Compositionally complex doping for zero-strain zero-cobalt layered cathodes.

The high volatility of the price of cobalt and the geopolitical limitations of cobalt mining have made the elimination of Co a pressing need for the automotive industry1. Owing to their high energy density and low-cost advantages, high-Ni and low-Co or Co-free (zero-Co) layered cathodes have become the most promising cathodes for next-generation lithium-ion batteries2,3. However, current high-Ni cathode materials, without exception, suffer severely from their intrinsic thermal and chemo-mechanical instabilities and insufficient cycle life. Here, by using a new compositionally complex (high-entropy) doping strategy, we successfully fabricate a high-Ni, zero-Co layered cathode that has extremely high thermal and cycling stability. Combining X-ray diffraction, transmission electron microscopy and nanotomography, we find that the cathode exhibits nearly zero volumetric change over a wide electrochemical window, resulting in greatly reduced lattice defects and local strain-induced cracks. In-situ heating experiments reveal that the thermal stability of the new cathode is significantly improved, reaching the level of the ultra-stable NMC-532. Owing to the considerably increased thermal stability and the zero volumetric change, it exhibits greatly improved capacity retention. This work, by resolving the long-standing safety and stability concerns for high-Ni, zero-Co cathode materials, offers a commercially viable cathode for safe, long-life lithium-ion batteries and a universal strategy for suppressing strain and phase transformation in intercalation electrodes.

Japanese encephalitis virus NS1 and NS1' protein disrupts the blood-brain barrier through macrophage migration inhibitory factor-mediated autophagy.

Flaviviruses in the Japanese encephalitis virus (JEV) serogroup, such as JEV, West Nile virus, and St. Louis encephalitis virus, can cause severe neurological diseases. The nonstructural protein 1 (NS1) is a multifunctional protein of flavivirus that can be secreted by infected cells and circulate in the host bloodstream. NS1' is an additional form of NS1 protein with 52 amino acids extension at its carboxy-terminal and is produced exclusively by flaviviruses in the JEV serogroup. In this study, we demonstrated that the secreted form of both NS1 and NS1' can disrupt the blood-brain barrier (BBB) of mice, with NS1' exhibiting a stronger effect. Using the in vitro BBB model, we found that treatment of soluble recombinant JEV NS1 or NS1' protein increases the permeability of human brain microvascular endothelial cells (hBMECs) and leads to the degradation of tight junction proteins through the autophagy-lysosomal pathway. Consistently, NS1' protein exhibited a more pronounced effect compared to NS1 in these cellular processes. Further research revealed that the increased expression of macrophage migration inhibitory factor (MIF) is responsible for triggering autophagy after NS1 or NS1' treatment in hBMECs. In addition, TLR4 and NF-κB signaling was found to be involved in the activation of MIF transcription. Moreover, administering the MIF inhibitor has been shown to decrease viral loads and mitigate inflammation in the brains of mice infected with JEV. This research offers a novel perspective on the pathogenesis of JEV. In addition, the stronger effect of NS1' on disrupting the BBB compared to NS1 enhances our understanding of the mechanism by which flaviviruses in the JEV serogroup exhibit neurotropism.IMPORTANCEJapanese encephalitis (JE) is a significant viral encephalitis worldwide, caused by the JE virus (JEV). In some patients, the virus cannot be cleared in time, leading to the breach of the blood-brain barrier (BBB) and invasion of the central nervous system. This invasion may result in cognitive impairment, behavioral disturbances, and even death in both humans and animals. However, the mechanism by which JEV crosses the BBB remains unclear. Previous studies have shown that the flavivirus NS1 protein plays an important role in causing endothelial dysfunction. The NS1' protein is an elongated form of NS1 protein that is particularly produced by flaviviruses in the JEV serogroup. This study revealed that both the secreted NS1 and NS1' of JEV can disrupt the BBB by breaking down tight junction proteins through the autophagy-lysosomal pathway, and NS1' is found to have a stronger effect compared to NS1 in this process. In addition, JEV NS1 and NS1' can stimulate the expression of MIF, which triggers autophagy via the ERK signaling pathway, leading to damage to BBB. Our findings reveal a new function of JEV NS1 and NS1' in the disruption of BBB, thereby providing the potential therapeutic target for JE.

Single-nucleus RNA sequencing and lipidomics reveal characteristics of transcriptional and lipid composition in porcine longissimus dorsi muscle.

BACKGROUND: Global per capita meat consumption continues to rise, especially pork. Meat quality is influenced by the content of intramuscular fat (IMF) as a key factor. The longissimus dorsi muscle of Dahe pigs (DHM, IMF: 7.98% ± 1.96%) and Dahe black pigs (DHBM, IMF: 3.30% ± 0.64%) was studied to explore cellular heterogeneity and differentially expressed genes (DEGs) associated with IMF deposition using single-nucleus RNA sequencing (snRNA-seq). The lipid composition was then analyzed using non-targeted lipidomics. RESULTS: A total of seven cell subpopulations were identified, including myocytes, fibroblast/fibro/adipogenic progenitors (FAPs), satellite cells, endothelial cells, macrophages, pericytes, and adipocytes. Among them, FAPs and adipocytes were more focused because they could be associated with lipid deposition. 1623 DEGs in the FAPs subpopulation of DHBM were up-regulated compared with DHM, while 1535 were down-regulated. These DEGs enriched in the glycolysis/gluconeogenesis pathway. 109 DEGs were up-regulated and 806 were down-regulated in the adipocyte subpopulation of DHBM compared with DHM, which were mainly enriched in the PPAR signaling pathway and fatty acid (FA) biosynthesis. The expression level of PPARG, ABP4, LEP, and ACSL1 genes in DHM was higher than that in DHBM. Lipidomics reveals porcine lipid composition characteristics of muscle tissue. A total of 41 lipid classes and 2699 lipid species were identified in DHM and DHBM groups. The top ten relative peak areas of lipid classes in DHM and DHBM were triglyceride (TG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), diglyceride (DG), cardiolipin (CL), ceramides (Cer), Simple Glc series (Hex1Cer), sphingomyelin (phSM), and phosphatidylinositol (PI). The relative peak areas of 35 lipid species in DHM were lower than DHBM, and 28 lipid species that were higher. There was a significant increase in the TG fatty acyl chains C6:0, C17:0, and C11:4, and a significant decrease in C16:0, C18:1, C18:2, and C22:4 in DHBM (p < 0.05). CONCLUSIONS: C16:0 FA may downregulate the expression level of PPARG gene, which leads to the downregulation of fat metabolism-related genes such as ACSL, PLIN2, and FABP4 in DHBM compared with DHM. This may be the reason that the lipid deposition ability of Dahe pigs is stronger than that of Dahe black pigs, which need further investigation.

The neutrophil-to-lymphocyte ratio is associated with all-cause and cardiovascular mortality among individuals with hypertension.

BACKGROUND: Identifying reliable prognostic markers is crucial for the effective management of hypertension. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential inflammatory marker linked to cardiovascular outcomes. This study aims to investigate the association of NLR with all-cause and cardiovascular mortality among patients with hypertension. METHODS: This study analyzed data from 3067 hypertensive adults in the National Health and Nutritional Examination Surveys (NHANES) from 2009 to 2014. Mortality details were obtained from the National Death Index (NDI). Restricted cubic spline (RCS) was deployed to visualize the association of the NLR with mortality risk. Weighted Cox proportional hazards models were employed to assess the independent association of NLR with mortality risk. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to access the predictive ability of NLR for survival. Mediation analysis was used to explore the indirect impact of NLR on mortality mediated through eGFR. RESULTS: Over a median 92.0-months follow-up, 538 deaths occurred, including 114 cardiovascular deaths. RCS analysis revealed a positive association between NLR and both all-cause and cardiovascular mortality. Participants were stratified into higher (> 3.5) and lower (≤ 3.5) NLR groups. Weighted Cox proportional hazards models demonstrated that individuals with higher NLR had a significantly increased risk of all-cause (HR 1.96, 95% confidence interval (CI) 1.52-2.52, p < 0.0001) and cardiovascular mortality (HR 2.33, 95% CI 1.54-3.51, p < 0.0001). Stratified and interaction analysis confirmed the stability of the core results. Notably, eGFR partially mediated the association between NLR and both all-cause and cardiovascular mortality by a 5.4% and 4.7% proportion, respectively. Additionally, the areas under the curve (AUC) of the 3-, 5- and 10- year survival was 0.68, 0.65 and 0.64 for all-cause mortality and 0.68, 0.70 and 0.69 for cardiovascular mortality, respectively. CONCLUSION: Elevated NLR independently confers an increased risk for both all-cause and cardiovascular mortality in individuals with hypertension.

Single-cell insights: pioneering an integrated atlas of chromatin accessibility and transcriptomic landscapes in diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) poses a growing health threat, elevating heart failure risk in diabetic individuals. Understanding DCM is crucial, with fibroblasts and endothelial cells playing pivotal roles in driving myocardial fibrosis and contributing to cardiac dysfunction. Advances in Multimodal single-cell profiling, such as scRNA-seq and scATAC-seq, provide deeper insights into DCM's unique cell states and molecular landscape for targeted therapeutic interventions. METHODS: Single-cell RNA and ATAC data from 10x Multiome libraries were processed using Cell Ranger ARC v2.0.1. Gene expression and ATAC data underwent Seurat and Signac filtration. Differential gene expression and accessible chromatin regions were identified. Transcription factor activity was estimated with chromVAR, and Cis-coaccessibility networks were calculated using Cicero. Coaccessibility connections were compared to the GeneHancer database. Gene Ontology analysis, biological process scoring, cell-cell communication analysis, and gene-motif correlation was performed to reveal intricate molecular changes. Immunofluorescent staining utilized various antibodies on paraffin-embedded tissues to verify the findings. RESULTS: This study integrated scRNA-seq and scATAC-seq data obtained from hearts of WT and DCM mice, elucidating molecular changes at the single-cell level throughout the diabetic cardiomyopathy progression. Robust and accurate clustering analysis of the integrated data revealed altered cell proportions, showcasing decreased endothelial cells and macrophages, coupled with increased fibroblasts and myocardial cells in the DCM group, indicating enhanced fibrosis and endothelial damage. Chromatin accessibility analysis unveiled unique patterns in cell types, with heightened transcriptional activity in myocardial cells. Subpopulation analysis highlighted distinct changes in cardiomyocytes and fibroblasts, emphasizing pathways related to fatty acid metabolism and cardiac contraction. Fibroblast-centered communication analysis identified interactions with endothelial cells, implicating VEGF receptors. Endothelial cell subpopulations exhibited altered gene expressions, emphasizing contraction and growth-related pathways. Candidate regulators, including Tcf21, Arnt, Stat5a, and Stat5b, were identified, suggesting their pivotal roles in DCM development. Immunofluorescence staining validated marker genes of cell subpopulations, confirming PDK4, PPARγ and Tpm1 as markers for metabolic pattern-altered cardiomyocytes, activated fibroblasts and endothelial cells with compromised proliferation. CONCLUSION: Our integrated scRNA-seq and scATAC-seq analysis unveils intricate cell states and molecular alterations in diabetic cardiomyopathy. Identified cell type-specific changes, transcription factors, and marker genes offer valuable insights. The study sheds light on potential therapeutic targets for DCM.

Digitization method for a photonic analog-to-digital converter with phase-shifted optical quantization.

This Letter proposes a novel, to the best of our knowledge, matrix digitization method for a photonic analog-to-digital converter with phase-shifted optical quantization (PSOQ-ADC). This method overcomes the issues of excessive bit width of the output code and the generation of invalid codes encountered by the traditional direct digitization method. A PSOQ-ADC was fabricated on a lithium niobate on insulator (LNOI) platform, and an experimental platform was built. The results show that RF signals at 1/2/5 GHz, which were sampled by a 50GS/s optical pulse train, were digitized successfully with the matrix digitization method, producing 5-bit codes without invalid codes. In comparison, the direct digitization method yields 10-bit codes, and as the optical signal-to-noise ratio (OSNR) decreases, the ratio of invalid codes increases in the direct digitization method; even with Hamming distance correction, its effective number of bits (ENOB) remains smaller than that of the matrix digitization.

Differentially Expressed Proteins in the Serum of Elderly Patients Who Experienced Perioperative Neurocognitive Disorders Following Transurethral Resection of the Prostate.

OBJECTIVE: Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND. METHODS: A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression. RESULTS: Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase. CONCLUSION: The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND. CLINICAL TRIAL REGISTRATION: Registered (ChiCTR2000028836). Date (20190306).

Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs.

BACKGROUND: As the largest substantive organ of animals, the liver plays an essential role in the physiological processes of digestive metabolism and immune defense. However, the cellular composition of the pig liver remains poorly understood. This investigation used single-nucleus RNA sequencing technology to identify cell types from liver tissues of pigs, providing a theoretical basis for further investigating liver cell types in pigs. RESULTS: The analysis revealed 13 cells clusters which were further identified 7 cell types including endothelial cells, T cells, hepatocytes, Kupffer cells, stellate cells, B cells, and cholangiocytes. The dominant cell types were endothelial cells, T cells and hepatocytes in the liver tissue of Dahe pigs and Dahe black pigs, which accounts for about 85.76% and 82.74%, respectively. The number of endothelial cells was higher in the liver tissue of Dahe pigs compared to Dahe black pigs, while the opposite tendency was observed for T cells. Moreover, functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic endothelial cells were significantly enriched in the protein processing in endoplasmic reticulum, MAPK signaling pathway, and FoxO signaling pathway. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic T cells were significantly enriched in the thyroid hormone signaling pathway, B cell receptor signaling pathway, and focal adhesion. Functional enrichment analysis demonstrated that the differentially expressed genes in pig hepatic hepatocytes were significantly enriched in the metabolic pathways. CONCLUSIONS: In summary, this study provides a comprehensive cell atlas of porcine hepatic tissue. The number, gene expression level and functional characteristics of each cell type in pig liver tissue varied between breeds.

H3K27me3 of Rnf19a promotes neuroinflammatory response during Japanese encephalitis virus infection.

Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that infection with Japanese encephalitis virus (JEV) leads to an increase in H3K27me3 in BV2 microglial cell line, primary mouse microglia and mouse brain. Inhibition of H3K27me3 modification through EZH2 knockdown and treatment with EZH2 inhibitor significantly reduces the production of pro-inflammatory cytokines during JEV infection, which suggests that H3K27me3 modification plays a crucial role in the neuroinflammatory response caused by JEV infection. The chromatin immunoprecipitation-sequencing (ChIP-sequencing) assay revealed an increase in H3K27me3 modification of E3 ubiquitin ligases Rnf19a following JEV infection, which leads to downregulation of Rnf19a expression. Furthermore, the results showed that Rnf19a negatively regulates the neuroinflammatory response induced by JEV. This is achieved through the degradation of RIG-I by mediating its ubiquitination. In conclusion, our findings reveal a novel mechanism by which JEV triggers extensive neuroinflammation from an epigenetic perspective.

KIN17 promotes cell migration and invasion through stimulating the TGF-ß/Smad2 pathway in hepatocellular carcinoma.

KIN17 DNA and RNA binding protein (Kin17) is involved in the regulation of tumorigenesis of diverse human cancers. However, its role in the cancer progression and metastasis in hepatocellular carcinoma (HCC) remains largely unknown. Bioinformatics and immunohistochemistry staining were used to investigate the expression pattern of KIN17 and its prognostic value in HCC patients. The transwell, wound-healing assay was employed to determine the effects of KIN17 on migration and invasion of HCC cells in vitro. The tail veins model was employed to determine the effects of KIN17 on lung metastasis in vivo. The biological mechanisms involved in cell migration and invasion regulated by KIN17 were determined with Western blot analysis method. KIN17 expression was significantly increased in HCC tissues compared with adjacent normal tissues, with particularly higher in portal vein tumor thrombus and intrahepatic metastasis tissues. Patients with higher KIN17 expression experienced poor overall and disease free survival. KIN17 knockdown in HuH7 and HepG2 cells significantly reduced cell migration and invasion abilities, whereas its overexpression promoted migration and invasion in MHCC-97L and HepG2 cells in vitro and in vivo. In HuH7 and HepG2 cells, KIN17 knockdown inhibited the TGF-ß/Smad2 pathway. In contrast, KIN17 overexpression stimulated TGF-ß/Smad2 pathway in MHCC-97L and HepG2 cells, along with the genes involved in the epithelial-mesenchymal transition. These findings suggest that KIN17 promotes migration and invasion in HCC cells by stimulating the TGF-ß/Smad2 pathway. KIN17 could be a promising prognostic biomarker, as well as a potential therapeutic target in HCC.

Experimental demonstration of a dynamic range enhancement method for a phase-shifted PADC by using a modulo operation.

We propose what we believe to be a novel approach to enhance the dynamic range of a photonic analog-to-digital converter (PADC) without the need of additional custom-designed circuits or components. The method utilizes the unique characteristic of our previously reported multimode interference (MMI) coupler-based optical quantizer that exploits the periodicity of the optical phase to realize a modulo operation. Experiments were carried out to verify the effectiveness of the proposed method on our phase-shifted optical quantization ADC (PSOQ-ADC) chip. Experimental results show that our proposed method enhance the dynamic range from [-V π, V π] to [-2V π, 2V π] and has the potential to be further extended. Additionally, we successfully reconstructed radio frequency (RF) signals at a sampling rate of 30 Gs/s. Our work provides a promising solution for achieving a high dynamic range in on-chip PSOQ-ADC.

"On-Off" Control for On-Demand H2 Release upon Dimethylamineborane Hydrolysis over Ru0.8Ni0.2/MoS2 Nanohybrids.

In spite of the fact that remarkable developments are achieved in the design and development of novel nanocatalysts for H2 release upon dimethylamineborane hydrolysis, the development of an "on-off" switch for demand-based H2 evolution upon dimethylamineborane hydrolysis is still a matter of supreme importance, however. Herein, we synthesized a string of MoS2 nanosheet-supported RuNi bimetallic nanohybrids (RuxNi1-x/MoS2), by fixation of RuNi nanoparticles at the MoS2 surface, for the H2 evolution upon the hydrolysis of dimethylamineborane at 30 °C. For safely and effectively generating, transporting, and storing H2 gas, the selective "on-off" switch for on-demand H2 evolution upon dimethylamineborane hydrolysis over the Ru0.8Ni0.2/MoS2 nanohybrid has been successfully realized by the Zn2+/EDTA-2Na system. In particular, the H2 evolution is totally switched off by adding Zn(NO3)2. It seems that Zn2+ ions are attached and anchored at the Ru0.8Ni0.2/MoS2 surface, inhibiting their surface-active sites, leading to the termination of H2 evolution. Then, the H2 generation is subsequently reactivated by adding the EDTA-2Na solution because of its excellent coordination ability with Zn2+ ions. This study not only offers a new and efficient RuNi nanocatalyst for dimethylamineborane hydrolysis but also proposes a new method for the demand-based H2 production.

Prevalence and Trends of Thyroid Disease Among Adults, 1999-2018.

BACKGROUND: Thyroid disease is a prominent endocrine disorder, yet the clinical epidemiology of this condition remains unclear. This study aims to describe the recent trends in the prevalence of thyroid disease in US adults from 1999-2018. METHODS: This cross-sectional study used nationally representative data collected through the National Health and Nutrition Examination Survey (NHANES) from January 1, 1999 to December 31, 2018. Patients with thyroid disease were defined as patients who reported having a thyroid disease and were on thyroid-related treatment. Age-standardized prevalence of thyroid disease was calculated within 4-year survey periods (1999-2002, 2003-2006, 2007-2010, 2011-2014, and 2015-2018). RESULTS: During the NHANES 1999-2018, a total of 57 540 participants were examined. The age-standardized prevalence of thyroid disease was 5.05% (95% CI, 4.55%-5.60%) from 2015-2018, signifying a significant increase from the 1999-2002 period (P <.0002). However, prevalent thyroid disease remained steady between 2003 and 2014. The highest prevalence of thyroid disease was observed in non-Hispanic Whites (8.1%; 95% CI, 7.3%-9.0%), individuals aged ≥60 years (15.4%; 95% CI, 13.3%-17.8%), and tended to be higher in women (7.6%; 95% CI, 6.8%-8.5%). Multiple regression analysis revealed that age, women sex, non-Hispanic White and Mexican American, body mass index, higher education and incomes were independently associated with increased risks of thyroid disease. CONCLUSION: The age-standardized prevalence of thyroid disease among US adults increased from 1999-2003, remained stable between 2003 and 2014, and then saw an increase from 2014-2018, with the highest rate observed among elders, women, and non-Hispanic Whites.

Improving Mitochondrial Function in Skeletal Muscle Contributes to the Amelioration of Insulin Resistance by Nicotinamide Riboside.

High-fat diet (HFD)-induced insulin resistance (IR) in skeletal muscle is often accompanied by mitochondrial dysfunction and oxidative stress. Boosting nicotinamide adenine dinucleotide (NAD) using nicotinamide riboside (NR) can effectively decrease oxidative stress and increase mitochondrial function. However, whether NR can ameliorate IR in skeletal muscle is still inconclusive. We fed male C57BL/6J mice with an HFD (60% fat) ± 400 mg/kg·bw NR for 24 weeks. C2C12 myotube cells were treated with 0.25 mM palmitic acid (PA) ± 0.5 mM NR for 24 h. Indicators for IR and mitochondrial dysfunction were analyzed. NR treatment alleviated IR in HFD-fed mice with regard to improved glucose tolerance and a remarkable decrease in the levels of fasting blood glucose, fasting insulin and HOMA-IR index. NR-treated HFD-fed mice also showed improved metabolic status regarding a significant reduction in body weight and lipid contents in serum and the liver. NR activated AMPK in the skeletal muscle of HFD-fed mice and PA-treated C2C12 myotube cells and upregulated the expression of mitochondria-related transcriptional factors and coactivators, thereby improving mitochondrial function and alleviating oxidative stress. Upon inhibiting AMPK using Compound C, NR lost its ability in enhancing mitochondrial function and protection against IR induced by PA. In summary, improving mitochondrial function through the activation of AMPK pathway in skeletal muscle may play an important role in the amelioration of IR using NR.

Flower-like Gold Nanoparticles for In Situ Tailoring Luminescent Molecules for Synergistic Enhanced Chemiluminescence.

In recent years, gold nanoparticles (AuNPs) have attracted much attention due to their ease of surface modification, excellent biocompatibility, and extraordinary optoelectronic and catalytic activities. Herein, based on a AuNP-catalyzed reaction, a strategy for tailoring luminescent molecules in situ is proposed to trigger an ultrastrong chemiluminescence (CL). In the strategy, flower-like AuNPs are prepared using CL molecular probes (Probe-OH for NaClO/ONOO-) via one-pot synthesis and subsequently act as a tailor for Probe-OH to generate novel CL molecules, allowing a synergistic CL enhancement about 4 times that of initial Probe-OH. Furthermore, by modification with poly(vinylpyrrolidone) (PVP) on the surface, the CL signals (only for NaClO) are amplified by 100 times based on an intermolecular chemically initiated electron exchange luminescence (CIEEL) mechanism. Given the improved sensitivity and selectivity over Probe-OH, the thus-formed CIEEL nanoplatform (PVP-Au) is successfully developed for detecting NaClO in a wide range of 2.5-100 µM, and the detection limit is 10.68 nM. This work provides unprecedented perspectives for expanding this facile and effective strategy for CL amplification based on AuNP catalysis.

Serum potassium level, variability and in-hospital mortality in acute myocardial infarction.

OBJECTIVE: Clinical guidelines recommend an optimal serum potassium concentration between 4.0 and 5.0 mmol/L in patients with acute myocardial infarction (AMI), which was based on lower-quality evidence from more than 20 years ago. Therefore, it is essential to re-evaluate the range of optimal potassium levels in patients with AMI in intensive care unit (ICU). METHODS: This was a retrospective study based on Philips eICU Collaborative Research Database, which covered 9776 patients with AMI between 2014 and 2015. All patients had more than or equal to 2 serum potassium measurements and were categorized by the mean serum potassium level (<3.5, 3.5-4.5, 4.5-5.5, ≥5.5 mmol/L) and potassium variability (1st, 2nd, and ≥3rd standard deviation (SD)). Binary logistic regression was used to determine the association between mean potassium levels, variability and in-hospital mortality in AMI. RESULTS: Of all 9776 AMI patients in ICU, 8731 (89.3%) patients were included. A total of 69847 potassium measurements were performed in these patients. There was a J-shaped relationship between mean serum potassium level and in-hospital mortality. The lowest mortality (mortality rate, 7.2%; 95% CI, 6.57%-7.76%) was observed in patients with mean potassium level between 3.5 and 4.5 mmol/L and a low potassium variability within the 1st SD. Logistic regression showed that the risk of in-hospital mortality is highest when the mean potassium level ≥5.5 mmol/L (57.6%; 95% Cl, 45.02%-70.24%; multivariable adjusted OR, 14.8; 95% CI, 8.4-26.2) compared to the reference group of 3.5-4.5 mmol/L and potassium variability within the 3rd SD (16.5%; 95% Cl, 15.19%-17.88%; multivariable adjusted OR, 3.3; 95% CI, 2.7-4.1) compared to 1st SD. Several sensitivity analyses confirmed these results. CONCLUSION: Among AMI patients in ICU, the minimum risk of in-hospital mortality was observed in those with mean potassium levels between 3.5 and 4.5 mmol/L or a minimal potassium variability compared to those who had higher or lower values.

The Japanese Encephalitis Virus NS1' Protein Inhibits Type I IFN Production by Targeting MAVS.

Japanese encephalitis virus (JEV) is a mosquito-borne Flavivirus that causes severe neurologic disease in humans. NS1' is a NS1-related protein only reported in the Japanese encephalitis serogroup members of Flavivirus It is produced through programmed -1 ribosomal frameshift in NS2A. Our previous study demonstrated that JEV NS1' could antagonize type I IFN (IFN-I) production, but the mechanism is still unclear. In the current study, we found that JEV NS1' inhibits the expression of MAVS, and knockdown of MAVS hampers inhibition of IFN-ß induction by NS1', suggesting that JEV NS1' inhibits IFN-I production by targeting MAVS. This finding is further supported by the result of the in vivo assay that showed the similar mortality caused by NS1'-deficient virus and its wild type virus in MAVS-deficient mice. Based on our previous sequencing results of noncoding RNA in JEV-infected cells, microRNA-22 (miR-22) was identified to be a key regulator for MAVS expression during JEV infection. Furthermore, we demonstrated that JEV NS1' could induce the expression of miR-22 by increasing the binding of transcriptional factors, CREB and c-Rel, to the promoter elements of miR-22. Taken together, our results reveal a novel mechanism by which JEV NS1' antagonizes host MAVS by regulating miR-22, thereby inhibiting the IFN-I production and facilitating viral replication.

Comparison of New Glucose-Lowering Drugs on the Risk of Pancreatitis in Type 2 Diabetes: A Network Meta-Analysis.

OBJECTIVE: To explore whether new glucose-lowering drugs increase the risk of pancreatitis in individuals with type 2 diabetes. This present network meta-analysis aimed to investigate the risk of pancreatitis associated with the use of glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched. The literature was published from the date of their inception to July 21, 2021, including placebo-controlled or head-to-head trials of 2 new glucose-lowering drugs. The relative ratio (RR) and 95% confidence interval (CI) were used to assess the risk of GLP-1 agonists and DPP-4 inhibitors for pancreatitis or pancreatic cancer among patients with type 2 diabetes. RESULTS: Seventeen studies were identified, covered 102 257 participants. The pooled results showed a neutral relationship between GLP-1 agonists and pancreatitis (overall RR, 0.96; 95% CI, 0.31-3.00) or pancreatic cancer (overall RR, 1.10; 95% CI, 0.31-4.10) compared with placebo. Meanwhile, DPP-4 inhibitors were not associated with the increased risk of pancreatitis (overall RR, 1.60; 95% CI, 0.25-11.00) or pancreatic cancer (overall RR, 0.79; 95% CI, 0.26-2.40). Among them, lixisenatide and saxagliptin may be the safest drugs compared with other drugs according to the ranking of probability. Sensitivity and subgroup analysis confirmed the stability of the core results. CONCLUSION: The most obvious finding of this study is that GLP-1 agonists and DPP-4 inhibitors are safe with respect to the risk of pancreatitis and pancreatic cancer compared with placebo. This conclusion may provide useful evidence for correlated clinical researches.

The global burden of periodontal diseases in 204 countries and territories from 1990 to 2019.

AIMS: The aim of this study was to report the incidence, prevalence, and disability-adjusted life-years (DALYs) of periodontal diseases during the period 1990-2019. METHODS: Data on periodontal diseases were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. The estimated annual percentage changes were calculated to evaluate the changing trend of age-standardized incidence, prevalence, and DALY rates related to periodontal diseases. RESULTS: Globally, there were 1,087,367,744.0 cases with 91,518,820.6 new incidence and 7,090,390.3 DALYs of periodontal diseases in 2019, almost twice as many as in 1990. Moreover, the pace of increase in age-standardized incidence, age-standardized prevalence, and age-standardized DALY rates had accelerated during the 1990-2019 time period, with EAPC of 0.29 (95% CI, 0.22 to 0.35), 0.34 (95% CI, 0.26 to 0.43), and 0.35 (95% CI, 0.27 to 0.44) separately. The corresponding age-standardized percentage changes were more pronounced in females, Southeast Asia, and low-middle SDI regions. Western Sub-Saharan Africa was the high-risk area of standardized periodontal diseases burden in 2019, among which Gambia was the country with the heaviest burden. CONCLUSION: The globally incidence, prevalence, and DALYs of periodontal diseases are substantially increased from 1990 to 2019, which highlights the importance and urgency of periodontal care.

Traditional Chinese Nursing Using Fennel With Coarse Salt for Ironing and Umbilical Moxibustion for Epigastric Pain With Spleen-stomach Vacuity Cold.

Context: Spleen-stomach vacuity cold is the primary TCM pattern for epigastric pain, accounting for 75% of the patients. According to the TCM theory of treating both the tip and the root, epigastric pain requires the caregiver to dissipate cold and relieve pain, the treatments for the tip, which warm and supplement the spleen and stomach, the treatments for the root. Objective: This study aimed to explore effectiveness of traditional Chinese nursing care using fennel mixed with coarse salt for ironing,with umbilical moxibustion, for epigastric pain, with a pattern of spleen-stomach vacuity cold. Design: The research team designed a randomized control trial (RCT). Setting: The study was conducted at Ruikang Affiliated Hospital of Guangxi University of Chinese Medicine in the capital city of the Guangxi Zhuang autonomous region in the People's Republic of China. Participants: Participants were 96 patients who had been admitted to the hospital between October and November 2020 with epigastric pain resulting from the TCM spleen-stomach vacuity cold pattern, equivalent to chronic atrophic gastritis in Western medicine. Intervention: The research team randomly divided participants into an intervention group (n = 48) and a control group (n = 48) using a random digits table. The intervention group received fennel mixed with coarse salt for ironing, combined with umbilical moxibustion, whereas the control group received routine care. Outcome Measures: The study's instruments included the Traditional Chinese Medicine (TCM) Syndrome Score Scale (TCMSSS), Medical Outcome Study (MOS) Short Form 36 (SF-36), and Satisfaction with TCM Nursing Program (STCMNP). Data were collected and analyzed through descriptive statistics a Chi-square test and independent t test. A significance level of P < .05 was accepted for all statistical analyses. Results: The intervention group had mean scores that indicated significantly higher decreases in epigastric pain, and increases in quality of life and level of satisfaction with the traditional Chinese nursing care than the control group did (P < .05). Conclusions: The traditional Chinese nursing care was able to improve epigastric pain, enhance quality of life, and increase satisfaction with the traditional Chinese nursing care.