosis.

Effects of Niacin on Resistance to Enterotoxigenic Escherichia coli Infection in Weaned Piglets.

Nicotinic acid (NA) has been used to treat different inflammatory disease with positive influence, the mechanisms by which NA exerts its anti-inflammatory effects remain largely undefined. Here we proposed a new hypothesis that NA manipulated endogenous antimicrobial peptides (AMPs) which contributed to the elimination of enterotoxigenic Escherichia coli (ETEC) K88, and thus affects the alleviation of inflammation. Therefore, an experiment in weaned piglets treated with 40 mg NA for 3 days before ETEC K88 challenge was designed to investigate the effects of NA on resistance to enterotoxigenic E. coli infection in weaned piglets. Twenty-four weaned piglets were randomly assigned to 1 of 4 treatments based on weight and sex. The control and NA treated groups were administered 20 mL normal saline or 20 mL NA solution. The K88 challenged and NA treated plus K88 challenged groups were administered 20 mL normal saline or 20 mL nicotinic acid solution once daily for 3 consecutive days. On the fourth day, the K88 and K88 + NA groups were treated with oral administration of 4 × 109 cfu/mL ETEC K88. The results showed that NA alleviated the clinical symptoms of weaned piglets infected with ETEC K88. NA significantly reduced the amount of ETEC K88 in the spleen and liver (P < 0.05). The intestinal morphological damage caused by ETEC K88 infection was alleviated by NA in weaned piglets. In addition, NA significantly alleviated the expression of inflammatory cytokine [Interleukin-6 (IL-6), Interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α)] in the serum and intestines of weaned piglets infected with ETEC K88 (P < 0.05). NA significantly increased the content of secretory IgA (SIgA) and the expression of antimicrobial peptides [porcine ß defensin-2 (pBD2), protegrin1-5 (PG1-5) and PR39] in intestines of weaned pigs. NA increased the diversity of microflora in colonic contents, while NA significantly reduced the relative abundance of Bacteroidetes, Bacteroidales, and Bacteroidia in weaned piglets infected with ETEC K88 (P < 0.05). Furthermore, the NA group significantly reduced the level of HDAC7 in jejunum (P < 0.05) and increased the level of SIRT1 in the colon compared with the Control group. Moreover, NA significantly increased the levels phosphorylation of histone H3 at Ser10 (pH3S10) in ileum and the levels of acetylation of lysine 9 on histone 3 (acH3K9) and acH3K27 in colon (P < 0.05) in weaned piglets infected with ETEC K88 (P < 0.05). In conclusion, NA can alleviate the clinical symptoms, the damage of intestinal morphology, and intestinal inflammation in weaned piglets infected ETEC K88 through enhancing the expression of endogenous AMPs by associating the histone acetylation modification.

Phylogeography and evolutionary dynamics analysis of porcine delta-coronavirus with host expansion to humans.

From 2003 onwards, three pandemics have been caused by coronaviruses: severe acute respiratory syndrome coronavirus (SARS-CoV); middle east respiratory syndrome coronavirus (MERS-CoV); and, most recently, SARS-CoV-2. Notably, all three were transmitted from animals to humans. This would suggest that animals are potential sources of epidemics for humans. The emerging porcine delta-coronavirus was reported to infect children. This is a red flag that marks the ability of PDCoV to break barriers of cross-species transmission to humans. Therefore, we conducted molecular genetic analysis of global clade PDCoV to characterize spatiotemporal patterns of viral diffusion and genetic diversity. PDCoV was classified into three major lineages, according to distribution and phylogenetic analysis of PDCoV. It can be inferred based on the analysis results of the currently known PDCoV strains that PDCoV might originate in Asia. We also selected six special spike amino acid sequences to align and analyze to find seven significant mutation sites. The accumulation of these mutations may enhance dynamic movements, accelerating spike protein membrane fusion events and transmission. Altogether, our study offers a novel insight into the diversification, evolution, and interspecies transmission and origin of PDCoV and emphasizes the need to study the zoonotic potential of the PDCoV and comprehensive surveillance and enhanced biosecurity precautions for PDCoV.

A Neutrophil Extracellular Traps Signature Predicts the Clinical Outcomes and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.

Background: Neutrophil extracellular traps (NETs) play an important role in the occurrence, metastasis and immune escape of cancers. This study aimed to investigate NET-related genes, their clinical prognostic value and their correlation with immunotherapy and anticancer drugs in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Differentially expressed NET-related genes in HNSCC were identified based on multiple public databases. To improve the clinical practicability and avoid overfitting, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were used to construct a prognostic risk model. A nomogram was further used to explore the clinical value of the model. Internal and external validation were conducted to test the model. Furthermore, the immune microenvironment, immunophenoscore (IPS) and sensitivity to anticancer drugs in HNSCC patients with different prognostic risks were explored. Results: Six NET-related genes were screened to construct the risk model. In the training cohort, Kaplan-Meier (K-M) analysis showed that the overall survival (OS) of low-risk HNSCC patients was significantly better than that of high-risk HNSCC patients (p < 0.001). The nomogram also showed a promising prognostic value with a better C-index (0.726 vs 0.640) and area under the curve (AUC) (0.743 vs 0.706 at 3 years, 0.743 vs 0.645 at 5 years) than those in previous studies. Calibration plots and decision curve analysis (DCA) also showed the satisfactory predictive capacity of the nomogram. Internal and external validation further strengthened the credibility of the clinical prognostic model. The level of tumor mutational burden (TMB) in the high-risk group was significantly higher than that in the low-risk group (p = 0.017), and the TMB was positively correlated with the risk score (R = 0.11; p = 0.019). Moreover, the difference in immune infiltration was significant in HNSCC patients with different risks (p < 0.05). Furthermore, the IPS analysis indicated that anti-PD-1 (p < 0.001), anti-CTLA4 (p < 0.001) or combining immunotherapies (p < 0.001) were more beneficial for low-risk HNSCC patients. The response to anticancer drugs was also closely correlated with the expression of NET-related genes (p < 0.001). Conclusion: This study identified a novel prognostic model that might be beneficial to develop personalized treatment for HNSCC patients.

Evolution of the Interfacial Layer and Its Impact on Electric-Field-Cycling Behaviors in Ferroelectric Hf1-xZrxO2.

Doped HfO2 thin films, which exhibit robust ferroelectricity even with aggressive thickness scaling, could potentially enable ultralow-power logic and memory devices. The ferroelectric properties of such materials are strongly intertwined with the voltage-cycling-induced electrical and structural changes, leading to wake-up and fatigue effects. Such field-cycling-dependent behaviors are crucial to evaluate the reliability of HfO2-based functional devices; however, its genuine nature remains elusive. Herein, we demonstrate the coupling mechanism between the dynamic change of the interfacial layer and wake-up/fatigue phenomena in ferroelectric Hf1-xZrxO2 (HZO) thin films. Comprehensive atomic-resolution microscopy studies have revealed that the interfacial layer between the HZO and neighboring nonoxide electrode experienced a thickness/composition evolution during electrical cycling. Two theoretical models associated with the depolarization field are adopted, giving consistent results with the thickening of the interfacial layer during electrical cycling. Furthermore, we found that the electrical properties of the HZO devices can be manipulated by controlling the interface properties, e.g., through the choice of electrode match and hybrid cycling process. Our results unambiguously reveal the relationship between the interfacial layer and field-cycling behaviors in HZO, which would further permit the reliability improvement in HZO-based ferroelectric devices through interface engineering.