Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer.

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.

A prospective cohort study exploring the joint influence of sunlight exposure and tanning bed use on basal cell carcinoma, squamous cell carcinoma, and melanoma risk.

Exposure to solar ultraviolet (UV) radiation and use of UV-emitting tanning devices are known risk factors for skin cancer. Few studies have explored the interaction between these risk factors, namely how the risk of skin cancer increases among those who both have been exposed to high levels of natural sunlight and regularly use tanning beds. Nurses' Health Study II followed 116,430 women, aged 25-42, from 1991 to 2011. Cumulative average UV exposure was based on participants' residences at follow-up periods. History of severe sunburn during ages 15-20 was used as a proxy for early-life sunlight exposure. Tanning bed use in early life data was collected. Participants reported melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) diagnoses. We built multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of skin cancer associated with joint effects of sunlight exposure and tanning bed use. Participants with high sunlight exposure and tanning bed use during high school/college had an increased risk of BCC (HR = 1.53, 95% CI 1.37-1.71, Pinteraction=0.01; vs. low sun exposure and no tanning bed use). Participants with a history of severe sunburns and tanning bed use during high school/college were at increased risk of BCC (HR = 1.62, 95% CI 1.47-1.79, Pinteraction=0.02; vs. no sunburns and no tanning bed use). No significant interactions were found between sunlight exposure and tanning bed use on SCC and melanoma risk. We found significant interactions between sunlight exposure and tanning bed use on the risk of BCC.

Predictive Value of 5-Methoxytryptophan on Long-Term Clinical Outcome after PCI in Patients with Acute Myocardial Infarction-a Prospective Cohort Study.

BACKGROUND: In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties. METHODS: In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan-Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI. RESULTS: Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17-0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13-0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65 years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics. CONCLUSIONS: Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics.

A Prospective Cohort Study Exploring the Joint Influence of Sunlight Exposure and Tanning Bed Use on Basal Cell Carcinoma, Squamous Cell Carcinoma, and Melanoma Risk.

Exposure to solar ultraviolet (UV) radiation and use of UV-emitting tanning devices are known risk factors for skin cancer. Few studies have explored the interaction between these risk factors, namely how the risk of skin cancer increases among those who both have been exposed to high levels of natural sunlight and regularly use tanning beds. Nurses' Health Study II followed 116,430 women, aged 25-42, from 1991 to 2011. Cumulative average UV exposure was based on participants' residences at follow-up periods. History of severe sunburn during ages 15-20 was used as a proxy for early-life sunlight exposure. Tanning bed use in early life data was collected. Participants reported melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) diagnoses. We built multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of skin cancer associated with joint effects of sunlight exposure and tanning bed use. Participants with high sunlight exposure and tanning bed use during high school/college had an increased risk of BCC (HR=1.53, CI 1.37-1.71, P interaction =0.01; vs. low UV exposure and no tanning bed use). Participants with a history of severe sunburns and tanning bed use during high school/college were at increased risk of BCC (HR=1.62, CI 1.47-1.79, P interaction =0.02; vs. no sunburns and no tanning bed use). No significant interactions were found between sunlight exposure and tanning bed use on SCC and melanoma risk. We found significant interactions between sunlight exposure and tanning bed use on the risk of BCC.

Xianglian Pill combined with 5-fluorouracil enhances antitumor activity and reduces gastrointestinal toxicity in gastric cancer by regulating the p38 MAPK/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Perioperative or postoperative adjuvant chemotherapy based on 5-fluorouracil (5-FU) is a common first-line adjuvant therapy for gastric cancer (GC). However, drug resistance and the side effects of 5-FU have reduced its efficacy. Among these side effects, gastrointestinal (GI) toxicity is one of the most common. Xianglian Pill (XLP) is a Chinese patent medicine that is commonly used for the treatment of diarrhoea. It can reduce inflammation and has a protective effect on the intestinal mucosa. Recent studies have shown that many components of XLP can inhibite tumor cell growth. However, the therapeutic effect of XLP in combination with 5-FU on GC is unclear. AIM OF THE STUDY: To investigate whether the combination of XLP and 5-FU can enhance anti-GC activity while reducing GI toxicity. MATERIALS AND METHODS: XLP was administered orally during intraperitoneal injection of 5-FU in GC mice model. Mice were continuously monitored for diarrhea and xenograft tumor growth. After 2 weeks, the mice were sacrificed and serum was collected to determine interleukin-6 levels. Pathological changes, the expression of pro-inflammatory factors and p38 mitogen-activated protein kinase (MAPK) in GI tissue were determined by Western blot analysis. Pathological changes, apoptosis levels and p38 MAPK expression levels in xenograft tissues were also determined. RESULTS: The results showed that XLP could alleviate GI mucosal injury caused by 5-FU, alleviated diarrhea, and inhibited the expression of nuclear factor (NF)-κB and myeloid differentiation primary response-88. Besides, XLP could promote the 5-FU-induced apoptosis of GC cells and enhance the inhibitory effect of 5-FU on tumor xenografts. Further study showed that XLP administration could regulate the expression of p38 MAPK. CONCLUSIONS: XLP in combination with 5-FU could alleviate its GI side effects and enhance its inhibitory effect on xenograft tumor. Moreover, these effects were found to be related to the regulation of the p38 MAPK/NF-κB pathway.

Enhanced impact of psoriasis severity on the treatment demands of patients during the COVID-19 pandemic: a cross-sectional study based on a national psoriasis registry in China.

OBJECTIVES: The personalised treatment demands of patients with psoriasis did not get significant attention during the pandemic lockdown. This study aimed to investigate the treatment demands of patients with psoriasis with different severities, stratified by COVID-19 pandemic conditions. DESIGN: Cross-sectional study design. SETTING: Multicentre study based on a national psoriasis registry in China. PARTICIPANTS: A total of 22 425 adult patients with psoriasis were enrolled between August 2020 and September 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were patient demands for quick healing of skin lesions and improving mental health, which were collected by questionnaires. Multivariable logistic models were used to examine the impact of disease severity, as measured by Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Investigator's Global Assessment (IGA), on treatment demands, as stratified by COVID-19 pandemic conditions (lockdown vs non-lockdown). RESULTS: Increasing PASI score significantly increased patient demands for rapid healing of skin lesions and improving mental health during non-lockdown periods. The magnitude of both associations further increased during the COVID-19 lockdown from an OR of 1.45 (95% CI 1.27 to 1.65) to 2.19 (95% CI 1.57 to 3.05) and 2.21 (95% CI 2.03 to 2.40) to 2.82 (95% CI 2.24 to 3.55), respectively. The skin lesion healing demand was more triggered by the overall irritation level (measured by IGA, OR 1.64, 95% CI 1.35 to 1.99 during non-lockdown periods vs OR 2.70, 95% CI 1.63 to 4.49 during lockdowns), while the mental health improving demand was more triggered by lesion coverage (measured by BSA, OR 2.01, 95% CI 1.85 to 2.19 vs OR 3.27, 95% CI 2.57 to 4.15). CONCLUSIONS: Psoriasis aggravation significantly increased patients' treatment demands, especially during lockdowns. The used psoriasis severity measures highlighted patients' treatment demands differently. This suggests more accessible and personalised healthcare for patients with psoriasis should be available during future pandemics.

A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

Trends in physical activity and sedentary time among U.S. adults with diabetes: 2007-2020.

AIMS: To examine temporal trends in physical activity and sedentary time among U.S. adults with diabetes from 2007 to 2020. METHODS: We performed serial cross-sectional analyses for participants aged ≥ 20 years with diagnosed diabetes from the U.S. National Health and Nutrition Examination Survey from 2007 to 2020. Participants completed the Global Physical Activity Questionnaire. RESULTS: The analytic sample comprised 5096 adults with diabetes (mean age: 60.3 years; 48.2% females; 60.1% White people; mean body mass index: 33.0 kg/m2). From 2007-2008 through 2017-March 2020, the proportion of being physically sufficiently active increased from 41.5% (95% CI, 35.9%-47.2%) to 55.8% (95% CI, 51.3%-60.3%) (P-trend<0.001), whereas that of physical inactivity declined from 43.7% (95% CI, 38.1%-49.2%) to 31.0% (95% CI, 27.7%-34.3%) (P-trend<0.001). The decline was driven by increasing engagement in work-related and leisure-time activity. However, engagement in transportation-related activity stayed persistently low (16.7% [95% CI, 14.8%-18.8%] in 2017-March 2020) (P-trend = 0.25), and the mean daily sitting hours remained unaltered (6.2 [95% CI, 5.9-6.5] in 2017-March 2020) (P-trend = 0.60). Adults who were middle-aged or older, or with class III obesity, cardiovascular or chronic kidney concomitants were less likely to be sufficiently active and prone to prolonged sitting. CONCLUSIONS: Physical activity levels in U.S. adults with diabetes have increased from 2007 to 2020, but about one in two remains inactive or insufficiently active. Sedentary time has not decreased. For diabetes management, nationwide efforts are needed to promote transportation-related physical activity while minimizing prolonged sitting, especially among those who are middle-aged or older, or with severe obesity or other complications.

The level of serum total bile acid is related to atherosclerotic lesions, prognosis and gut Lactobacillus in acute coronary syndrome patients.

BACKGROUND: Bile acids play crucial roles in various metabolisms, as well as Lactobacillus in the intestine. But studies on their roles in acute coronary syndrome (ACS) are still insufficient. The aim of this study was to investigate their role and potential association with the severity of coronary lesions and the prognosis of ACS. METHODS: Three hundred and sixty ACS patients were selected. Detection of gut Lactobacillus levels was done through 16S rDNA sequence analysis. Evaluation of the extent of lesions was done using the SYNTAX (SS) score. Mediation analysis was used to assess the relationship between serum total bile acid (TBA), Lactobacillus, atherosclerotic lesions and prognosis of ACS. RESULTS: Logistic regressive analysis disclosed that serum TBA and Lactobacillus were independent predictors of coronary lesions (high vs. low SS: serum TBA adjusted odds ratio (aOR) = 0.8, 95% confidence interval (CI): 0.6-0.9, p < .01; Lactobacillus: aOR = 0.9, 95% CI: 0.9-1.0, p = .03). According to multivariate Cox regression analysis, they were negatively correlated with the overall risk of all-cause death (serum TBA: adjusted hazard ratio (aHR) = 0.1, 95% CI: 0.0-0.6, p = .02; Lactobacillus: aHR = 0.6, 95% CI: 0.4-0.9, p = .01), especially in acute myocardial infarction (AMI) but not in unstable angina pectoris (UAP). Ulteriorly, mediation analysis showed that serum TBA played an important role as a mediation effect in the following aspects: Lactobacillus (17.0%, p < .05) â†’ SS association (per 1 standard deviation (SD) increase), Lactobacillus (43.0%, p < .05) â†’ all-cause death (per 1 SD increase) and Lactobacillus (45.4%, p < .05) â†’ cardiac death (per 1 SD increase). CONCLUSIONS: The lower serum TBA and Lactobacillus level in ACS patients, especially in AMI, was independently linked to the risk of coronary lesions, all-cause death and cardiac death. In addition, according to our mediation model, serum TBA served as a partial intermediate in predicting coronary lesions and the risk of death by Lactobacillus, which is paramount to further exploring the mechanism of Lactobacillus and bile acids in ACS.KEY MESSAGESLower level of serum total bile acid (TBA) was highly associated with the severity of coronary lesions, myocardial damage, inflammation and gut Lactobacillus in acute coronary syndrome (ACS) patients, especially in acute myocardial infarction (AMI).Lower level of serum TBA was highly associated with mortality (including all-cause death and cardiac death) in patients with ACS, especially with AMI.Serum TBA had a partial mediating effect rather than regulating effect between gut Lactobacillus and coronary lesions and prognosis of ACS.

Metabolite Alterations and Interactions with Microbiota in Helicobacter pylori-Associated Gastric Lesions.

Metabolites and their interactions with microbiota may be involved in Helicobacter pylori-associated gastric lesion development. This study aimed to explore metabolite alterations upon H. pylori eradication and possible roles of microbiota-metabolite interactions in progression of precancerous lesions. Targeted metabolomics assays and 16S rRNA gene sequencing were conducted to investigate metabolic and microbial alterations of paired gastric biopsy specimens in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment. Integrative analyses were performed by combining the metabolomics and microbiome profiles from the same intervention participants. A total of 81 metabolites were significantly altered after successful eradication compared to failed treatment, including acylcarnitines, ceramides, triacylglycerol, cholesterol esters, fatty acid, sphingolipids, glycerophospholipids, and glycosylceramides, with P values of <0.05 for all. The differential metabolites showed significant correlations with microbiota in baseline biopsy specimens, such as negative correlations between Helicobacter and glycerophospholipids, glycosylceramide, and triacylglycerol (P < 0.05 for all), which were altered by eradication. The characteristic negative correlations between glycosylceramides and Fusobacterium, Streptococcus, and Gemella in H. pylori-positive baseline biopsy specimens were further noticed in active gastritis and intestinal metaplasia (P < 0.05 for all). A panel including differential metabolites, genera, and their interactions may help to discriminate high-risk subjects who progressed from mild to advanced precancerous lesions in short-term and long-term follow-up periods with areas under the curve (AUC) of 0.914 and 0.801, respectively. Therefore, our findings provide new insights into the metabolites and microbiota interactions in H. pylori-associated gastric lesion progression. IMPORTANCE In this study, a panel was established including differential metabolites, genera, and their interactions, which may help to discriminate high-risk subjects for progression from mild lesions to advanced precancerous lesions in short-term and long-term follow-up.

The prediction value of platelet-derived growth factor for major adverse cardiovascular events in patients with acute non-ST-segment elevation myocardial infarction.

BACKGROUND: The value of plasma Platelet-Derived Growth Factor (PDGF) as a biomarker in predicting major adverse cardiovascular events (MACEs) in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. METHODS: A total of 242 patients with NSTEMI were enrolled in this observational cohort study. The correlation between PDGF and MACEs was evaluated during a five-year follow-up. Kaplan-Meier survival analysis with Cox proportional-hazards regression was used to identify predictive values of PDGF. RESULTS: The mean follow-up of NSTEMI patients was 1334 days. It was found that as the PDGF level increased, a significant uptrend in the incidence of MACEs and all-cause death, including the MACEs of 30 days, 180 days, 1 year, 5 years and the death of 1 year and 5 years (All Log-rank p < .05). Subgroup analysis further showed that PDGF had better predictive value for patients with age >65 years, GRACE score ≥140 and platelet count (PLT) >200 × 109/L. CONCLUSION: PDGF levels can predict short-term and long-term MACEs in NSTEMI patients after discharge, especially for patients with older age, higher GRACE score and baseline PLT > 200 × 109/L.Key messagesPDGF is a risk factor for short- and long-term MACEs in patients with STEMI.PDGF has a better prognostic value in patients with older age and PLT > 200 × 109/L.Baseline plasma PDGF levels were positively correlated with GRACE score.

Allium vegetable intake associated with the risk of incident gastric cancer: a continuous follow-up study of a randomized intervention trial.

BACKGROUND: Allium vegetable components have antibacterial, antioxidative, and immune modulation properties, thus potentially exhibiting antitumor effects. Despite evidence from case-control studies, prospective studies linking allium vegetables with gastric cancer (GC) have been sparse. OBJECTIVE: In a prospective study, we examined whether allium vegetable intake would change the risk of GC occurrence and whether the associations would be modified by vitamin supplementation, garlic supplementation, and Helicobacter pylori (H. pylori) treatment. METHODS: The study was conducted on the basis of the Shandong Intervention Trial, a randomized, placebo-controlled, factorial-designed trial (1995-2003) in a well-recognized high-risk area for GC in China. Participants were continuously followed up to December 2017 for 22.3 y (1995-2017). A total of 3229 subjects were included, with information on the intake of allium vegetables (garlic vegetables and scallions), collected by structured questionnaires in 1994. The associations of total and individual allium vegetable intake with the risk of GC were examined, respectively. RESULTS: During the follow-up, 144 incident cases of GC were identified. Garlic vegetable intake was associated with a decreased risk of incident GC (P-trend = 0.02; OR: 0.83; 95% CI: 0.70, 0.98, per 1 kg/y increment), whereas scallion intake showed no association (P-trend = 0.80). An inverse association of the risk of GC with total allium vegetable and garlic vegetable intake was particularly stronger among those receiving the placebo for vitamin supplementation or garlic supplementation, indicating potential effect modifications by nutritional supplementation on allium vegetable intake and the risk of developing GC. Similar findings were found for analyses of the combined prevalence of dysplasia or GC. CONCLUSIONS: We found a significant reduction in the risk of developing GC with increasing dietary intake of allium vegetables, particularly garlic vegetables. The findings add to the literature on the potential inverse association of garlic vegetable intake with the risk of GC, therefore holding public health implications for dietary recommendations. This trial was registered at clinicaltrials.gov as NCT00339768.

Variations in genetic diversity in cultivated Pistacia chinensis.

Identification of the evolution history and genetic diversity of a species is important in the utilization of novel genetic variation in this species, as well as for its conservation. Pistacia chinensis is an important biodiesel tree crop in China, due to the high oil content of its fruit. The aim of this study was to uncover the genetic structure of P. chinensis and to investigate the influence of intraspecific gene flow on the process of domestication and the diversification of varieties. We investigated the genetic structure of P. chinensis, as well as evolution and introgression in the subpopulations, through analysis of the plastid and nuclear genomes of 39 P. chinensis individuals from across China. High levels of variation were detected in the P. chinensis plastome, and 460 intraspecific polymorphic sites, 104 indels and three small inversions were identified. Phylogenetic analysis and population structure using the plastome dataset supported five clades of P. chinensis. Population structure analysis based on the nuclear SNPs showed two groups, clearly clustered together, and more than a third of the total individuals were classified as hybrids. Discordance between the plastid and nuclear genomes suggested that hybridization events may have occurred between highly divergent samples in the P. chinensis subclades. Most of the species in the P. chinensis subclade diverged between the late Miocene and the mid-Pliocene. The processes of domestication and cultivation have decreased the genetic diversity of P. chinensis. The extensive variability and structuring of the P. chinensis plastid together with the nuclear genomic variation detected in this study suggests that much unexploited genetic diversity is available for improvement in this recently domesticated species.

Urine proteomic signatures predicting the progression from premalignancy to malignant gastric cancer.

BACKGROUND: Early detection of gastric cancer (GC) remains challenging. We aimed to examine urine proteomic signatures and identify protein biomarkers that predict the progression of gastric lesions and risk of GC. METHODS: A case-control study was initially designed, covering subjects with GC and gastric lesions of different stages. Subjects were aged 40-69 years, without prior diagnosis of renal or urological diseases. We enrolled a total of 255 subjects, with 123 in the discovery stage from Linqu, China, a high-risk area for GC and 132 in the validation stage from Linqu and Beijing. A prospective study was further designed for a subset of 60 subjects with gastric lesions, which were followed for 297-857 days. FINDINGS: We identified 43 differentially expressed urine proteins in subjects with GC vs. mild or advanced gastric lesions. Baseline urinary levels of ANXA11, CDC42, NAPA and SLC25A4 were further positively associated with risk of gastric lesion progression. Three of them, except for SLC25A4, also had higher expression in GC than non-GC tissues. Integrating these four proteins showed outstanding performance in predicting the progression of gastric lesions (AUC (95% CI): 0.92 (0.83-1.00)) and risk of GC (AUC (95% CI): 0.81 (0.73-0.89) and 0.84 (0.77-0.92) for GC vs. mild or advanced gastric lesions respectively). INTERPRETATION: This study revealed distinct urine proteomic profiles and a panel of proteins that may predict the progression of gastric lesions and risk of GC. These biomarkers in a non-invasive approach may have translational significance for defining high-risk populations of GC and its early detection. FUNDING: Funders are listed in the Acknowledgement.

A chromosome-level genome assembly of the Chinese cork oak (Quercus variabilis).

Quercus variabilis (Fagaceae) is an ecologically and economically important deciduous broadleaved tree species native to and widespread in East Asia. It is a valuable woody species and an indicator of local forest health, and occupies a dominant position in forest ecosystems in East Asia. However, genomic resources from Q. variabilis are still lacking. Here, we present a high-quality Q. variabilis genome generated by PacBio HiFi and Hi-C sequencing. The assembled genome size is 787 Mb, with a contig N50 of 26.04 Mb and scaffold N50 of 64.86 Mb, comprising 12 pseudo-chromosomes. The repetitive sequences constitute 67.6% of the genome, of which the majority are long terminal repeats, accounting for 46.62% of the genome. We used ab initio, RNA sequence-based and homology-based predictions to identify protein-coding genes. A total of 32,466 protein-coding genes were identified, of which 95.11% could be functionally annotated. Evolutionary analysis showed that Q. variabilis was more closely related to Q. suber than to Q. lobata or Q. robur. We found no evidence for species-specific whole genome duplications in Quercus after the species had diverged. This study provides the first genome assembly and the first gene annotation data for Q. variabilis. These resources will inform the design of further breeding strategies, and will be valuable in the study of genome editing and comparative genomics in oak species.

Periodic structural changes in Pd nanoparticles during oscillatory CO oxidation reaction.

Nanoparticle (NP) catalysts are ubiquitous in energy systems, chemical production, and reducing the environmental impact of many industrial processes. Under reactive environments, the availability of catalytically active sites on the NP surface is determined by its dynamic structure. However, atomic-scale insights into how a NP surface reconstructs under reaction conditions and the impact of the reconstruction on catalytic activity are still lacking. Using operando transmission electron microscopy, we show that Pd NPs exhibit periodic round-to-flat transitions altering their facets during CO oxidation reaction at atmospheric pressure and elevated temperatures. This restructuring causes spontaneous oscillations in the conversion of CO to CO2 under constant reaction conditions. Our study reveals that the oscillatory behavior stems from the CO-adsorption-mediated periodic restructuring of the nanocatalysts between high-index-faceted round and low-index-faceted flat shapes. These atomic-scale insights into the dynamic surface properties of NPs under reactive conditions play an important role in the design of high-performance catalysts.

Traditional Chinese medicine: An important source for discovering candidate agents against hepatic fibrosis.

Hepatic fibrosis (HF) refers to the pathophysiological process of connective tissue dysplasia in the liver caused by various pathogenic factors. Nowadays, HF is becoming a severe threat to the health of human being. However, the drugs available for treating HF are limited. Currently, increasing natural agents derived from traditional Chinese medicines (TCMs) have been found to be beneficial for HF. A systemic literature search was conducted from PubMed, GeenMedical, Sci-Hub, CNKI, Google Scholar and Baidu Scholar, with the keywords of "traditional Chinese medicine," "herbal medicine," "natural agents," "liver diseases," and "hepatic fibrosis." So far, more than 76 natural monomers have been isolated and identified from the TCMs with inhibitory effect on HF, including alkaloids, flavones, quinones, terpenoids, saponins, phenylpropanoids, and polysaccharides, etc. The anti-hepatic fibrosis effects of these compounds include hepatoprotection, inhibition of hepatic stellate cells (HSC) activation, regulation of extracellular matrix (ECM) synthesis & secretion, regulation of autophagy, and antioxidant & anti-inflammation, etc. Natural compounds and extracts from TCMs are promising agents for the prevention and treatment of HF, and this review would be of great significance to development of novel drugs for treating HF.

Isorhamnetin: A Novel Natural Product Beneficial for Cardiovascular Disease.

Cardiovascular disease (CVD) has become a severe threat to human beings with increasing morbidity and mortality. Isorhamnetin (Iso) shows multiple bioactivities, especially in the cardiovascular system. A literature retrieval strategy was conducted in databases of PubMed, GeenMedical, Sci-Hub, Web of Science, China National Knowledge Infrastructure (CNKI), and Baidu Scholar, with keywords defined as: "Isorhamnetin", "cardiovascular diseases", "pharmacological effects", "phytochemistry", "pharmacokinetics", "clinical application" and "toxicity". The language is restricted to Chinese and English, and publish date ranges from January, 2011 to September, 2021. So far, Iso has been isolated and identified from several natural medicines, including Hippophae rhamnoides L., Ginkgo biloba L. and Typha angustifolia L., etc. The effects of Iso on CVD are pharmacological, including anti-atherosclerosis, reducing blood fat, anti-inflammation, antioxidation, endothelial protection, antithrombosis, antiplatelet aggregation, myocardial protection, and anti-hypertension. Iso could inhibit the activities of CYPs in liver microsomes and suppress hepatocyte injury in vitro. However, no toxicity was observed in vivo. Taken together, Iso has a wide range of positive effects on CVD with safe and multiple pharmacological activities on the cardiovascular system and may be an ideal candidate drug for the prevention and treatment of CVD. Therefore, further studies, especially on its clinic use, need to be conducted. The present review summarizes the recent progress in phytochemistry, pharmacology, and mechanisms of action and provides a reference for future studies on Iso.

Complete mitochondrial genome sequence of Acer miaotaiense (Aceraceae).

Acer miaotaiense P. C. Tsoong is a rare and endangered tree endemic to the Qinling Mountains of China and is listed as a national third-class protected plant. In this study, we sequenced the complete mitochondrial genome of Acer miaotaiense using the Illumina Novaseq 6000 and Nanopore platforms. The total mitochondrial genome length is 819,227 bp and has 69 genes, including 41 protein-coding, 25 tRNA, and 3 rRNA genes. The genome nucleotide composition was asymmetric, with an overall G + C content of 45.7%. Phylogenetic analysis indicated that Acer miaotaiense is closely related to the congeneric Acer yangbiense.