Sympathetic Neuronal Activation Triggers Myeloid Progenitor Proliferation and Differentiation.

There is a growing body of research on the neural control of immunity and inflammation. However, it is not known whether the nervous system can regulate the production of inflammatory myeloid cells from hematopoietic progenitor cells in disease conditions. Myeloid cell numbers in diabetic patients were strongly correlated with plasma concentrations of norepinephrine, suggesting the role of sympathetic neuronal activation in myeloid cell production. The spleens of diabetic patients and mice contained higher numbers of tyrosine hydroxylase (TH)-expressing leukocytes that produced catecholamines. Granulocyte macrophage progenitors (GMPs) expressed the ß2 adrenergic receptor, a target of catecholamines. Ablation of splenic sympathetic neuronal signaling using surgical, chemical, and genetic approaches diminished GMP proliferation and myeloid cell development. Finally, mice lacking TH-producing leukocytes had reduced GMP proliferation, resulting in diminished myelopoiesis. Taken together, our study demonstrates that catecholamines produced by leukocytes and sympathetic nerve termini promote GMP proliferation and myeloid cell development.

Major Facilitator Superfamily Domain Containing 5 Inhibition Reduces Lipoprotein(a) Uptake and Calcification in Valvular Heart Disease.

BACKGROUND: High circulating levels of Lp(a) (lipoprotein[a]) increase the risk of atherosclerosis and calcific aortic valve disease, affecting millions of patients worldwide. Although atherosclerosis is commonly treated with low-density lipoprotein-targeting therapies, these do not reduce Lp(a) or risk of calcific aortic valve disease, which has no available drug therapies. Targeting Lp(a) production and catabolism may provide therapeutic benefit, but little is known about Lp(a) cellular uptake. METHODS: Here, unbiased ligand-receptor capture mass spectrometry was used to identify MFSD5 (major facilitator superfamily domain containing 5) as a novel receptor/cofactor involved in Lp(a) uptake. RESULTS: Reducing MFSD5 expression by a computationally identified small molecule or small interfering RNA suppressed Lp(a) uptake and calcification in primary human valvular endothelial and interstitial cells. MFSD5 variants were associated with aortic stenosis (P=0.027 after multiple hypothesis testing) with evidence suggestive of an interaction with plasma Lp(a) levels. CONCLUSIONS: MFSD5 knockdown suppressing human valvular cell Lp(a) uptake and calcification, along with meta-analysis of MFSD5 variants associating with aortic stenosis, supports further preclinical assessment of MFSD5 in cardiovascular diseases, the leading cause of death worldwide.

Rupture process of the 2021 M7.4 Maduo earthquake and implication for deformation mode of the Songpan-Ganzi terrane in Tibetan Plateau.

The deformation mode of the Tibetan Plateau is of crucial importance for understanding its construction and extrusion processes, as well as for the assessment of regional earthquake potential. Block motion and viscous flow models have been proposed to describe the deformation field but are not fully supported by modern geophysical observations. The 2021 Mw 7.4 Maduo earthquake, which occurred inside the Songpan-Ganzi terrane (SGT) in central-east Tibet, provides a chance to evaluate the associated deformation mode of the region. We conduct a joint inversion for this earthquake and resolve a bilateral rupture process, which is characterized by super- and subshear rupture velocities, respectively. We interpret this distinct rupture behavior to be the result of the respective slip concentration depths of the two ruptured segments. We analyze geological, seismic, and geodetic evidence and find that the SGT upper crust shows distributed shear deformation and distinct transverse anisotropy, which are associated with folded structures originating from compression of the paleo-Tethys ocean accretional prism realigned by following shear deformation. The SGT receives lateral shear loading from its NS boundary and accommodates a right-step sinistral motion across the terrane boundary faults. The unique tectonic setting of the SGT defines locations and behaviors of internal faulting and strong earthquakes such as the 2021 Maduo earthquake, with the latter occurring on slow-moving faults at intervals of several thousands of years.

The outer membrane protein Tp92 of Treponema pallidum delays human neutrophil apoptosis via the ERK, PI3K/Akt, and NF-κB pathways.

Syphilis is a persistent sexually transmitted disease caused by infiltration of the elusive pathogen Treponema pallidum. Despite the prevalence of human polymorphonuclear neutrophils (hPMNs) within cutaneous lesions, which are characteristic of incipient syphilis, their role in T. pallidum infection remains unclear. Tp92 is the only T. pallidum helical outer membrane protein that exhibits structural features similar to those of outer membrane proteins in other gram-negative bacteria. However, the functional mechanism of this protein in immune cells remains unclear. Neutrophils are short-lived cells that undergo innate apoptosis in response to external stimuli that typically influence this process. In this study, we determined that Tp92 impedes the activation of procaspase-3 via the ERK MAPK, PI3K/Akt, and NF-κB signaling pathways, consequently suppressing caspase-3 activity within hPMNs, and thereby preventing hPMNs apoptosis. Furthermore, Tp92 could also modulate hPMNs apoptosis by enhancing the expression of the anti-apoptotic protein Mcl-1, stimulating IL-8 secretion, and preserving the mitochondrial membrane potential. These findings provide valuable insights into the molecular mechanisms underlying T. pallidum infection and suggest potential therapeutic targets for syphilis treatment.

Prognostic value of the Naples prognostic score in patients with intrahepatic cholangiocarcinoma after hepatectomy.

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Peripheral Ischemia Imprints Epigenetic Changes in Hematopoietic Stem Cells to Propagate Inflammation and Atherosclerosis.

BACKGROUND: Peripheral ischemia caused by peripheral artery disease is associated with systemic inflammation, which may aggravate underlying comorbidities such as atherosclerosis and heart failure. However, the mechanisms of increased inflammation and inflammatory cell production in patients with peripheral artery disease remain poorly understood. METHODS: We used peripheral blood collected from patients with peripheral artery disease and performed hind limb ischemia (HI) in Apoe-/- mice fed a Western diet and C57BL/6J mice with a standard laboratory diet. Bulk and single-cell RNA sequencing analysis, whole-mount microscopy, and flow cytometry were performed to analyze hematopoietic stem and progenitor cell (HSPC) proliferation, differentiation, and relocation. RESULTS: We observed augmented numbers of leukocytes in the blood of patients with peripheral artery disease and Apoe-/- mice with HI. RNA sequencing and whole-mount imaging of the bone marrow revealed HSPC migration into the vascular niche from the osteoblastic niche and their exaggerated proliferation and differentiation. Single-cell RNA sequencing demonstrated alterations in the genes responsible for inflammation, myeloid cell mobilization, and HSPC differentiation after HI. Heightened inflammation in Apoe-/- mice after HI aggravated atherosclerosis. Surprisingly, bone marrow HSPCs expressed higher amounts of the receptors for IL (interleukin)-1 and IL-3 after HI. Concomitantly, the promoters of Il1r1 and Il3rb had augmented H3K4me3 and H3K27ac marks after HI. Genetic and pharmacological inhibition of these receptors resulted in suppressed HSPC proliferation, reduced leukocyte production, and ameliorated atherosclerosis. CONCLUSIONS: Our findings demonstrate increased inflammation, HSPC abundance in the vascular niches of the bone marrow, and elevated IL-3Rb and IL-1R1 (IL-1 receptor 1) expression in HSPC following HI. Furthermore, the IL-3Rb and IL-1R1 signaling plays a pivotal role in HSPC proliferation, leukocyte abundance, and atherosclerosis aggravation after HI.

Lifetime prevalence and associated factors of itch with skin conditions: Atopic dermatitis, psoriasis and dry skin in individuals aged over 50.

BACKGROUND: Itch, common in dermatological conditions, is often accompanied by psychological distress and reduced quality of life. However, research on the prevalence and associated factors of itch with skin conditions in general populations is limited. OBJECTIVES: This cross-sectional study aimed to determine the lifetime prevalence of itch with skin conditions and identify its associated factors in middle-aged and elderly individuals. METHODS: Participants from the Rotterdam Study, a population-based cohort, were interviewed to assess whether they had ever had an itchy skin condition, defining lifetime itch with skin conditions. Over 20 demographic, lifestyle, dermatological, and non-dermatological factors were collected. Multivariable logistic regression analysis explored associations between these factors and itch with skin conditions, reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: 5,246 eligible participants (age range: 51-100, median age: 67, female: 56.0%) revealed a lifetime prevalence of 33.7% for itch with skin conditions. Female sex (OR (95% CI): 1.26 (1.11-1.43)), body mass index (1.02 (1.01-1.03)), self-reported and presence of atopic dermatitis (4.29 (3.74-4.92), and 1.97 (1.60-2.43)), self-reported and presence of psoriasis (2.31 (1.77-3.01), and 2.11 (1.55-2.87)), self-reported dry skin (1.95 (1.73-2.29)), self-reported asthma (1.40 (1.08-1.83)), renal impairment (1.45 (1.17-1.79)), and clinically relevant depressive and anxiety symptoms (1.85 (1.52-2.25), and 1.36 (1.11-1.66)) were significantly associated with it. CONCLUSIONS: This study reveals a substantial one-third lifetime prevalence of itch with skin conditions in individuals aged over 50. Significant associations with diverse lifestyle, demographic, dermatological and, intriguingly, non-dermatological factors including renal impairment, imply additional contributors to itch induction or persistence in individuals with skin conditions.

Reducing economic burden through split-shared care model for people living with uncontrolled type 2 diabetes and polypharmacy: a multi-center randomized controlled trial.

BACKGROUND: Interprofessional collaborative care such as a split-shared care model involving family physicians and community pharmacists can reduce the economic burden of diabetes management. This study aimed to evaluate the economic outcome of a split-shared care model between family physicians and community pharmacists within a pharmacy chain in managing people with uncontrolled type 2 diabetes and polypharmacy. METHOD: This was a multi-center, parallel arm, open label, randomized controlled trial comparing the direct and indirect economic outcomes of people who received collaborative care involving community pharmacists (intervention) versus those who received usual care without community pharmacist involvement (control). People with uncontrolled type 2 diabetes, defined as HbA1c > 7.0% and taking ≥ 5 chronic medications were included while people with missing baseline economic data (such as consultation costs, medication costs) were excluded. Direct medical costs were extracted from the institution's financial database while indirect costs were calculated from self-reported gross income and productivity loss, using Work Productivity Activity Impairment Global Health questionnaire. Separate generalized linear models with log link function and gamma distribution were used to analyze changes in direct and indirect medical costs. RESULTS: A total of 175 patients (intervention = 70, control = 105) completed the trial and were included for analysis. The mean age of the participants was 66.9 (9.2) years, with majority being male and Chinese. The direct medical costs were significantly lower in the intervention than the control group over 6 months (intervention: -US$70.51, control: -US$47.66, p < 0.001). Medication cost was the main driver in both groups. There were no significant changes in productivity loss and indirect costs in both groups. CONCLUSION: Implementation of split-shared visits with frontline community partners may reduce economic burden for patient with uncontrolled type 2 diabetes and polypharmacy. TRIAL REGISTRATION: Clinicaltrials.gov Reference Number: NCT03531944 (Date of registration: June 6, 2018).

Extracellular matrix-regulator MMPA is required for the orderly proliferation of neoblasts and differentiation of ectodermal progenitor cells in the planarian Dugesia japonica.

Matrix metalloproteinases (MMPs) are members of a family of zinc-dependent metallopeptidase proteins that are widely found in plants, animals, and microorganisms. As the regulators of the extracellular matrix and basement membrane, MMPs play an important role in embryogenesis, development, innate immunity, and regeneration. However, the function of MMP family in planarian, a model for regeneration research, is still ambiguous. Here, we cloned 5 MMPs genes from Dugesia japonica and found that DjMMPA was associated with the process of regeneration, neoblasts cell maintenance confusion and destruction. Loss of DjMMPA led to homeostasis confusion and eventually death, owing to neoblasts proliferation disorder. Additionally, DjMMPA RNAi-treated animals had impaired regeneration after amputation. Furthermore, knockdown of DjMMPA had noticeable defects in cell differentiation of ectoderm, especially in eyes and neural progenitor cells, possibly by inhibiting Wnt signaling. Our results suggest that extracellular matrix-regulator MMPA is required for the orderly proliferation of neoblasts and differentiation of ectodermal progenitor cells in the planarian, which provide valuable information for further explorations into the molecular mechanism of MMPS, stem cells, and regeneration.

Research progress on the mechanism of Treponema pallidum breaking through placental barrier.

Congenital syphilis, a significant cause of fetal mortality worldwide, is a congenital infectious disease instigated by the vertical transmission of Treponema pallidum during pregnancy. Clinical manifestations include preterm delivery, stillbirth, neonatal skin lesions, skeletal abnormalities, and central nervous system aberrations. The ongoing increase in the incidence of congenital syphilis, coupled with complexities in diagnosis, necessitates a detailed understanding of its pathogenesis for the development of improved diagnostic approaches, and to interrupt the route of vertical transmission. Drawing from the broader body of research associated with vertical transmission pathogens, we aim to clarify the potential mechanisms by which Treponema pallidum breaches the placental barrier to infect the fetus.

Characterization of the lipidomic profile of clam Meretrix petechialis in response to Vibrio parahaemolyticus infection.

Vibrio parahaemolyticus is a devastating pathogen of clam Meretrix petechialis, which brings about huge economic losses in aquaculture breeding industry. In our previous study, we have found that Vibrio infection is closely associated with lipid metabolism of clams. In this study, an untargeted lipidomics approach was used to explore the lipid profiling changes upon Vibrio infection. The results demonstrated that the hepatopancreas of clams was composed of five lipid categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids and sterol lipids. And the content of lipid classes altered during Vibrio infection, implying that Vibrio infection altered intracellular lipid homeostasis in clams. Meanwhile, a total of 200 lipid species including 82 up-regulated and 118 down-regulated significantly were identified in response to Vibrio infection, of which ceramide (Cer), phosphatidylcholine (PC) and triglyceride (TG) accounted for the largest proportion. Notably, all Cers showed a significantly decreased trend while nearly all TG species were increased significantly during Vibrio infection, which suggested that Cer and TG could be determined as effective biomarkers. Furthermore, these differentially expressed lipid species were enriched in 20 metabolic pathways and sphingolipid metabolism was one of the most enriched pathways. These results evidenced how the lipid metabolism altered in the process of Vibrio infection and opened a new perspective on the response of marine bivalves to pathogen infection.

Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification.

AIM: Lipoprotein(a) [Lp(a)] is a potential causal factor in the pathogenesis of aortic valve disease. However, the relationship of Lp(a) with new onset and progression of aortic valve calcium (AVC) has not been studied. The purpose of the study was to assess whether high serum levels of Lp(a) are associated with AVC incidence and progression. METHODS AND RESULTS: A total of 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men), whose Lp(a) measurements were available, underwent non-enhanced cardiac computed tomography imaging at baseline and after a median follow-up of 14.0 [interquartile range (IQR) 13.9-14.2] years. New-onset AVC was defined as an AVC score >0 on the follow-up scan in the absence of AVC on the first scan. Progression was defined as the absolute difference in AVC score between the baseline and follow-up scan. Logistic and linear regression analyses were performed to evaluate the relationship of Lp(a) with baseline, new onset, and progression of AVC. All analyses were corrected for age, sex, body mass index, smoking, hypertension, dyslipidaemia, and creatinine. AVC progression was analysed conditional on baseline AVC score expressed as restricted cubic splines. Of the 702 individuals without AVC at baseline, 415 (59.1%) developed new-onset AVC on the follow-up scan. In those with baseline AVC, median annual progression was 13.5 (IQR = 5.2-37.8) Agatston units (AU). Lipoprotein(a) concentration was independently associated with baseline AVC [odds ratio (OR) 1.43 for each 50 mg/dL higher Lp(a); 95% confidence interval (CI) 1.15-1.79] and new-onset AVC (OR 1.30 for each 50 mg/dL higher Lp(a); 95% CI 1.02-1.65), but not with AVC progression (ß: -71 AU for each 50 mg/dL higher Lp(a); 95% CI -117; 35). Only baseline AVC score was significantly associated with AVC progression (P < 0.001). CONCLUSION: In the population-based Rotterdam Study, Lp(a) is robustly associated with baseline and new-onset AVC but not with AVC progression, suggesting that Lp(a)-lowering interventions may be most effective in pre-calcific stages of aortic valve disease.

Protective Immunity against Chlamydia psittaci Lung Infection Induced by a DNA Plasmid Vaccine Carrying CPSIT_p7 Gene Inhibits Dissemination in BALB/c Mice.

Chlamydia psittaci (C. psittaci), a zoonotic pathogen, poses a potential threat to public health security and the development of animal husbandry. Vaccine-based preventative measures for infectious diseases have a promising landscape. DNA vaccines, with many advantages, have become one of the dominant candidate strategies in preventing and controlling the chlamydial infection. Our previous study showed that CPSIT_p7 protein is an effective candidate for a vaccine against C. psittaci. Thus, this study evaluated the protective immunity of pcDNA3.1(+)/CPSIT_p7 against C. psittaci infection in BALB/c mice. We found that pcDNA3.1(+)/CPSIT_p7 can induce strong humoral and cellular immune responses. The IFN-γ and IL-6 levels in the infected lungs of mice immunized with pcDNA3.1(+)/CPSIT_p7 reduced substantially. In addition, the pcDNA3.1(+)/CPSIT_p7 vaccine diminished pulmonary pathological lesions and reduced the C. psittaci load in the lungs of infected mice. It is worth noting that pcDNA3.1(+)/CPSIT_p7 suppressed C. psittaci dissemination in BALB/c mice. In a word, these results demonstrate that the pcDNA3.1(+)/CPSIT_p7 DNA vaccine has good immunogenicity and immunity protection effectiveness against C. psittaci infection in BALB/c mice, especially pulmonary infection, and provides essential practical experience and insights for the development of a DNA vaccine against chlamydial infection.

EGF signaling promotes the lineage conversion of astrocytes into oligodendrocytes.

BACKGROUND: The conversion of astrocytes activated by nerve injuries to oligodendrocytes is not only beneficial to axonal remyelination, but also helpful for reversal of glial scar. Recent studies have shown that pathological niche promoted the Sox10-mediated astrocytic transdifferentiation to oligodendrocytes. The extracellular factors underlying the cell fate switching are not known. METHODS: Astrocytes were obtained from mouse spinal cord dissociation culture and purified by differential adherent properties. The lineage conversion of astrocytes into oligodendrocyte lineage cells was carried out by Sox10-expressing virus infection both in vitro and in vivo, meanwhile, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) inhibitor Gefitinib were adopted to investigate the function of EGF signaling in this fate transition process. Pharmacological inhibition analyses were performed to examine the pathway connecting the EGF with the expression of oligodendrogenic genes and cell fate transdifferentiation. RESULTS: EGF treatment facilitated the Sox10-induced transformation of astrocytes to O4+ induced oligodendrocyte precursor cells (iOPCs) in vitro. The transdifferentiation of astrocytes to iOPCs went through two distinct but interconnected processes: (1) dedifferentiation of astrocytes to astrocyte precursor cells (APCs); (2) transformation of APCs to iOPCs, EGF signaling was involved in both processes. And EGF triggered astrocytes to express oligodendrogenic genes Olig1 and Olig2 by activating extracellular signal-regulated kinase 1 and 2 (Erk1/2) pathway. In addition, we discovered that EGF can enhance astrocyte transdifferentiation in injured spinal cord tissues. CONCLUSIONS: These findings provide strong evidence that EGF facilitates the transdifferentiation of astrocytes to oligodendrocytes, and suggest that targeting the EGF-EGFR-Erk1/2 signaling axis may represent a novel therapeutic strategy for myelin repair in injured central nervous system (CNS) tissues.

TREM2 knockdown improves the therapeutic effect of PD-1 blockade in hepatocellular carcinoma.

Triggering receptor expressed on myeloid cells 2 (TREM2), which is typically expressed in microglia/macrophage, is a crucial receptor modulating the activation of immune cells. Recent single-cell RNA sequencing studies of the tumor microenvironment (TME) have found that TREM2 is highly expressed in several subgroups of tumor-associated macrophages (TAMs) with immunosuppressive activity. TREM2 knockout mice are more resistant to tumor growth than wild-type mice in multiple mice tumor models. But the function of TREM2 expression in TAMs of hepatocellular carcinoma (HCC) is still unclear. Here we used a self-complementary adeno-associated virus (scAAV) with macrophage tropism to efficiently knockdown TREM2 in TAMs in vivo and found that the growth of hepatocellular carcinoma was suppressed by TREM2 knockdown. Moreover, we found that TREM2 knockdown remodeled TAMs to an immune-stimulating status and enhanced the therapeutic effect of PD-1 immune-checkpoint blockade in HCC.

DjApi5 is required for homeostasis in planarian Dugesia japonica.

Orchestrated apoptosis in planarian Dugesia japonica is very important for its degrowth and regeneration. Apoptosis Inhibitor-5 (API5) is an anti-apoptotic factor that negatively regulates cell apoptosis. We characterized the conserved structure of DjApi5, however, the biological function of DjApi5 in planarians needs further investigation. In this study, we found that DjApi5 and its interacting molecular DjAcinus are required for planarian homeostasis, which may be correlated with their specific localization in neoblasts in addition to their anti-apoptosis functions. We further demonstrated the increased expression of DjApi5 during planarian regeneration, and DjApi5 deficiency affects normal regeneration processes. These results indicated new functions of DjApi5 in development.

Treponema pallidum Tp0751 alters the expression of tight junction proteins by promoting bEnd3 cell apoptosis and IL-6 secretion.

BACKGROUND: Neurosyphilis is a serious complication caused by the invasion of the central nervous system by Treponema pallidum subsp. pallidum (T. pallidum). However, the molecular mechanism by which T. pallidum crosses the blood-brain barrier has not been fully elucidated. OBJECTIVES: The primary purpose of this experimental design was to explore the effect of the T. pallidum adhesion protein Tp0751 on the blood-brain barrier and cerebrovascular endothelial cells. METHODS: BEnd3 cells were used to construct a monolayer blood-brain barrier model in vitro. The integrity of blood-brain barrier model was evaluated by a transendothelial cell resistance meter and transmission electron microscope after the stimulation of recombinant protein TP0751. Hoechst 33258 staining and flow cytometry were used to detect the apoptosis rate. Western blotting assay was used to measure the expression of tight junction proteins and apoptosis-related proteins. The enzyme activity detection kit was responsible for detecting the enzyme activities of Caspase 3, Caspase 8 and Caspase 9. The expression of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 at the transcription and translation levels were detected by qRT-PCR and ELISA, respectively. RESULTS: The results showed that, the tight junction structures between cells showed no obvious fragmentation, but the levels of the tight junction proteins zonula occludens-1 and occludin were reduced by the effects of Tp0751 on bEnd3 cells. In addition, further research demonstrated that after incubation with bEnd3 cells, Tp0751 induced cell apoptosis in a concentration- and time-dependent manner via the caspase 8/caspase 3 pathway. These apoptotic processes may have contributed to the changes in tight junction proteins expression. Furthermore, the Tp0751 protein may be involved in the pathogenic process by which T. pallidum crosses the blood-brain barrier by promoting secretion of the proinflammatory factor interleukin-6. CONCLUSIONS: On the whole, this study is the first to reveal and highlight that Tp0751 may affect the expression of tight junction proteins by inducing apoptosis and promoting the secretion of the inflammatory cytokine IL-6, thus playing a role in the progression of neurosyphilis caused by T. pallidum.

Chlamydia psittaci inhibits apoptosis of human neutrophils by activating P2X7 receptor expression.

This study tested the hypothesis that Chlamydia psittaci (C. psittaci) survives and multiplies in human neutrophils by activating P2X7, a nonselective cationic channel receptor expressed constitutively on the surface of these cells. Findings illustrated that P2X7 receptor expression was enhanced in C. psittaci-infected neutrophils. C. psittaci was able to inhibite spontaneous apoptosis of neutrophils through mitochondrial-induced ATP release and IL-8 production. Importantly, inhibiting ATP activation of the P2X7 receptor with AZ10606120 promotes apoptosis, while stimulating P2X7 receptor expression with BzATP delayed spontaneous apoptosis of human neutrophils, suggesting that C. psittaci inhibits apoptosis of human neutrophils by activating P2X7 receptor. This study reveals new insights into the survival advantages of the latent persistent state of C. psittaci and the mechanism by which it evades the innate immune response.

Optical characteristics of bilayer decoupling MoS2 grown by the CVD method.

Study of exciton recombination process is of great significance for the optoelectronic device applications of two-dimensional transition metal chalcogenides (TMDCs). This research investigated the decoupling MoS2 structures by photoluminescence (PL) measurements. First, PL intensity of the bilayer MoS2 (BLM) is about twice of that of the single layer MoS2 (SLM) at low temperature, indicating no transition from direct bandgap to indirect bandgap for BLM due to the decrease of interlayer coupling which can be shown by Raman spectra. Then, the localized exciton emission appears for SLM at 7 K but none for BLM, showing different exciton localization characteristics. The PL evolution with respect to the excitation intensity and the temperature further reveal the filling, interaction, and the redistribution among free exciton states and localized exciton states. These results provide very useful information for understanding the localized states and carrier dynamics in BLM and SLM.

Expression of Mir-489-3p as an Effective Marker of Poor Prognosis in Patients with Non-small-cell Lung Carcinoma.

Context: Lung carcinoma accounts for the majority of cancer deaths, and its 5-year survival rate isn't optimistic. Remarkable progress has been made in recent decades toward understanding the biological behavior of non-small-cell lung carcinoma (NSCLC) and creating targeted molecular therapies for diagnosis and treatment. However, little literature is available on the topic, and the clinical significance and application of miR-489-3p for NSCLC can't yet be determined. Objective: The study intended to determine if miR-489-3p can predict prognosis for patients with NSCLC. Design: The research team designed a prospective study to examine in depth and analyze the molecular science of NSCLC tumors in a clinical setting. Setting: The study took place in the Department of the Special Ward at the Shanxi Provincial Cancer Hospital in Taiyuan, Shanxi, China. Participants: Participants were 116 patients with NSCLC at the hospital and 87 healthy people. Outcome Measures: A type of microRNA (miRNA), MiR-489-3p, was detected using nano-polymerase chain reaction (PCR). The diagnostic value of miR-489-3p for lung carcinoma and its predictive value for death from the disease were analyzed using a receiver operating characteristic (ROC) curve, and the three-year prognosis for patients was examined. Human NSCLC cell lines and normal, human, lung epithelial cells were obtained, and miR-489-3p was detected to assess the biological effects on lung-cancer cells. Results: MiR-489-3p has low expression in lung-cancer tissues, which indicates its good predictive value for prognosis for and death of lung-cancer patients. The activity of tumor cells increased after the inhibition of miR-489-3p. Conclusions: A low level of miR-489-3p indicates a poor prognosis for patients with NSCLC. A deeper understanding of the mechanism of miR-489-3p in lung carcinoma may be the key to the earlier diagnosis and treatment of lung carcinoma.