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In this paper, the content of active ingredients and antioxidant capacity of different parts of Hoxylon and Red Willow Cistanche deserticola, from Hotan Cele County, Xinjiang, were evaluated. The results showed that the active substances, including total phenols, total flavonoids, total sugars, and verbascoside of Red Willow Cistanche deserticola, were the highest in the lower part of the plant, and decreased in the middle and upper parts. In terms of total phenols and total flavonoids, the contents of the lower part of Red Willow Cistanche deserticola (38.35 mg GAE/g DW, 35.61 mg RE/g DW) were 2.47 and 10.95 times compared to the lower part of Hoxylon Cistanche deserticola, respectively. The upper part of Hoxylon Cistanche deserticola showed the highest content of echinacoside with 92.93 mg/g DW. And the total triterpene content of the lower part-especially that of Hoxylon Cistanche deserticola was significantly higher than the upper and middle part (P

Abstract Background and objective The value of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) assessment in the context of metabolic abnormalities is growing in importance. Nevertheless, the relationship between NHHR and hyperuricemia (HUA) is unknown. This study seeks to investigate the relationship between NHHR and HUA. Methods The data derived from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) included 7,876 adult participants. The multivariable logistic regression model, subgroup analysis and smooth fitting curve were utilized in order to investigate the association between NHHR and HUA. Results In the fully adjusted model 3, NHHR was significantly associated with HUA. Specifically, participants in the highest quartile of NHHR had 1.95 times higher odds of HUA prevalence compared to those in the lowest quartile [2.95 (2.39, 3.64), P

Background Gestational diabetes can lead to increased blood pressure in offspring, accompanied by impaired renal sodium excretion function and vasoconstriction and diastole dysfunction. However, there are few studies on whether it is accompanied by increased sympathetic nerve activity.Methods Pregnant C57BL/6 mice were intraperitoneally injected with streptozotocin (35 mg/kg) or citrate buffer at day 0 of gestation. The mice of control mother offspring (CMO) and diabetic mother offspring (DMO) at 16 weeks of age were infused with vehicle (artificial cerebrospinal fluid, aCSF, 0.4 μL/h) or tempol (1 mmol/L, 0.4 μL/h) into the bilateral paraventricular nucleus (PVN) of mice for 4 weeks, respectively.Results Compared with CMO group, SBP and peripheral sympathetic nerve activity (increased heart rate, LF/HF and plasma norepinephrine and decreased SDNN and RMSSD) were increased in DMO group, which was accompanied by increased angiotensin II type-1 receptor (AT1R) expression and function in PVN. The increase in AT1R expression levels was attributed to a decrease in the methylation level of the AT1R promoter region, resulting in an increase in AT1R mRNA levels in PVN of DMO. Moreover, compared with CMO group, the levels of oxidative stress were increased and DNMT1 expression was decreased in PVN of DMO. Bilateral PVN infusion of tempol attenuated oxidative stress increased the level of DNMT1 expression and the binding of DNMT1 to the AT1R promoter region, which reduced mRNA and protein expression level of AT1R, heart rate and SBP in DMO, but not in CMO.Conclusions The present study provides evidence for overactive sympathetic nervous systems in the pathogenesis of gestational diabetes-induced hypertension in offspring. Central antioxidant intervention in the PVN may be an important treatment strategy for fetal-programmed hypertension.

Lilium pumilum DC (L. pumilum DC) plays an important role in the rational utilization of salinized soil. To explore the molecular mechanism of salt-tolerant L. pumilum, the LpMYB4 was cloned. LpMYB4 close relationship with Bambusa emeiensis and Zea mays MYB4 throughout the phylogenetic tree construction. LpMYB4 protein was found to be localized in the nucleus. Prokaryotic and eukaryotic bacterial solution resistance experiments proved that the exogenous introduction of LpMYB4 made the overexpression strains obtain better survival ability under saline-alkaline stress. Compared with wild-type plants, tobacco plants overexpressing LpMYB4 had better growth and lower leaf wilting and lodging, the content of chlorophyll was higher, the content of hydrogen peroxide and superoxide anion was lower, the activity of peroxidase and superoxide dismutase was higher and the relative conductivity was lower under saline-alkaline stress. The analysis of seed germination and seedling resistance of transgenic plants under salt stress showed that LpMYB4 transgenic seeds were more tolerant to salt stress during germination and growth. Yeast two-hybrid and two-luciferase complementation experiments showed that LpMYB4 interacted with yeast two-hybrid and LpGPX6. The analysis of the role of LpMYB4 in improving plant saline-alkali resistance is helpful to the transformation of plant germplasm resources and has great significance for agriculture and sustainable development.

Background and objectiveAlbuminuria is an important early marker of kidney damage and progression of chronic kidney disease and is also linked to several chronic systemic diseases. The Prognostic Nutritional Index (PNI) is widely used in the assessment of multiple diseases. However, research dealing with the relationship between PNI and albuminuria remains scarce. This research project aims to examine this association.Methods and materialsThe present study employed data from the National Health and Nutrition Examination Survey (NHANES) between 2017 and 2020, including 7,737 adult participants who met the study criteria. PNI was analyzed as a quartile-categorized variable. Multivariable regression models and smoothing curve fitting were adopted to examine the relationship between PNI and albuminuria. In order to ascertain the stability of the association across different populations, subgroup analyses were performed.ResultsThe study found a statistically significant inverse relationship between higher PNI levels and the prevalence of albuminuria. The fully adjusted model indicates that a one-unit increase in PNI is associated with a 4% reduced odds of albuminuria prevalence [0.96 (0.93, 0.98)]. Quartile analysis showed a stable inverse relationship, with the highest PNI quartile having the significantly lower odds of albuminuria prevalence [0.76 (0.62, 0.94), p for trend = 0.0004]. Smooth curve fitting and two-piecewise linear regression models indicated a nonlinear relationship between PNI and albuminuria, with a turning point at 42. Subgroup analysis confirmed the reliability of the inverse relationship between PNI and albuminuria across all groups.ConclusionThe findings of this study indicated that higher PNI levels are significantly inversely related to the odds prevalence of albuminuria. PNI could serve as an important predictor for the occurrence of albuminuria. Further prospective studies are needed to validate this association.

Background and objectiveHigh-sensitivity C-reactive protein (hs-CRP), a classical indicator of inflammation, holds significant clinical value in various diseases. The relationship between hs-CRP and gallstones, however, remains poorly studied at present. The relationship between hs-CRP and gallstones will be investigated in this study.MethodsData from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) were analyzed, focusing on participants aged 20 years and older who provided complete hs-CRP and gallstone information. Due to the skewed distribution of hs-CRP, the data were log-transformed [Log (hs-CRP)] to achieve normalization. Logistic regression analysis, subgroup analysis, and smoothed fitted curves were applied to determine the relationship between Log (hs-CRP) and the presence of gallstones.ResultsThe study included 4,484 participants with an average Log (hs-CRP) of 1.18 ± 0.74. The prevalence of gallstones was 11.15%, increasing with higher Log (hs-CRP) levels (quartile 1: 8.31%; quartile 2: 8.76%; quartile 3: 11.98%; quartile 4: 16.36%; p

Walnut kernel (WK) is a globally popular health food known for its potent antioxidant properties. WK shows a promising prospect in protecting against liver damage induced by salt processed psoraleae fructus (SPF). This study explored the impact of WK in mitigating liver damage induced by SPF in an ovariectomized (OVX) rat model. Serum metabolomics was employed to explore potential detoxification mechanisms. The levels of Farnesoid X receptor (FXR), Bile salt export pump (BSEP), and Cholesterol 7α-hydroxylase (CYP7A1) proteins were determined through western blot analysis. The results demonstrated that WK exhibits a noteworthy protective effect against liver damage induced by SPF. The WK normalized the metabolic disorder and reversed sixteen liver injury biomarkers and five metabolic pathways induced by SPF. These results demonstrated that WK exhibits a protective effect against SPF-induced liver damage in OVX rats by regulating bile acid metabolism.

To improve the activity of single-atom nanozymes (SAzymes) for applications in food analysis, a new bimetal SAzyme FeCe/NC was developed. Its oxidase-like activity is 40% higher than that of single metal SAzyme Fe/NC. Based on a series of characterization investigations, the catalytic mechanism is that it directly catalyzed O2 to generate •OH, O2•-and 1O2. It could directly catalyze oxidation 3,3′,5,5′-tetramethylbenzidine (TMB) to blue oxTMB, thereunder, a FeCe/NC SAzyme-TMB colorimetric method for the detection of tannic acid (TA) was constructed after the optimization of catalytic conditions. The method has a high R2 of 0.995, a low limit of detection (LOD) of 0.26 μmol/L, and high stability. The detection performance was validated by the real samples (tea). Therefore, the prepared bimetallic SAzyme FeCe/NC can be applied for TA detection without the addition of H2O2, and will have broad applications in the areas of food, feed, and life science.

GC-IMS (gas chromatography-ion mobility spectroscopy) was used to analyze the differences between the volatile substances of two hosts of Cistanches deserticola in the Hotan area, Xinjiang. The results showed that 35 volatile substances were detected by GC-IMS, among which 27 volatile substances were identified qualitatively, including 8 aldehydes, 5 alcohols, 4 esters, and 1 ketone, predominantly aldehydes, and alcohols. There were obvious differences in the volatile substances of Cistanche deserticola between 'Red Willow' and 'Hoxylon'. The main substances that differed between the two were 2-phenylacetaldehyde, benzaldehyde, (E)-2-heptenal, 3-(Methylmercapto) propionaldehyde, 1-hexanal, heptanal, 3-methyl-2-butenal, acetic acid methyl ester, acetic acid hexyl ester, 1-hexanol, 3-hydroxy-2-butanone, 2-methyl-1-propanol, acetic acid ethyl ester. The two different hosts of Cistanche deserticola could be effectively distinguished by principal component analysis, and the cumulative variance contribution of PC1 and PC2 reached 91%. Meanwhile, by constructing the heat map of volatile substances clustering and fingerprinting, they can provide theoretical references for the identification of different hosts of Cistanche deserticola and the study of volatile substances.

BackgroundEmerging observational studies indicated an association between hyperthyroidism and gastrointestinal disorders. However, it remains unclear whether this association is causal, particularly in the case of gastroesophageal reflux (GERD) and esophageal cancer.MethodsTo assess the potential causal relationship between hyperthyroidism and GERD or esophageal cancer, we conducted a bidirectional 2-sample Mendelian randomization study. Independent genetic instruments for hyperthyroidism from the UK Biobank (N case=3,545 and N control=459,388) and public genome-wide association study (GWAS) dataset (N case=3,731 and N control=480,867) were used to investigate the association with esophageal cancer in the UK Biobank study (N case=740 and N control=372,016) and GERD in the public GWAS database (N case=20,381 and N control=464,217). Four different approaches (inverse variance weighted (IVW), weighted mode, MR-Egger, and weighted median regression) were used to ensure that our results more reliable. Additional sensitivity analyses were also performed to validate our results.ResultsWhen hyperthyroidism was considered as the exposure factor, it appeared to act as a protective factor for GERD (ORIVW = 0.88, 95% CI, 0.79-0.99, P = 0.039), while as a risk factor for esophageal cancer (ORIVW = 1.03, 95% CI, 1.01-1.06, P = 0.003). However, there is no evidence supporting a reverse causal relationship between genetic susceptibility to hyperthyroidism and GERD or esophageal cancer.ConclusionOur findings provided genetic evidence supporting bidirectional causal relationships between hyperthyroidism and GERD or esophageal cancer. These results substantiate certain discoveries from previous observational studies on a causal level and provide insight into relevant genetic susceptibility factors.

ObjectiveEmerging evidence suggests alterations in gut microbiota (GM) composition following thyroid nodules (TNs) development, yet the causal relationship remains unclear. Utilizing Mendelian Randomization (MR), this study aims to elucidate the causal dynamics between GM and TNs.MethodsEmploying summary statistics from the MiBioGen consortium (n=18,340) and FinnGen consortium (1,634 TNs cases, 263,704 controls), we conducted univariable and multivariable MR analyses to explore the GM-TNs association. Techniques including inverse variance weighted, MR-Egger regression, weighted median, and MR-PRESSO were utilized for causal inference. Instrumental variable heterogeneity was assessed through Cochran’s Q statistic and leave-one-out analysis. Reverse MR was applied for taxa showing significant forward MR associations, with multivariate adjustments for confounders.ResultsOur findings suggest that certain microbiota, identified as Ruminococcaceae_NK4A214_group (OR, 1.89; 95%CI, 0.47-7.64; p = 0.040), Senegalimassilia (OR, 1.72; 95%CI, 1.03-2.87; p =0.037), Lachnospiraceae (OR,0.64; 95%CI,0.41-0.99; p =0.045), exhibit a protective influence against TNs’ development, indicated by negative causal associations. In contrast, microbiota categorized as Desulfovibrionales (OR, 0.63; 95%CI, 0.41-0.95; p =0.028), Prevotella_7 (OR, 0.79; 95%CI, 0.63-1.00; p =0.049), Faecalibacterium (OR, 0.66; 95%CI, 0.44-1.00; p =0.050), Desulfovibrionaceae (OR, 0.55; 95%CI, 0.35-0.86; p =0.008), Deltaproteobacteria (OR, 0.65; 95%CI, 0.43-0.97; p =0.036) are have a positive correlation with with TNs, suggesting they may serve as risk factors. Reverse MR analyses did not establish significant causal links. After comprehensive adjustment for confounders, taxa Desulfovibrionales (Order), Desulfovibrionaceae (Family), Deltaproteobacteria (Class) remain implicated as potential contributors to TNs’ risk.DiscussionThis study substantiates a significant causal link between GM composition and TNs development, underscoring the thyroid-gut axis’s relevance. The findings advocate for the integration of GM profiles in TNs’ prevention and management, offering a foundation for future research in this domain.

Abstract Recent studies have highlighted the biological significance of cuproptosis in disease occurrence and development. However, it remains unclear whether cuproptosis signaling also has potential impacts on tumor initiation and prognosis of gastric cancer (GC). In this study, 16 cuproptosis‐related genes (CRGs) transcriptional profiles were harnessed to perform the regularized latent variable model‐based clustering in GC. A cuproptosis signature risk scoring (CSRS) scheme, based on a weighted sum of principle components of the CRGs, was used to evaluate the prognosis and risk of individual tumors of GC. Four distinct cuproptosis signature‐based clusters, characterized by differential expression patterns of CRGs, were identified among 1136 GC samples across three independent databases. The four clusters were also associated with different clinical outcomes and tumor immune contexture. Based on the CSRS, GC patients can be divided into CSRS‐High and CSRS‐Low subtypes. We found that DBT, MTF1, and ATP7A were significantly elevated in the CSRS‐High subtype, while SLC31A1, GCSH, LIAS, DLAT, FDX1, DLD, and PDHA1 were increased in the CSRS‐Low subtype. Patients with CSRS‐Low score were characterized by prolonged survival time. Further analysis indicated that CSRS‐Low score also correlated with greater tumor mutation burden (TMB) and higher mutation rates of significantly mutated genes (SMG) in GC. In addition, the CSRS‐High subtype harbored more significantly amplified focal regions related to tumorigenesis (3q27.1, 12p12.1, 11q13.3, etc.) than the CSRS‐Low tumors. Drug sensitivity analyses revealed the potential compounds for the treatment of gastric cancer with CSRS‐High score, which were experimentally validated using GC cells. This study highlights that cuproptosis signature‐based subtyping is significantly associated with different clinical features and molecular landscape of GC. Quantitative evaluation of the CSRS of individual tumors will strengthen our understanding of the occurrence and development of cuproptosis and the treatment progress of GC.

BackgroundWe aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2 infection-free adults in China.MethodsThis is a single-center, randomized, double-blind, placebo-controlled phase 3 clinical trial enrolling healthy adult participants (≥18 years) who had completed two or three doses of inactivated COVID-19 vaccines at least 6 months before, in Bengbu, Anhui province, China. Eligible participants were randomly assigned (1:1) to receive a booster intramuscular vaccination with an LVRNA012 vaccine (100ug) or placebo. The primary endpoint was the protective efficacy of a booster dose of the LVRNA012 vaccine or placebo against symptomatic COVID-19 of any severity 14 days after vaccination. Laboratory-confirmed COVID-19 infections were identified from 14 days to 180 days after intervention, with active surveillance for symptomatic illness 8 times per month between 7 to 90 days and at least once per month between 90 to 180 days after intervention.Results2615 participants were recruited and randomly assigned in a 1:1 ratio to either the vaccine group (1308) or the placebo group (1307). A total of 141 individuals (46 in the LVRNA012 group and 95 in the placebo group) developed symptomatic COVID-19 infection 14 days after the booster immunization, showing a vaccine efficacy of 51.9% (95% CI, 31.3% to 66.4%). Most infections were detected 90 days after intervention during a period when XBB was prevalent in the community. Adverse reactions were reported by 64% of participants after the LVRNA012 vaccination, but most of them were mild or moderate. The booster vaccination with the LVRNA012 mRNA vaccine could significantly enhance neutralizing antibody titers against the Omicron variant XBB.1.5 (GMT 132.3 [99.8, 175.4]) than did those in the placebo group (GMT 12.5 [8.4, 18.7]) at day 14 for the previously immunized individuals.ConclusionThe LVRNA012 mRNA vaccine is immunogenic, and shows robust efficacy in preventing COVID-19 during the omicron-predominate period.Clinical trial registrationClinicalTrials.gov, identifier NCT05745545.

IntroductionInflammatory and thrombotic biomarkers are simple prognostic indicators of adverse clinical outcomes in patients with ischemic stroke (IS). However, isolated assessment of inflammatory or thrombus biomarkers in patients with IS is limited in clinical practice.MethodsThis study aimed to evaluate the predictive value of a novel, simplified thrombo-inflammatory prognostic score (TIPS) that combines both inflammatory and thrombus biomarkers in the early phase of IS and to identify high-risk patients at the time of admission. The study population comprised 915 patients with a primary diagnosis of IS in the emergency departments of five grade A tertiary hospitals in China.ResultsPatients were divided into two groups based on the modified Rankin Scale (mRS):

BackgroundBrucella infection is uncommon among peritoneal dialysis (PD) patients in non-endemic areas, and the occurrence of both peritonitis and abdominal aortitis is rare.Case presentationIn December 2023, a 63-year-old male patient undergoing PD was admitted to Shaoxing Second Hospital due to fever, abdominal pain, and cloudy dialysate. Upon physical examination, diffuse mild abdominal pain and tenderness were observed. Subsequent investigation into the patient's medical history revealed consumption of freshly slaughtered lamb from local farmers 3 days prior to the onset of symptoms. Various diagnostic tests, including routine blood tests, procalcitonin levels, and PD fluid analysis, indicated the presence of infection. Abdominal computed tomography (CT) imaging revealed localized lumen widening of the abdominal aorta with surrounding exudative changes. On the sixth day in the hospital, blood and PD fluid cultures confirmed Brucella melitensis infection. The patient was diagnosed with brucella-associated peritonitis and aortitis. Treatment was adjusted to include rifampin and doxycycline for 6 weeks, and the decision was made to keep the PD catheter. Remarkably, the patient exhibited resolution of peritonitis and abdominal aortitis within the initial week of the adjusted treatment. Currently, the patient continues to receive ongoing clinical monitoring.ConclusionBrucella is rare but can cause PD-associated peritonitis and arteritis. Prompt diagnosis and treatment can lead to a good outcome in PD patients. Dual therapy is effective, but the need for catheter removal is unclear. Consider international guidelines and patient factors when deciding on catheter removal.

Abstract Background Health impact assessment (HIA) is a procedure, method and tool for evaluating the potential health impacts of policies, plans and construction projects, as well as the distribution of these impacts on population. Majority of international studies on health impact assessment have focussed on conceptual papers or case evaluations, neglecting participants’ views on policies. Methods A semi-structured interview with 30 health impact assessment experts was employed in this study, and the Nvivo software was utilized to analyse factors that influence policy identification. Subsequently, a multi-stage stratified random sampling method was adopted to survey 655 pilot staff members involved in health impact assessment in Zhejiang Province. Descriptive statistics were used to describe the current status and identify the factors influencing policy identification. In addition, hierarchical linear regression analysis and structural equation modelling were employed to determine the relationship between policy identification and influencing factors. Results Statistically significant differences were found among participants in the level of identification of policies across three dimensions. The policy sentiment dimension had the highest score (4.137 ± 0.664), followed by policy cognition (4.075 ± 0.632) and policy evaluation (3.631 ± 0.797) dimensions. Subject trust had a positive impact on policy cognition (β = 0.503, P 0.05). Policy identification is influenced by age and average monthly salary among other factors. Conclusion These results highlight the importance of subjective trust and procedural justice in policy identification of health impact assessment. They provide valuable insights to developing interventions to overcome barriers to the implementation and enhancement of global identification of policies. Going forward, cross-sectoral synergies, enhanced international communication and training to increase participants’ trust in the policy should be optimized to improve health impact assessment. Additional measures should be taken, such as ensuring seamless communication channels, embedding health impact assessment in administrative mechanisms, and establishing strong oversight and grievance mechanisms to improve fairness and transparency in the implementation and results of health impact assessment.

Abstract Background Several kinds of physical activities have been applied to improve the prognosis of patients with hemodialysis (HD). However, the comparative efficacy of physical activities on the outcomes in HD patients is still unknown. This study explored the effectiveness and safety of all exercise types in HD patients. Methods We searched randomized clinical trials from the PubMed, EMBASE, and Cochrane Library databases. Physical exercises interventions included resistance exercise (RE), aerobic exercise (AE), electrical muscle stimulation (EMS), range of motion (ROM), resistance exercise + aerobic exercise (RE + AE), stretching exercise (STE), respiratory muscle training (RMT), peripheral muscle training (PMT), walking exercise (WE), or usual care/sham exercise (UC/SE). Primary outcomes were six-minute walk test (6-mwt) and quality of life (QOL). Secondary outcomes were Kt/V, VO2max, hemoglobin (Hb), C-reactive protein (CRP), interleukin-6 (IL-6), and systolic and diastolic blood pressure (sbp and dbp). Frequentist network meta-analysis with multivariate random effects models provided mean with 95% confidence intervals (95%CI). Results A total of 58 eligible studies were included. AE, RMT, and RE + AE significantly improved 6-mwt compared with UC/SE. SE was the worst intervention and reduced QOL much more than the UC/SE and other exercise types. AE and RE + AE were associated with higher VO2max, while ROM and RE + AE induced higher Hb levels. All physical activities did not elevate blood pressure, CRP and IL-6. Only ROM decreased sbp/dbp. CRP is significantly lower in RE. Conclusion Physical activities play a crucial role in the different outcomes of HD patients. They can be applied to specific area for their specific efficacy.

In recent years, recommender systems—which provide personalized recommendations by analyzing users’ historical behavior to infer their preferences—have become essential tools across various domains, including e-commerce, streaming media, and social platforms. Recommender systems play a crucial role in enhancing user experience by mining vast amounts of data to identify what is most relevant to users. Among these, deep learning-based recommender systems have demonstrated exceptional recommendation performance. However, these “black-box” systems lack reasonable explanations for their recommendation results, which reduces their impact and credibility. To address this situation, an effective strategy is to provide a personalized textual explanation along with the recommendation. This approach has received increasing attention from researchers because it can enhance users’ trust in recommender systems through intuitive explanations. In this context, our paper introduces a novel explainable recommendation model named GCLTE. This model integrates Graph Contrastive Learning with transformers within an Encoder–Decoder framework to perform rating prediction and reason generation simultaneously. In addition, we cleverly combine the neural network layer with the transformer using a straightforward information enhancement operation. Finally, our extensive experiments on three real-world datasets demonstrate the effectiveness of GCLTE in both recommendation and explanation. The experimental results show that our model outperforms the top existing models.

Abstract Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration. The expression of LHPP was assessed in human GC specimens and cell lines. Various assays were employed to evaluate the impact of LHPP on GC cells. RNA sequencing and Gene Set Enrichment Analysis were conducted to unravel the mechanism through which LHPP regulates GC cell behavior. Additionally, xenograft nude mouse models were utilized to investigate the in vivo effects of LHPP. The findings indicate that LHPP, functioning as a tumor suppressor, is downregulated in both GC tissues and cells. LHPP emerges as an independent risk factor for GC patients, and its expression level exhibits a positive correlation with patient prognosis. LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin‐like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.

Abstract Although various measurements (including organic amendments) have been used to ameliorate saline–alkaline soils, soil organic matter (SOM) remains low in most salt-affected agriculture soils. It was hypothesized that lower SOM level was partly attributable to weaker SOM stability (thus greater desorption) in the salt-affected soils. To test this hypothesis, we conducted a 16-week incubation experiment using low- and high-salinity soils to evaluate the effects of soil ameliorants (gypsum, CaCO3, rice straw and biochar) on SOM labile fractions, i.e., water extractable organic carbon (WEOC) and nitrogen (WEON), together with microbial biomass carbon (MBC) and nitrogen (MBN). Our results showed an increase in MBC and MBN under all amendments in both low- and high-salinity soils, reflecting improvements in soil properties. Gypsum amendment led to a decrease in both WEOC (by 15–21%) and WEON (by 14–31%). CaCO3 amendment only caused a decrease in WEON (by 14–27%), with a greater decrease found in the high-salinity soil. There was an increase in WEOC (by 13–66%) but a decrease in WEON (7.6–46%) under biochar and straw amendments in both low- and high-salinity soils. WEOC:SOC ratio (an indicator for SOC desorption) showed a decrease under gypsum and biochar amendments but an increase with CaCO3 and straw treatments. There was a decrease in WEON:TN ratio (an indicator for ON desorption) under all amendments, with the greatest decrease under biochar treatment. Our analyses demonstrated an enhancement in SOC or ON adsorption under all amendments, indicating that SOM stability might be enhanced in association with soil amelioration. Our study also highlights that there is strong decoupling between carbon and nitrogen cycles and further studies are needed to examine the impacts of such decoupling on SOM stability.

ABSTRACTBackground With increasing knowledge about the gut – bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being conducted. Based on our previous work, this study was conducted to further investigate the therapeutic effects of Lactobacillus rhamnosus GG (LGG) on ovariectomized (OVX) model rats and the immunological and microecological mechanisms involved.Results We found a protective effect of LGG treatment in OVX rats through changes in bone microarchitecture, bone biomechanics, and CTX-I, PINP, Ca, and RANKL expression levels. LGG was more advantageous in promoting osteogenesis, which may be responsible for the alleviation of osteoporosis. Th17 cells were imbalanced with Treg cells in mediastinal lymph nodes and bone marrow, with RORγt and FOXP3 expression following a similar trend. TNF-α and IL-17 expression in colon and bone marrow increased, while TGF-β and IL-10 expression decreased; however, LGG treatment modulated these changes and improved the Th17/Treg balance significantly. Regarding the intestinal barrier, we found that LGG treatment ameliorated estrogen deficiency-induced inflammation and mucosal damage and increased the expression of GLP-2 R and tight junction proteins. Importantly, 16S rRNA sequencing showed a significant increase in the Firmicutes/Bacteroidetes ratio during estrogen deficiency. Dominant intestinal flora showed significant differences in composition; LGG treatment regulated the various genera that were imbalanced in OVX, along with modifying those that did not change significantly in other groups with respect to the intestinal barrier, inflammation development, and bile acid metabolism.Conclusions Overall, LGG ameliorated estrogen deficiency-induced osteoporosis by regulating the gut microbiome and intestinal barrier and stimulating Th17/Treg balance in gut and bone.

Abstract Background Thraustochytrids accumulate lipids with a high content of docosahexaenoic acid (DHA). Although their growth and DHA content are significantly affected by the dissolved oxygen (DO) supply, the role of DO on the transcriptional regulation of metabolism and accumulation of intracellular metabolites remains poorly understood. Here we investigate the effects of three different DO supply conditions (10%, 30%, and 50%) on the fed-batch culture of the Aurantiochytrium PKU#Mn16 strain to mainly reveal the differential gene expressions and metabolite profiles. Results While the supply of 10% DO significantly reduced the rates of biomass and DHA production in the early stages of fermentation, it achieved the highest amounts of biomass (56.7 g/L) and DHA (6.0 g/L) on prolonged fermentation. The transcriptome analyses of the early stage (24 h) of fermentation revealed several genes involved in the central carbon, amino acid, and fatty acid metabolism, which were significantly downregulated at a 10% DO level. The comparative metabolomics results revealed the accumulation of several long-chain fatty acids, amino acids, and other metabolites, supporting the transcriptional regulation under the influence of a low oxygen supply condition. In addition, certain genes involved in antioxidative systems were downregulated under 10% DO level, suggesting a lesser generation of reactive oxygen species that lead to oxidative damage and fatty acid oxidation. Conclusions The findings of this study suggest that despite the slow growth and metabolism in the early stage of fermentation of Aurantiochytrium sp. PKU#Mn16, a constant supply of low dissolved oxygen can yield biomass and DHA content better than that with high oxygen supply conditions. The critical information gained in this study will help to further improve DHA production through bioprocess engineering strategies.

Purpose – Large displacement misalignment under the action of active faults can cause complex three-dimensional deformation in subway tunnels, resulting in severe damage, distortion and misalignment. There is no developed system of fortification and related codes to follow. There are scientific problems and technical challenges in this field that have never been encountered in past research and practices. Design/methodology/approach – This paper adopted a self-designed large-scale active fault dislocation simulation loading system to conduct a similar model test of the tunnel under active fault dislocation based on the open-cut tunnel project of the Urumqi Rail Transit Line 2, which passes through the Jiujiawan normal fault. The test simulated the subway tunnel passing through the normal fault, which is inclined at 60°. This research compared and analyzed the differences in mechanical behavior between two types of lining section: the open-cut double-line box tunnel and the modified double-line box arch tunnel. The structural response and failure characteristics of the open-cut segmented lining of the tunnel under the stick-slip part of the normal fault were studied. Findings – The results indicated that the double-line box arch tunnel improved the shear and longitudinal bending performance. Longitudinal cracks were mainly distributed in the baseplate, wall foot and arch foot, and the crack position was basically consistent with the longitudinal distribution of surrounding rock pressure. This indicated that the longitudinal cracks were due to the large local load of the cross-section of the structure, leading to an excessive local bending moment of the structure, which resulted in large eccentric failure of the lining and formation of longitudinal cracks. Compared with the ordinary box section tunnel, the improved double-line box arch tunnel significantly reduced the destroyed and damage areas of the hanging wall and footwall. The damage area and crack length were reduced by 39 and 59.3%, respectively. This indicates that the improved double-line box arch tunnel had good anti-sliding performance. Originality/value – This paper adopted a self-designed large-scale active fault dislocation simulation loading system to conduct a similar model test of the tunnel under active fault dislocation. This system increased the similarity ratio of the test model, improved the dislocation loading rate and optimized the simulation scheme of the segmented flexible lining and other key factors affecting the test. It is of great scientific significance and engineering value to investigate the structure of subway tunnels under active fault misalignment, to study its force characteristics and damage modes, and to provide a technical reserve for the design and construction of subway tunnels through active faults.

A multispecies energetic particle intensity enhancement event at 1 au is analyzed. We identify this event as a corotating interaction region (CIR) structure that includes a stream interface (SI), a forward-reverse shock pair, and an embedded heliospheric current sheet (HCS). The distinct feature of this CIR event is that (1) the high-energy (>1 MeV) ions show significant flux enhancement at the reverse wave (RW)/shock of the CIR structure, following their passage through the SI and HCS. The flux amplification appears to depend on the energy per nucleon. (2) Electrons in the energy range of 40.5–520 keV are accelerated immediately after passing through the SI and HCS regions, and the flux quickly reaches a peak for low-energy electrons. At the RW, only high-energy electrons (∼520 keV) show significant local flux enhancement. The CIR structure is followed by a fast-forward perpendicular shock driven by a coronal mass ejection (CME), and we observed a significant flux enhancement of low-energy protons and high-energy electrons. Specifically, the 210–330 keV proton and 180–520 keV electron fluxes are enhanced by approximately 2 orders of magnitude. This suggests that the later ICME-driven shock may accelerate particles out of the suprathermal pool. In this paper, we further present that for CIR-accelerated particles, the increase in turbulence power at SI and RWs may be an important factor for the observed flux enhancement in different species. The presence of ion-scale waves near the RW, as indicated by the spectral bump near the proton gyrofrequency, suggests that the resonant wave–particle interaction may act as an efficient energy transferrer between energetic protons and ion-scale waves.

Magnetic reconnection is an important physical process of energy conversion in the heliosphere. Parker Solar Probe (PSP) passes through current sheets of the inner heliosphere and is likely to encounter magnetic reconnection events there. PSP traversed a magnetic reconnection exhaust region that occurred in the coronal streamer during its perihelion Encounter 8. We report an observation of the counterstream of strahl electrons and compressible waves in the exhaust region on the antisunward side of the reconnection site. We analyze the wave characteristics using electromagnetic singular value decomposition techniques and find that the propagation direction of the compressible waves is quasi-perpendicular to the local magnetic field. Combining with the topology of the magnetic field, we infer that the compressible waves converge from the edge to the center of the exhaust region, and then propagate away from it. Further, we select 12 magnetic reconnection events during Encounter 5–8 for statistics and find that the oblique compressible waves are commonly detected throughout the inner heliospheric current sheet. In addition, we discuss the possible nature of wave branches for these compressible waves. Our work shows that magnetic reconnection in the heliosphere not only changes the topology of the large-scale magnetic field in the heliosphere, but also affects the transport characteristics of solar wind plasma and suprathermal particles, and regulates the states of waves and turbulence in the heliosphere.

Parker Solar Probe (PSP) observed sub-Alfvénic solar wind intervals during encounters 8–14, and low-frequency magnetohydrodynamic (MHD) turbulence in these regions may differ from that in super-Alfvénic wind. We apply a new mode decomposition analysis to the sub-Alfvénic flow observed by PSP on 2021 April 28, identifying and characterizing entropy, magnetic islands, forward and backward Alfvén waves, including weakly/nonpropagating Alfvén vortices, forward and backward fast and slow magnetosonic (MS) modes. Density fluctuations are primarily and almost equally entropy- and backward-propagating slow MS modes. The mode decomposition provides phase information (frequency and wavenumber k ) for each mode. Entropy density fluctuations have a wavenumber anisotropy of k _∥ ≫ k _⊥ , whereas slow-mode density fluctuations have k _⊥ > k _∥ . Magnetic field fluctuations are primarily magnetic island modes ( δ B ^i ) with an O (1) smaller contribution from unidirectionally propagating Alfvén waves ( δ B ^A+ ) giving a variance anisotropy of $\langle {\delta {B}^{i}}^{2}\rangle /\langle {\delta {B}^{A}}^{2}\rangle =4.1$ . Incompressible magnetic fluctuations dominate compressible contributions from fast and slow MS modes. The magnetic island spectrum is Kolmogorov-like ${k}_{\perp }^{-1.6}$ in perpendicular wavenumber, and the unidirectional Alfvén wave spectra are ${k}_{\parallel }^{-1.6}$ and ${k}_{\perp }^{-1.5}$ . Fast MS modes propagate at essentially the Alfvén speed with anticorrelated transverse velocity and magnetic field fluctuations and are almost exclusively magnetic due to β _p ≪ 1. Transverse velocity fluctuations are the dominant velocity component in fast MS modes, and longitudinal fluctuations dominate in slow modes. Mode decomposition is an effective tool in identifying the basic building blocks of MHD turbulence and provides detailed phase information about each of the modes.

We study the radial evolution of the inertial-range solar wind plasma turbulence and its anisotropy in the outer heliosphere. We use magnetic field ( B ) measurements from the Voyager 2 spacecraft for heliocentric distances R from 1 to 33 au. We find that the perpendicular and trace power spectral densities (PSDs) of the magnetic field ( ${E}_{{{\rm{B}}}_{\perp }}$ and ${E}_{{{\rm{B}}}_{\mathrm{Tr}}}$ ) still follow a Kolmogorov-like spectrum until 33 au. The parallel magnetic field PSD, ${E}_{{B}_{\parallel }}$ , transits from a power-law index of −2 to −5/3 as the distance crosses R ∼ 10 au. The PSD at frequencies 0.01 Hz < f < 0.2 Hz flattens at R > 20 au, gradually approaching an f ^−1 spectrum, probably due to instrument noise. At 0.002 Hz < f < 0.1 Hz, quasi-parallel propagation dominates at 1 au < R < 7 au, with quasi-perpendicular propagation gradually emerging at R > 5 au. For R > 7 au, oblique propagation becomes the primary mode of propagation. At smaller frequencies of f < 0.01 Hz, ${E}_{{{\rm{B}}}_{\perp }}$ increases with propagation angle at 1 au < R < 5 au, and in contrast decreases with propagation angle at R > 5 au due to the enhanced power level at propagation angles smaller than 20°. Such enhancement may derive from the injection of wave energy from the pickup ion source into the background turbulent cascade, and the injected wave energy is transferred across scales without leaving local enhancements in ${E}_{{{\rm{B}}}_{\perp }}$ or ${E}_{{{\rm{B}}}_{\mathrm{Tr}}}$ .

Aiming at the nonlinear and multiple disturbances in the multi-quadcopter UAV system, this paper proposes a leader–follower composite formation control strategy based on an improved super-twisted sliding mode controller (ISTSMC) and a finite-time extended state observer (FTESO). For the designed sliding mode control algorithm, the integral term’s switching function is replaced with a non-smooth term to reduce the vibration in the control, further improving the overall performance of the system. For external disturbances, the finite-time extended state observer achieves rapid and accurate observation of external disturbances. Finally, through formation control experiments, the reliability and superiority of the proposed composite formation controller (CFC) is validated.

With the rapid development of unmanned aerial vehicle technology and its increasing application across various fields, current airspace resources are insufficient for unmanned aerial vehicles’ needs. This paper, taking Zigong General Aviation Airport in Sichuan as a case study, explores the lateral safety spacing in a mixed operation mode of unmanned aerial vehicles and manned aircraft. Currently, there are no standardized regulations for the safe spacing of the fusion operation of unmanned and manned aircraft. Theoretical research is essential to provide a reference for actual operations. It introduces the UM-Event (unmanned and manned aircraft-event) collision risk model, an adaptation of the Event collision risk model, considering factors like communication, navigation, surveillance performance, human factors, collision avoidance equipment performance, and meteorology. Safety spacing was determined via simulation experiments and actual data analysis, adhering to the target safety level (TSL). Findings indicate that surveillance performance has a minor impact on safety spacing, while communication and navigation significantly influence it. The safety spacing, influenced solely by CNS (communication performance, navigation performance, surveillance performance) and combined factors, increased from 4.42 to 4.47 nautical miles. These results offer theoretical guidance for unmanned aerial vehicle safety in non-segregated airspace.

Due to the complexity of extremely high altitude, topography, and climate, accurately estimating regional biomass is essential yet challenging in alpine regions such as the Qinghai-Tibet Plateau (QTP). Here, we conducted an intensive grid-field survey using a matched-measured biomass dataset of 2,040 field plots on the QTP to obtain high-resolution biomass estimates and their unique response to the environment. The biomass differed significantly among different vegetation types and was highest in evergreen coniferous forests and lowest in alpine grasslands. In addition to traditional mean temperature and precipitation, ultraviolet radiation of growing season (UVGS), and the partial pressure of CO2 (PCO2) were also important factors influencing the spatial variation of vegetation biomass on the QTP. Furthermore, we simulated the spatial distribution of aboveground, belowground, and total biomass on the QTP at a 1-km resolution using the random forest algorithm, with the coefficient of determination (R2) as 0.78, 0.57, and 0.72, respectively. The new estimate of vegetation biomass on the QTP with the intensive field-survey data was 3.16 Gt, including 1.80 Gt in forests, 0.77 Gt in shrubs, 0.52 Gt in grasslands, and 0.07 Gt in deserts. Because of the unique response of biomass to the external environment, such as UVGS and PCO2, we assessed the underlying response of terrestrial ecosystems to global change more comprehensively, especially for sensitive alpine or high-latitude regions in the future. The high-resolution biomass maps may serve as support for regional carbon sink assessment and ecosystem management and conservation, and may provide important parameters for ecological process modeling.

Abstract Existing bone tissue engineering strategies aim to achieve minimize surgical trauma, stabilize the injured area, and establish a dynamic osteogenic microenvironment. The cutting‐edge bone glue developed in this study satisfies these criteria. Inspired by the excellent adhesive properties of mussels, herein, a super osteogenic glue (L‐DPZ) that integrates poly(vinyl alcohol), L‐dopa amino acid, and zeolitic imidazolate framework‐8 characterized by catechol–metal coordination is used to successfully adhere to hard tissue with a maximum adhesive strength of 10 MPa, which is much higher than those of commercial and previously reported bone glues. The stable hard tissue adhesion also enables it to adhere strongly to luxated or broken teeth, Bio‐Oss (a typical bone graft material), and splice fragments from comminuted fractures of the rabbit femur. Then, it is testified that the L‐DPZ hydrogels exhibit satisfactory biocompatibility, stable degradability, and osteogenic ability in vitro. Moreover, the ability to anchor Bio‐Oss and sustained osteogenesis of L‐DPZ result in satisfactory healing in calvarial bone defect models in rabbits, as observed by increased bone thickness and the ingrowth of new bone tissue. These results are expected to demonstrate solutions to clinical dilemmas such as comminuted bone fracture fixation, bone defect reconstruction, and teeth dislocation replantation.

The blood-retinal barrier (BRB) is a well-recognized mechanism that underlies the retina’s immunological privilege. The BRB is formed locally by inhibitory molecules that bind to cell membranes, as well as by the suppression of systemic immune responses. Recent studies have revealed that microglial cells are essential for maintaining immunological privilege within the retina by regulating the immune response. They achieve this by enhancing or reducing ocular inflammation. Furthermore, retinal pigment epithelium (RPE) regulates the behavior of immune cells within the retina, which can lead microglial cells to reduce inflammation and promote immunological tolerance. With the aim of better understanding the biology of immunological processes within the retina, this article reviews the BRB and discusses the factors, systemic immune responses, microglia, RPE, and their associated enzymes that enable the BRB.

Solvent molecules under nanoconfinement dictates several key physical properties. Here, the authors reveal the behaviour of a quasi-solid electrolyte by using a microporous metal-organic framework with a small amount of liquid electrolyte influencing a number of properties in a lithium-metal pouch-cell.

Diffuse type gastric cancer was identified with relatively worse prognosis than other Lauren’s histological classification. Integrin β1 (ITGB1) was a member of integrin family which played a markedly important role in tumorigenesis and progression. However, the influence of ITGB1 in diffuse gastric cancer (DGC) remains uncertain. Here, we leveraged the transcriptomic and proteomic data to explore the association between ITGB1 expression and clinicopathologic information and biological process in DGC. Cell phenotype experiments combined with quantitative-PCR (q-PCR) and western blotting were utilized to identify the potential molecular mechanism underling ITGB1.Transcriptomics and proteomics both revealed that the higher ITGB1 expression was significantly associated with worse prognosis in DGC, but not in intestinal GC. Genomic analysis indicated that the mutation frequency of significantly mutated genes of ARID1A and COL11A1, and mutational signatures of SBS6 and SBS15 were markedly increased in the ITGB1 low expression subgroup. The enrichment analysis revealed diverse pathways related to dysregulation of ITGB1 in DGC, especially in cell adhesion, proliferation, metabolism reprogramming, and immune regulation alterations. Elevated activities of kinase-ROCK1, PKACA/PRKACA and AKT1 were observed in the ITGB1 high-expression subgroup. The ssGSEA analysis also found that ITGB1 low-expression had a higher cuproptosis score and was negatively correlated with key regulators of cuproptosis, including FDX1, DLAT, and DLST. We further observed that the upregulated expression of mitochondrial tricarboxylic acid (TCA) cycle in the ITGB1 low-expression group. Reduced expression of ITGB1 inhibited the ability of cell proliferation and motility and also potentiated the cell sensitive to copper ionophores via western blotting assay. Overall, this study revealed that ITGB1 was a protumorigenic gene and regulated tumor metabolism and cuproptosis in DGC.

Magnetic switchbacks, which are large angular deflections of the interplanetary magnetic field, are frequently observed by Parker Solar Probe (PSP) in the inner heliosphere. Magnetic switchbacks are believed to play an important role in the heating of the solar corona and the solar wind as well as the acceleration of the solar wind in the inner heliosphere. Here, we analyze magnetic field data and plasma data measured by PSP during its second and fourth encounters, and select 71 switchback events with reversals of the radial component of the magnetic field at times of unchanged electron-strahl pitch angles. We investigate the anisotropic thermal kinetic properties of plasma during switchbacks in a statistical study of the measured proton temperatures in the parallel and perpendicular directions as well as proton density and specific proton fluid entropy. We apply the “genetic algorithm” method to directly fit the measured velocity distribution functions in field-aligned coordinates using a two-component bi-Maxwellian distribution function. We find that the protons in most switchback events are hotter than the ambient plasma outside the switchbacks, with characteristics of parallel and perpendicular heating. Specifically, significant parallel and perpendicular temperature increases are seen for 45 and 62 of the 71 events, respectively. We find that the density of most switchback events decreases rather than increases, which indicates that proton heating inside the switchbacks is not caused by adiabatic compression, but is probably generated by nonadiabatic heating caused by field–particle interactions. Accordingly, the proton fluid entropy is greater inside the switchbacks than in the ambient solar wind.

The acceleration and heating of solar wind particles by magnetic reconnection are important mechanisms in space physics. Although alpha particles ( ^4 He ^2+ ) are the second most abundant population of solar wind ions, their kinetic behavior in solar wind magnetic reconnection is not well understood. Using the high-energy (1500–3000 eV) range of the Solar Wind Analyser/Proton–Alpha Sensor instrument on board Solar Orbiter, we study the kinetic features of alpha particles in an exhaust region of a Pestchek-like solar-wind reconnection event with a weak guide field. A pair of back-to-back compound discontinuities is observed in the exhaust region. We find that the plasma in the magnetic exhaust region is heated and bounded by slow shocks (SSs), while the accelerated reconnection jet is bounded by rotational discontinuities (RDs). The SSs are outside the RDs, which is not expected from the magnetohydrodynamical prediction. We suggest this different location of the discontinuities is due to the enhanced parallel temperature T _p _∥ > T _p _⊥ , which reduces the local Alfvén speed in the exhaust region, allowing the SSs to propagate faster than the RDs. Inside the exhaust region, the guide field is dominant. We find a two-population distribution of the alpha particles. These two populations are field aligned downstream the SSs and shift to have a perpendicular offset in the reconnection jet, suggesting that the change of the magnetic field at the RDs has similar timescales with the proton gyroperiod, but faster than those of the alpha particles, such that the alpha particles behave like pickup ions.

Abstract Matrix regression has attracted much attention due to directly select some meaningful features from matrix data. However, most existing matrix regressions do not consider the global and local structure of the matrix data simultaneously. To this end, we propose a low‐rank nonnegative sparse representation and local preserving matrix regression (LNSRLP‐MR) model for image feature selection. Here, the loss function is defined by the left and right regression matrices. To capture the global structure and discriminative information of the training images and reduce the effect of heterogeneous data and noises, we impose the low‐rank constraint on the self‐representation error matrix and the nonnegative sparse constraint on the coefficient vector. The graph matrix can be learned adaptively through representation coefficients, so that accurate local structure information in samples can be revealed. Feature selection is performed by obtained row sparse transformation matrix. An optimization procedure and its performance are also present. Experimental results on several image datasets show that compared with the‐state‐of‐the‐art method, the average classification accuracy of the proposed method is improved by at least 1.2% and up to 3.3%. For images with noise or occlusion, the accuracy is improved significantly, up to 4%, which indicates that this method has strong robustness.

Gout is a common form of arthritis caused by the deposition of sodium urate crystals in the joints and tissues around them. MicroRNAs (miRNAs) are noncoding RNAs that have been shown to be involved in regulating the pathogenesis of gout through multiple cellular signaling pathways, which may be potential targets for the treatment of gout. In this review, we systematically discuss the regulatory roles of related miRNAs in gout, which will provide help for the treatment of gout and miRNAs is expected to become a potential biomarker for gout diagnosis.

Inflammation is a response of the body to external stimuli (eg. chemical irritants, bacteria, viruses, etc.), and when the stimuli are persistent, they tend to trigger chronic inflammation. The presence of chronic inflammation is an important component of the tumor microenvironment produced by a variety of inflammatory cells (eg. macrophages, neutrophils, leukocytes, etc.). The relationship between chronic inflammation and cancer development has been widely accepted, and chronic inflammation has been associated with the development of many cancers, including chronic bronchitis and lung cancer, cystitis inducing bladder cancer. Moreover, chronic colorectitis is more likely to develop into colorectal cancer. Therefore, the specific relationship and cellular mechanisms between inflammation and cancer are a hot topic of research. Recent studies have identified phosphodiesterase 4B (PDE4B), a member of the phosphodiesterase (PDEs) protein family, as a major cyclic AMP (cAMP) metabolizing enzyme in inflammatory cells, and the therapeutic role of PDE4B as chronic inflammation, cancer. In this review, we will present the tumors associated with chronic inflammation, and PDE4B potential clinical application.

The surrounding rock and high water pressure in weak watery strata have adverse effects on the mechanical properties of tunnel support structures. In order to optimize the anti-drainage design of tunnels in weak watery strata and evaluate their structural safety, this paper relies on the Taidacun Tunnel of the China–Laos Railway to carry out field monitoring research. A dual-field fluid–solid coupling calculation model is established to optimize the tunnel’s waterproof and drainage design, combined with a bending moment curvature model to evaluate structural safety. The main conclusions are as follows: Under the action of high water and soil pressure, the structural safety margin of the water-rich fine sand section of the Taidacun Tunnel is small, and waterproof and drainage design optimization is required. Combined with the proposed average pressure reduction coefficient, the influence of the water level and annular blind pipe spacing on the water pressure of the lining is proved, and then the optimal annular blind pipe spacing in the water-rich area of the tunnel is determined. A structural safety evaluation method based on the bending moment curvature model is proposed. Two models of elastic beam and moment–curvature beam are used to analyze the mechanical characteristics and optimization effects of the structure under optimal annular blind pipe spacing.

Monitoring and analyzing radio interference sources play a crucial role in ensuring the safe operation of civil aviation navigation, communication, airport management, and air traffic control. Traditional ground monitoring methods are slow and inadequate for tracking aerial and mobile interference sources effectively. Although flight methods such as helicopters and airships can effectively monitor aerial interference, the flight approval process is time-consuming and expensive. This paper investigates a novel approach to locating civil aviation radio interference sources using four unmanned aerial vehicles (UAVs) to address this issue. It establishes a model for aerial positioning of radio interference sources with the four UAVs and proposes a method for time synchronization and data communication among them. The paper conducts simulations of the four-UAV time–frequency difference positioning method, analyzing the geometric accuracy dilution with different deployment configurations of the UAVs, positioning biases, and root mean square errors (RMSEs) under varying interference source movement speeds. The simulation results provide crucial data to support subsequent experiments.

Decision making is a key to business or project success in any sectors, especially in construction that requires handling numerous information and knowledge. Multiple criteria decision making (MCDM) is an important tool for decision problem solving due to simultaneous consideration of multiple criteria and objectives. Various MCDM methods are continually emerging and tend to be increasingly adopted to address the real-world construction problems. Therefore, it is urged to systematically review the existing body of literature to demonstrate the evolution of the mainstream MCDM methods in general and their application status in construction. A total of 530 construction articles published from 2000 to 2019 are selected in this study and then categorized into seven major application areas using a novel systematic literature review (SLR) methodology. The bibliometric analysis is then used to describe the research trend. Subsequently, the qualitative discussion by themes is conducted to analyze the application of MCDM methods in construction. A further discussion makes it possible to identify the potential challenges (e.g. applicability, robustness, postpone effect, dynamic and prospective challenges and scale problem) to existing research. It also contributes to the recommendation of future directions for the development of MCDM methods that would benefit construction research and practice.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of systemic autoimmune diseases, which is typified by inflammatory necrosis predominantly affecting the small vessels and often accompanied by positive ANCA. Clinically, AAV primarily includes microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). It has been found that in AAV pathogenesis, both innate and adaptive immunity are related to neutrophil function mutually. Many proteins, such as myeloperoxidase (MPO) and proteinase 3 (PR3), in neutrophil cytoplasm lead to the production of proteins such as MPO-ANCA and PR3-ANCA by activating adaptive immunity. In addition, through the process of neutrophil extracellular trap (NET) formation, activation of an alternative complement pathway and the respiratory burst can stimulate the neutrophils close to vascular endothelial cells and will participate the vessel inflammation. This review aims to reveal the potential mechanisms regulating the association between the neutrophils and various types of AAVs and to emphasize the results of recent findings on these interactions. Moreover, multiple underlying signaling pathways involved in the regulation of neutrophils during AAV processes have also been discussed. The ultimate goal of this review is to identify novel biomarkers and therapeutic targets for AAV management in the future.

Docosahexaenoic acid (DHA) has attracted attention from researchers because of its pharmacological and nutritional importance. Currently, DHA production costs are high due to fermentation inefficiency; however, improving DHA yield by metabolic engineering in thraustochytrids is one approach to reduce these costs. In this study, a high-yielding (53.97% of total fatty acids) DHA production strain was constructed by disrupting polyunsaturated fatty acid beta-oxidation via knockout of the 2,4-dienyl-CoA reductase (DECR) gene (KO strain) in Aurantiochytrium sp. Slight differences in cell growth was observed in the wild-type and transformants (OE and KO), with cell concentrations in stationary of 2.65×106, 2.36×106 and 2.56×106 cells mL-1 respectively. Impressively, the KO strain yielded 21.62% more neutral lipids and 57.34% greater DHA production; moreover, the opposite was observed when overexpressing DECR (OE strain), with significant decreases of 30.49% and 64.61%, respectively. Furthermore, the KO strain showed a prolonged DHA production period with a sustainable increase from 63 to 90 h (170.03 to 203.27 mg g−1 DCW), while that of the wildtype strain decreased significantly from 150.58 to 140.10 mg g−1 DCW. This new approach provides an advanced proxy for the construction of sustainable DHA production strains for industrial purposes and deepens our understanding of the metabolic pathways of Aurantiochytrium sp.

Media supplementation has proven to be an effective technique for improving byproduct yield during microbial fermentation. This study explored the impact of different concentrations of bioactive compounds, namely alpha-tocopherol, mannitol, melatonin, sesamol, ascorbic acid, and biotin, on the Aurantiochytrium sp. TWZ-97 culture. Our investigation revealed that alpha-tocopherol was the most effective compound in reducing the reactive oxygen species (ROS) burden, both directly and indirectly. Adding 0.7 g/L of alpha-tocopherol led to an 18% improvement in biomass, from 6.29 g/L to 7.42 g/L. Moreover, the squalene concentration increased from 129.8 mg/L to 240.2 mg/L, indicating an 85% improvement, while the squalene yield increased by 63.2%, from 19.82 mg/g to 32.4 mg/g. Additionally, our comparative transcriptomics analysis suggested that several genes involved in glycolysis, pentose phosphate pathway, TCA cycle, and MVA pathway were overexpressed following alpha-tocopherol supplementation. The alpha-tocopherol supplementation also lowered ROS levels by binding directly to ROS generated in the fermentation medium and indirectly by stimulating genes that encode antioxidative enzymes, thereby decreasing the ROS burden. Our findings suggest that alpha-tocopherol supplementation can be an effective method for improving squalene production in Aurantiochytrium sp. TWZ-97 culture.

Abstract Background The human skin microbiota is considered to be essential for skin homeostasis and barrier function. Comprehensive analyses of its function would substantially benefit from a catalog of reference genes derived from metagenomic sequencing. The existing catalog for the human skin microbiome is based on samples from limited individuals from a single cohort on reference genomes, which limits the coverage of global skin microbiome diversity. Results In the present study, we have used shotgun metagenomics to newly sequence 822 skin samples from Han Chinese, which were subsequently combined with 538 previously sequenced North American samples to construct an integrated Human Skin Microbial Gene Catalog (iHSMGC). The iHSMGC comprised 10,930,638 genes with the detection of 4,879,024 new genes. Characterization of the human skin resistome based on iHSMGC confirmed that skin commensals, such as Staphylococcus spp, are an important reservoir of antibiotic resistance genes (ARGs). Further analyses of skin microbial ARGs detected microbe-specific and skin site-specific ARG signatures. Of note, the abundance of ARGs was significantly higher in Chinese than Americans, while multidrug-resistant bacteria (“superbugs”) existed on the skin of both Americans and Chinese. A detailed analysis of microbial signatures identified Moraxella osloensis as a species specific for Chinese skin. Importantly, Moraxella osloensis proved to be a signature species for one of two robust patterns of microbial networks present on Chinese skin, with Cutibacterium acnes indicating the second one. Each of such “cutotypes” was associated with distinct patterns of data-driven marker genes, functional modules, and host skin properties. The two cutotypes markedly differed in functional modules related to their metabolic characteristics, indicating that host-dependent trophic chains might underlie their development. Conclusions The development of the iHSMGC will facilitate further studies on the human skin microbiome. In the present study, it was used to further characterize the human skin resistome. It also allowed to discover the existence of two cutotypes on the human skin. The latter finding will contribute to a better understanding of the interpersonal complexity of the skin microbiome. Video abstract

Abstract The pore‐scale imbibition mechanism in fractured water‐wetted reservoirs has been acknowledged as an efficient tool to enhance oil recovery. Most rock in a natural reservoir is mixed‐wetted, but most studies on the pore‐scale imbibition process only focused on the water‐wetted rock. This paper adopts two mixed‐wetted core samples for microspontaneous imbibition experiment, micro‐CT scanning, and nuclear magnetic resonance (NMR) test. The results indicate that the pore radius distribution of the segmented CT images is consistent with that of the NMR test. The microimbibition recovery ratio of core No. 34‐1 and core No. 64 in the spontaneous imbibition experiment are 27.7% and 58.2%, which agrees well with that computed by the micro‐CT scanning image (27.63% and 56.09%). Based on the segmented images, the influences of the Jamin's effect, pore size distribution, and wettability on the microspontaneous imbibition are visualized and quantitatively studied. The Jamin's effect is the important factor that hinders the microimbibition process. The main pore size of imbibition distributes in the range of 1‐25 μm. Furthermore, the pore‐scale spontaneous imbibition process in a single pore with mixed wettability is investigated and analyzed. The relationships among the contact angle, capillary force, recovery ratio, wettability, and the microimbibition recovery are revealed.

Objective: To clarify the molecular mechanism of TMEM88 regulating lipid synthesis and metabolism cytokine in NAFLD.Methods:In vivo, NAFLD model mice were fed by a Methionine and Choline-Deficient (MCD) diet. H&E staining and immunohistochemistry experiments were used to analyze the mice liver tissue. RT-qPCR and Western blotting were used to detect the lipid synthesis and metabolism cytokine. In vitro, pEGFP-C1-TMEM88 and TMEM88 siRNA were transfected respectively in free fat acid (FFA) induced AML-12 cells, and the expression level of SREBP-1c, PPAR-α, FASN, and ACOX-1 were evaluated by RT-qPCR and Western blotting.Results: The study found that the secretion of PPAR-α and its downstream target ACOX-1 were upregulated, and the secretion of SREBP-1c and its downstream target FASN were downregulated after transfecting with pEGFP-C1-TMEM88. But when TMEM88 was inhibited, the experimental results were opposite to the aforementioned conclusions. The data suggested that it may be related to the occurrence, development, and end of NAFLD. Additionally, the study proved that TMEM88 can inhibit Wnt/β-catenin signaling pathway. Meanwhile, TMEM88 can accelerate the apoptotic rate of FFA-induced AML-12 cells.Conclusion: Overall, the study proved that TMEM88 takes part in regulating the secretion of lipid synthesis and metabolism cytokine through the Wnt/β-catenin signaling pathway in AML-12 cells. Therefore, TMEM88 may be involved in the progress of NAFLD. Further research will bring new ideas for the study of NAFLD.

Thraustochytrids are unicellular marine heterotrophic protists, which have recently shown a promising ability to produce omega-3 fatty acids from lignocellulosic hydrolysates and wastewaters. Here we studied the biorefinery potential of the dilute acid-pretreated marine macroalgae (Enteromorpha) in comparison with glucose via fermentation using a previously isolated thraustochytrid strain (Aurantiochytrium limacinum PKU#Mn4). The total reducing sugars in the Enteromorpha hydrolysate accounted for 43.93% of the dry cell weight (DCW). The strain was capable of producing the highest DCW (4.32 ± 0.09 g/L) and total fatty acids (TFA) content (0.65 ± 0.03 g/L) in the medium containing 100 g/L of hydrolysate. The maximum TFA yields of 0.164 ± 0.160 g/g DCW and 0.196 ± 0.010 g/g DCW were achieved at 80 g/L of hydrolysate and 40 g/L of glucose in the fermentation medium, respectively. Compositional analysis of TFA revealed the production of equivalent fractions (% TFA) of saturated and polyunsaturated fatty acids in hydrolysate or glucose medium. Furthermore, the strain yielded a much higher fraction (2.61–3.22%) of eicosapentaenoic acid (C20:5n-3) in the hydrolysate medium than that (0.25–0.49%) in the glucose medium. Overall, our findings suggest that Enteromorpha hydrolysate can be a potential natural substrate in the fermentative production of high-value fatty acids by thraustochytrids.