A multifunctional smart field-programmable radio frequency surface.

Antennas that can operate across multiple communication standards have remained a challenge. To address these limitations, we propose a Field-Programmable Radio Frequency Surface (FPRFS), which is based on manipulating current flow on its surface to achieve desirable RF characteristics. In this work, we demonstrate that substantial enhancements in radiation efficiency can be achieved while preserving the high reconfigurability of antenna structures implemented on the FPRFS. This is accomplished by utilizing an asymmetric excitation, directing the excitation to the low-loss contiguous surface, and dynamically manipulating the imaged return current on a segmented ground plane by switches. This important insight allows for adaptable antenna performance that weakly depends on the number of RF switches or their loss. We experimentally validate that FPRFS antennas can achieve efficiencies comparable to traditionally implemented antenna counterparts. This permits the FPRFS to be effectively utilized as a productive antenna and impedance-matching network with real-time reconfigurability.

Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.

Antimicrobial Resistance and Genomic Characteristics of Escherichia coli Strains Isolated from the Poultry Industry in Henan Province, China.

Escherichia coli (E. coli) is an important foodborne pathogen and a biomarker for monitoring antimicrobial resistance. Investigating the prevalence of E. coli in the poultry industry holds great importance, particularly in Henan province, a major poultry-producing region in China. Here, we investigated the antimicrobial resistance (AMR) phenotypes of E. coli strains obtained from the poultry industry in Henan, China. A total of 344 E. coli strains were isolated from 638 samples collected from seven farms, three slaughterhouses, and ten terminal markets. Approximately 96.4%, 81.7%, and 52.5% of the isolates from the farms, slaughterhouses, and terminal markets exhibited multidrug resistance. Whole-genome sequencing was performed on 169 strains to reveal their genomic characteristics. The sequence type (ST) analysis revealed that ST10 and ST156 were the most frequent types within the poultry supply chain, whereas ST10 and ST162 were commonly found across the farms, slaughterhouses, and terminal markets. Fourteen ST10 E. coli strains belonged to phylogenetic group A, while fifteen ST165 and six ST162 E. coli strains belonged to phylogenetic group B1. In addition, several antimicrobial resistance genes and virulence factor genes were identified. The blaNDM-5 gene mediated carbapenem resistance in two E. coli strains, while mcr-1-mediated colistin resistance was detected in nine E. coli strains. Phylogenetic group A exhibited fewer virulence genes compared to other groups of E. coli. Plasmid replicons, such as IncFIB (AP001918), IncX1, IncFIC (FII), and IncFII (pHN7A8), were frequently observed. These findings provide valuable insights into the current AMR profiles of E. coli strains isolated from the poultry industry in Central China and highlight the need to implement good manufacturing practices and reduce antibiotic usage to mitigate potential risks associated with E. coli.

Application of Recombinant Lactic Acid Bacteria (LAB) Live Vector Oral Vaccine in the Prevention of F4+ Enterotoxigenic Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in piglets. The current primary approach for ETEC prevention and control relies on antibiotics, as few effective vaccines are available. Consequently, an urgent clinical demand exists for developing an effective vaccine to combat this disease. Here, we utilized food-grade Lactococcus lactis NZ3900 and expression plasmid pNZ8149 as live vectors, together with the secreted expression peptide Usp45 and the cell wall non-covalent linking motif LysM, to effectively present the mutant LTA subunit, the LTB subunit of heat-labile enterotoxin, and the FaeG of F4 pilus on the surface of recombinant lactic acid bacteria (LAB). Combining three recombinant LAB as a live vector oral vaccine, we assessed its efficacy in preventing F4+ ETEC infection. The results demonstrate that oral immunization conferred effective protection against F4+ ETEC infection in mice and piglets lacking maternal antibodies during weaning. Sow immunization during late pregnancy generated significantly elevated antibodies in colostrum, which protected piglets against F4+ ETEC infection during lactation. Moreover, booster immunization on piglets during lactation significantly enhanced their resistance to F4+ ETEC infection during the weaning stage. This study highlights the efficacy of an oral LAB vaccine in preventing F4+ ETEC infection in piglets by combining the sow immunization and booster immunization of piglets, providing a promising vaccination strategy for future prevention and control of ETEC-induced diarrhea in piglets.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study.

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Occurrence, distribution, and potential ecological risks of antibiotics in a seasonal freeze-thaw basin.

Antibiotics have gained increasing attention as pharmaceuticals widely existing in human society. Under low temperature conditions, antibiotics tend to have higher environmental persistence, which poses a potential threat to ecological environment, but research on antibiotics in low-temperature basins is still lacking. Therefore, for investigating occurrence, spatio-temporal distributions, and ecological risks of antibiotics in a seasonal freeze-thaw basin, rivers in Tumen River basin were selected and sampled, including 25 samples during the river-freezing season and 27 samples during the non-freezing season. Overall, climate characteristics of different latitudes and renewal frequency of antibiotics are important factors that lead to diversity of antibiotics in basins. Eleven target antibiotics were detected and their average concentrations during the river-freezing season (0.83-27.5 ng L-1) were lower than that during the non-freezing season (2.80-45.30 ng L-1), severely impacted by river flow, ice sealed-melting, and local feeding practices. In addition, total antibiotic concentrations are usually highest in downstream areas of human settlements, receiving input from husbandry and sewage, respectively. Through ecological risk assessment, norfloxacin and amoxicillin posed high risks to algae, which were identified as high-risk pollutants in basin.

Examining the extraction of parafoveal semantic information in Tibetan.

This study conducted two experiments to investigate the extraction of semantic preview information from the parafovea in Tibetan reading. In Experiment 1, a single-factor (preview type: identical vs. semantically related vs. unrelated) within-subject experimental design was used to investigate whether there is a parafoveal semantic preview effect (SPE) in Tibetan reading. Experiment 2 used a 2 (contextual constraint: high vs. low) × 3 (preview type: identical vs. semantically related vs. unrelated) within-subject experimental design to investigate the influence of contextual constraint on the parafoveal semantic preview effect in Tibetan reading. Supporting the E-Z reader model, the experimental results showed that in Tibetan reading, readers could not obtain semantic preview information from the parafovea, and contextual constraint did not influence this process. However, comparing high- and low-constrained contexts, the latter might be more conducive to extracting semantic preview information from the parafovea.

Brain Structural and Functional Alterations in Native Tibetans Living at High Altitude.

Tibetans have adapted to high altitude environments. However, the genetic effects in their brains have not been identified. Twenty-five native Tibetans living in Lhasa (3650 m) were recruited for comparison with 20 Han immigrants who originated from lowlands and had been living in Lhasa for two years. The physiological characteristics, brain structure and neuronal spontaneous activity were investigated. Compared with Han immigrants, Tibetans showed higher peripheral oxygen saturation (SpO2), and lower heart rate, red blood cell counts, hematocrit, and hemoglobin. Tibetans showed increased gray matter volume in the visual cortex, hippocampus, and rectus; increased the amplitudes of low-frequency fluctuations (ALFF) values in the left putamen and left fusiform gyrus; and decreased voxel-mirrored homotopic connectivity (VMHC) values in the precentral gyrus. Moreover, Tibetans have decreased functional connectivity (FC) between the left precentral gyrus and the frontal gyrusand right precuneus. In Tibetans and Han immigrants, hemoglobin and hematocrit were negatively correlated with total gray matter volume in males, SpO2 was also positively correlated with ALFF in the left fusiform gyrus, while hemoglobin, and hematocrit were positively correlated with VMHC in the precentral gyrus and FC in the precentral gyrus with other brain regions, SpO2 was also found to be negatively correlated with VMHC in the precentral gyrus, and hemoglobin and hematocrit were negatively correlated with ALFF in the left putamen and left fusiform gyrus. In summary, genetic mutations may result in modulation of some brain regions, which was further confirmed by the identification of correlations with hemoglobin and hematocrit in these regions.

Whole-genome metagenomic analysis of the oral microbiota in patients with obstructive sleep apnea.

PURPOSE: The oral microbiota is closely associated with systemic health, but few studies have investigated the oral microbiota in patients with obstructive sleep apnea (OSA). This study aimed to identify the variation of oral microbiota among patients with severe OSA, and the change of oral microbiota after treatment with continuous positive airway pressure (CPAP). METHODS: Participants were enrolled in the study from November 2020 to August 2021. Sleep parameters using full nocturnal polysomnography (PSG) were collected on healthy controls, patients with severe OSA, and patients with severe OSA after CPAP treatment for 3 months. Oral samples were also collected by rubbing disposable medical sterile swabs on the buccal mucosa. Routine blood tests and biochemical indicators were measured using the fully automated biochemical analyzer. Oral microbial composition of oral samples were determined using whole-genome metagenomic analysis in all participants. Correlations were analyzed between the oral microbiota and blood lipids. RESULTS: Study enrollment included 14 participants, 7 healthy controls and 7 patients with severe OSA. At the species level, the relative abundances of Prevotella, Alloprevotella, Bacteroides, Veillonella_tobetsuensis, Candidatus saccharimonas, and Leptotrichia in the groups with severe OSA were significantly lower than those in the healthy controls (P both < 0.05). The abundances of Capnocytophaga, Veillonella, Bacillus_anthracis, Eikenella, and Kingella were significantly higher whereas the abundances of Gordonia and Streptococcus were significantly lower in the group with severe OSA compared to the severe OSA-CPAP group (P < 0.05 for both). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), 4 pathways changed in the group with severe OSA compared with healthy controls (P both < 0.05). Pathways related to Novobiocin biosynthesis, 2-Oxocarboxylic acid metabolism, and Histidine metabolism were enriched in the patients with severe OSA. Nine pathways showed significant differences with regard to the relative abundances of phenylalanine metabolism; alanine, aspartate, and glutamate metabolism; one carbon pool by folate; monobactam biosynthesis; 2-oxocarboxylic acid metabolism; arginine biosynthesis and vitamin B6 metabolism; novobiocin biosynthesis; and arginine and proline metabolism, which were significantly higher in the group with severe OSA compared to the severe OSA-CPAP group (P both < 0.05). The Spearman correlation analysis between blood lipid parameters and oral microbiota components showed that negative correlations were observed between total cholesterol and Streptomyces (r = - 0.893, P = 0.007), and high-density lipoprotein cholesterol (HDL-C) and Gordonia (r = - 0.821, P = 0.023); positive correlations were observed between HDL-C and Candidatus saccharimonas (r = 0.929, P = 0.003), and low-density lipoprotein cholesterol (LDL-C) and Capnocytophaga (r = 0.893, P = 0.007). CONCLUSION: There was an apparent discrepancy of the oral microbiota and metabolic pathways between the group with severe OSA and controls, and CPAP significantly changed oral microbial abundance and metabolic pathways in patients with severe OSA. Correlation analysis showed that these oral bacteria were strongly correlated with the blood lipids level.

Optical microscope with a large tilt angle and a long focal length for a nano-size angle-resolved photoemission spectroscopy.

Angle-resolved photoemission spectroscopy with nanoscale spatial resolution (Nano-ARPES) is a powerful tool for the investigation of electronic structures of materials and their spatial configurations. In order to capture the area of interest in Nano-ARPES measurements effectively, an optical microscope can be used to provide real space optical images as a reference. In this work, a new type of optical microscope for Nano-APRES spectrometer with a large tilt angle of ∼30 degrees and a long focal length of ∼12 mm has been designed. Large magnifications by 7 × to 20 × and a spatial resolution of 3 um have been achieved, which can effectively assist optical alignment for Nano-ARPES. In addition, the strong boundary sensitivity observed in such a tilt design demonstrates its special capability in detecting the fine features of surface coarseness.

Eye Movement Control in Tibetan Reading: The Roles of Word Length and Frequency.

We investigated the effects of word length and frequency on eye movement control during Tibetan reading through two experiments. A preliminary experiment examined the predictive effect of word length and frequency on fixation duration and landing position using multiple linear regression analysis. In the formal experiment, we manipulated the length and frequency of target words simultaneously to investigate the effects of word length and frequency on fixation duration and landing position in Tibetan reading. In this study, we found that: (1) there were significant word-length and word-frequency effects affecting all lexical processing in Tibetan reading; (2) there are preferred viewing locations in Tibetan reading; specifically, for short words, it is the end, whereas for long words, it spans from the center to the beginning of the word; (3) word frequency does not affect preferred viewing location in Tibetan reading; (4) the preferred viewing position and the interaction of word length and viewing position found in this study supported the "strategy-tactics" approach.

Rabphilin 3A binds the N-peptide of SNAP-25 to promote SNARE complex assembly in exocytosis.

Exocytosis of secretory vesicles requires the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and small GTPase Rabs. As a Rab3/Rab27 effector protein on secretory vesicles, Rabphilin 3A was implicated to interact with SNAP-25 to regulate vesicle exocytosis in neurons and neuroendocrine cells, yet the underlying mechanism remains unclear. In this study, we have characterized the physiologically relevant binding sites between Rabphilin 3A and SNAP-25. We found that an intramolecular interplay between the N-terminal Rab-binding domain and C-terminal C2AB domain enables Rabphilin 3A to strongly bind the SNAP-25 N-peptide region via its C2B bottom α-helix. Disruption of this interaction significantly impaired docking and fusion of vesicles with the plasma membrane in rat PC12 cells. In addition, we found that this interaction allows Rabphilin 3A to accelerate SNARE complex assembly. Furthermore, we revealed that this interaction accelerates SNARE complex assembly via inducing a conformational switch from random coils to α-helical structure in the SNAP-25 SNARE motif. Altogether, our data suggest that the promotion of SNARE complex assembly by binding the C2B bottom α-helix of Rabphilin 3A to the N-peptide of SNAP-25 underlies a pre-fusion function of Rabphilin 3A in vesicle exocytosis.

Antimicrobial resistance and population genomics of multidrug-resistant Escherichia coli in pig farms in mainland China.

The expanding use of antimicrobials in livestock is an important contributor to the worldwide rapid increase in antimicrobial resistance (AMR). However, large-scale studies on AMR in livestock remain scarce. Here, we report findings from surveillance of E. coli AMR in pig farms in China in 2018-2019. We isolated E. coli in 1,871 samples from pigs and their breeding environments, and found AMR in E. coli in all provinces in mainland China. We detected multidrug-resistance in 91% isolates and found resistance to last-resort drugs including colistin, carbapenems and tigecycline. We also identified a heterogeneous group of O-serogroups and sequence types among the multidrug-resistant isolates. These isolates harbored multiple resistance genes, virulence factor-encoding genes, and putative plasmids. Our data will help to understand the current AMR profiles of pigs and provide a reference for AMR control policy formulation for livestock in China.

The Mechanism of Word Satiation in Tibetan Reading: Evidence from Eye Movements.

Two eye-tracking experiments were used to investigate the mechanism of word satiation in Tibetan reading. The results revealed that, at a low repetition level, gaze duration and total fixation duration in the semantically unrelated condition were significantly longer than in the semantically related condition; at a medium repetition level, reaction time in the semantically related condition was significantly longer than in the semantically unrelated condition; at a high repetition level, the total fixation duration and reaction time in the semantically related condition were significantly longer than in the semantically unrelated condition. However, fixation duration and reaction time showed no significant difference between the similar and dissimilar orthography at any repetition level. These findings imply that there are semantic priming effects in Tibetan reading at a low repetition level, but semantic satiation effects at greater repetition levels, which occur in the late stage of lexical processing.

Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality.

The coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) erupted in Hubei Province of China in December 2019 and has become a pandemic. Severe COVID-19 patients who suffer from acute respiratory distress syndrome (ARDS) and multi-organ dysfunction have high mortality. Several studies have shown that this is closely related to the cytokine release syndrome (CRS), often loosely referred to as cytokine storm. IL-6 is one of the key factors and its level is positively correlated with the severity of the disease. The molecular mechanisms for CRS in COVID-19 are related to the effects of the S-protein and N-protein of the virus and its ability to trigger NF-κB activation by disabling the inhibitory component IκB. This leads to activation of immune cells and the secretion of proinflammatory cytokines such as IL-6 and TNF-α. Other mechanisms related to IL-6 include its interaction with GM-CSF and interferon responses. The pivotal role of IL-6 makes it a target for therapeutic agents and studies on tocilizumab are already ongoing. Other possible targets of treating CRS in COVID-19 include IL-1ß and TNF-α. Recently, reports of a CRS like illness called multisystem inflammatory syndrome in children (MIS-C) in children have surfaced, with a variable presentation which in some cases resembles Kawasaki disease. It is likely that the immunological derangement and cytokine release occurring in COVID-19 cases is variable, or on a spectrum, that can potentially be governed by genetic factors. Currently, there are no approved biological modulators for the treatment of COVID-19, but the urgency of the pandemic has led to numerous clinical trials worldwide. Ultimately, there is great promise that an anti-inflammatory modulator targeting a cytokine storm effect may prove to be very beneficial in reducing morbidity and mortality in COVID-19 patients.

RIPK3 Induces Cardiomyocyte Necroptosis via Inhibition of AMPK-Parkin-Mitophagy in Cardiac Remodelling after Myocardial Infarction.

Receptor-interacting protein 3- (RIPK3-) modulated necroptosis plays a critical role in cardiac remodelling after myocardial infarction (MI). However, the precise regulatory mechanism is not fully elucidated yet. In the present study, we showed that RIPK3 expression was upregulated in myocardial tissue after MI in a mouse model by coronary artery ligation, as well as in the cardiomyocytes following hypoxic injury in vitro. The increase of RIPK3 expression was found to be accompanied by severe cardiac remodelling, cardiac dysfunction, and higher mortality. Elevated RIPK3 expression subsequently abrogated the AMPK pathway that was accompanied by inhibition of Parkin-mediated mitophagy. Loss of mitophagy increased the opening of mitochondrial permeability transition pore (mPTP), which ultimately induced the cardiomyocyte necroptosis. In contrast, genetic ablation of Ripk3 induced the AMPK/Parkin-mitophagy pathway, favouring a prosurvival state that eventually inhibited mPTP opening and induced the necroptosis of cardiomyocytes in the post-MI cardiac remodelling. In conclusion, our results revealed a key mechanism by which necroptosis could be mediated by RIPK3 via the AMPK/Parkin-mitophagy/mPTP opening axis, which provides a potential therapeutic target in the management of heart failure after MI.

Association of Metabolic Syndrome With Long-Term Cardiovascular Risks and All-Cause Mortality in Elderly Patients With Obstructive Sleep Apnea.

BACKGROUND: Evidence suggests that an increased risk of major adverse cardiac events (MACE) and all-cause mortality is associated with obstructive sleep apnea (OSA), particularly in the elderly. Metabolic syndrome (MetS) increases cardiovascular risk in the general population; however, less is known about its influence in patients with OSA. We aimed to assess whether MetS affected the risk of MACE and all-cause mortality in elderly patients with OSA. METHODS: From January 2015 to October 2017, 1,157 patients with OSA, aged ≥60 years, no myocardial infarction (MI), and hospitalization for unstable angina or heart failure were enrolled at baseline and were followed up prospectively. OSA is defined as an apnea-hypopnea index of ≥5 events per hour, as recorded by polysomnography. Patients were classified on the basis of the presence of MetS, according to the definition of the National Cholesterol Education Program (NCEP). Incidence rates were expressed as cumulative incidence. Cox proportional hazards analysis was used to estimate the risk of all events. The primary outcomes were MACE, which included cardiovascular death, MI, and hospitalization for unstable angina or heart failure. Secondary outcomes were all-cause mortality, components of MACE, and a composite of all events. RESULTS: MetS was present in 703 out of 1,157 (60.8%) elderly patients with OSA. During the median follow-up of 42 months, 119 (10.3%) patients experienced MACE. MetS conferred a cumulative incidence of MACE in elderly patients with OSA (log-rank, P < 0.001). In addition, there was a trend for MACE incidence risk to gradually increase in individuals with ≥3 MetS components (P = 0.045). Multivariate analysis showed that MetS was associated with an incidence risk for MACE [adjusted hazard ratio (aHR), 1.86; 95% confidence interval (CI), 1.17-2.96; P = 0.009], a composite of all events (aHR, 1.54; 95% CI, 1.03-2.32; P = 0.036), and hospitalization for unstable angina (aHR, 2.01; 95% CI, 1.04-3.90; P = 0.039). No significant differences in the risk of all-cause mortality and other components of MACE between patients with and without MetS (P > 0.05). Subgroup analysis demonstrated that males (aHR, 2.23; 95% CI, 1.28-3.91, P = 0.05), individuals aged <70 years (aHR, 2.36; 95% CI, 1.27-4.39, P = 0.006), overweight and obese individuals (aHR, 2.32; 95% CI, 1.34-4.01, P = 0.003), and those with moderate-severe OSA (aHR, 1.81;95% CI: 1.05-3.12, P = 0.032) and concomitant MetS were at a higher risk for MACE. CONCLUSION: MetS is common in elderly patients with OSA in the absence of MI, hospitalization for unstable angina or heart failure. Further, it confers an independent, increased risk of MACE, a composite of all events, and hospitalization for unstable angina. Overweight and obese males, aged <70 years with moderate-severe OSA combined with MetS presented a significantly higher MACE risk.

Herring egg phosphopeptides as calcium carriers for improving calcium absorption and bone microarchitecture in vivo.

Phosphorylation may enhance the functional properties of proteins/peptides. Herring egg phosphopeptides (HEPPs) have been found to be more effective than the non-phosphorylated variant in calcium-binding activities due to the introduced phosphate groups. However, whether HEPPs as calcium carriers will be superior to herring egg peptides (HEPs) in improving calcium bioavailability in vivo, for the equivalent calcium intake prerequisite, remains to be clarified. This study aimed to evaluate the effect of HEPPs-calcium complex and HEPs-calcium complex on calcium absorption and bioavailability in calcium-deficient mice. Results showed that the remarkably lower calcium absorption and bone calcium deposition induced by long-term calcium deficiency were accompanied by deterioration of the trabecular bone microarchitecture (P < 0.05). The HEPPs-Ca supplements significantly improved the apparent calcium absorption, increased the serum calcium level, decreased the alkaline phosphatase activity, strengthened the bone biomechanical property, and increased bone volume/tissue volume (BV/TV) and trabecular number (Tb·N) in calcium-deficient mice (P < 0.05), as determined by micro-computed tomography (micro-CT) assay. The effect of HEPPs-Ca on calcium absorption and bioavailability was comparable to that of CPPs-Ca, but better than that of HEPs-Ca and CaCO3. This study brings new insights into the potential of HEPPs as an alternative to CPPs for use in calcium supplements.

Pirfenidone alleviates lipopolysaccharide-induced lung injury by accentuating BAP31 regulation of ER stress and mitochondrial injury.

Pirfenidone has been widely used in the treatment of idiopathic pulmonary fibrosis (IPF). However, the role of pirfenidone in LPS-induced acute lung injury (ALI) remains unclear. This study aims to investigate the protective effects of pirfenidone in ALI and to explore its underlying mechanism. Pirfenidone clearly reduces LPS-triggered ALI as indicated by significant pathological alterations, reduced oxidative stress and inflammatory responses in vivo. Furthermore, pirfenidone also blocks apoptosis of LPS-induced alveolar epithelial type II (ATII) cells through inhibition of endoplasmic reticulum (ER) stress and mitochondrial injury in vivo and in vitro. A lower expression level of BAP31, an ER transmembrane protein, was found to be associated with ALI followed LPS challenge. The reintroduction of BAP31 blunted LPS induced ER stress and mitochondrial damage and therefore alleviated ATII cell apoptosis, which correlated with pirfenidone treatment. Knockdown of BAP31 expression in pirfenidone treated ATII cells re-activated ER stress, mitochondrial damage and followed cellular apoptosis. In summary, this study confirms the beneficial effect of pirfenidone on ER stress and mitochondrial dysfunction mediated apoptosis via upregulation of BAP31. Our results demonstrated that pirfenidone may be considered as a potential agent for the treatment of ALI in the future.

Clinical Pathway for Early Diagnosis of COVID-19: Updates from Experience to Evidence-Based Practice.

The COVID-19 pandemic is a significant global event in the history of infectious diseases. The SARS-CoV-2 appears to have originated from bats but is now easily transmissible among humans, primarily through droplet or direct contact. Clinical features of COVID-19 include high fever, cough, and fatigue which may progress to ARDS. Respiratory failure can occur rapidly after this. The primary laboratory findings include lymphopenia and eosinopenia. Elevated D-dimer, procalcitonin, and CRP levels may correlate with disease severity. Imaging findings include ground-glass opacities and patchy consolidation on CT scan. Mortality is higher in patients with hypertension, cardiac disease, diabetes mellitus, cancer, and COPD. Elderly patients are more susceptible to severe disease and death, while children seem to have lower rates of infection and lower mortality. Diagnostic criteria and the identification of persons under investigation have evolved as more data has emerged. However, the approach to diagnosis is still very variable from region to region, country to country, and even among different hospitals in the same city. The importance of a clinical pathway to implement the most effective and relevant diagnostic strategy is of critical importance to establish the control of this virus that is responsible for more and more deaths each day.