Search

Pyroptosis is an inflammatory programmed cell death, showing potentials to be a novel anti-cancer approach. However, the roles of pyroptosis-related (PR) genes (PRGs) in pancreatic adenocarcinoma (PAAD) remain elusive. In the present study, we constructed a novel PR risk signature through the lasso regression analysis. The risk signature was greatly conducive to PAAD prognostic assessment. PR risk score was identified as an independent prognostic factor and could distinguish the prognostic differences of most clinical subgroups. Meanwhile, it could improve the traditional prognostic models based on TNM-staging. Next, its prognostic value was also tested in five validation cohorts. Using CIBERSORT, ESTIMATE, and ssGSEA algorithms, the effects of PR risk signature on tumor immune microenvironment (TIM) were explored. High PR risk suppressed antitumor immune through decreasing the infiltrating levels of CD8 T and NK cells. The genomic information and histological expression of risk PRGs were uncovered by USCA and HPA databases. Somatic mutation, methylation alteration, and homozygous CNV of eight PRGs barely occurred in PAAD samples. As for therapeutic correlation, PR risk score may not predict the efficacy of PD-1/L1 inhibitors and was weakly associated with multiple drug susceptibilities. Finally, the biofunctions of toll like receptor 3 (TLR3) in pancreatic cancer (PC) cells were investigated through qPCR, MTT, colony formation, and Transwell assays. Overexpression of TLR3 could promote the proliferation, migration, and invasion of PC cells. In conclusion, PRGs play crucial roles in prognosis, progression, and immune microenvironment of PAAD. TLR3 is expected to be a promising therapeutic target.

Behavioral synchronization has been found to facilitate social bonding and prosociality but the neural mechanisms underlying such effects are not well understood. In the current study, 60 dyads were hyperscanned using functional near-infrared spectroscopy while they performed either a synchronous key-pressing task or a control task. After the task, they were asked to perform the dictator game to assess their prosocial behavior. We also measured three potential mediating variables: self–other overlap, perceived similarity and interpersonal neural synchronization. Results showed that dyads in the synchronization group were higher in behavioral synchronization, interpersonal neural synchronization (INS) at the right dorsolateral prefrontal cortex, self–other overlap, perceived similarity and prosociality than those in the control group. INS was significantly associated with prosocial behaviors and self–other overlap. After testing four meditation models, we found that self–other overlap and INS played a serial mediation role in the effect of behavioral synchronization on prosociality. These results contribute to our understanding of the neural and cognitive mechanisms underlying the effect of behavioral synchronization on prosocial behavior.

Aims: A noninvasive indicator of renal histological lesions and disease activity in lupus nephritis (LN) is needed for timely and targeted treatment before overt renal injury. Here, we tested the utility of urinary angiotensinogen (UAGT) to predict renal disease activity in LN. Results: A prospective, three-stage study was performed in patients with LN. In stage I, UAGT was measured in 140 newly diagnosed LN patients. UAGT significantly increased in LN patients, correlating well with kidney angiotensinogen expression and histological activity. Patients with LN class IV exhibited the highest UAGT compared with other histopathological classes of LN. For identifying LN class IV, a particularly aggressive type of LN, UAGT outperformed the conventional clinical measures and improved their performance. In stage II, UAGT was monitored in 61 subjects from stage I for up to 12 months. UAGT decreased after induction therapy and remained low in patients with LN remission during follow-up. For predicting therapy success at month 12, the area under the receiver operating characteristics curve of UAGT reduction at month 4 was 0.83, outperforming that of 24-h proteinuria. In stage III, UAGT was monitored in 12 LN patients before, during, and after the onset of renal flares. An elevation in UAGT predicted recurrence of LN, and a decline in UAGT after a renal flare heralded the remission of disease before conventional clinical measures. Innovation and Conclusion: UAGT in LN is a promising indicator for dynamic surveillance of renal disease activity and prediction of renal flares. Antioxid. Redox Signal. 31, 1289-1301.

Invasive group B Streptococcus (GBS) remains a leading cause of illness and death among infants globally. We conducted prospective and retrospective laboratory-based surveillance of GBS-positive cultures from infants

Due to the genetic feature of high diversity than other DNA markers, short tandem repeat (STR) plays key roles in forensic, anthropology, and population genetics. Newly introduced multiple STR kit is more valuable because of the greatly improved discriminatory power with the increase in the number of STR loci. The genetic polymorphic data are essential for the application and research in specific population. This study aims to investigate the genetic polymorphism of Han population residing in Yuncheng district, Shanxi Province, to evaluate the application of 23 STR loci in forensic personal identification and paternity test, and to explore the genetic relationship of Han population between Yuncheng and other populations.A total of 23 STR loci were amplified from 525 healthy unrelated individuals from the Han nationality in Yuncheng, Shanxi Province using the AGCU EX25 amplification kit. The products were detected and separated by ABI 3500 Genetic Analyzer. Alleles were genotyped by GeneMapper ID (Version 3.2) software, and corresponding frequencies and forensic parameters were calculated. We calculated the genetic distance and plotted the neighboring-joining tree with other 13 population.The allele frequency of the 23 STRs ranged from 0.0010 to 0.5090. No deviation from Hardy-Weinberg equilibrium (These 23 STRs are highly genetic polymorphic and informative in the Han population of Yuncheng, Shanxi Province, which can provide basic data for forensic personal identification, paternity testing, and population genetic research.

One of the major obstacles to prevent AKI-CKD transition is the lack of effective methods to follow and predict the ongoing kidney injury after an AKI episode. In the present study, we test the utility of urinary angiotensinogen (UAGT) for dynamically evaluating renal structural changes and predicting AKI-CKD progression by using both mild and severe bilateral renal ischemia/reperfusion injury mice. UAGT returns to pre-ischemic levels 14 days after mild AKI followed by kidney architecture restoration, whereas sustained increase in UAGT accompanies by ongoing renal fibrosis after severe AKI. UAGT at day 14–42 correlates with renal fibrosis 84 days after AKI. For predicting fibrosis at day 84, the area under receiver operating characteristics curve of UAGT at day 14 is 0.81. Persistent elevation in UAGT correlates with sustained activation of intrarenal renin–angiotensin system (RAS) during AKI-CKD transition. Abrogating RAS activation post AKI markedly reduced renal fibrosis, with early RAS intervention (from 14 days after IRI) more beneficial than late intervention (from 42 days after IRI) in alleviating fibrosis. Importantly, UAGT decreases after RAS intervention, and its level at day 14–28 correlates with the extent of renal fibrosis at day 42 post RAS blockade. A pilot study conducted in patients with acute tubular necrosis finds that compared with those recovered, patients with AKI-CKD progression exhibits elevated UAGT during the 3-month follow-up after biopsy. Our study suggests that UAGT enables the dynamical monitoring of renal structural recovery after an AKI episode and may serve as an early predictor for AKI-CKD progression and treatment response.

In this paper, we consider the exponential stabilization of coupled wave equations with spatially-varying coefficients and internal anti-damping. In contrast to the previous work in the literature, the kernel equations of this system are much more complicated. Using the backstepping method, we verify the kernel equations, which is a system of coupled linear wave equations with spatially-varying coefficients. Then by designing a new characteristic line, the well-posedness of the kernel equations is obtained. Finally we use a Lyapunov function to get the exponential stabilization. A numerical example is presented to illustrate the result.

Objective Flares of lupus nephritis (LN) are frequent and associated with impaired renal prognosis. One major management obstacle in LN flare is the lack of effective methods to identify at-risk patients earlier in their disease course. This study was undertaken to test the utility of measurement of urinary matrix metalloproteinase 7 (MMP-7) for the dynamic surveillance of renal disease activity and prediction of renal flares in LN. Methods A prospective, 2-stage cohort study was performed in patients with LN. Urinary MMP-7 levels at the time of biopsy were evaluated in 154 patients with newly diagnosed LN in 2 independent cohorts. Urinary MMP-7 levels were assessed for correlation with renal histologic activity. Furthermore, after a minimum period of 12 months of renal disease remission, urinary MMP-7 levels were monitored bimonthly for 2 years in 65 patients with LN. The association between urinary MMP-7 levels and development of LN flare was analyzed. Results Urinary MMP-7 levels were elevated in patients with LN. A higher urinary MMP-7 level in LN was associated with greater renal histologic activity. As a marker for identifying LN patients with more severe renal histologic activity (i.e., a histologic activity index of ≥7), the level of urinary MMP-7 outperformed other clinical markers and improved their predictive performance, thus linking urinary MMP-7 levels to renal disease activity. Furthermore, among patients who had follow-up measurements of urinary MMP-7 after achievement of long-term remission of renal disease activity, an elevated urinary MMP-7 level during follow-up was independently associated with an increased risk of LN flare. This elevation in the urinary MMP-7 level hinted at the risk of an LN flare at an earlier time point prior to indications using conventional laboratory measures. Thus, use of the urinary MMP-7 level in conjunction with other clinical measures improved the prognostic value for prediction of an LN flare. Conclusion Urinary MMP-7 levels in LN are correlated with renal histologic activity. An elevated urinary MMP-7 level detected after achievement of long-term renal disease remission is associated with a higher risk of incident renal flare in patients with LN.

Insulin resistance (IR) has been considered as the common pathological basis and developmental driving force for most metabolic diseases. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators in modulation of glucose and lipid metabolism. However, the comprehensive profile of lncRNAs in skeletal muscle cells under the insulin resistant status and the possible biological effects of them were not fully studied. In this research, using C2C12 myotubes as cell models in vitro, deep RNA-sequencing was performed to profile lncRNAs and mRNAs between palmitic acid-induced IR C2C12 myotubes and control ones. The results revealed that a total of 144 lncRNAs including 70 up-regulated and 74 down-regulated (|fold change| > 2, q < 0.05) were significantly differentially expressed in palmitic acid-induced insulin resistant cells. In addition, functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases revealed that the target genes of the differentially expressed lncRNAs were significantly enriched in fatty acid oxidation, lipid oxidation, PPAR signaling pathway, and insulin signaling pathway. Moreover, Via qPCR, most of selected lncRNAs in myotubes and db/db mice skeletal muscle showed the consistent expression trends with RNA-sequencing. Co-expression analysis also explicated the key lncRNA–mRNA interactions and pointed out a potential regulatory network of candidate lncRNA ENSMUST00000160839. In conclusion, the present study extended the skeletal muscle lncRNA database and provided novel potential regulators for future genetic and molecular studies on insulin resistance, which is helpful for prevention and treatment of the related metabolic diseases.

Differences in behavior and neural mechanisms between expert and novice teachers when collaborating with students are poorly understood. This study investigated whether expert teachers do better in collaborating with students than novice teachers and explored the neural basis of such differences. Novice teacher and student (NT-S) dyads and expert teacher and student (ET-S) dyads were recruited to complete an interactive task consisting of a cooperation and an independent condition. During the experiment, neural activity in the prefrontal cortex of the participants was recorded with functional near-infrared spectroscopy. The results show higher accuracy for the ET-S dyads than the NT-S dyads in the cooperation condition; however, no difference was found in the independent condition. Increased interpersonal brain synchronization (IBS) was detected in the left dorsolateral prefrontal cortex of participants in ET-S dyads, but not in NT-S dyads in the cooperation condition. Moreover, an interaction effect of dyad type and conditions on IBS was observed, revealing IBS was stronger in ET-S dyads than in NT-S dyads. In ET-S dyads, IBS was positively correlated with the teachers’ perspective-taking ability and accuracy. These findings suggest that expert teachers collaborate better with students than novice teachers, and IBS might be the neural marker for this difference.

Cervical cancer (CC) is a common tumor of women worldwide. Here, we conducted a non-targeted lipidomic study to discover novel lipid biomarkers for early-stage CC.The lipidomic analysis of 71 samples in discovery set and 72 samples in validation set were performed by coupling ultra-high-pressure liquid chromatography (UHPLC) with quadrupole time-of-flight tandem mass spectrometry (Q-TOF-MS). Lipids with variable importance (VIP) values greater than 1, adj. p 0.05 (the adjusted p value obtained from false discovery rate correction) and fold change (FC) higher than 1.5 were reserved as potential biomarkers. Subsequently, receiver operating characteristic (ROC) curve and binary logistic regression were implemented to assess the diagnostic potential of these biomarkers and to acquire the best biomarker combination.A lipid biomarker panel, including phosphatidylcholine (PC, PC 14:0/18:2) and phosphatidylethanolamine (PE, PE 15:1e/22:6 and PE 16:1e/18:2), was established. This panel was effective in distinguishing between CC and non-CC (squamous intraepithelial lesions [SIL] and healthy controls) within the area under the ROC curve (AUC), sensitivity, and specificity reaching 0.966, 0.952, and 0.860 for discovery set and 0.961, 0.920, and 0.915 for external validation set. Furthermore, this panel was also capable of discriminating early-stage CC from SIL with AUC, sensitivity, and specificity reaching 0.946, 0.952, and 0.800 for discovery set and 0.956, 0.960, and 0.815 for external validation set.The combination of PC 14:0/18:2, PE 15:1e/22:6, and PE 16:1e/18:2 could serve as a promising serum biomarker for discriminating early-stage CC from SIL and healthy subjects.

Group B Streptococcus (GBS) is a cause of neonatal sepsis, pneumonia, and meningitis that can lead to neurological sequelae in infants less than 3 months of age. The GBS disease burden is not known in China, therefore it cannot receive major attention. The main objectives of this study are the evaluation of the incidence of neonatal GBS infection, GBS case-fatality ratio, its serotypes and genotypes, bacterial resistance, clinical treatment and outcomes in China. We are conducting a nation-wide, population-based, multi-center, prospective, observational cohort study in China from May 2016 to December 2017. Eighteen large urban tertiary care hospitals from 16 provinces were selected that cover the eastern, southern, western, northern and central regions of China. Meanwhile, we retrospectively collected data and GBS strains from January 2015 to April 2016 from selected hospitals. The incidence rate per 1000 live births will be defined as the total number of confirmed GBS cases born in the selected hospitals divided by the number of live births in the hospitals during the study period. All GBS cases detected in selected hospitals will be used to calculate the case-fatality ratio and for the typing analysis. GBS isolates will be serotyped using the Strep-B-Latex® rapid latex agglutination test for serotyping of Group B streptococci. Multi-locus sequence typing (MLST) will be performed by sequencing the internal fragments of seven house-keeping genes. Antimicrobial susceptibility will be tested per interpretive standards established by the Clinical and Laboratory Standards Institute. The presence of the common resistance genes ermA, ermB, mefA, tetI, tetO and tetM will be tested by PCR. We are conducting the first national study to estimate the invasive GBS disease burden and antimicrobial resistance of GBS among infants in China. Study findings will provide important evidence for improving clinical practice to ensure timely diagnosis of GBS disease and decisions for preventive measures. Surveillance of antimicrobial resistance will promote the rational use of antimicrobials. The study was retrospectively registered at http://clinicaltrials.gov on June 13, 2016. It was granted a registration number of “NCT02812576”.

Streptococcus suis serotype 2 is an emerging zoonotic pathogen responsible for a wide range of life-threatening diseases in pigs and humans. However, the pathogenesis of S. suis serotype 2 infection is not well understood. In this study, we report that an orphan response regulator, CovR, globally regulates gene expression and negatively controls the virulence of S. suis 05ZYH33, a streptococcal toxic shock syndrome (STSS)-causing strain. A covR -defective (Δ covR ) mutant of 05ZYH33 displayed dramatic phenotypic changes, such as formation of longer chains, production of thicker capsules, and increased hemolytic activity. Adherence of the Δ covR mutant to epithelial cells was greatly increased, and its resistance to phagocytosis and killing by neutrophils and monocytes was also significantly enhanced. More importantly, inactivation of covR increased the lethality of S. suis serotype 2 in experimental infection of piglets, and this phenotype was restored by covR complementation. Colonization experiments also showed that the Δ covR mutant exhibited an increased ability to colonize susceptible tissues of piglets. The pleiotropic phenotype of the Δ covR mutant is in full agreement with the large number of genes controlled by CovR as revealed by transcription profile analysis: 2 genes are positively regulated, and 193 are repressed, including many that encode known or putative virulence factors. These findings suggested that CovR is a global repressor in virulence regulation of STSS-causing S. suis serotype 2.

To determine the levels of urinary soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) in patients with lupus nephritis (LN), and explore their correlation with renal disease activity.Urine samples were collected from 92 renal biopsy-proven LN patients and 20 healthy controls. Renal disease activity was determined according to the ISN/RPS 2003 Revised Classification of Lupus Nephritis. The urine levels of sICAM-1 and VCAM-1 were detected by enzyme-linked immunosorbent assay, and the expressions of intrarenal ICAM-1 and VCAM-1 were evaluated by immunohistochemisty staining.Urinary sICAM-1 and VCAM-1 levels were elevated in LN patients compared with the controls. Significantly higher levels of urinary sICAM-1 and VCAM-1 were found in patients with active LN, who had also significantly increased intrarenal expressions of ICAM-1 and VCAM-1 compared with patients in remission. A strong positive correlation was noted between intrarenal expression and urine levels of ICAM-1 and VCAM-1. The receiver-operating characteristic (ROC) curve of urine sICAM-1 showed tan area under ROC curve of 0.874 for all participants in the test. A cutoff of 1095.00 pg/mg creatinine yielded a good sensitivity (0.945) and specificity (0.789). The ROC curve of urine VCAM-1 showed an area under ROC of 0.882 for all the participants, and a cutoff of 898.11 pg/mg creatinine yielded a good sensitivity (0.982) and specificity (0.667).Urine sICAM-1 and VCAM-1 levels are positively correlated with their intrarenal expressions and reflect the activity of the nephritis, and therefore they may serve as potential biomarkers for early diagnosis of active LN.

A baseline investigation into heavy metal status in the mangrove sediments was conducted in Shenzhen, China where rapid urban development has caused severe environmental contamination. It is found that heavy metal contamination in this mangrove wetland is characterized by the dominant presence of tungsten and cobalt, which is markedly different from the neighboring Hong Kong and other parts of the world. The vertical variation pattern of these two metals along the sediment profile differed from other heavy metals, suggesting an increasing influx of tungsten and cobalt into the investigated mangrove habitat, as a result of uncontrolled discharge of industrial wastewater from factories that produce or use chemical compounds or alloys containing these two heavy metals. Laboratory simulation experiment indicated that seawater had a stronger capacity to mobilize sediment-borne tungsten and cobalt, as compared to deionized water, diluted acetic, sulfuric and nitric acids.

Periodontitis is a chronic inflammatory disease characterized by the destruction of tooth supporting tissues. Hypoxia, the mainly changes of the plateau environment, can induce severe periodontitis by animal experiments. There is, however, very little information on hypoxia and lipopolysaccharide (LPS) induced cytokine expression in periodontal ligament (PDL) cells. In this article, we characterized hypoxia or P. gingivalis lipopolysaccharide (Pg LPS) induced tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 expression by human periodontal ligament (hPDL) cells. We found that hypoxia augmented Pg LPS induced TNF-α, IL-1β, and IL-6 expression in hPDL cells. We also demonstrated that nuclear factor kappa B pathway was involved in hypoxia augmenting Pg LPS induced cytokine expression in hPDL cells. Thus, our results suggest that the hypoxic environment may enhance the immune function of hPDL cells that is induced by Pg LPS.

Sortase A (SrtA), originally identified as a transpeptidase in Staphylococcus aureus, plays key roles in full virulence of pathogenic bacteria. In silico genome-wide search suggested a srtA homologue from 05ZYH33, a Chinese human isolate of streptococcal toxic shock syndrome (STSS)-causing Streptococcus suis serotype 2 (S. suis 2, SS2). An isogenic srtA mutant (DeltasrtA) of 05ZYH33 strain was obtained by homologous recombination. Immunofluorescence analysis revealed that two known virulence-associated surface proteins featuring Leu-Pro-X-Thr-Gly motif, muramidase-released protein and surface antigen one, were absent in the DeltasrtA. Piglet infection experiments showed that deletion of srtA attenuated the full virulence of 05ZYH33 strain, and impaired its colonizing potential in specific organs. Furthermore, the DeltasrtA displayed significant reduction in adherence to human cells (Hep-2 and human umbilical vein endothelial cells). Collectively, we concluded that SrtA was involved in the virulence manifestation of STSS-causing SS2.