Glutathione S-transferase activity facilitates rice tolerance to the barnyard grass root exudate DIMBOA.

BACKGROUND: In paddy fields, the noxious weed barnyard grass secretes 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) to interfere with rice growth. Rice is unable to synthesize DIMBOA. Rice cultivars with high or low levels of allelopathy may respond differently to DIMBOA. RESULTS: In this study, we found that low concentrations of DIMBOA (≤ 0.06 mM) promoted seedling growth in allelopathic rice PI312777, while DIMBOA (≤ 0.08 mM) had no significant influence on the nonallelopathic rice Lemont. DIMBOA treatment caused changes in the expression of a large number of glutathione S-transferase (GST) proteins, which resulting in enrichment of the glutathione metabolic pathway. This pathway facilitates plant detoxification of heterologous substances. The basal levels of GST activity in Lemont were significantly higher than those in PI312777, while GST activity in PI312777 was slightly induced by increasing DIMBOA concentrations. Overexpression of GST genes (Os09g0367700 and Os01g0949800) in these two cultivars enhanced rice resistance to DIMBOA. CONCLUSIONS: Taken together, our results indicated that different rice accessions with different levels of allelopathy have variable tolerance to DIMBOA. Lemont had higher GST activity, which helped it tolerate DIMBOA, while PI312777 had lower GST activity that was more inducible. The enhancement of GST expression facilitates rice tolerance to DIMBOA toxins from barnyard grass root exudates.

Involvement of IGF1 in endoplasmic reticulum stress contributes to cataract formation through regulating Nrf2/NF-κB signaling.

Endoplasmic reticulum (ER) stress is reportedly involved in the development of ophthalmic diseases. This study aimed to investigate the role and potential mechanism of insulin-like growth factor 1 (IGF1) in ER stress. A mouse cataract model was constructed by subcutaneous injection of sodium selenite, and sh-IGF1 was used to evaluate the effect of silencing IGF1 on cataract progression. Slit-lamp and histological examination of the lens were performed to examine lens damage. The regulatory effects of IGF1 on inflammatory responses, oxidative stress, and ER stress were evaluated using ELISA, reverse transcription-quantitative PCR (RT-qPCR), and immunoblotting analysis. Tunicamycin was used to induce ER stress in the lens of epithelial cells. The NF-E2 related factor-2 (Nrf2) inhibitor ML385 and nuclear factor-κB (NF-κB) agonist diprovocim were used to confirm whether IGF1 regulates inflammation and ER stress through Nrf2/NF-κB signaling. Silencing IGF1 alleviated lens damage and reduced lens turbidity in the cataract mice. Silencing IGF1 inhibited inflammatory response, oxidative stress and ER stress response. Meanwhile, IGF1 was highly expressed in sodium selenite-treated lens epithelial cells. The ER stress agonist tunicamycin suppressed cell viability as well as induced ER stress, oxidative stress and inflammation. Silencing IGF1 increased cell viability, EdU-positive rate and migration. Also, silencing of IGF1 reduced inflammation and ER stress via regulating Nrf2/NF-κB pathway. This study reveals silencing IGF1 attenuated cataract through regulating Nrf2/NF-κB signaling, which shares novel insights into the underlying mechanism of cataract and provides potential therapeutic target for cataract.

Phase 1 dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of FCN-159 in adults with neurofibromatosis type 1-related unresectable plexiform neurofibromas.

BACKGROUND: Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. METHODS: This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. RESULTS: Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug-related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. CONCLUSIONS: FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

[Research and development strategies of new Chinese medicines based on new regulations].

In recent years, only a small number of new Chinese medicines have been approved for marketing, which has embodied the bottleneck in the development of the Chinese medicine industry. To tackle this problem, the National Medical Products Administration has issued a series of regulations and technical requirements. In the context of new regulations, this study deeply explored the research and development strategies of new Chinese medicines under the guidance of the new classification of drug registration, and discussed the key technical issues in the research and development.

Combined polymorphisms in genes encoding the inflammasome components NLRP3 and CARD8 confer risk of ischemic stroke in men.

INTRODUCTION: Previous studies have reported the involvement of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in the inflammatory activation and pathophysiology of Ischemic Stroke (IS). Variations in genes encoding the constituent proteins of NLRP3 inflammasome can alter the risk of IS. OBJECTIVE: We investigated the role of the NLRP3 inflammasome in the pathogenesis of IS by establishing associations between combined polymorphisms of caspase recruitment domain-containing protein 8 (CARD8) rs2043211 and NLRP3 rs10754558 and the susceptibility to IS in a Chinese population. METHODS: Single nucleotide polymorphisms (SNPs) in CARD8 rs2043211 and NLRP3 rs10754558 were analyzed using TaqMan SNP genotyping assays in patients with IS (n=234) and healthy controls (n=115). Logistic regression analysis was carried out to evaluate potential interactions between CARD8 and NLRP3. RESULTS: Compared with healthy controls, there were no significant differences in the minor allele frequency (MAF) and the genotype frequency of NLRP3 rs10754558 or CARD8 rs2043211 in patients with IS(P>0.05). After stratification by gender, there was an increased risk for IS in men carrying heterozygous CARD8 rs2043211 when a co-dominant genetic model was applied (P=0.021, OR=3.83[1.22-12.03]). Logistic regression analysis indicated that men carrying both CARD8 rs2043211 AT and NLRP3 rs10754558 CG had a significantly higher risk of IS (P=0.046, OR=7.116[1.033-49.044]). CONCLUSIONS: Nucleotide variations in the genes encoding NLRP3 inflammasome proteins may be important to IS, and men carrying CARD8 rs2043211 and NLRP3 rs10754558, both heterozygous, confer a higher risk of IS.

Application of iTRAQ-Based Quantitative Proteomics Approach to Identify Deregulated Proteins Associated with Liver Toxicity Induced by Polygonum Multiflorum in Rats.

BACKGROUND/AIMS: Clinical reports on adverse reactions that result from Polygonum multiflorum (PM) and its preparations, especially regarding liver injury, have recently received widespread attention. This study aimed to investigate the mechanism of hepatotoxicity induced by different PM extracts through iTRAQ quantitative proteomics. METHODS: The different PM extracts were orally administrated for 90 days to rats, and the hepatotoxicity effect was evaluated through measurement of biochemical indexes, oxidative damage indexes and hematoxylin-eosin (HE) staining. Then, the hepatotoxicity mechanism was investigated by iTRAQ quantitative proteomics. RESULTS: The results of biochemical and histopathological analyses showed that liver injury occurred in all groups of rats given by various PM extracts, which proved all of the PM extracts could induce hepatotoxicity. The hepatotoxicity mechanism may differ between the total extract group and the other groups through the results of biochemical indicators. The iTRAQ proteomics study showed that hepatotoxicity resulting from PM was mainly related to the abnormal activity of mitochondrion function-related oxidative phosphorylation pathways. CONCLUSION: This iTRAQ proteomics study revealed that the hepatotoxicity induced by PM is primarily related to the oxidative phosphorylation pathways. NADH dehydrogenase family proteins and Slc16a2 could be potential biomarkers of hepatotoxicity resulting from PM.

Identification of potential crucial genes associated with early-onset pre-eclampsia via a microarray analysis.

AIM: This study aimed to identify potential key genes related to early-onset pre-eclampsia (EOPET), and to obtain a better understanding of the molecular mechanisms of this disease. METHODS: The microarray dataset GSE44711 was obtained from the Gene Expression Omnibus, including eight chorionic villi samples from EOPET placentas and eight normal controls. The differentially expressed genes (DEG) were identified using the LIMMA package, and their potential functions were predicted by Gene Ontology (GO) enrichment analysis. Furthermore, protein-protein interactions (PPI) were obtained from the STRING database, and the PPI network was visualized by Cytoscape software. Then, significant modules were screened out from the PPI network, and GO enrichment analysis for DEG in modules was performed. Also, the potential transcription factors (TF) regulating DEG in modules were predicted, and TF-DEG network was visualized by Cytoscape. RESULTS: A total of 270 upregulated and 200 downregulated DEG were identified. A set of DEG was related to functions such as female pregnancy and hormone metabolic process (e.g. NGF). In PPI network modules, some DEG (e.g. SERPINE1 and FN1) were significantly associated with anatomical structure morphogenesis, and some other DEG (e.g. GZMA) were relevant to the immune system process. Furthermore, SERPINE1, NGF, and FN1 interacted with each other and were regulated by RELA. CONCLUSION: The DEG related to hormone metabolic process (e.g. NGF), anatomical structure morphogenesis (e.g. SERPINE1 and FN1), and immune system process (e.g. GZMA) are predicted to play significant roles in the progress of EOPET, which will be confirmed by experiments in future.

Analysis of differentially expressed genes between endometrial carcinosarcomas and endometrioid endometrial carcinoma by bioinformatics.

PURPOSE: This study aimed to explore the underlying molecular mechanisms of endometrial carcinosarcomas (ECS) and endometrioid endometrial carcinoma (EEC) by bioinformatics analysis. METHODS: Gene expression profile GSE33723 was downloaded from the Gene Expression Omnibus. A total of 15 ECS and 23 EEC samples were used to identify the differentially expressed genes (DEGs) by significance analysis of microarrays. After construction of protein-protein interaction (PPI) network, Gene Ontology (GO) functional and pathway enrichment analyses of DEGs were performed, followed by network module analysis. RESULTS: A total of 49 DEGs were identified between EEC and ECS samples. In the PPI network, TP53 (tumor protein p53) was selected as the highest degree, hub centrality and betweenness. The top 10 enriched GO terms including regulation of cell death and top 10 significant pathways including cell cycle were selected. After network module analysis, PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1) and AKT2 (v-akt murine thymoma viral oncogene homolog 2) were selected as the co-expressed genes in the states of ECS while STAT3 (signal transducer and activator of transcription 3) and JAZF (JAZF zinc finger 1) were selected as the co-expressed genes in the states of EEC. CONCLUSIONS: The DEGs, such as TP53, PIK3R1 and AKT2 may be used for targeted diagnosis and treatment of ECS while STAT3 and JAZF1 may be served as a target for EEC.

[Matrix formulation of chaizhi cataplasma optimized by D-optimal mixture design combined with multiple mechanical indicators and its in vitro evaluation].

To optimize the matrix formulation of Chaizhi cataplasma (CC) and investigate its release and transdermal absorption properties in vitro. The optimized matrix formulation of cataplasma containing liquid herbal extract is determined by using D-optimal mixture design, with initial bonding strength, endurance bonding strength and gel strength as the evaluating indicators. Modified Franz diffusion cells were used to study the in vitro release and transdermal absorption of geniposide in CC. The optimized matrix formulation of CC contained NP700, aluminum glycinate, tartaric acid, glycerin, PVPK90 and water (9∶0.7∶0.8∶30∶5∶30.5). Cumulative release rate of geniposide in CC was (77.02±3.73)% in 24 h. The percutaneous penetration rate of geniposide was 7.25 µg•cm⁻²â€¢h⁻¹ and the 24 h permeated amount was (156.22±4.90) µg•cm⁻². The optimized CC prepared by the D-optimal mixture design showed a good adhesion and formability. The in vitro release of the geniposide in CC was in accordance with the first order equation, while its in vitro transdermal absorption was close to the zero order equation.

Simultaneous determination of 14 constituents of Radix polygoni multiflori from different geographical areas by liquid chromatography-tandem mass spectrometry.

Radix polygoni multiflori (RPM) has antioxidative, anti-aging, liver-protective and antihuman cytomegalovirus activity. It has been proved to be hepatotoxic. Considering multiple ingredients to control RPM quality is essential. The aim of this study was to establish a simple, rapid method using resolution liquid chromatography coupled with a triple quadruple mass spectrometry to identify and quantify the major bioactive constituents in RPM. The method was applied to analyze 14 marker batches from manufacturers from the same province. The ultrasonic extracts of all samples were determined by LC-MS/MS, and assessed by hierarchical cluster analysis. The proposed method was applied to analyze 21 batches of samples with acceptable linearity (R(2) , 0.9930-0.9998), precision (relative standard deviation, RSD, 0.45-4.73%) repeatability (RSD, 1.14-9.41%), stability (RSD, 1.29-12.88%) and recovery (RSD, 1.80-12.15%) of the 14 compounds. Furthermore, the hierarchical cluster analysis was applied to classify 21 samples on the basis of characteristics of the 14 compound markers. The developed method was demonstrated to be simple, sensitive and reproducible, and has significant importance and comprehensive evaluation for quality control of RPM and related preparations. Hierarchical cluster analysis clearly indicated that the RPM from the same province was similar, whereas samples of RPM from different provinces were significantly different.

Characterization of the constituents in rat plasma after oral administration of radix polygoni multiflori extracts by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

An ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry method was established to detect as many constituents in rat plasma as possible after oral administration of Radix polygoni multiflori (RPM) extract. A C18 column (150 × 2.0 mm, 4 µm) was adopted to separate the samples, and mass spectra were acquired in negative modes. The fingerprints of RPM extract were established, resulting in 39 components being detected. Among these compounds, 29 were identified by comparing the retention times and mass spectral data with those of reference standards and relevant references, and eight compounds were separated and detected in RPM for the first time. In vivo, 23 compounds were observed in dosed rat plasma, 16 of 23 compounds were indicated as prototype components of RPM, and seven compounds were predicted to be metabolites of RPM. A high-speed and sensitive method was developed and was successfully utilized for screening and characterizing the ingredients and metabolites of RPM.

A new method for estimating Sharpe ratio function via local maximum likelihood.

The Sharpe ratio function is a commonly used risk/return measure in financial econometrics. To estimate this function, most existing methods take a two-step procedure that first estimates the mean and volatility functions separately and then applies the plug-in method. In this paper, we propose a direct method via local maximum likelihood to simultaneously estimate the Sharpe ratio function and the negative log-volatility function as well as their derivatives. We establish the joint limiting distribution of the proposed estimators, and moreover extend the proposed method to estimate the multivariate Sharpe ratio function. We also evaluate the numerical performance of the proposed estimators through simulation studies, and compare them with existing methods. Finally, we apply the proposed method to the three-month US Treasury bill data and that captures a well-known covariate-dependent effect on the Sharpe ratio.

Storage and redistribution of anthropogenic CO2 in the western North Pacific: The role of subtropical mode water transportation.

Oceanic uptake and storage of anthropogenic CO2 (CANT) are regulated by ocean circulation and ventilation. To decipher the storage and redistribution of CANT in the western North Pacific, where a major CANT sink develops, we investigated the water column carbonate system, dissolved inorganic radiocarbon and ancillary parameters in May and August 2018, spanning the Kuroshio Extension (KE, 35-39 °N), Kuroshio Recirculation (KR, 27-35 °N) and subtropical (21-27 °N) zones. Water column CANT inventories were estimated to be 40.5 ± 1.1 mol m-2 in the KR zone and 37.2 ± 0.9 mol m-2 in the subtropical zone. In comparison with historical data obtained in 2005, relatively high rates of increase of the CANT inventory of 1.05 ± 0.20 and 1.03 ± 0.12 mol m-2 yr-1 in the recent decade were obtained in the KR and subtropical zones, respectively. Our water-mass-based analyses suggest that formation and transport of subtropical mode water dominate the deep penetration, storage, and redistribution of CANT in those two regions. In the KE zone, however, both the water column CANT inventory and the decadal CANT accumulation rate were small and uncertain owing to the dynamic hydrology, where the naturally uplifting isopycnal surfaces make CANT penetration relatively shallow. The findings of this study improve the understanding of the spatiotemporal variations of CANT distribution, storage, and transport in the western North Pacific.

Identification of rare variants in PTCH2 associated with non-syndromic orofacial clefts.

Orofacial clefts (OFCs) represent the most prevalent congenital craniofacial anomalies, significantly impacting patients' appearance, oral function, and psychological well-being. Among these, non-syndromic OFCs (NSOFCs) are the most predominant type, with the etiology attributed to a combination of genetic and environmental factors. Rare variants of key genes involved in craniofacial development-related signaling pathway are crucial in the occurrence of NSOFCs, and our recent studies have identified PTCH1, a receptor-coding gene in the Hedgehog signaling pathway, as a causative gene for NSOFCs. However, the role of PTCH2, the paralog of PTCH1, in pathogenesis of NSOFCs remains unclear. Here, we perform whole-exome sequencing to explore the genetic basis of 144 sporadic NSOFC patients. We identify five heterozygous variants of PTCH2 in four patients: p.L104P, p.A131G, p.R557H, p.I927S, and p.V978D, with the latter two co-occurring in a single patient. These variants, all proven to be rare through multiple genomic databases, with p.I927S and p.V978D being novel variants and previously unreported. Sequence alignment suggests that these affected amino acids are evolutionarily conserved across vertebrates. Utilizing predictive structural modeling tools such as AlphaFold and SWISS-MODEL, we propose that these variants may disrupt the protein's structure and function. In summary, our findings suggest that PTCH2 may be a novel candidate gene predicted to be associated with NSOFCs, thereby broadening the spectrum of causative genes implicated in the craniofacial anomalies.

[Correlation study on lignin contents of Schisandra chinensis and ecological factors].

The contents of schisandrin, schizandrin A, B and C were determined by HPLC, and the effects of the climate factors and altitude on lignin contents were analyzed in order to select the optimal cultivation area of S. chinensis. The lignin contents were analyzed by HPLC using a ZORBAX SB-C18 column (4.6 mm x 250 mm, 5 microm). The column temperature and detection wave length were set at 35 degrees C and 254 nm, respectively. Methanol-water was used as the mobile phase in gradient elution mode and the flow-rate was 1.0 mL min(-1). The method had a good repeatability, stability and accuracy. The correlation of climate factors and lignins contents was analyzed by SPSS software. The results showed that the schizandrin A content in S. chinensis fruits were higher than 0.4% in Ji'an, Liuhe, Antu and Fusong in Jilin province, which met the quality requirement. It had significant linear negative correlation relationship between schisandrin, schizandrin A, B and altitude, the contents decreased with the increase of altitude. The significant negative linear fitting coefficient was 0.844 1 between schisandrin and altitude; but it had not significant correlation between schizandrin C and altitude. A significant positive correlation of climate factors and the contents of S. chinensis lignins were mainly the temperature factors (the average annual temperature, the highest temperature in July, the average temperature in July, the highest temperature in January, the average temperature in January) and precipitation factor (average annual precipitation), which reveals that higher temperature and precipitation were helpful to the formation and accumulation of lignins of S. chinensis. So the cultivation area of S. chinensis should be in the low elevations region with warm and rainy climate.

[Construction of prokaryotic expression vector, expression and purification of ginseng Cu/Zn superoxide dismutase].

The total RNA was extracted from ginseng leaves of Panax ginseng. The Cu/Zn-SOD gene was amplified via RT-PCR and the pET-28(a)-Cu/Zn-SOD expression vector was constructed. The pET-28 (a)-Cu/Zn-SOD recombinant plasmid was transformed into Escherichia coli BL21 (DE3) competent cells and was induced by IPTG in order to select optimal induction of expression conditions. The target protein was purified by the nickel ions (Ni ) affinity chromatography and the target protein enzyme activity was determinated by the xanthine oxidase method. The similarity of the Cu/Zn-SOD gene sequences and the Cu/Zn-SOD gene sequences of Korean ginseng in NCBI was 99. 00%. The target protein expression level was about 44.42%, and the molecular weight was 16.30 kDa after the pET-28(a)-Cu/Zn-SOD recombinants were induced by IPTG. The purified Cu/Zn-SOD protease activity reached 10,596.69 U x mg(-1). The P. ginseng pET-28(a)-Cu/Zn-SOD prokaryotic expression vector was built by the method of molecular biology, which provided the foundation for studying the Cu/Zn-SOD biology function.

Concentrations and controls of dissolved inorganic carbon in Arctic summer sea ice and adjacent surface seawaters.

The carbonate chemistry of sea ice plays a critical role in global ocean carbon cycles, particularly in polar regions which are subject to significant climate change-induced sea ice variation. However, less is known about the interaction of carbonate system between sea ice and its adjacent seawaters due to sparse sampling and disparities in reported results. Here we provide an insight into this issue by collecting and measuring dissolved inorganic carbon (DIC) and associated environmental parameters in Arctic sea ice during a cruise in the summer of 2014. Our observations show that DIC in Arctic summer sea ice has a mean concentration of 463.3 ± 213.0 µmol/kg and appears to be controlled mainly by the fraction of brine water in the ice. The low Chl a and nutrients content in sea ice indicate minor contribution of biological uptake to sea-ice DIC in the western Arctic Ocean. The DIC concentration in surface water (<100 m depth) decreased from a mean of 2108.3 ± 45.4 µmol/kg in 1994 to a mean of 2052.4 ± 98.6 µmol/kg in 2014, due to the enhanced sea ice melting that dilutes the DIC concentrations of surrounding seawaters.

The complete change in bile acids and steroids in systematic metabolomics applied to the intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific hepatobiliary disease, leading to an abnormal increase in total bile acid in the blood of pregnant women. To systematically explore the similarities and differences in metabolites and metabolic pathways among three types of biological samples from ICP women, a study of 18 ICP and 6 healthy (as a normal control) pregnant women was performed to investigate their clinical information and biochemical features. Based on validated LC-MS/MS methods 1-5 for hydrophilic and hydrophobic metabolites (molecular weight <2000 Dalton), an untargeted-metabolomic strategy was applied to 24 pregnant women to determine the metabolites from 22 serum, 15 placental and 22 urine samples. Then 1137 metabolites from serum, 876 metabolites from placental tissue and 311 metabolites from urine with a coefficient of variation <30% in the pooled quality control samples were found. Furthermore, orthogonal partial least squares-discriminate analysis (OPLS-DA), correlation analysis, chemical enrichment analysis and metabolic pathway analysis were carried out by a bioinformatics process. On the OPLS-DA model analysis, the metabolites in urine were better than those in serum or placental tissue to reflect the metabolic changes of ICP disease. Some metabolites were significantly changed in serum (n = 71), placental tissue (n = 46) and urine (n = 36), such as bile acids, triacylglycerols, lysoPCs, and steroids. Primary bile acid biosynthesis was the main metabolic pathway in ICP disease, and taurine and hypotaurine metabolism and sphingolipid metabolism were also found. More specifically, bile acids increased and steroids decreased in the serum, placental and urine samples. For complex metabolic diseases such as ICP disease, untargeted-metabolomic analysis of multiple biological samples could provide a systematic understanding of the changes in metabolic types and pathways.

Are Older Adults More Optimistic? Evidence From China, Israel, and the United States.

OBJECTIVES: Optimistic bias refers to the phenomenon that individuals believe bad things are less likely to happen to themselves than to others. However, whether optimistic bias could vary across age and culture is unknown. The present study aims to investigate (a) whether individuals exhibit optimistic bias in the context of coronavirus disease 2019 (COVID-19) pandemic, and (b) whether age and culture would moderate such bias. METHOD: 1,051 participants recruited from China, Israel, and the United States took the online survey. Risk perceptions consist of 3 questions: estimating the infected probability of different social distance groups (i.e., self, close others, and nonclose others), the days that it would take for the number of new infections to decrease to zero and the trend of infections in regions of different geographical distances (i.e., local place, other places inside participants' country, and other countries). Participants in China and the United States also reported their personal communal values measured by Schwartz's Value Survey. RESULTS: Results from Hierarchical Linear Modeling generally confirmed that (a) all participants exhibited optimistic bias to some extent, and (b) with age, Chinese participants had a higher level of optimistic bias than the Israeli and U.S. participants. Compared to their younger counterparts, older Chinese are more likely to believe that local communities are at lower risk of COVID-19 than other countries. DISCUSSION: These findings support the hypothesis that age differences in risk perceptions might be influenced by cultural context. Further analysis indicated that such cultural and age variations in optimistic bias were likely to be driven by age-related increase in internalized cultural values.

Panax quinquefolius Polysaccharides Ameliorate Antibiotic-Associated Diarrhoea Induced by Lincomycin Hydrochloride in Rats via the MAPK Signaling Pathways.

American ginseng (Panax quinquefolius L.) is an herbal medicine with polysaccharides as its important active ingredient. The purpose of this research was to identify the effects of the polysaccharides of P. quinquefolius (WQP) on rats with antibiotic-associated diarrhoea (AAD) induced by lincomycin hydrochloride. WQP was primarily composed of galacturonic acid, glucose, galactose, and arabinose. The yield, total sugar content, uronic acid content, and protein content were 6.71%, 85.2%, 31.9%, and 2.1%, respectively. WQP reduced the infiltration of inflammatory cells into the ileum and colon, reduced the IL-1ß, IL-6, IL-17A, and TNF-α levels, increased the levels of IL-4 and IL-10 in colon tissues, improved the production of acetate and propionate, regulated the gut microbiota diversity and composition, improved the relative richness of Lactobacillus and Bacteroides, and reduced the relative richness of Blautia and Coprococcus. The results indicated that WQP can enhance the recovery of the intestinal structure in rats, reduce inflammatory cytokine levels, improve short-chain fatty acid (SCFA) levels, promote recovery of the gut microbiota and intestinal mucosal barrier, and alleviate antibiotic-related side effects such as diarrhoea and microbiota dysbiosis caused by lincomycin hydrochloride. We found that WQP can protect the intestinal barrier by increasing Occludin and Claudin-1 expression. In addition, WQP inhibited the MAPK inflammatory signaling pathway to improve the inflammatory status. This study provides a foundation for the treatment of natural polysaccharides to reduce antibiotic-related side effects.