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Abstract The recent development of nanobiomaterials has shed some light on the field of periodontal tissue regeneration. Laponite (LAP), an artificially synthesized two-dimensional (2D) disk-shaped nanosilicate, has garnered substantial attention in regenerative biomedical applications owing to its distinctive structure, exceptional biocompatibility and bioactivity. This study endeavors to comprehensively evaluate the influence of LAP on periodontal regeneration. The effects of LAP on periodontal ligament cells (PDLCs) on osteogenesis, cementogenesis and angiogenesis were systematically assessed, and the potential mechanism was explored through RNA sequencing. The results indicated that LAP improved osteogenic and cementogenic differentiation of PDLCs, the regulatory effects of LAP on PDLCs were closely correlated with activation of PI3K-AKT signaling pathway. Moreover, LAP enhanced angiogenesis indirectly via manipulating paracrine of PDLCs. Then, LAP was implanted into rat periodontal defect to confirm its regenerative potential. Both micro-CT and histological analysis indicated that LAP could facilitate periodontal tissue regeneration in vivo. These findings provide insights into the bioactivity and underlying mechanism of LAP on PDLCs, highlighting it might be a potential therapeutic option in periodontal therapy.

Abstract Achieving high-luminescence organic light-emitting devices (OLEDs) with narrowband emission and high color purity is important in various optoelectronic fields. Laser displays exhibit outstanding advantages in next-generation display technologies owing to their ultimate visual experience, but this remains a great challenge. Here, we develop a novel OLED based organic single crystals. By strongly coupling the organic exciton state to an optical microcavity, we obtain polariton electroluminescent (EL) emission from the polariton OLEDs (OPLEDs) with high luminance, narrow-band emission, high color purity, high polarization as well as excellent optically pumped polariton laser. Further, we evaluate the potential for electrically pumped polariton laser through theoretical analysis and provide possible solutions. This work provides a powerful strategy with a material–device combination that paves the way for electrically driven organic single-crystal-based polariton luminescent devices and possibly lasers.

With the development of satellite technology, low-orbit satellites equipped with high-resolution magnetometers have become an important tool for measuring the Earth's magnetic field, which provides continuous observations around the world regardless of ground and low-altitude weather conditions. Currents in the space, particularly the ionospheric currents, are the main source to cause the magnetic field perturbations at ground and the low Earth orbit (LEO) satellite altitudes. In this paper, we briefly introduce the development history of LEO satellites for measuring the Earth's magnetic field, and the in-orbit calibration processes of magnetic data. In addition, the findings and generation mechanisms of ionospheric currents are reviewed, and the methods for reverting ionospheric currents by using the satellite magnetic measurements are introduced in detail. Currents derived from ground-based and satellite magnetic measurements are not always consistent, and sometimes there are significant differences. Reasons to cause such differences may be related to different data sources (e.g., ground-to-satellite, satellite-to-satellite) and the assumptions in inversion algorithms of currents. Based on limited observations, inversion is often based on assumptions about the geometry and location of the currents, that may not fully agree with the real current distributions. Therefore, combination of ground-based and satellite magnetic measurements, through cross-comparison and cross-verification, is an effective way to test and improve the rationality of the assumptions in the ionospheric current inversion algorithms. Establish the theory and method of space weather monitoring based on the combined and fused magnetic field measurements, will greatly improve our understanding of the ionospheric electrodynamics, the state of the magnetosphere, as well as the coupling mechanisms between ionosphere and magnetosphere.

BackgroundInhibition of indolamine-2,3-dioxygenase 1 (IDO1) has been proposed as a promising strategy for cancer immunotherapy; however, it has failed in clinical trials. Macrophages in the tumor microenvironment (TME) contribute to immune escape and serve as potential therapeutic targets. This study investigated the expression pattern of IDO1 in TME and its impact on prognosis and therapeutic response of patients with esophageal squamous cell carcinoma (ESCC).MethodsRNA sequencing data from 95 patients with ESCC from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic value of IDO1. Bioinformatics tools were used to estimate scores for stromal and immune cells in tumour tissues, abundance of eight immune cell types in TME, and sensitivity of chemotherapeutic drugs and immune checkpoint (IC) blockage. The results were validated using digitalized immunohistochemistry and multiplexed immunofluorescence in ESCC tissue samples obtained from our clinical center.ResultsTCGA and validation data suggested that high expression of IDO1 was associated with poor patient survival, and IDO1 was an independent prognostic factor. IDO1 expression positively correlated with macrophages in TME and PDCD1 within diverse IC genes. Single-cell RNA sequencing data analysis and multiplexed immunofluorescence verified the coexpression of IDO1 and PD-1 in tumor-associated macrophages (TAMs). Patients with high IDO1 expression showed increased sensitivity to various chemotherapeutic drugs, while were more likely to resist IC blockage.ConclusionThis study identifies IDO1 as an independent prognostic indicator of OS in patients with ESCC, reveals a compelling connection of IDO1, PD-1, and TAMs, and explores the sensitivity of patients with high IDO1 expression to chemotherapeutic drugs and their resistance to IC blockade. These findings open new avenues for potential targets in ESCC immunotherapy.

In this study, we provide the first detailed analysis of variations in the spacecraft potential (Vs) of the three Swarm satellites, which are flying at about 400–500 km. Unlike previous studies that have investigated extreme charging events, usually with spacecraft potentials as negative as −100 V, this study is focused on variations of Swarm Vs readings, which fall within a few negative volts. The Swarm observations show that spacecraft at low Earth orbital (LEO) altitudes are charged only slightly negatively, varying between −7 V and 0 V, with the majority of recorded potentials at these altitudes clustering close to −2 V. However, a second peak of Vs data is found at −5.5 V, though the event numbers for these more-negative observations are less, by an order of magnitude, than for incidents near the −2 V peak. These two distinct Vs peaks suggest two different causes. We have thus divided the Swarm spacecraft Vs data into two categories: less-negatively charged (−5 < Vs < 0 V) and more-negatively-charged (−6.5 < Vs < −5 V). These two Vs categories exhibit different spatial and temporal distributions. The Vs observations in the first category remain relatively closer to 0 V above the magnetic equator, but become much more negative at low and middle latitudes on the day side; at high latitudes, these first-category Vs readings are relatively more-negative during local summer. Second-category Vs events cluster into two bands at the middle latitudes (between ±20°–50° magnetic latitude), but with slightly more negative readings at the South Atlantic Anomaly (SAA) region; at high latitudes, these rarer but more-negative second-category Vs events exhibit relatively more-negative values during local winter, which is opposite to the seasonal pattern seen in the first category. By comparing Vs data to the distributions of background plasma density at Swarm altitudes, we find for the first category that more-negative Vs readings are recorded at regions with higher background plasma density, while for the second category the more-negative Vs data are observed at regions with lower background plasma density. This can be explained as follows: the electron and ion fluxes incident on Swarm surface, whose differences determine the potential of Swarm, are dominated by the background “cold” plasma (due to ionization) and “hot” plasma (due to precipitated particles from magnetosphere) for the two Vs categories, respectively.

Abstract Background Glioma is the most common malignant primary brain tumor and is characterized by a poor prognosis and limited therapeutic options. ISG20 expression is induced by interferons or double-stranded RNA and is associated with poor prognosis in several malignant tumors. Nevertheless, the expression of ISG20 in gliomas, its impact on patient prognosis, and its role in the tumor immune microenvironment have not been fully elucidated. Methods Using bioinformatics, we comprehensively illustrated the potential function of ISG20, its predictive value in stratifying clinical prognosis, and its association with immunological characteristics in gliomas. We also confirmed the expression pattern of ISG20 in glioma patient samples by immunohistochemistry and immunofluorescence staining. Results ISG20 mRNA expression was higher in glioma tissues than in normal tissues. Data-driven results showed that a high level of ISG20 expression predicted an unfavorable clinical outcome in glioma patients, and revealed that ISG20 was possibly expressed on tumor-associated macrophages and was significantly associated with immune regulatory processes, as evidenced by its positive correlation with the infiltration of regulatory immune cells (e.g., M2 macrophages and regulatory T cells), expression of immune checkpoint molecules, and effectiveness of immune checkpoint blockade therapy. Furthermore, immunohistochemistry staining confirmed the enhanced expression of ISG20 in glioma tissues with a higher WHO grade, and immunofluorescence assay verified its cellular localization on M2 macrophages. Conclusions ISG20 is expressed on M2 macrophages, and can serve as a novel indicator for predicting the malignant phenotype and clinical prognosis in glioma patients.

Background: There is a great obstacle in prenatal diagnosis of fetal anomalies due to their considerable genetic and clinical heterogeneity. Whole-exome sequencing (WES) has been confirmed as a successful option for genetic diagnosis in pediatrics, but its clinical utility for prenatal diagnosis remains to be limited.Methods: A total of 60 fetuses with abnormal ultrasound findings underwent karyotyping or chromosomal microarray analysis (CMA), and those with negative results were further subjected to WES. The identified variants were classified as pathogenic or likely pathogenic (P/LP) and the variant of uncertain significance (VUS). Pregnancy outcomes were obtained through a telephone follow-up.Results: Twelve (20%, 12/60) fetuses were diagnosed to have chromosomal abnormalities using karyotyping or CMA. Of the remaining 48 cases that underwent WES, P/LP variants were identified in 14 cases (29.2%), giving an additional diagnostic yield of 23.3% (14/60). The most frequently affected organ referred for prenatal WES was the head or neck system (40%), followed by the skeletal system (39.1%). In terms of pathogenic genes, FGFR3 was the most common diagnostic gene in this cohort. For the first time, we discovered five P/LP variants involved in SEC24D, FIG4, CTNNA3, EPG5, and PKD2. In addition, we identified three VUSes that had been reported previously. Outcomes of pregnancy were available for 54 cases, of which 24 cases were terminated.Conclusion: The results confirmed that WES is a powerful tool in prenatal diagnosis, especially for fetuses with ultrasonographic anomalies that cannot be diagnosed using conventional prenatal methods. Additionally, newly identified variants will expand the phenotypic spectrum of monogenic disorders and greatly enrich the prenatal diagnostic database.

ABSTRACTExtraintestinal pathogenic Escherichia coli (ExPEC) is an important zoonotic pathogen. Recently, ExPEC has been reported to be an emerging problem in pig farming. However, the mechanism of pathogenicity of porcine ExPEC remains to be revealed. In this study, we constructed a transposon (Tn) mutagenesis library covering Tn insertion in over 72% of the chromosome-encoded genes of a virulent and multi-drug resistant porcine ExPEC strain PCN033. By using a mouse infection model, a transposon-directed insertion site sequencing (TraDIS) assay was performed to identify in vivo fitness factors. By comparing the Tn insertion frequencies between the input Tn library and the recovered library from different organs, 64 genes were identified to be involved in fitness during systemic infection. 15 genes were selected and individual gene deletion mutants were constructed. The in vivo fitness was evaluated by using a competitive infection assay. Among them, ΔfimG was significantly outcompeted by the WT strain in vivo and showed defective adhesion to host cells. rfa which was involved in lipopolysaccharide biosynthesis was shown to be critical for in vivo fitness which may have resulted from its role in the resistance to serum killing. In addition, several metabolic genes including fepB, sdhC, fepG, gltS, dcuA, ccmH, ddpD, narU, glpD, malM, and yabL and two regulatory genes metJ and baeS were shown as important determinants of in vivo fitness of porcine ExPEC. Collectively, this study performed a genome-wide screening for in vivo fitness factors which will be important for understanding the pathogenicity of porcine ExPEC.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation “sensitizes” the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35–STARD4 axis is a promising therapeutic target for NAFLD.

Abstract Background hsa_circ_0001727 (circZKSCAN1) has been reported to be a tumor-associated circRNA by sponging microRNAs. Intriguingly, we found that circZKSCAN1 encoded a secretory peptide (circZKSaa) in the liver. The present study aims to elucidate the potential role and molecular mechanism of circZKSaa in the regulation of hepatocellular carcinoma (HCC) progression. Methods The circRNA profiling datasets (RNA-seq data GSE143233 and GSE140202) were reanalyzed and circZKSCAN1 was selected for further study. Mass spectrometry, polysome fractionation assay, dual-luciferase reporter, and a series of experiments showed that circZKSCAN1 encodes circZKSaa. Cell proliferation, apoptosis, and tumorigenesis in nude mice were examined to investigate the functions of circZKSaa. Mechanistically, the relationship between the circZKSaa and mTOR in HCC was verified by immunoprecipitation analyses, mass spectrometry, and immunofluorescence staining analyses. Results Receiver operating characteristic (ROC) analysis demonstrated that the secretory peptide circZKSaa encoded by circZKSCAN1 might be the potential biomarker for HCC tissues. Through a series of experiments, we found that circZKSaa inhibited HCC progression and sensitize HCC cells to sorafenib. Mechanistically, we found that the sponge function of circZKSCAN1 to microRNA is weak in HCC, while overexpression of circZKSaa promoted the interaction of FBXW7 with the mammalian target of rapamycin (mTOR) to promote the ubiquitination of mTOR, thereby inhibiting the PI3K/AKT/mTOR pathway. Furthermore, we found that the high expression of cicZKSCAN1 in sorafenib-treated HCC cells was regulated by QKI-5. Conclusions These results reveal that a novel circZKSCAN1-encoded peptide acts as a tumor suppressor on PI3K/AKT/mTOR pathway, and sensitizes HCC cells to sorafenib via ubiquitination of mTOR. These findings demonstrated that circZKSaa has the potential to serve as a therapeutic target and biomarker for HCC treatment.

IntroductionSepsis is the leading cause of death in intensive care units and is characterized by multiple organ failure, including dysfunction of the immune system. In the present study, we performed an integrative analysis on publicly available datasets to identify immune-related genes (IRGs) that may play vital role in the pathological process of sepsis, based on which a prognostic IRG signature for 28-day mortality prediction in patients with sepsis was developed and validated.MethodsWeighted gene co-expression network analysis (WGCNA), Cox regression analysis and least absolute shrinkage and selection operator (LASSO) estimation were used to identify functional IRGs and construct a model for predicting the 28-day mortality. The prognostic value of the model was validated in internal and external sepsis datasets. The correlations of the IRG signature with immunological characteristics, including immune cell infiltration and cytokine expression, were explored. We finally validated the expression of the three IRG signature genes in blood samples from 12 sepsis patients and 12 healthy controls using qPCR.ResultsWe established a prognostic IRG signature comprising three gene members (LTB4R, HLA-DMB and IL4R). The IRG signature demonstrated good predictive performance for 28-day mortality on the internal and external validation datasets. The immune infiltration and cytokine analyses revealed that the IRG signature was significantly associated with multiple immune cells and cytokines. The molecular pathway analysis uncovered ontology enrichment in myeloid cell differentiation and iron ion homeostasis, providing clues regarding the underlying biological mechanisms of the IRG signature. Finally, qPCR detection verified the differential expression of the three IRG signature genes in blood samples from 12 sepsis patients and 12 healthy controls.DiscussionThis study presents an innovative IRG signature for 28-day mortality prediction in sepsis patients, which may be used to facilitate stratification of risky sepsis patients and evaluate patients’ immune state.

Digital beamforming techniques find wide applications in the field of underwater acoustic array signal processing. However, their azimuthal resolution has long been constrained by the Rayleigh limit, consequently limiting their detection performance. In this paper, we propose a novel two-dimensional Hessian–sparse deconvolution algorithm based on image processing techniques. This method assumes a priori that the underwater acoustic bearing time record (BTR) images exhibit sparsity, and then it first constructs partial differential equations in the beamforming domain with sparsity-norm constraints for optimal noise reduction. Subsequently, a two-dimensional deconvolution operation is applied to narrow the main lobe, aiming to achieve additional temporal gains in two-dimensional processing. The simulation and real sea trial data processing results show that the main lobe width of the proposed method is about 1.3 degrees at 0 dB. It effectively reduces the main lobe width and enhances the detection resolution of BTRs in the post-processing part, especially in low-signal-to-noise-ratio (SNR) environments. Therefore, the proposed method provides nice opportunities to further improve the target-detecting ability of hydrophone arrays.

Abstract Background Cordyceps militaris is cultured widely as an edible mushroom and accumulating evidence in mice have demonstrated that the polysaccharides of Cordyceps species have lipid-lowering effects. However, lipid metabolism in mice is significantly different from that in humans, making a full understanding of the mechanisms at play critical. Methods After 5 months, the hamsters were weighed and sampled under anesthesia after overnight fasting. The lipid-lowering effect and mechanisms of the polysaccharide CM1 was investigated by cellular and molecular technologies. Furthermore, the effect of the polysaccharide CM1 (100 μg/mL) on inhibiting adipocyte differentiation was investigated in vitro. Results CM1, a polysaccharide from C. militaris, significantly decreased plasma total cholesterol, triglyceride and epididymal fat index in LDLR (+/−) hamsters, which have a human-like lipid profile. After 5 months’ administration, CM1 decreased the plasma level of apolipoprotein B48, modulated the expression of key genes and proteins in liver, small intestine, and epididymal fat. CM1 also inhibited preadipocyte differentiation in 3T3-L1 cells by downregulating the key genes involved in lipid droplet formation. Conclusions The polysaccharide CM1 lowers lipid and adipocyte differentiation by several pathways, and it has potential applications for hyperlipidemia prevention.

Abstract Recent studies revealed that the long-lasting daytime ionospheric enhancements of Total Electron Content (TEC) were sometimes observed in the Asian sector during the recovery phase of geomagnetic storms (e.g., Lei (J Geophys Res Space Phys 123: 3217–3232, 2018), Li (J Geophys Res Space Phys 125: e2020JA028238, 2020). However, they focused only on the dayside ionosphere, and no dedicated studies have been performed to investigate the nighttime ionospheric behavior during such kinds of storm recovery phases. In this study, we focused on two geomagnetic storms that happened on 7–8 September 2017 and 25–26 August 2018, which showed the prominent daytime TEC enhancements in the Asian sector during their recovery phases, to explore the nighttime large-scale ionospheric responses as well as the small-scale Equatorial Plasma Irregularities (EPIs). It is found that during the September 2017 storm recovery phase, the nighttime ionosphere in the American sector is largely depressed, which is similar to the daytime ionospheric response in the same longitude sector; while in the Asian sector, only a small TEC increase is observed at nighttime, which is much weaker than the prominent daytime TEC enhancement in this longitude sector. During the recovery phase of the August 2018 storm, a slight TEC increase is observed on the night side at all longitudes, which is also weaker than the prominent daytime TEC enhancement. For the small-scale EPIs, they are enhanced and extended to higher latitudes during the main phase of both storms. However, during the recovery phases of the first storm, the EPIs are largely enhanced and suppressed in the Asian and American sectors, respectively, while no prominent nighttime EPIs are observed during the second storm recovery phase. The clear north–south asymmetry of equatorial ionization anomaly crests during the second storm should be responsible for the suppression of EPIs during this storm. In addition, our results also suggest that the dusk side ionospheric response could be affected by the daytime ionospheric plasma density/TEC variations during the recovery phase of geomagnetic storms, which further modulates the vertical plasma drift and plasma gradient. As a result, the growth rate of post-sunset EPIs will be enhanced or inhibited.

The accumulation of various genetic and epigenetic changes in colonic epithelial cells has been identified as one of the fundamental processes that drive the initiation and progression of colorectal cancer (CRC). This study aimed to explore functional genes regulated by DNA methylation and their potential utilization as biomarkers for the prediction of CRC prognoses. Methylation‐driven genes (MDGs) were explored by applying the integrative analysis tool (methylmix) to The Cancer Genome Atlas CRC project. The prognostic MDG panel was identified by combining the Cox regression model with the least absolute shrinkage and selection operator regularization. Gene set enrichment analysis was used to determine the pathways associated with the six‐MDG panel. Cluster of differentiation 40 (CD40) expression and methylation in CRC samples were validated by using additional datasets from the Gene Expression Omnibus. Methylation‐specific PCR and bisulfite sequencing were used to confirm DNA methylation in CRC cell lines. A prognostic MDG panel consisting of six gene members was identified: TMEM88, HOXB2, FGD1, TOGARAM1, ARHGDIB and CD40. The high‐risk phenotype classified by the six‐MDG panel was associated with cancer‐related biological processes, including invasion and metastasis, angiogenesis and the tumor immune microenvironment. The prognostic value of the six‐MDG panel was found to be independent of tumor node metastasis stage and, in combination with tumor node metastasis stage and age, could help improve survival prediction. In addition, the expression of CD40 was confirmed to be regulated by promoter region methylation in CRC samples and cell lines. The proposed six‐MDG panel represents a promising signature for estimating the prognosis of patients with CRC.

Introduction: This retrospective study aimed to compare the efficacy and safety of transarterial chemoembolization plus lenvatinib and programmed death 1 (PD-1) inhibitors versus transarterial chemoembolization plus lenvatinib or sorafenib in patients with unresectable hepatocellular carcinoma. Methods: Consecutive patients with unresectable hepatocellular carcinoma who received transarterial chemoembolization plus lenvatinib and PD-1 inhibitors, lenvatinib, or sorafenib were retrospectively identified in our institution between January 2018 and August 2020. The primary endpoint was overall survival. Results: A total of 84 patients were included in this analysis. The median overall survival was significantly improved in the transarterial chemoembolization plus lenvatinib and PD-1 inhibitor group compared with the transarterial chemoembolization plus sorafenib group (26.7 months [95% confidence interval 25.2-31.6] vs 14.4 months [95% confidence interval 9.5-18.9]; hazard ratio 0.39 [95% confidence interval 0.17-0.72]; P = .007) or the transarterial chemoembolization plus lenvatinib group (26.7 months [95% confidence interval 25.2-31.6] vs 17.9 [95% confidence interval 13.4-22.2] months; hazard ratio 0.45 [95% confidence interval 0.17-0.87]; P = .031). Transarterial chemoembolization plus lenvatinib and PD-1 inhibitor also significantly prolonged median progression-free survival compared with transarterial chemoembolization plus sorafenib group (8.2 months [95% confidence interval 3.3-13.0] vs 6.0 months [95% confidence interval 4.2-7.8]; hazard ratio 0.47 [95% confidence interval 0.24-0.74]; P = .005) or the transarterial chemoembolization plus lenvatinib group (8.2 months [95% confidence interval 3.3-13.0] vs 6.6 [95% confidence interval 4.3-7.9] months; hazard ratio 0.58 [95% confidence interval 0.31-0.96]; P = .047). No significant difference was seen between groups in the incidence of an adverse event or grade 3 or higher adverse event. Conclusion: Transarterial chemoembolization plus lenvatinib, and PD-1 inhibitor was associated with better survival benefits and acceptable toxicities, which may provide an additional therapeutic option for unresectable hepatocellular carcinoma.

Dyslipidemias are disorders of plasma levels of lipids, such as elevated levels of total cholesterol and triglyceride, that are associated with various human diseases including cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Statins are the first-line drugs for treatment of dyslipidemia. However, a substantial proportion of patients cannot reach the recommended LDL-c level even with the highest tolerated doses of statins, and there is no available drug specifically for NAFLD therapy. Sea cucumbers are one of the widely distributed invertebrates, and are an important resource of food and medicine. Sea cucumbers have many valuable nutrients including saponins, fatty acids, phospholipids, cerebrosides, sulfated polysaccharides, as well as proteins and peptides. In recent years, these natural products derived from sea cucumbers have attracted attentions for treatment of CVD and NAFLD because of their lipid-lowering effect and low toxicity. However, the hypolipidemic mechanisms of action and the structure-activity relationship of these bioactive components have not been well-documented in literature. This review article summarizes the signaling pathways and the potential structure-activity relationship of sea cucumber-derived bioactive compounds including saponins, lipids, carbohydrates as well as peptides and proteins. This article will provide information useful for the development of sea cucumber-derived lipid-lowering compounds as well as for investigation of hypolipidemic compounds that are derived from other natural resources.

Carbon (C), nitrogen (N), and phosphorus (P) stoichiometric ratios give valuable insight into ecosystem function. The purpose of the present study is to probe into the C, N, and P stoichiometric characteristics in various organs and their relationships with soil factors of the dominant deciduous conifer plant species (Taxodium ascendens and Taxodium distichum) during afforestation in the riparian zone of Three Gorges Reservoir. The results showed only a small change in the concentration of C in different plant organs and soils. T. ascendens contained mean N and P concentrations of 7.63 and 1.54 g/kg in fine roots, 5.10 and 0.56 g/kg in stems, and 15.48 and 2.30 g/kg in leaves, respectively. Whereas T. distichum had a mean N and P concentration of 7.08 and 1.37 g/kg in fine roots, 4.84 and 0.59 g/kg in stems, and 16.89 and 2.23 g/kg in leaves. The N:P ratios in all organs were below 14, indicating that N may have inhibited tree growth. The fine roots P and N:P of T. distichum were weak plasticity and weak homeostasis, and those of T. ascendens were plasticity and weak plasticity. Their stems and leaves adhere to strict homeostasis. N concentrations were significantly positively related to P concentrations in every tissue (except the stems of T. ascendens), and C concentrations were significantly positively associated with P concentrations in the stems and leaves of T. ascendens and T. distichum (p < 0.05). Likewise, soil P and fine root P were positively associated (p < 0.01). This study contributes to the understanding of deciduous conifer plant stoichiometry. It demonstrates N, P, and N:P stoichiometric homeostasis in T. ascendens and T. distichum, which can withstand flooding and are suitable for vegetation restoration in the hydro-fluctuation zone.

Severe trauma and sepsis can lead to multiple organ dysfunction syndrome, which is a leading cause of death in intensive care units with mortality rates in excess of 50%. In addition to infection, the degree of immuno-inflammatory response also influences the outcome. The genomic changes observed after a variety of pathophysiological insults, such as trauma, sepsis, burns are similar, and consist of innate immune activation and adaptive immunity suppression. However, the characteristics of the shared mechanisms of aforementioned critical illnesses and the clinical relevance remain less explored. In the present study, we performed a data analysis to identify functional genes concurrently involved in critical illnesses across differing etiologies (trauma and sepsis derived from community-acquired pneumonia/abdominal source) and explored the shared signaling pathways these common genes involved in to gain insight into the underlying molecular mechanisms. A number of immune-related biological functions were found to be dysregulated in both trauma and sepsis in the present study, so we continued to identify immune-related common genes, profiled the immune cell proportion, and explored the relationships between them. The diagnostic and prognostic value of the immune-related common genes was also evaluated to address their potential clinical utilization as novel biomarkers. Notably, we identified a list of 14 immune-related genes concurrently dysregulated in trauma and sepsis showing favorable diagnostic value, among which S100P can predict prognosis of sepsis patients. Moreover, a spectrum of immune cell subsets including naïve B cells, CD8+ T cells, CD4+ memory resting T cells, activated NK cells, resting dendritic cells, plasma cells, Tregs, macrophages M0 and macrophages M1 was found to be concurrently dysregulated in both trauma and sepsis, and a close relation between above identified immune-related genes and immune cell subsets was observed. Our data-driven findings lay a foundation for future research to elucidate the pathophysiology regarding the aspect of inflammatory and immune response in critical illnesses, and suggest future studies focus on interpreting the function roles of the identified immune-related genes, as well as the reactive immune cell subsets.

Cardiovascular disease (CVD) is still the leading cause of death globally, and atherosclerosis is the main pathological basis of CVDs. Low-density lipoprotein cholesterol (LDL-C) is a strong causal factor of atherosclerosis. However, the first-line lipid-lowering drugs, statins, only reduce approximately 30% of the CVD risk. Of note, atherosclerotic CVD (ASCVD) cannot be eliminated in a great number of patients even their LDL-C levels meet the recommended clinical goals. Previously, whether the elevated plasma level of triglyceride is causally associated with ASCVD has been controversial. Recent genetic and epidemiological studies have demonstrated that triglyceride and triglyceride-rich lipoprotein (TGRL) are the main causal risk factors of the residual ASCVD. TGRLs and their metabolites can promote atherosclerosis via modulating inflammation, oxidative stress, and formation of foam cells. In this article, we will make a short review of TG and TGRL metabolism, display evidence of association between TG and ASCVD, summarize the atherogenic factors of TGRLs and their metabolites, and discuss the current findings and advances in TG-lowering therapies. This review provides information useful for the researchers in the field of CVD as well as for pharmacologists and clinicians.

For identifying each vessel from ship-radiated noises with only a very limited number of data samples available, an approach based on the contrastive learning was proposed. The input was sample pairs in the training, and the parameters of the models were optimized by maximizing the similarity of sample pairs from the same vessel and minimizing that from different vessels. In practical inference, the method calculated the distance between the features of testing samples and those of registration templates and assigned the testing sample into the closest templates for it to achieve the parameter-free classification. Experimental results on different sea-trial data demonstrated the advantages of the proposed method. On the five-ship identification task based on the open-source data, the proposed method achieved an accuracy of 0.68 when only five samples per vessel were available, that was significantly higher than conventional solutions with accuracies of 0.26 and 0.48. Furthermore, the convergence of the method and the behavior of its performance with increasing data samples available for the training were discussed empirically.

Bearing time record (BTR) is widely used in the field of passive sonar information processing for target detecting and tracking. One of its challenges is to obtain high-resolution beamforming power spectral to facilitate the directions estimating of arrivals, namely DOA estimating. This paper proposes a new algorithm framework Block Matching - Subband Extrema Energy Detection (BM-SEED) to supplement the resolution and enhance the weak targets of BTRs. It extracts the peak features of target trajectories within the conventional beamforming (CBF)-based BTRs by using an improved sub-band peak energy detection (SPED) algorithm, and then enhances the weak targets and suppresses the false-alarm targets through time-spatial autocorrelation analysis. Simulations and sea-trial data evaluations demonstrate that the method of this paper can enhance weak targets, eliminate the interferences of false targets and improve the resolution of BTR targets to 1 degree under −20 dB.

The twin-arginine translocation (Tat) system is involved in a variety of important bacterial physiological processes. Conserved among bacteria and crucial for virulence, the Tat system is deemed as a promising anti-microbial drug target. However, the mechanism of how the Tat system functions in bacterial pathogenesis has not been fully understood. In this study, we showed that the Tat system was critical for the virulence of an extra-intestinal pathogenic E. coli (ExPEC) strain PCN033. A total of 20 Tat-related mutant strains were constructed, and competitive infection assays were performed to evaluate the relative virulence of these mutants. The results demonstrated that several Tat substrate mutants, including the ΔsufI, ΔamiAΔamiC double mutant as well as each single mutant, ΔyahJ, ΔcueO, and ΔnapG, were significantly outcompeted by the WT strain, among which the ΔsufI and ΔamiAΔamiC strains showed the lowest competitive index (CI) value. Results of individual mouse infection assay, in vitro cell adhesion assay, whole blood bactericidal assay, and serum bactericidal assay further confirmed the virulence attenuation phenotype of the ΔsufI and ΔamiAΔamiC strains. Moreover, the two mutants displayed chained morphology in the log phase resembling the Δtat and were defective in stress response. Our results suggest that the Tat system and its dependent cell division proteins SufI, AmiA, and AmiC play critical roles during ExPEC pathogenesis.

Abstract Multiple organ dysfunction is an important cause of death in patients with sepsis. Currently, few studies have focused on the impact of sepsis on bone marrow (BM), especially on the cell components of BM niche. In this study, we performed mouse sepsis models by intraperitoneal injection of LPS and cecal ligation and puncture (CLP). The changes of niche major components in the mouse BM among vascular structures, mesenchymal stem cells and Treg cells were observed and analyzed. The results showed that pathological changes in BM was earlier and more prominent than in other organs, and various cell components of the BM niche changed significantly, of which vascular endothelial cells increased transiently with vascular remodeling and the regulatory T cells decreased over a long period of time. These results indicated that the components of the BM niche underwent series of adaptive changes in sepsis.

The exponential family random graph modeling (ERGM) framework provides a highly flexible approach for the statistical analysis of networks (i.e., graphs). As ERGMs with dyadic dependence involve normalizing factors that are extremely costly to compute, practical strategies for ERGMs inference generally employ a variety of approximations or other workarounds. Markov Chain Monte Carlo maximum likelihood (MCMC MLE) provides a powerful tool to approximate the maximum likelihood estimator (MLE) of ERGM parameters, and is generally feasible for typical models on single networks with as many as a few thousand nodes. MCMC-based algorithms for Bayesian analysis are more expensive, and high-quality answers are challenging to obtain on large graphs. For both strategies, extension to the pooled case-in which we observe multiple networks from a common generative process-adds further computational cost, with both time and memory scaling linearly in the number of graphs. This becomes prohibitive for large networks, or cases in which large numbers of graph observations are available. Here, we exploit some basic properties of the discrete exponential families to develop an approach for ERGM inference in the pooled case that (where applicable) allows an arbitrarily large number of graph observations to be fit at no additional computational cost beyond preprocessing the data itself. Moreover, a variant of our approach can also be used to perform Bayesian inference under conjugate priors, again with no additional computational cost in the estimation phase. The latter can be employed either for single graph observations, or for observations from graph sets. As we show, the conjugate prior is easily specified, and is well-suited to applications such as regularization. Simulation studies show that the pooled method leads to estimates with good frequentist properties, and posterior estimates under the conjugate prior are well-behaved. We demonstrate the usefulness of our approach with applications to pooled analysis of brain functional connectivity networks and to replicated x-ray crystal structures of hen egg-white lysozyme.

A study on the large amplitude vibration of doubly curved graphene-reinforced composite (GRC) laminated panels is presented in this paper. A doubly curved panel is made of piece-wise GRC layers with functionally graded (FG) arrangement along the thickness direction of the panel. A GRC layer consists of polymer matrix reinforced by aligned graphene sheets. The material properties of the GRC layers are temperature dependent and can be estimated by the extended Halpin-Tsai micromechanical model. The modelling of the large amplitude vibration of the panels is based on the Reddy’s higher order shear deformation theory and the effects of the von Kármán geometric nonlinearity, the panel-foundation interaction and the temperature variation are included in the derivation of the motion equations of the panels. The solutions for the large amplitude vibration of the doubly curved FG-GRC laminated panels are obtained by applying a two-step perturbation approach. A parametric study is carried out to determine the influences of foundation stiffness, temperature variation, FG distribution pattern, in-plane boundary condition and panel curvature ratio on the natural frequencies and the nonlinear to linear frequency ratios of the doubly curved FG-GRC laminated panels.

Atherosclerotic cardiovascular disease has a high mortality worldwide. Our lab previously purified a polysaccharide designated as CM1 with (1→4)-β-D-Glcp and (1→2)-α-D-Manp glycosyls as the backbone. In this study, we investigated the anti-atherosclerosis effect of CM1 and the underlying mechanisms of action in a low-density lipoprotein receptor knockout (LDLR(-/-) mouse model. It was found that CM1 significantly decreased the formation of atherosclerotic plaques. Mechanistically, CM1 enhanced plasma level of apolipoprotein A-I and decreased the plasma levels of triglyceride, apolipoprotein B, and total cholesterol. In the absence of LDLR, CM1 elevated the expression of very low-density lipoprotein receptor for liver uptake of plasma apolipoprotein B-containing particles and reduced hepatic triglyceride synthesis by inhibiting sterol regulatory element binding protein 1c. CM1 improved lipids excretion by increasing the liver X receptor α/ATP-binding cassette G5 pathway in small intestine. CM1 reduced lipogenesis and lipolysis by inhibiting peroxisome proliferator-activated receptor γ and adipose triglyceride lipase in epididymal fat. Furthermore, CM1 improved lipid profile in C57BL/6J mice. Collectively, CM1 can modulate lipid metabolism by multiple pathways, contributing to reduced plasma lipid level and formation of atherosclerotic plaques in LDLR(−/−) mice. This molecule could be explored as a potential compound for prevention and treatment of hyperlipidemia and atherosclerosis.

Artificial intelligence (AI) has been deeply applied in the medical field and has shown broad application prospects. Pre-consultation system is an important supplement to the traditional face-to-face consultation. The combination of the AI and the pre-consultation system can help to raise the efficiency of the clinical work. However, it is still challenging for the AI to analyze and process the complicated electronic health record (EHR) data. Our pre-consultation system uses an automated natural language processing (NLP) system to communicate with the patients through the mobile terminals, applying the deep learning (DL) techniques to extract the symptomatic information, and finally outputs the structured electronic medical records. From November 2019 to May 2020, a total of 2,648 pediatric patients used our model to provide their medical history and get the primary diagnosis before visiting the physicians in the outpatient department of the Shanghai Children's Medical Center. Our task is to evaluate the ability of the AI and doctors to obtain the primary diagnosis and to analyze the effect of the consistency between the medical history described by our model and the physicians on the diagnostic performance. The results showed that if we do not consider whether the medical history recorded by the AI and doctors was consistent or not, our model performed worse compared to the physicians and had a lower average F1 score (0.825 vs. 0.912). However, when the chief complaint or the history of present illness described by the AI and doctors was consistent, our model had a higher average F1 score and was closer to the doctors. Finally, when the AI had the same diagnostic conditions with doctors, our model achieved a higher average F1 score (0.931) compared to the physicians (0.92). This study demonstrated that our model could obtain a more structured medical history and had a good diagnostic logic, which would help to improve the diagnostic accuracy of the outpatient doctors and reduce the misdiagnosis and missed diagnosis. But, our model still needs a good deal of training to obtain more accurate symptomatic information.

In order to explore the clinical characteristics of pediatric patients admitted to the pediatric intensive care unit (PICU) who suffered from hematological neoplasms complicated with acute respiratory distress syndrome (ARDS), we retrospectively analyzed 45 ARDS children with hematological neoplasms who were admitted to the PICU of Shanghai Children's Medical Center from January 1, 2014, to December 31, 2020. The 45 children were divided into a survival group and a non-survival group, a pulmonary ARDS group and an exogenous pulmonary ARDS group, and an agranulocytosis group and a non-agranulocytosis group, for statistical analysis. The main clinical manifestations were fever, cough, progressive dyspnea, and hypoxemia; 55.6% (25/45) of the children had multiple organ dysfunction syndrome (MODS). The overall mortality rate was 55.6% (25/45). The vasoactive inotropic score (VIS), pediatric critical illness scoring (PCIS), average fluid volume in the first 3 days and the first 7 days, and the incidence of MODS in the non-survival group were all significantly higher than those in the survival group (P < 0.05). However, total length of mechanical ventilation and length of hospital stay and PICU days in the non-survival group were significantly lower than those in the survival group (P < 0.05). The PCIS (OR = 0.832, P = 0.004) and the average fluid volume in the first 3 days (OR = 1.092, P = 0.025) were independent risk factors for predicting death. Children with exogenous pulmonary ARDS were more likely to have MODS than pulmonary ARDS (P < 0.05). The mean values of VIS, C-reactive protein (CRP), and procalcitonin (PCT) in children with exogenous pulmonary ARDS were also higher (P < 0.05). After multivariate analysis, PCT was independently related to exogenous pulmonary ARDS. The total length of hospital stay, peak inspiratory pressure (PIP), VIS, CRP, and PCT in the agranulocytosis group were significantly higher than those in the non-agranulocytosis group (P < 0.05). Last, CRP and PIP were independently related to agranulocytosis. In conclusion, children with hematological neoplasms complicated with ARDS had a high overall mortality and poor prognosis. Children complicated with MODS, positive fluid balance, and high VIS and PCIS scores were positively correlated with mortality. In particular, PCIS score and average fluid volume in the first 3 days were independent risk factors for predicting death. Children with exogenous pulmonary ARDS and children with agranulocytosis were in a severely infected status and more critically ill.

With the explosive growth of data, it has become increasingly popular to deploy the powerful cloud to manage data. Meanwhile, as the cloud is not always fully trusted, personal and sensitive data have to be encrypted before being outsourced to the cloud. Naturally, this brings a serious challenge for the cloud to provide secure and efficient query services over huge volumes of data. Although existing works have proposed some solutions to solve the above challenge, most of them just focus on the single keyword query and cannot directly support multi-keyword query. Even though some works have discussed solutions for the multi-keyword query, they cannot well balance the efficiency and privacy. Therefore, in this paper, we propose a novel multi-keyword conjunctive query scheme over cloud, which can achieve high query efficiency with small privacy leakage. In specific, we first design a tree-based index to support the multi-keyword conjunctive query and employ Boneh-Goh-Nissim (BGN) homomorphic encryption technique to protect its privacy. Then, based on the tree-based index, we propose a wildcard search algorithm to improve its query efficiency. Finally, the detailed security analysis shows that the proposed scheme is really privacy-preserving, and extensive simulation results also demonstrate its efficient.

Bear time records, which are the accumulations of spatial spectrum estimates on the time axis, are often employed for passive sonar information processing. Multi-target jamming is a common difficulty in this approach due to the constraints of Rayleigh limit, and neither the conventional beamforming (CBF) nor minimum variance distortionless response (MVDR) technique can handle it well. This work presents a post-processing tracking framework based on visual pattern recognition algorithms to track weak acoustic targets within jamming environments, which includes target motion analysis, matched filtering, and principal component analysis-based denoising, and we call this ‘P-Gabor’ algorithm. The simulations and sea-trial experiments show that the proposed method can track a weak target successfully under −23 dB (signal-to-interference ratio) SIR, which is more effective than the references, especially in terms of using real-world data from sea trials. We further demonstrate that the method also has stable tracking performance at even −25 dB SNR (signal-to-noise ratio) circumstances.

Static light scattering is a popular physical chemistry technique that enables calculation of physical attributes such as the radius of gyration and the second virial coefficient for a macromolecule (e.g., a polymer or a protein) in solution. The second virial coefficient is a physical quantity that characterizes the magnitude and sign of pairwise interactions between particles, and hence is related to aggregation propensity, a property of considerable scientific and practical interest. Estimating the second virial coefficient from experimental data is challenging due both to the degree of precision required and the complexity of the error structure involved. In contrast to conventional approaches based on heuristic ordinary least squares estimates, Bayesian inference for the second virial coefficient allows explicit modeling of error processes, incorporation of prior information, and the ability to directly test competing physical models. Here, we introduce a fully Bayesian model for static light scattering experiments on small-particle systems, with joint inference for concentration, index of refraction, oligomer size, and the second virial coefficient. We apply our proposed model to study the aggregation behavior of hen egg-white lysozyme and human γS-crystallin using in-house experimental data. Based on these observations, we also perform a simulation study on the primary drivers of uncertainty in this family of experiments, showing in particular the potential for improved monitoring and control of concentration to aid inference.

Semiconductor optical amplifier (SOA) is considered an excellent candidate for power amplification at O-band due to its low cost and small footprint. In passive optical networks (PONs), SOA is popular as a booster and pre-amplifier to improve the link power budget. However, whether as a booster or pre-amplifier, SOA will induce different degrees of nonlinearity when the output power is high, which degrades the transmission performance of the system and leads to a limited receiver dynamic range. In this paper, we experimentally demonstrate the feasibility of using SOA in both transmitter and receiver sides for power budget improvement in 100 Gb/s/λ four-level pulsed amplitude modulation (PAM-4) time division multiplexed PON (TDM-PON) system at O-band. For compensating the linear and nonlinear impairments induced by transceivers and SOA, a look-up-table (LUT) pre-compensation at the optical line terminal (OLT) side and a simple feed-forward equalizer (FFE) at the optical network unit (ONU) side are adopted for downstream transmission. For upstream transmission, a 2nd-order Volterra nonlinear equalizer (VNLE) is utilized at the OLT side, and no pre-compensation is used at the transmitter of the ONU, which releases the digital signal processing (DSP) pressure of ONUs in a multi-user scenario. For the soft-decision FEC (SD-FEC) threshold (1 × 10−2), the IEEE PR-30 power budget requirement is met, and >18 dB dynamic range is achieved in both 25 km downstream and upstream transmission.

Obesity is a major risk factor for many chronic diseases, including diabetes, fatty livers, and cancer. Expansion of the adipose mass has been shown to be related to adipogenic differentiation of adipose-derived mesenchymal stem cells (ASCs). However, the underlying mechanism of this effect has yet to be elucidated. We found that osteopontin (OPN) is downregulated in ASCs and adipose tissues of obese mice and overweight human beings because of methylation on its promoter, indicating that OPN may affect the development of obesity. Silencing of OPN in wild-type ASCs promotes adipogenic differentiation, while reexpression of OPN reduced adipogenic differentiation in OPN−/− ASCs. The role of extracellular OPN in ASC differentiation was further demonstrated by supplementation and neutralization of OPN. Additionally, OPN suppresses adipogenic differentiation in ASCs through the C/EBP pathways. Consistent with these in vitro results, by intravenous injection of OPN-expressing adenovirus to the mice, we found OPN can delay the development of obesity and improve insulin sensitivity. Therefore, our study demonstrates an important role of OPN in regulating the development of obesity, indicating OPN might be a novel target to attenuate obesity and its complications.

Coordinated development of economy and environment is the common responsibility and pursuit of the international community. In this context, China is beginning to transform and upgrade its economy in a new model of coordinated economic and environmental development. Taking the VOCs emissions of atmospheric pollutants as object of study, this paper studies the relationship between environmental governance of pollutants emission and economic growth in Hunan Province, its characteristics, and also the mechanism of the relationship between the two. Besides, it also studies the measurement of the coordinated development of environment and economy. The study found that after 2015, the pollutant emission index of Hunan Province showed a linear downward trend, and the coordination degree between the environment and economic system decreased first and then gradually increased in the defined interval of coordination degree. The source of economic growth in Hunan Province comes from capital investment and environmental consumption. The improvement of environmental performance in Hunan Province is mainly driven by technological progress, and the emission reduction effect restricts the further growth of environmental performance.

The aim of this study is to identify and consolidate reliable endoscopic features associated with H. pylori infection in gastric mucosa, which is one of the major causes of gastric cancer. A total of 256 Chinese patients with symptomatic stomach disturbances were enrolled. Pathological examination was conducted using a light microscope and biopsy specimens stained with hematoxylin-eosin. Endoscopic examination was performed using a high resolution video endoscope. The association between endoscopic features and pathological H. pylori diagnosis was compared, and endoscopic features significantly associated with H. pylori infection were identified. A total of 14 endoscopic features were observed. Six of the 14 endoscopic features, including mucus on the gastric mucosa, diffuse redness, spotty redness of fundic mucosa, enlarged fold, mucosal edema, and RAC (type D and type I), were highly associated with H. pylori infection and were significantly sensitive and specific predictors for H. pylori diagnosis. The type R RAC was not significantly associated with H. pylori diagnosis. Our results indicate that conventional endoscopy features can be used to diagnose H. pylori in Chinese patients and can help determine the risk factor for gastric cancer.

Location-based services (LBS), as one of the most popular location-awareness applications, has been further developed to achieve low-latency with the assistance of fog computing. However, privacy issues remain a research challenge in the context of fog computing. Therefore, in this paper, we present a fine-grained and privacy-preserving query scheme for fog computing-enhanced location-based services, hereafter referred to as FGPQ. In particular, mobile users can obtain the fine-grained searching result satisfying not only the given spatial range but also the searching content. Detailed privacy analysis shows that our proposed scheme indeed achieves the privacy preservation for the LBS provider and mobile users. In addition, extensive performance analyses and experiments demonstrate that the FGPQ scheme can significantly reduce computational and communication overheads and ensure the low-latency, which outperforms existing state-of-the art schemes. Hence, our proposed scheme is more suitable for real-time LBS searching.

BACKGROUND: Recently, there have been a number of studies on the association between XRCC1 polymorphisms and childhood acute lymphoblastic leukemia (ALL) risk. However, the results of previous reports are inconsistent. Thus, we performed a meta-analysis to clarify the effects of XRCC1 variants on childhood ALL risk. METHODS: A meta-analysis was performed to examine the association between XRCC1 polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) and childhood ALL risk. We critically reviewed 7 studies with a total of 880 cases and 1311 controls for Arg399Gln polymorphism, 3 studies with a total of 345 cases and 554 controls for Arg280His polymorphism, and 6 studies with a total of 783 cases and 1180 controls for Arg194Trp polymorphism, respectively. Odds ratio (OR) and its 95% confidence interval (CI) were used. RESULTS: Significant association between XRCC1 Arg399Gln polymorphism and childhood ALL risk was observed in total population analyses (OR(additive model) = 1.501, 95% CI 1.112-2.026, P(OR) = 0.008; OR(dominant model) = 1.316, 95% CI = 1.104-1.569, P(OR) = 0.002) and Asian subgroup analyses (OR(additive model) = 2.338, 95%CI = 1.254-4.359, P(OR) = 0.008; OR(dominant model) = 2.108, 95%CI = 1.498-2.967, P(OR) = 0.000). No association was detected in Caucasians, Metizo and mixed populations. Ethnicity was considered as a significant source of heterogeneity in the meta-regression model. For the other two XRCC1 polymorphisms, no association with childhood ALL risk was found. CONCLUSIONS: The meta-analysis results suggested that XRCC1 Arg399Gln polymorphism might be associated with elevated childhood ALL risk among Asian population.