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The staggered work hours (SWH) policy is a practical strategy for managing travel demand, aiming to spread out the temporal distribution of travel volume by adjusting the schedules of travelers' activities. The influence of the SWH policy on the commuting patterns of passengers using bus transit is not yet clear. We addressed this issue in a many-to-one bus line, treating commuters as Q-learning agents learning to minimize regrets by selecting appropriate bus runs. The learning outcomes reveal a SWH-induced equilibrium, where commuters departing from the same station with the same work start time experience identical minimal commuting costs, regardless of the chosen bus. Subsequently, we investigate the effectiveness of SWH policy by manipulating two key control variables: the division of travel demand between two categories of travelers and the staggered time interval. The results confirm that congestion during peak hours can potentially be mitigated by carefully selecting the above two key parameters. Correspondingly, we provide optimal control boundaries for these two parameters to design an effective SWH policy. Furthermore, we explore the combined impact of physical distancing and SWH policy on traffic flow patterns during an epidemic outbreak. Concurrently, we assess the infection risk through a surrogate index, revealing that the SWH policy has a positive effect in mitigating the risk of contact exposure. [ABSTRACT FROM AUTHOR]

The traditional method of relieving boarding congestion is to reduce aisle and seat conflicts by optimizing the boarding strategy. Here, we focus on another way of smoothing the passenger flow for a novel cabin installed with side-slip seats. Three aspects are discussed in this work. First, we explore the characteristics of fast boarding sequences that benefit most from side-slip seats using a simulated annealing algorithm. Second, we introduce three alternative strategies and evaluate their efficiencies using a realistic aircraft boarding model. The result shows that the boarding time could be largely reduced by adopting the new strategies. Sensitivity analyses also imply that side-slip seats are tolerable to the number of inexperienced passengers who are unfamiliar with the side-slip seats. Besides, the infection risk is also discussed as a function of ticket validation time at the check desk. Third, a boarding assistant system is designed to implement the proposed strategies. [ABSTRACT FROM AUTHOR]

In this study, the effect of iron-loaded sludge biochar (ISBC) on the Cr enrichment capacity of Leersia hexandra swartz (L. hexandra) in hydroponic tests was investigated at different Cr treatment levels (5 mg/L, 10 mg/L and 20 mg/L). The results showed that the plant height and biomass of L. hexandra were significantly increased with the rise of ISBC dose (p < 0.01), while the Cr content in L. hexandra showed a significant downward trend (p < 0.01). However, the Cr accumulation capacity of L. hexandra was significantly increased as ISBC dose was raised (p < 0.01), which was attributed to the significant improvement of its biomass. According to Cr accumulation capacity, the appropriate ISBC dose was recommended to be 50 g/L for all Cr treatment levels. Compared to the control (no ISBC; 0.105 mg, 0.167 mg and 0.193 mg), the Cr accumulation capacity of L. hexandra at different Cr treatment levels were increased by 77.40%, 59.72% and 88.41%, respectively. The comparative analysis throughout the test cycle indicated that the addition of ISBC could convert more Cr(VI) to Cr(III), which was beneficial to the biomass and the Cr accumulation capacity of L. hexandra. Meanwhile, the relationship between changes in the concentrations of NH 4 +, PO 4 3− and K+ and the incremental biomass of L. hexandra was well described by the Logistic model, while the relationship between changes in their concentrations and the Cr accumulation capacity of L. hexandra also followed this model well. Moreover, their effects were found throughout the test, while the contribution of Ca2+ was mainly at the beginning and end of the test. In summary, the enhancement of ISBC on Cr accumulation capacity of L. hexandra was attributed to detoxification and fertilizer supply. • ISBC was able to significantly promote the growth of L. hexandra (p < 0.01). • ISBC enhanced Cr accumulation (CA) of L. hexandra due to its increase of biomass. • ISBC at 50 g/L increased CA by 77.40%, 59.72% and 88.41% at different Cr treatment. • ISBC converted more Cr(VI) to Cr(III), resulting in increased biomass and CA. • NH 4 +, PO 4 3−, K+ and Ca2+ from ISBC facilitated the enhancement of biomass and CA. [ABSTRACT FROM AUTHOR]

Phospholipids are the main constituents of biological membranes and their biological function has been increasingly recognized. Therefore, there is an unmet need to develop methods capable of quantifying a wide range of phospholipids with high sensitivities and high throughput. We employed an ultrahigh-performance liquid chromatography system coupled to a triple-quadrupole mass spectrometer (UHPLC-MS) and developed a method that can quantitatively analyze 10 major classes of phospholipids in biological samples in 11 min. These are phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, sphingomyelin, lysophosphatidic acid, lysophosphatidylcholine and lysophosphatidylethanolamine. The limit of detection (LOD) and limit of quantitation (LOQ) are 0.04–33 pmol mL−1 and 0.1–110 pmol mL−1, respectively. The method takes three steps: first and second steps identified phospholipid structures in a mixture containing aliquots of all the samples using the combinations of multiple reaction monitoring (MRM), product ion scan and retention time in the positive and negative ion modes. These steps enabled the identification of phospholipids present in the samples and provided information on efficient sample analysis in the final step of sample quantitative analysis. We have developed fast and sensitive label-free quantitation with normalization of the acyl chain length to achieve more accurate quantification. The method developed was applied to analyze 6 different biological samples (plasma, cells and tissues) for applicability validation, where a total of 308 phospholipid species across 10 phospholipid classes were identified and 295 phospholipid species were quantified. The method is highly efficient, sensitive, and is universally applicable. [ABSTRACT FROM AUTHOR]

This work offers a novel approach to prepare manganese oxides with heterointerface structure as a superior catalyst for the catalytic combustion of Volatile Organic Compounds (VOCs). The α-MnO 2 /δ-MnO 2 with heterointerfaces were prepared via annealing δ-MnO 2 precursors which were obtained from the redox precipitation between HCl and KMnO 4. The characterization results indicate that the heterointerface structure of α-MnO 2 /δ-MnO 2 optimizes energy level structure and provides abundant surface defects, showing superior low-temperature reducibility and preferable mobility of oxygen species. Such features significantly enhance the catalytic activity of the α-MnO 2 /δ-MnO 2 with heterointerfaces catalysts for the complete oxidation of toluene (the toluene conversion rates of 10 % and 90 % are 191 °C and 213 °C, respectively). Moreover, the catalysts show high stability for 50 h. The presented catalysts disclose an avenue to address current obstacles in the catalytic oxidation of VOCs. The α-MnO 2 /δ-MnO 2 sample with heterointerfaces was successfully prepared and had superior catalytic activity for toluene combustion. [Display omitted] • A facile synthesis strategy of α-MnO 2 /δ-MnO 2 with heterointerface is proposed. • α-MnO 2 /δ-MnO 2 heterostructure displays excellent catalytic combustion for toluene. • Heterointerfaces optimize energy level structure and create surface defects. [ABSTRACT FROM AUTHOR]

Background/Aims: A series of reports revealed that autophagy and apoptosis exerted detrimental effects on the pathology of cardiac ischemia/reperfusion (I/R) injury. Ginsenoside compound K (CK), a major intestinal metabolite underlying the pharmacological actions of orally administered ginseng, has a protective effect against myocardial I/R injury. However, the molecular mechanisms by which CK protects against I/R injury remain unclear. In this study, we hypothesized that the cardioprotective effects of CK against I/R injury are mediated by inhibiting autophagy/apoptosis-related signaling pathways in H9c2 cardiomyocyte cells. Methods: H9c2 cells were incubated with CK and exposed to I/R. Cell viability and damage was analyzed by MTT and lactate dehydrogenase assays. Reactive oxygen species (ROS) generation, mitochondrial damage, and cell apoptosis were analyzed by flow cytometry and TUNEL staining. The expression of autophagy, apoptosis, and related signaling proteins was analyzed by Western blotting and immunofluorescence staining. Results: CK pretreatment promoted cell viability and attenuated ROS accumulation and intracellular mitochondrial damage induced by I/R injury Moreover, CK reduced autophagy by regulating the formation of phagocytic precursors to autophagosomes and also inhibited apoptosis through a mitochondrial-mediated pathway. Additionally the cardioprotective effect of CK against I/R injury was mainly through the activation of the PI3K-Akt signaling pathway. Conclusions: CK pretreatment inhibits autophagy-mediated apoptosis induced by I/R injury through the activation of the PI3K-Akt signaling pathway, which reveals that CK may be one of the key bioactive ingredients of ginseng for the treatment of myocardial I/R injury. [ABSTRACT FROM AUTHOR]

The holding strategy performs well in resisting bus bunching in the dedicated bus route. Yet, its efficiency in a non-dedicated bus route has not been well studied, and its external effects on other road participants are unclear. We study this topic in a circular two-lane traffic system consisting of buses and cars. A cellular automaton model is used to depict the vehicles' dynamic behaviors. By numerical simulations, we obtained the phase diagram of the bus system, and identified the four states concerning the stability and level of service. Then we analyzed the flow and velocity characteristics and distinguished three states of the traffic system. Our simulations prove the separation effect of car flows on the bus headway regulation. Combined with this effect, the holding strategy makes the bus running more homogeneous and the bus utilization more evenly in the mixed traffic flow condition. Interestingly, from a macro perspective, the holding strategy incurs no detrimental effects on the whole traffic system, though it might intensify local interference between buses and cars near bus stops. Under certain conditions, the average speed of buses and cars increases, eventually increasing the system's capacity. • Interference between buses and cars in mixed traffic flow conditions is analyzed. • Bus operating states with and without the holding are investigated. • The bus line characters and traffic conditions determine the holding effeteness. • External effects of the bus holdings on the car flows are discussed. [ABSTRACT FROM AUTHOR]

Panax ginseng C. A. Meyer (P. ginseng) is effective in the prevention and treatment of myocardial ischemia-reperfusion (I/R) injury. The mechanism by which P. ginseng exerts cardioprotective effects is complex. P. ginseng contains many pharmacologically active ingredients, such as molecular glycosides, polyphenols, and polysaccharides. P. ginseng and each of its active components can potentially act against myocardial I/R injury. Myocardial I/R was originally a treatment for myocardial ischemia, but it also induced irreversible damage, including oxygen-containing free radicals, calcium overload, energy metabolism disorder, mitochondrial dysfunction, inflammation, microvascular injury, autophagy, and apoptosis. This study aimed to clarify the protective effects of P. ginseng and its active ingredients against myocardial I/R injury, so as to provide experimental evidence and new insights for the research and application of P. ginseng in the field of myocardial I/R injury. This review was based on a search of PubMed, NCBI, Embase, and Web of Science databases from their inception to February 21, 2022, using terms such as "ginseng," "ginsenosides," and "myocardial reperfusion injury." In this review, we first summarized the active ingredients of P. ginseng , including ginsenosides, ginseng polysaccharides, and phytosterols, as well as the pathophysiological mechanisms of myocardial I/R injury. Importantly, preclinical models with myocardial I/R injury and potential mechanisms of these active ingredients of P. ginseng for the prevention and treatment of myocardial disorders were generally summarized. P. ginseng and its active components can regulate oxidative stress related proteins, inflammatory cytokines, and apoptosis factors, while protecting the myocardium and preventing myocardial I/R injury. Therefore, P. ginseng can play a role in the prevention and treatment of myocardial I/R injury. P. ginseng has a certain curative effect on myocardial I/R injury. It can prevent and treat myocardial I/R injury in several ways. When ginseng exerts its effects, should be based on the theory of traditional Chinese medicine and with the help of modern medicine; the clinical efficacy of P. ginseng in preventing and treating myocardial I/R injury can be improved. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights: [•] Human epidermal melanocytes were isolated, cultured and purified. [•] The practicability of supporting materials of cultured melanocytes was investigated. [•] Polyethylene terephthalate film was proved to be an ideal supporting material for melanocyte culture. [•] The application of polyethylene terephthalate film enables melanocytes and their dendrites to be sectioned longitudinally. [•] Ultrastructures of melanocytes and transferring pattern of melanosomes were observed. [ABSTRACT FROM AUTHOR]

This paper investigates the interactions between buses and cars traveling along a two-lane bus corridor. The dynamic behavior of these two kinds of vehicles is mimicked using a cellular automata model. A phase diagram of the operation of buses is obtained, and four phases are identified: (I) homogeneous and sufficient capability, (II) homogeneous and insufficient capability, (III) bunching and sufficient capability, and (IV) bunching and insufficient capability. In addition, the flow characteristics of cars are explored and the phase transition from a free-flow region to a saturated-flow region is observed. The latter relies not only on the probability of cars entering the corridor, but also on bus operation conditions due to the bottleneck effect. Interestingly, we find that the stability of bus fleets does not always deteriorate as a result of a higher probability of cars entering the corridor. In the case of high travel demand and frequent bus service, there is actually less variation in bus headway. • The mixed traffic flow dynamics of buses and cars are investigated. • A cellular automata model with open boundary is proposed. • Phase diagram of bus operation is obtained and four phases are identified. • Phase transition from free-flow to saturation-flow is observed for cars. • The stability of bus operation is not always deteriorated by the cars' influence. [ABSTRACT FROM AUTHOR]

Green polyvinyl alcohol/poly(D,L-lactide-co-glycolide) (PVA/PLGA) composite materials were developed by dissolving PVA and PLGA in hexafluoroisopropanol (HFIP), followed by the subsequent layout of PVA/PLGA/HFIP liquid film and the removal of HFIP. Interestingly, the PVA/PLGA composite materials display remarkedly enhanced tensile strength, elongation at break, biodegradability and biocompatibility. Systematic investigations have been completed to reveal the effects of PVA/PLGA mass ratio on the tensile strength, elongation at break, biodegradability and biocompatibility. Meanwhile, the morphology, crystallinity and chemical structure of the PVA/PLGA material and possible interaction between PVA and PLGA are also investigated using scanning electron micrograph, infrared spectra and X-ray diffraction techniques. [ABSTRACT FROM AUTHOR]

Ginseng is a kind of traditional Chinese herbal medicine, known as "king of herbs" and widely used in China, South Korea, and other Asian countries. Ginsenosides are one of active components of Panax ginseng Meyer, which have many pharmacological effects, such as enhancing memory, improving immunity and cardiovascular system, delaying aging, and preventing cancer. This review aims to summarize the recent findings for ginsenosides targeting Sirtuin 1 (SIRT1) signaling pathway for the prevention and treatment of a series of diseases. An up-to-August 2020 search was carried out in databases such as PubMed, ScienceDirect, Google Scholar, China National Knowledge Infrastructure, and classic books of traditional Chinese medicine using the keywords: "SIRT1", and/or paired with "ginseng", and "ginsenosides". SIRT1 is a class-III histone deacetylase (HDAC), a nicotinamide adenine dinucleotide (NAD+)-dependent enzyme, which is deeply involved in a series of pathological processes. Based on specific intracellular localization, SIRT1 has various cytoplasmic and nuclear targets and plays a potential role in energy metabolism, oxidative stress, inflammation, tumorigenesis, and aging. Ginsenosides are generally classified into three groups and microbially transformed to final metabolites. Among of them, most ginsenosides have been reported as SIRT1 activators, especially those ginsenosides with two glucopyranosyl groups on the C-3 position. Importantly, many ginsenosides can be used to prevent and treat oxidative stress, inflammation, aging, tumorigenesis, depression, and others by targeting SIRT1 signaling pathway. This paper reviews recent evidences of ginsenosides targeting SIRT1 for the first time, which could provide new insights on the preclinical and clinical researches for ginsenosides against multiple disorders. Image 1 [ABSTRACT FROM AUTHOR]

Stroke is the leading cause of long-term disability, demanding an ever-increasing need to find treatment. Transient receptor potential (TRP) channels are nonselective Ca2+-permeable channels, among which TRPC, TRPM, and TRPV are widely expressed in the brain. Dysfunction of the blood brain barrier (BBB) is a core feature of stroke and is associated with severity of injury. As studies have shown, TRP channels influence various neuronal functions by regulating the BBB. Here, we briefly review the role of TRP channel in the BBB dysfunction after stroke, and explore the therapeutic potential of TRP-targeted therapy. [ABSTRACT FROM AUTHOR]

Oxygen and glucose deprivation and reperfusion (OGD/R) injury contributes to the pathophysiology after ischemic stroke, which needs to urgently develop treatment strategies. Previous studies have demonstrated that autophagy in reperfusion period exerted adverse effects on the cerebral ischemic injury. Ginsenoside monomer compound K (CK) is the main intestinal metabolite of ginseng that exerts the pharmacological activities and has a protective effect against cerebral OGD/R injury. However, the specific molecular mechanism of CK protects against OGD/R injury in neurons is still unclear. In this study, cell viability, reactive oxygen species (ROS) generation, Ca2+ overload, mitochondrial membrane potential depolarization, autophagy and apoptosis were investigated in OGD/R-induced neuronal cells injury after pretreatment with CK and in combination with BML-275 or rapamycin. Our study found that pretreatment with CK protected neurons against OGD/R injury by increasing cell viability and decreasing the ROS generation, mitochondrial damage, and Ca2+ overload. Moreover, CK cut down autophagy-mediated apoptosis via promoting the process of forming autophagosomes into phagocytic precursors. Furthermore, our study clarified the neuroprotective of CK against OGD/R-induced neural autophagy and apoptosis through the regulation of the AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathway. Taken together, our study provides credible experimental evidence and explains the potential molecular mechanism of CK as one of the main bioactive ingredients of ginseng for the treatment of cerebral ischemia/reperfusion injury. Unlabelled Image • Compound K decreased the ROS generation, mitochondrial damage and Ca2+ overload. • Compound K reduced apoptosis and autophagy by regulating the formation of phagocytic precursors to autophagosomes. • Compound K regulated the AMPK-mTOR pathway in OGD/R-induced neuronal cells injury. • Compound K is the key bioactive ingredients of ginseng for the treatment of cerebral ischemia stoke. [ABSTRACT FROM AUTHOR]

Summary: Background: The PNPLA3 and TM6SF2 gene variants have been found to cause NAFLD with a favourable cardiovascular risk profile. Aims: To investigate the effects of the NAFLD risk alleles on the all‐cause and cause‐specific mortality in 5581 Chinese adults. Methods: The genome‐wide genotypes were detected using a genotyping array and serum lipoprotein profiles were examined using 1H NMR platform. Liver fat content (LFC) was measured using a quantitative ultrasound method. The vital status was determined using official registration data. Results: Genome‐wide association analysis showed that a series of variants in PNPLA3 were associated with LFC, including rs738409 C>G variant (P = 8.6 × 10−7). Further analyses validated the associations of TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants with NAFLD. During 29 425.1 person‐years of follow‐up, the overall mortality was 816 per 100 000 person‐years, where 299 deaths were attributable to cardiovascular disease and 85 to liver disease. The PNPLA3 rs738409 C>G variant was independently associated with increased liver‐specific mortality (P for trend = 0.034) but reduced cardiovascular mortality (P for trend = 0.047). A composite genetic‐predisposition score of PNPLA3, TM6SF2, and MBOAT7 risk alleles presented similar opposite effects on liver‐specific and cardiovascular mortality. Moreover, interactions of the NAFLD risk alleles with adiposity for liver‐specific mortality were found (Pinteraction < 0.05). The reduced serum VLDL1 concentration was responsible for the increased liver‐specific mortality related to NAFLD risk alleles. Conclusion: The PNPLA3 rs738409 C>G variant and its combination with TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants increase liver‐specific mortality but reduce cardiovascular mortality in overweight/obese Chinese. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B Virus (HBV) infection has high morbidity, high pathogenicity and unclear pathogenesis. To elucidate the relationship between HBV replication and host phospholipid metabolites, we measured 10 classes of phospholipids in serum of HBV infected patients and cells using ultra performance liquid chromatograph-triple quadruple mass spectrometry. We found that the levels of phosphatidylcholine (PC), phosphatidylethanolamine, and lyso-phosphatidic acid were increased in HBsAg (+) serum of infected patients compared with HBsAg (−), while phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and sphingomyelin were decreased, which were confirmed in an HBV infected HepG2.2.15 cell line. We further evaluated the enzyme levels of PC pathways and found that PCYT1A and LPP1 for PC synthesis were up-regulated after HBV infection. Moreover, HBV replication was inhibited when PCYT1A and LPP1 were inhibited. These results indicated that the PC synthesis in HBV infected host are regulated by PCYT1A and LPP1, which suggests that PCYT1A, LPP1 could be new potential targets for HBV treatment. [ABSTRACT FROM AUTHOR]

ZhiShiXiaoPi Tang (ZSXPT) is a Chinese traditional medicine formula that contains 10 Chinese traditional medicine substances. It has been widely used to treat patients with functional dyspepsia (FD). However, the protective effect of ZSXPT and its molecular mechanisms in FD still remain elusive. To investigate the protective effect of ZSXPT on autophagy induced by Corticosterone (Cort) in PC12 cells which have typical neuron characteristics and have been widely used as a model system for depression studies and FD rats, and explore its underlying mechanisms. In this study, high-performance liquid chromatography fingerprint analysis was performed to characterize the chemical composition of ZSXPT. Depression-induced autophagy, ROS generation, and changes in mitochondrial membrane potential (MMP) were investigated in Cort-induced PC12 cells and in FD rats to evaluate the protective effects of ZSXPT. Our results show that ZSXPT treatment protects neurons against Cort-induced damage and apoptosis by increasing cell viability and reducing the release of lactate dehydrogenase. ZSXPT decreased Cort-induced ROS generation, increased MMP, and accelerated autophagy through the blockade of the mammalian target of rapamycin (mTOR) pathway. Moreover, we observed similar findings when we studied ZSXPT in a rat model of FD. Our in vitro and in vivo results indicate that the neuroprotective effect of ZSXPT against autophagy-induced damage and apoptosis occurs mainly by blocking the mTOR pathway in Cort-induced PC12 cells and in FD rats. Taken together, these data provide reliable experimental evidence and explain the molecular mechanism by which ZSXPT ameliorates FD. Image 1 [ABSTRACT FROM AUTHOR]

The asymmetric simple exclusion process (ASEP) is a paradigmatic model for nonequilibrium systems and has been used in many applications. Airplane boarding provides another interesting example where this framework can be applied. We propose a simple model for boarding process, in which a particle moves along a one-dimensional aisle after being injected, and finally is removed at a reserved site. Different from the typical ASEP model, particles are removed in a disorderly or a parallel way. Detailed calculations and discussions of some related characteristics, such as mean boarding time and parallelism indicator, are provided based on Monte-Carlo simulations. Results show that three phases exist in the boarding process: free-flow, jamming and maximum current. Transitions between these phases are governed by the difference between the injection and removal rate. Further analysis shows how the scaling behavior depends on the system size and the boarding conditions. Those results emphasize the importance of utilizing the whole length of the aisle to reduce the boarding time when designing an efficient boarding strategy. [ABSTRACT FROM AUTHOR]

Background: Generally, low-density lipoprotein (LDL) particle size can be inferred from the LDL cholesterol concentration to total apolipoprotein B concentration ratio (LDL-C/ApoB ratio, hereinafter called LAR), which is a good predictor of cardiovascular disease. However, the predictive ability of LAR for mortality risk in the general population is still unclear. This study aimed to explore the association between LAR and cardiovascular as well as all-cause mortality among American adults. Methods: The present study was a secondary analysis of existing data from the National Health and Nutrition Examination Survey (NHANES). The final analysis included 12,440 participants from 2005 to 2014. Survival differences between groups were visualized using Kaplan‒Meier curves and the log-rank test. The association of LAR with cardiovascular and all-cause mortality was evaluated using multivariate Cox regression and restricted cubic spline analysis. Age, sex, coronary artery disease, diabetes, lipid-lowering medication use and hypertriglyceridemia were analyzed in subgroup analyses. Results: The median age in the study cohort was 46.0 years [interquartile range (IQR): 31.0–62.0], and 6,034 (48.5%) participants were male. During the follow-up period, there were 872 (7.0%) all-cause deaths and 150 (1.2%) cardiovascular deaths. Compared with individuals without cardiovascular events, those who experienced cardiovascular deaths had a lower LAR (1.13 vs. 1.25) (P < 0.001). The adjusted Cox regression model indicated that lower LAR was an independent risk factor for both cardiovascular [hazard ratio (HR) = 0.304, 95% confidence interval (CI): 0.114–0.812] and all-cause mortality (HR = 0.408, 95% CI: 0.270–0.617). Moreover, a significant age interaction was observed (P for interaction < 0.05), and there was a strong association between LAR and mortality among participants over 65 years of age. Further analysis showed an inverse association between LAR and both cardiovascular and all-cause mortality. Conclusions: LAR can independently predict cardiovascular and all-cause mortality in the general population. [ABSTRACT FROM AUTHOR]

Objective·Previous studies showed that hepatitis B virus (HBV) infection caused outstanding changes in host lipoproteins. However, there are no reports on such component changes of lipoprotein subfractions. This study aimed to quantify the HBV-caused changes in the serum lipoprotein subfractions and their components. Methods·Hepatitis B surface antigen-positive [HBsAg (+ )] patients at Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March to June 2017 were included (n=40), and 40 HBsAg-negative [HBsAg (-)] population were matched as controls. Serum lipoprotein subfractions and their components were quantified by using 1H-NMR. Orthogonal partial least-squares discriminant analysis (OPLS-DA), variance analysis between the two groups, logistic regression analysis and Spearman correlation analysis were conducted to reveal the lipoprotein changes in chronic HBV patients against controls. Results·HBsAg (+) population had significantly lower levels in most lipoprotein subfractions than HBsAg (-) population. After adjustments for age, gender, hypertension, diabetes mellitus and coronary heart disease, the levels of total VLDL, VLDL1-VLDL3, IDL, HDL4, non-HDL and their components were protective factors for HBV infection (OR < 1, P < 0.01). In contrast, VLDL5-(TAG/LP) was a risk factor for HBV infection (OR > 1, P < 0.01). In addition, the severity of inflammation in the HBsAg (+) population was negatively correlated with the levels of lipids in HDL4 with correlation coefficient ranging from -0.71 to -0.51 (P≤ 0.002). Six lipoprotein subfractions were obtained through feature screening, and the AUC of HBV infection diagnosis model was 0.861. Conclusion·HBV infection causes significant changes in liver-excretion of lipoproteins and their circulation metabolism; the lipoprotein phenotypes can differentiate HBV-infected patients from controls. [ABSTRACT FROM AUTHOR]

To characterize the gut bacteriome, mycobiome and serum metabolome profiles in polycystic ovary syndrome (PCOS) patients with normal/overweight individuals and evaluate a potential microbiota-related diagnostic method development for PCOS, 16S rRNA and ITS2 gene sequencing using 88 fecal samples and 87 metabolome analysis from serum samples are conducted and PCOS classifiers based on multiomics markers are constructed. There are significant bacterial, fungal community and metabolite differences among PCOS patients and healthy volunteers with normal/overweight individuals. Healthy individuals with overweight/obesity display less abnormal metabolism than PCOS patients and uniquely higher abundance of the fungal genus Mortierella. Nine bacterial genera, 4 predicted pathways, 11 fungal genera and top 30 metabolites are screened out which distinguish PCOS from healthy controls, with AUCs of 0.84, 0.64, 0.85 and 1, respectively. The metabolite-derived model is more accurate than the microbe-based model in discriminating normal BMI PCOS (PCOS-LB) from normal BMI healthy (Healthy-LB), PCOS-HB from Healthy-HB. Featured bacteria, fungi, predicted pathways and serum metabolites display higher associations with free androgen index (FAI) in the cooccurrence network. In conclusion, our data reveal that hyperandrogenemia plays a central role in the dysbiosis of intestinal microecology and the change in metabolic status in patients with PCOS and that its effect exceeds the role of BMI. Healthy women with high BMI showed unique microbiota and metabolic features.The priority of predictive models in discriminating PCOS from healthy status in this study were serum metabolites, fungal taxa and bacterial taxa. [ABSTRACT FROM AUTHOR]

A simple airplane boarding model is built much like an asymmetric exclusion process (ASEP). The dynamics of the model is constrained by local interference between passengers and global seat assignments for individuals. We perform extensive Monte Carlo simulations by using a parallel update rule to determine quantities like boarding time and sequence correlation. Our results clarify the scaling behavior in boarding process and identify a critical value of arrival time interval for boarding time threshold. Three different phases (steady, intermediate and linear) with respect to the boarding time are distinguished and the mechanism behind phase transition is further discussed. [ABSTRACT FROM AUTHOR]

The increasing incidence of obesity has led to widespread attention in the exploration of natural ingredients. Ginseng polysaccharides (PGP), the main components from Panax ginseng , have been reported potential effect to attenuate obesity and regulate lipid metabolism. In this study, we found that PGP inhibited the high-fat diet (HFD)-induced weight gain, fat ratio and fat tissue weight after 8-week administration. Serum and liver lipid analysis showed that PGP decreased the levels of triglyceride and total cholesterol, which was mediated by the inhibition of key genes for fatty acid and cholesterol metabolisms. Metabolomics studies showed that the inhibitory effect of PGP on liver lipid accumulation was significantly correlated with its regulation of citric acid cycle and lysine degradation. PGP regulated the expression of genes related to lysine degradation in both liver tissue and hepatocytes. In addition, PGP reshaped the composition of fecal microbiota at the genus and species levels in obese mice. Spearman's correlation analysis demonstrated that Staphylococcus sciuri , Staphylococcus lentus , and Pseudoflavonifractor sp. An85 may be the potential targets that PGP maintains the abundance of l -lysine against obesity. It concluded that PGP can attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation. [ABSTRACT FROM AUTHOR]

Consistent retention time (t R) of metabolites is vital for identification in metabolomic analysis with ultrahigh-performance liquid-chromatography (UPLC). To minimize inter-experimental t R variations from the reversed-phase UPLC-MS, we developed an endo genous r etention- i ndex (endoRI) using in-sample straight-chain acylcarnitines with different chain-length (L C , C0–C26) without additives. The endoRI-corrections reduced the t R variations caused by the combined changes of mobile phases, gradients, flow-rates, elution time, columns and temperature from up to 5.1 min–0.2 min for most metabolites in a model metabolome consisting of 91 metabolites and multiple biological matrices including human serum, plasma, fecal, urine, A549 cells and rabbit liver extracts. The endoRI-corrections also reduced the inter-batch and inter-platform t R variations from 1.5 min to 0.15 min for 95 % of detected features in the above biological samples. We further established a quantitative model between t R and L C for predicting t R values of acylcarnitines when absent in samples. This makes it possible to compare metabolites' t R from different t R databases and the UPLC-based metabolomic data from different batches. [Display omitted] • An endo genous r etention- i ndex derived from in-sample acylcarnitines for minimizing inter-experimental t R variations in metabolomics with RPLC-MS. • The endoRI-correction reduced inter-batch t R variations to below 0.2 min for metabolites in multiple biological samples. • A mathematical model enables accurate prediction of t R for acylcarnitines with no standards. [ABSTRACT FROM AUTHOR]

Background: The aims of this study were to compare the efficacy of different androgens measured by liquid chromatography-mass spectrometry (LC-MS/MS) in representing hyperandrogenemia and to evaluate adrenal-origin androgens with a dexamethasone suppression test in patients with polycystic ovary syndrome (PCOS). Methods: One hundred and two patients with PCOS and 41 healthy volunteers were recruited and total serum testosterone (TT), androstenedione (AD), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were measured by LC-MS/MS. ROC analysis was performed to compare the efficacy of different androgens in representing hyperandrogenemia. Dexamethasone suppression test was performed in 51 patients with PCOS and above indicators were measured after dexamethasone administration. The prediction efficacy of DHEA and DHEA-S at baseline in the dexamethasone suppression test was evaluated with ROC analysis. Results: The AUCs of TT, AD, free androgen index (FAI) and DHEA-S in ROC analysis for representing hyperandrogenemia were 0.816, 0.842, 0.937 and 0.678, respectively. The optimal cutoff value of TT was 0.337 ng/ml, with a sensitivity of 72.0% and specificity of 82.93%. The optimal cutoff value for AD was 1.309 ng/ml, with a sensitivity of 81.0% and specificity of 73.17%. The optimal cutoff value of the FAI was 2.50, with a sensitivity of 87.0% and specificity of 92.68%. Alternatively, AD or FAI more than the optimal cutoff values as evidence of hyperandrogenemia had the highest sensitivity of 91.18%. The levels of cortisol, DHEA and DHEA-S were all suppressed to narrow ranges after dexamethasone administration. Nine and 8 of 51 patients with PCOS had significant decreases in TT and AD, respectively. DHEA can be used as a indicator for predicting significant decrease of TT in dexamethasone suppression test with cutoff value of 13.28 ng/ml. A total of 27.5% (14/51) of patients had DHEA-S excess, but only 1 of 9 patients who had a significant decrease in TT had elevated level of DHEA-S at baseline. Conclusions: AD measured by LC-MS/MS can represent hyperandrogenemia in PCOS patients and, combined with TT or FAI, can improve the screening efficiency of hyperandrogenemia. Seventeen percent of PCOS patients had adrenal-origin androgen dominance, with TT significantly decreasing after 2 days of dexamethasone administration. Adrenal-origin androgen dominance was not parallel with DHEA-S excess in patients with PCOS. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the efficacy of SHBG in predicting insulin resistance (IR) in newly diagnosed, untreated patients with polycystic ovary syndrome (PCOS). Hundred newly diagnosed, untreated patients with PCOS and 61 subjects without PCOS (41 healthy volunteers with normal BMI and 20 subjects with overweight/obese) were included in the study. Receiver-operating characteristic (ROC) analysis was used to assess the effectiveness of SHBG in predicting IR in overweight/obese and non-overweight PCOS patients and the optimal cut-off values of SHBG. The results showed negative correlations between log-SHBG and log-I0 (r = − 0.372, P < 0.001) and log-SHBG and log-Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (r = − 0.393, P < 0.001) after adjusting for blood pressure, serum lipid, age, and body mass index (BMI) in all of the PCOS patients. In patients with IR (defined as HOMA-IR ≥2.29), the area under the ROC curves (AUCs) of the SHBG for ROC analysis in the non-overweight group, overweight/obese group, and all PCOS patients were 0.774 (P = 0.0001), 0.922 (P = 0.0001), and 0.885 (P = 0.0001), respectively. The optimal cut-off value of SHBG was 37 nmol/L with a sensitivity of 97.62% and specificity of 80.85% in the overweight group. In patients with IR (HOMA-IR ≥2.5), the AUCs of SHBG for ROC analysis in the non-overweight group, overweight/obese group, and all PCOS patients were 0.741 (P = 0.0003), 0.928 (P = 0.0001), and 0.880 (P = 0.0001), respectively. The optimal cut-off value of SHBG was 30.2 nmol/L with a sensitivity of 97.44% and specificity of 82.69% in the overweight/obese group. In conclusion, this study observed a negative correlation between SHBG and HOMA-IR in PCOS patients after adjustment of confounding factors. SHBG was an independent influential factor of HOMA-IR and can be used as a positive predictive marker for IR in PCOS patients, especially in those who are overweight/obese. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of mortality and morbidity worldwide. Understanding the underlying mechanisms is important for developing effective therapies for treating stroke. Autophagy is a self-eating cellular catabolic pathway, which plays a crucial homeostatic role in the regulation of cell survival. Increasing evidence shows that autophagy, observed in various cell types, plays a critical role in brain pathology after ischemic stroke. Therefore, the regulation of autophagy can be a potential target for ischemic stroke treatment. In the present review, we summarize the recent progress that research has made regarding autophagy and ischemic stroke, including common signaling pathways, the role of autophagic subtypes (e.g. mitophagy, pexophagy, aggrephagy, endoplasmic reticulum-phagy, and lipophagy) in ischemic stroke, as well as the current methods for autophagy detection and potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

Atherosclerosis progression and regression studies are related to its prevention and treatment. Although we have gained extensive knowledge on germline phospholipid transfer protein (PLTP) deficiency, the effect of inducible PLTP deficiency in atherosclerosis remains unexplored. We generated inducible PLTP (iPLTP)-knockout (KO) mice and measured their plasma lipid levels after feeding a normal chow or a Western-type diet. Adenovirus associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9) was used to induce hypercholesterolemia in the mice. Collars were placed around the common carotid arteries, and atherosclerosis progression and regression in the carotid arteries and aortic roots were evaluated. On a normal chow diet, iPLTP-KO mice exhibited decreased cholesterol, phospholipid, apoA-I, and apoB levels compared with control mice. Furthermore, the overall amount of high-density lipoprotein (HDL) particles was reduced in these mice, but this effect was more profound for larger HDL particles. On a Western-type diet, iPLTP-KO mice again exhibited reduced levels of all tested lipids, even though the basal lipid levels were increased. Additionally, these mice displayed significantly reduced atherosclerotic plaque sizes with increased plaque stability. Importantly, inducible PLTP deficiency significantly ameliorated atherosclerosis by reducing the size of established plaques and the number of macrophages in the plaques without causing lipid accumulation in the liver. Induced PLTP deficiency in adult mice reduces plasma total cholesterol and triglycerides, prevents atherosclerosis progression, and promotes atherosclerosis regression. Thus, PLTP inhibition is a promising therapeutic approach for atherosclerosis. [Display omitted] • Inducible phospholipid transfer protein (PLTP) deficiency reduces plasma cholesterol levels and very low-density lipoproteins (VLDL) production. • Inducible PLTP deficiency attenuates AAV8-PCSK9- and Western-type diet-induced atherosclerosis progression. • Poor regression of atherosclerotic plaques after low-density lipoprotein cholesterol lowering in mice can be overcome by PLTP depletion. • Inhibiting PLTP in patients with atherosclerosis could be an effective approach for the treatment of the disease. [ABSTRACT FROM AUTHOR]

COVID‐19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID‐19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID‐19‐infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue‐specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN‐I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID‐19‐infected patients experiencing milder disease symptoms showed robust T‐cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS‐CoV‐2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID‐19. SYNOPSIS: Proteomics, metabolomics and RNAseq data map immune responses in COVID‐19 patients with different disease severity, revealing molecular makers associated with disease progression and alterations of tissue‐specific proteins. A multi‐omics profiling of the host response to SARS‐CoV2 infection in 66 clinically diagnosed and laboratory confirmed COVID‐19 patients and 17 uninfected controls.Significant correlations between multi‐omics data and key clinical parameters.Alteration of tissue‐specific proteins and exRNAs.Enhanced activation of immune responses is associated with COVID‐19 pathogenesis.Biomarkers to predict COVID‐19 clinical outcomes pending clinical validation as prospective marker. [ABSTRACT FROM AUTHOR]

The highly c -disordered hexagonal birnessite possessing abundant out-of-layer oxygen vacancies demonstrated enhanced catalytic performance toward ozone decomposition. [Display omitted] • The in-layer oxygen vacancy (V O) and the out-of-layer V O were identified on the c -disordered birnessites. • The out-of-layer V O was more abundant with the increase of c -disordering. • Compared to the in-layer V O , the out-of-layer V O was more advantageous to O 3 decomposition. Ozone pollution has long been a hazard to human health and ecosystems. Manganese oxides have been intensively investigated for O 3 decomposition, but improving the catalytic activity and stability of MnO x remains challenging. Herein, hexagonal birnessites with varying degrees of c -disordering were synthesized and showed strikingly different catalytic activities. As the degree of c -disordering increase, the highly disordered birnessite (HDB) possessed the highest content of oxygen vacancies (V O) and thus demonstrated the superior catalytic activity. The HDB remained a high O 3 conversion efficiency of 96% even after reaction for 24 h at a high space velocity of 600,000 mL·g−1·h−1 and under the relative humidity of 50%. At the same time, HDB could be easily regenerated after heating for 1 h at 200 °C under air atmosphere. We found two different types of V O (the in-layer V O and the out-of-layer V O) on the c -disordered birnessites, and the out-of-layer V O was more stable than the in-layer V O. The out-of-layer V O was beneficial to desorption of the intermediate O 2 2– and reduced the competitive adsorption of H 2 O, which accounted for the enhanced catalytic stability of HDB. This work may provide guidance for the V O engineering in metal oxides toward the catalytic purification of waste gases. [ABSTRACT FROM AUTHOR]

• Present a series of circle antipode experiments and recognize the trajectories. • Discover the motion navigation strategies and conflict avoidance behaviors. • Obtain the distribution law of route length, route potential, travel time and speed. • Build a macroscopic index based evaluation framework for pedestrian models. We organized a series of novel circle antipode experiments in which pedestrians are uniformly initialized on the circle and they are required to leave for their antipodal positions simultaneously. In the experiments, a conflicting area is naturally formulated in the center region due to the converged shortest routes, so the practical motion navigation strategies, as well as the conflict avoidance behaviors, can be explored and summarized. Besides, the symmetric experimental conditions of pedestrians, e.g., symmetric starting points, symmetric destination points, and symmetric surroundings, lay the foundation for further quantitative comparisons among participants. In the paper, the pedestrian trajectories are recognized, and the pedestrian dynamics are accordingly investigated from the perspective of macroscopic indexes, i.e., route length, route potential, travel time, velocity and time-series. It is found that the route length has a log-normal distribution, the route potential obeys the exponential distribution, and the travel time is normally distributed as well as the speed. Furthermore, a model evaluation based on the experimental results is performed, using four distribution indexes and two time series indexes in both space and time dimensions. We graded the simulated distribution indexes by applying a Kolmogorov-Smirnov (K-S) test based method and the simulated time series indexes by a Dynamic Time Warping (DTW) based method. We evaluated two models: the traditional social force model, the modified model with default parameters and with calibrated parameters. The evaluation results showed that the two models cannot well reproduce the six macroscopic indexes, which indicates that the models do not capture the route choice and conflict avoidance behaviors of pedestrians. Our study is expected to shed light on the pedestrian modeling. Specifically, it indicates that apart from classical indexes such as a fundamental diagram, more comprehensive indexes are needed to evaluate the pedestrian flow models. [ABSTRACT FROM AUTHOR]

Respiratory diseases mainly include asthma, influenza, pneumonia, chronic obstructive pulmonary disease, pulmonary hypertension, lung fibrosis, and lung cancer. Given their high prevalence and poor prognosis, the prevention and treatment of respiratory diseases are increasingly essential. In particular, the development for the novel strategies of drug treatment has been a hot topic in the research field. Ginsenosides are the major component of Panax ginseng C. A. Meyer (ginseng), a food homology and well-known medicinal herb. In this review, we summarize the current therapeutic effects and molecular mechanisms of ginsenosides in respiratory diseases. The reviewed studies were retrieved via a thorough analysis of numerous articles using electronic search tools including Sci-Finder, ScienceDirect, PubMed, and Web of Science. The following keywords were used for the online search: ginsenosides, asthma, influenza, pneumonia, chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), lung fibrosis, lung cancer, and clinical trials. We summarized the findings and the conclusions from 176 manuscripts on ginsenosides, including research articles and reviews. Ginsenosides Rb1, Rg1, Rg3, Rh2, and CK, which are the most commonly reported ginsenosides for treating of respiratory diseases, and other ginsenosides such as Rh1, Rk1, Rg5, Rd and Re, all primarily reduce pneumonia, fibrosis, and inhibit tumor progression by targeting NF-κB, TGF-β/Smad, PI3K/AKT/mTOR, and JNK pathways, thereby ameliorating respiratory diseases. This review provides novel ideas and important aspects for the future research of ginsenosides for treating respiratory diseases. [Display omitted] • 176 papers were reviewed for ginsenosides in the treatment of respiratory diseases. • Ginsenosides Rb1, Rg1, Rg3, Rh2, and CK are commonly for treating respiratory diseases. • The NF-κB, TGF-β/Smad, PI3K/AKT/mTOR, and JNK pathways are molecular mechanisms. [ABSTRACT FROM AUTHOR]

Panax spp. (Araliaceae family) are widely used medicinal plants and they mainly include Panax ginseng C.A. Meyer, Panax quinquefolium L. (American ginseng), and Panax notoginseng (notoginseng). Polysaccharides are the main active ingredients in these plants and have demonstrated diverse pharmacological functions, but comparisons of isolation methods, structural features, and bioactivities of these polysaccharides have not yet been reported. This review summarizes recent advances associated with 112 polysaccharides from ginseng, 25 polysaccharides from American ginseng, and 36 polysaccharides from notoginseng and it compares the differences in extraction, purification, structural features, and bioactivities. Most studies focus on ginseng polysaccharides and comparisons are typically made with the polysaccharides from American ginseng and notoginseng. For the extraction, purification, and structural analysis, the processes are similar for the polysaccharides from the three Panax species. Previous studies determined that 55 polysaccharides from ginseng, 18 polysaccharides from American ginseng, and 9 polysaccharides from notoginseng exhibited anti-tumor activity, immunoregulatory effects, anti-oxidant activity, and other pharmacological functions, which are mediated by multiple signaling pathways, including mitogen-activated protein kinase, nuclear factor kappa B, or redox balance pathways. This review can provide new insights into the similarities and differences among the polysaccharides from the three Panax species, which can facilitate and guide further studies to explore the medicinal properties of the Araliaceae family used in traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Higher levels of glucocorticoids (GCs), and impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis may cause or exacerbate the occurrence of metabolic and psychiatric disorders. It has been reported that ginseng saponin extract (GSE) has an inhibitory effect on the hyperactivity of the HPA axis induced by stresses and increased corticosterone level induced by intraperitoneal injection of adrenocorticotrophic hormone (ACTH) in mice. However, the molecular mechanisms by which GSE and its active ginsenosides inhibit corticosterone secretion remain elusive. Y1 mouse adrenocortical cells were treated with ACTH for up to 60 min to establish a cell model of corticosterone secretion. After treatment with different concentrations of GSE or ginsenoside monomers for 24 h prior to the addition of ACTH, analyses of cAMP content, PKA activity, and the levels of steroidogenesis regulators, melanocortin-2 receptor (MC2R), and melanocortin-2 receptor accessory protein (MRAP) in ACTH-induced Y1 cells were performed. We demonstrated that GSE inhibits ACTH-stimulated corticosterone production in Y1 cells by inhibiting factors critical for steroid synthesis. Ginsenoside Rd, an active ingredient of GSE, inhibits corticosterone secretion in the cells and impedes ACTH-induced corticosterone biosynthesis through down-regulation of proteins in the cAMP/PKA/CREB signaling pathway. In addition, Western blot and qPCR analyses showed that ginsenoside Rd attenuated the induction of MC2R and MRAP by ACTH. Our findings indicate that ginsenoside Rd inhibits ACTH-induced corticosterone production through blockading the MC2R-cAMP/PKA/CREB pathway in adrenocortical cells. Overall, this mechanism may represent an important therapeutic option for the treatment of stress-related disorders, further supporting the pharmacological benefits of ginseng. [ABSTRACT FROM AUTHOR]