Polymorphisms in PI3K/AKT genes and gene­smoking interaction are associated with susceptibility to tuberculosis.

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) are involved in the clearance of Mycobacterium tuberculosis (MTB) by macrophages. AIM: This study aimed to investigate the effects of polymorphisms in the PI3K/AKT genes and the gene-smoking interaction on susceptibility to TB. METHODS: This case-control study used stratified sampling to randomly select 503 TB patients and 494 control subjects. Logistic regression analysis was used to determine the association between the polymorphisms and TB. Simultaneously, the marginal structure linear dominance model was used to estimate the gene-smoking interaction. RESULTS: Genotypes GA (OR 1.562), AA (OR 2.282), and GA + AA (OR 1.650) at rs3730089 of the PI3KR1 gene were significantly associated with the risk to develop TB. Genotypes AG (OR 1.460), GG (OR 2.785), and AG + GG (OR 1.622) at rs1130233 of the AKT1 gene were significantly associated with the risk to develop TB. In addition, the relative excess risk of interaction (RERI) between rs3730089 and smoking was 0.9608 (95% CI: 0.5959, 1.3256, p < 0.05), which suggests a positive interaction. CONCLUSION: We conclude that rs3730089 and rs1130233 are associated with susceptibility to TB, and there was positive interaction between rs3730089 and smoking on susceptibility to TB.

Building a whole process policy framework promoting construction and demolition waste utilization in China.

The generation of construction and demolition waste1 (CDW) in China has increased dramatically in recent decades due to the rapid urbanization. Yet there is a very limited utilization of this waste, meaning that there is an urgent need to address this issue in order to reduce the reliance on virgin materials and improve the lived environment in China. This problem contrasts with the EU experience where many member states already exceed an 80% utilization rate of CDW due to extensive policy measures. We argue that the supervision of CDW is an important and underestimated element in addressing this waste stream, and that China and other rapidly developing states can build on the EU experience to address this issue rapidly and efficiently. This paper took a comparative policy analytical approach to summarize advanced experiences promoting CDW utilization, highlighting 14 advanced policy measures. We then conducted a case study approach applied to a Chinese metropolitan city, Wuhan, to identify the key measures to promote CDW utilization in the local area by questionnaire. On this basis, we then proposed a whole process supervision framework for the six most important policy measures, to cover the whole process of the generation, transport and recycling of this waste. This approach provides a mode for policymakers to prioritize the most important policy measures to address CDW problem in China through a timely and data-driven process.

A Novel Antithrombocytopenia Agent, Rhizoma cibotii, Promotes Megakaryopoiesis and Thrombopoiesis through the PI3K/AKT, MEK/ERK, and JAK2/STAT3 Signaling Pathways.

BACKGROUND: Cibotii rhizoma (CR) is a famous traditional Chinese medicine (TCM) used to treat bleeding, rheumatism, lumbago, etc. However, its therapeutic effects and mechanism against thrombocytopenia are still unknown so far. In the study, we investigated the effects of aqueous extracts of Cibotii rhizoma (AECRs) against thrombocytopenia and its molecular mechanism. METHODS: Giemsa staining, phalloidin staining, and flow cytometry were performed to measure the effect of AECRs on the megakaryocyte differentiation in K562 and Meg-01 cells. A radiation-induced thrombocytopenia mouse model was constructed to assess the therapeutic actions of AECRs on thrombocytopenia. Network pharmacology and experimental verification were carried out to clarify its mechanism against thrombocytopenia. RESULTS: AECRs promoted megakaryocyte differentiation in K562 and Meg-01 cells and accelerated platelet recovery and megakaryopoiesis with no systemic toxicity in radiation-induced thrombocytopenia mice. The PI3K/AKT, MEK/ERK, and JAK2/STAT3 signaling pathways contributed to AECR-induced megakaryocyte differentiation. The suppression of the above signaling pathways by their inhibitors blocked AERC-induced megakaryocyte differentiation. CONCLUSIONS: AECRs can promote megakaryopoiesis and thrombopoiesis through activating PI3K/AKT, MEK/ERK, and JAK2/STAT3 signaling pathways, which has the potential to treat radiation-induced thrombocytopenia in the clinic.

Targeting TLR2/Rac1/cdc42/JNK Pathway to Reveal That Ruxolitinib Promotes Thrombocytopoiesis.

BACKGROUND: Thrombocytopenia has long been considered an important complication of chemotherapy and radiotherapy, which severely limits the effectiveness of cancer treatment and the overall survival of patients. However, clinical treatment options are extremely limited so far. Ruxolitinib is a potential candidate. METHODS: The impact of ruxolitinib on the differentiation and maturation of K562 and Meg-01 cells megakaryocytes (MKs) was examined by flow cytometry, Giemsa and Phalloidin staining. A mouse model of radiation-injured thrombocytopenia (RIT) was employed to evaluate the action of ruxolitinib on thrombocytopoiesis. Network pharmacology, molecular docking, drug affinity responsive target stability assay (DARTS), RNA sequencing, protein blotting and immunofluorescence analysis were applied to explore the targets and mechanisms of action of ruxolitinib. RESULTS: Ruxolitinib can stimulate MK differentiation and maturation in a dose-dependent manner and accelerates recovery of MKs and thrombocytopoiesis in RIT mice. Biological targeting analysis showed that ruxolitinib binds directly to Toll Like Receptor 2 (TLR2) to activate Rac1/cdc42/JNK, and this action was shown to be blocked by C29, a specific inhibitor of TLR2. CONCLUSIONS: Ruxolitinib was first identified to facilitate MK differentiation and thrombocytopoiesis, which may alleviate RIT. The potential mechanism of ruxolitinib was to promote MK differentiation via activating the Rac1/cdc42/JNK pathway through binding to TLR2.

Effects of thyroid hormone on ovarian cell apoptosis in the rat.

Follicle development is a complicated process regulated by thyroid hormone (TH). TH dysregulation is associated with reproductive disorders; however, the mechanism underlying these relationships remains unclear. Glucose-related protein 78 (GRP78) is a well-characterised endoplasmic reticulum stress protein related to ovarian cell apoptosis. To clarify whether GRP78 is regulated by TH and the involvement of GRP78 in follicle development, we established rat models of hypothyroidism and hyperthyroidism and investigated the effects of TH dysregulation on levels of GRP78, C/EBP homologous protein (CHOP) and cleaved caspase-3. TH dysregulation decreased levels of GRP78 and increased those of CHOP and cleaved caspase-3 in both rat models. However, treatment with equine chorionic gonadotrophin reversed these effects, as well as granulosa cell apoptosis induced by TH dysregulation. Together, these results provide evidence that TH dysregulation alters the GRP78 expression profile, triggering the apoptotic signalling pathway, and suggest that GRP78 is a novel mediator of TH in follicle development.

Maternal immune activation-induced PPARγ-dependent dysfunction of microglia associated with neurogenic impairment and aberrant postnatal behaviors in offspring.

Maternal infection during pregnancy is an important factor involved in the pathogenesis of brain disorders in the offspring. Mounting evidence from maternal immune activation (MIA) animals indicates that microglial priming may contribute to neurodevelopmental abnormalities in the offspring. Because peroxisome proliferator-activated receptor gamma (PPARγ) activation exerts neuroprotective effects by regulating neuroinflammatory response, it is a pharmacological target for treating neurogenic disorders. We investigated the effect of PPARγ-dependent microglial activation on neurogenesis and consequent behavioral outcomes in male MIA-offspring. Pregnant dams on gestation day 18 received Poly(I:C) (1, 5, or 10 mg/kg; i.p.) or the vehicle. The MIA model that received 10 mg/kg Poly(I:C) showed significantly increased inflammatory responses in the maternal serum and fetal hippocampus, followed by cognitive deficits, which were highly correlated with hippocampal neurogenesis impairment in prepubertal male offspring. The microglial population in hippocampus increased, displayed decreased processes and larger soma, and had a higher expression of the CD11b, which is indicative of the M1 phenotype (classical activation). Activation of the PPARγ pathway by pioglitazone in the MIA offspring rescued the imbalance of the microglial activation and ameliorated the MIA-induced suppressed neurogenesis and cognitive impairments and anxiety behaviors. In an in vitro experiment, PPARγ-induced M2 microglia (alternative activation) promoted the proliferation and differentiation of neural precursor cells. These results indicated that the MIA-induced long-term changes in microglia phenotypes were associated with hippocampal neurogenesis and neurobehavioral abnormalities in offspring. Modulation of the microglial phenotypes was associated with a PPARγ-mediated neuroprotective mechanism in the MIA offspring and may serve as a potential therapeutic approach for prenatal immune activation-induced neuropsychiatric disorders.

Preparing CdS QDs in sodium alginate gel: realizing water solubility and stimuli responsiveness of QDs in an integrative way.

Quantum dots (QDs) are of great interest due to their excellent fluorescence properties and thus, they have been widely studied. Compared with the typical organometallic synthetic routes and hydrothermal methods usually carried out under high temperatures, methods employing colloidal templates can be used for preparing QDs in mild conditions and have gained increasing attention. In this prospect, a hydrogel is an ideal colloidal template for the preparation of QDs in an aqueous medium, while the related study for in situ preparation of QDs in a gel and the consequent functionalization of QDs are in demand. In this paper, we proposed a two-step method to prepare CdS QDs in a sodium alginate (SA) gel, which showed effective constraint in the uniform size distribution of QDs. Without the introduction of additional ligands, the prepared CdS-SA QDs exhibited responsiveness to pH and detection of Fe3+, thus providing a simplified way for the functionalization of QDs. CdS-SA QDs showed good biocompatibility and stability in a certain concentration, which indicated the prospective applications of CdS-SA QDs in the fields of biological labeling and environmental sensing.

An eco-friendly construction of superwetting alginate-based aerogels with self-cleaning performance for multifunctional water treatment.

The increasingly complex oily wastewater has become a severe environmental issue worldwide, calling for the eco-friendly methods toward multifunctionality, high efficiency and sustainability. This work presents a superwetting alginate-based aerogels prepared by a feasible mineralization without the assistance of intermediates. In this strategy, in-situ grown ß-FeOOH nanoparticles on whole porous alginate aerogels, not only provides the hierarchical topography and more -OH groups, enhancing underwater oleophobicity (152 ± 4.4°) and fouling resistance of porous aerogels, but also endows with the outstanding photo-Fenton self-cleaning ability for pollutant degradation. As a result, the outstanding separation selectivity for oil and water (>99.5 %), and superior reusability is achieved without the significant diminution of permeation ability (897-1136 L·m-2·h-1). Furthermore, with the advantage of excellent photocatalytic performance under sunlight, the oily wastewater containing soluble organic pollutants can be remediated by simultaneous separation and photocatalysis decomposition under a gravity-driven filtration solely, revealing a promising potential for complex oily wastewater treatment with the rationally usage of sunlight.

Comprehensive transcriptomic analysis of immune-related genes in diabetic foot ulcers: New insights into mechanisms and therapeutic targets.

BACKGROUND: Diabetic foot ulcers (DFU), affecting a quarter of diabetic patients and leading to high rates of amputation and mortality, pose significant health and economic burdens. Wound healing in DFU is often compromised by chronic inflammation, underscoring the critical role of immune cells. However, the systematic investigation of immune-related genes (IRGs) in DFU pathogenesis remains elusive. To address this gap, our study aims to explore the association between IRGs and DFU. METHODS: To explore biological changes in immune related gene expression in DFU, RNA-seq was performed on wound biopsies derived from 10 DFU patients and 11 healthy controls. Differentially expressed genes (DEGs) between DFU and normal samples were obtained by DEseq2. By intersecting the IRG list from the ImmPort database, the immune-related differentially expressed genes were identified. Function enrichment analysis and protein-protein interaction (PPI) analysis were applied by clusterProfiler and STRING database, and the hub genes of the PPI network were calculated by the cytoHubba plug-ins in Cytoscape. CIBERSORT algorithms was applied to analyze immune infiltration in DFU. And the correlation between immune cells infiltration and hub genes was explored by correlation analysis. Finally, to validate our findings, the transcriptional change of hub genes in DFU was confirmed using external scRNA-seq dataset and RT-qPCR. RESULTS: RNA-seq analysis detected 8,800 DEGs in DFUs, with 2,351 upregulated and 6,449 downregulated.526 differential IRGs were obtained from intersection of DEGs and IRGs. 526 differential IRGs were obtained from intersection of DEGs and IRGs. Enrichment function analysis of DEGs showed that they played a significant role in immune response. The PPI network was constructed, and the most significant module containing 4 hub genes was identified. CIBERSORT analysis showing that there was a significant difference between DFU and normal controls in the infiltration of immune cells. Compared with normal tissue, DFU tissue contained a higher proportion of resting NK cell, M0 macrophages, and activated mast cell, while resting dendritic cell, activated mast cell, and activated NK cell contributed to a relatively lower portion. Additionally, the analysis for M1/M2 polarization of macrophage cells shown that DFU tissue contained a higher M1/M2 ratio than normal group. Finally, the expression levels of 4 hub genes were confirmed by external scRNA-seq dataset and RT-qPCR. CONCLUSIONS: The immune related hub genes and the difference in immune infiltration between DFU tissue and normal controls might provide new insight for understanding DFU healing.

Impact of PD-L1 Gene Polymorphisms and Interactions with Cooking with Solid Fuel Exposure on Tuberculosis.

INTRODUCTION: Given that PD-L1 is a crucial immune checkpoint in regulating T-cell responses, the aim of this study was to explore the impact of PD-L1 gene polymorphisms and the interaction with cooking with solid fuel on susceptibility to tuberculosis (TB) in Chinese Han populations. METHODS: A total of 503 TB patients and 494 healthy controls were enrolled in this case-control study. Mass spectrometry technology was applied to genotype rs2297136 and rs4143815 of PD-L1 genes. The associations between single nucleotide polymorphism (SNPs) and TB were assessed using unconditional logistic regression analysis. Marginal structural linear odds models were used to estimate the gene-environment interactions. RESULTS: Compared with genotype CC, genotypes GG and CG+GG at rs4143815 locus were significantly associated with susceptibility to TB (OR: 3.074 and 1.506, respectively, p < 0.05). However, no statistical association was found between rs2297136 SNP and TB risk. Moreover, the relative excess risk of interaction between rs4143815 of the PD-L1 gene and cooking with solid fuel was 2.365 (95% CI: 1.922-2.809), suggesting positive interactions with TB susceptibility. CONCLUSION: The rs4143815 polymorphism of the PD-L1 gene was associated with susceptibility to TB in Chinese Han populations. There were significantly positive interactions between rs4143815 and cooking with solid fuel.

Adherence to Preventive Treatment for Latent Tuberculosis Infection in Close Contacts of Pulmonary Tuberculosis Patients: A Cluster-Randomized Controlled Trial in China.

OBJECTIVES: This study examined adherence rates to tuberculosis preventive treatment (TPT) among close contacts of individuals with pulmonary tuberculosis (PTB) and identified factors associated with TPT adherence in China. METHODS: A multicenter, cluster-randomized, open-label control trial was carried out across three sites involving 34 counties in China. Close contacts of bacteriologically confirmed rifampin and isoniazid-susceptible PTB cases were identified and screened for latent tuberculosis infection (LTBI). Eligible participants were randomly assigned to either the 3H2P2 group, which consisted of a three-month, twice-weekly regimen of rifapentine and isoniazid, or the 6H group, which entailed a six-month daily regimen of isoniazid. To assess the factors influencing adherence, a two-level logistic regression model was utilized. RESULTS: Out of the 2,434 close contacts who initiated TPT, 2,121 (87.1%) completed the regimen. Of the 313 individuals who did not complete TPT, 60.1% refused to continue, and 27.8% discontinued due to adverse effects. The two-level logistic regression model revealed several factors associated with enhanced TPT adherence: enrollment in the 3H2P2 group (odds ratio (OR)=2.09), management by a TB dispensary responsible for TPT (OR=2.55), supervision by healthcare workers (OR=6.40), and clinician incentives (OR=2.49). Conversely, the occurrence of any adverse effects (OR=0.08) was identified as a risk factor for non-adherence. CONCLUSIONS: Administering TPT to individuals with LTBI is feasible among close contacts. Adherence to TPT can be enhanced through shorter, safer treatment regimens and supportive interventions, such as directly supervised therapy for TPT recipients and incentives for healthcare providers managing TPT.

Farmers' Adaptive Behaviors to Heavy Metal-Polluted Cultivated Land in Mining Areas: The Influence of Farmers' Characteristics and the Mediating Role of Perceptions.

Heavy metal pollution in cultivated land poses a serious threat to environmental health and farmers' livelihoods. As the direct user of cultivated land, understanding farmers' adaptive behavior to heavy metal pollution, and its influencing factors, can provide insight and information relevant for decision-making, so as to better manage the hazards and risks of heavy metal pollution. We proposed a conceptual framework of "farmers' characteristics-perceptions-adaptive behaviors". Factor analysis and mediation effect analysis were used to explore the influence of characteristics and perceptions on adaptive behaviors. The data of 278 farmers in a typical mining area in Daye, China, show that local farmers perceive the hazards of heavy metal pollution, but their adaptive behaviors are hindered to a certain extent. The results of the mediation effect analysis show that perceptions of health impact, self-efficacy, and adaptive cost play a partial mediating role in the impact of characteristics on adaptive behaviors. In addition, the influence of the "factor of dependence on farmland" and the "factor of obstacles to action" on adaptive behavior have no significant relationship with perception levels. By comparing the influencing factors, we found that although farmers' perceptions have mediating effects between characteristics and adaptive behaviors, characteristics still play a decisive role in adaptive behaviors.

The potential effects and mechanisms of hispidulin in the treatment of diabetic retinopathy based on network pharmacology.

BACKGROUND: Diabetic retinopathy (DR), one of the most common and severe microvascular complication of diabetes mellitus (DM), is mainly caused by diabetic metabolic disorder. So far, there is no effective treatment for DR. Eriocauli Flos, a traditional Chinese herb, has been used in treating the ophthalmic diseases including DR. However, the active ingredients and molecular mechanisms of Eriocauli Flos to treat diabetic retinopathy remain elusive. METHODS: Here, the systems pharmacology model was developed via constructing network approach. 8 active components which were screened by oral bioavailability (OB ≥ 30%) and drug-likeness (DL ≥ 0.18) and 154 targets were selected from Eriocauli Flos through TCMSP database. Another 3593 targets related to DR were obtained from Genecards, OMIM, TTD, and Drugbank databases. The 103 intersecting targets of DR and Eriocauli Flos were obtained by Draw Venn Diagram. In addition, protein-protein interaction network was established from STRING database and the compound-target network was constructed by Cytoscape which screened top 12 core targets with cytoNCA module. Then the overlapping targets were analyzed by GO and KEGG enrichment. Moreover, two core targets were selected to perform molecular docking simulation. Subsequently, CCK8 assay, RT-PCR and Western blotting were applied to further reveal the mechanism of new candidate active component from Eriocauli Flos in high glucose-induced HRECs. RESULTS: The results showed that the overlapping targets by GO analysis were enriched in cellular response to chemical stress, response to oxidative stress, response to reactive oxygen species, reactive oxygen species metabolic process and so on. Besides, the overlapping targets principally regulated pathways such as AGE-RAGE signaling pathway in diabetic complications, lipid atherosclerosis, fluid shear stress and atherosclerosis, and PI3K-Akt signaling pathway. Molecular docking exhibited that VEGFA and TNF-α, had good bindings to the great majority of compounds, especially the compound hispidulin. In vitro, hispidulin ameliorated high-glucose induced proliferation by down-regulating the expression of p-ERK, p-Akt, and VEGFA; meanwhile inhibited the mRNA levels of TNF-α. CONCLUSIONS: In this study, through network pharmacology analysis and experimental validation, we found that hispidulin maybe has a potential targeted therapy effect for DR by decreasing the expression of p-Akt, p-ERK, and VEGFA, which resulted in ameliorating the proliferation in HRECs.

The Effect of Melatonin on OCT4 Expression and Granulosa Cell Growth in Female Mice.

Melatonin is mainly secreted by the pineal gland as a neurotransmitter. Moreover, melatonin is also produced by the ovary and plays important roles in female reproduction. However, it is unclear whether melatonin has any effect on the transition from the preantral follicle to the early antral follicle. Octamer-binding transcription factor 4 (OCT4) is important to granulosa cells development, which is regulated by gonadotropin. And these regulations are mediated by the GSK3ß/ß-catenin pathway via the activated PI3K/Akt signaling. The aim of the present study was to determine the effects and the possible mechanisms of melatonin on ovarian cells development. The results showed that melatonin inhibited granulosa cells development, which was accompanied by the downregulation of OCT4 expression. Meanwhile, melatonin also decreased the expression of p-GSK3ß (glycogen synthase kinase 3 beta), p-Akt, ß-catenin, and its translocation to the nucleus in granulosa cells. Moreover, melatonin attenuated the effects of FSH in vitro and eCG in vivo on these regulations. In conclusion, this study shows that melatonin inhibits ovarian cell development by downregulating the OCT4 expression level, which is possibly mediated by inhibiting the PI3K/Akt and GSK3ß/ß-catenin pathway. Melatonin attenuates the effects of gonadotropin on ovarian granulosa cells as a negative regulator.

Whole-Genome Sequencing and Epidemiological Investigation of Tuberculosis Outbreaks in High Schools in Hunan, China.

Background: Tuberculosis (TB) seriously threatens individual and public health. Recently, TB outbreaks in schools have been reported more frequently in China and have attracted widespread attention. We reported three TB outbreaks in high schools in Hunan Province, China. Methods: When a tuberculosis patient was reported in a school, we carried out field epidemiological investigations, including tuberculin skin testing (TST), chest X-ray (CXR) and laboratory test for all close contacts, and whole-genome sequencing (WGS) analyses to understand the transmission patterns, the causes and the risk factors for the outbreaks, thereby providing a foundation for the control of TB epidemics in schools. Results: A total of 49 students with TB patients were identified in the three schools where TB outbreaks occurred, including nine patients in School A, 14 patients in School B, and 26 patients in School C. In Schools A, B and C, the putative attack rates in the classes of the index case were 13.8% (8/58), 7.6% (5/66), and 40.4% (21/52), while the putative attack rates of expanding screening in the school were 0.3% (1/361), 0.2% (9/3955), and 0.2% (5/2080), respectively. Thirteen patients had patient delay, with a median delay interval of 69 days (IQR 30.5-113 days). Twelve patients had a healthcare diagnostic delay with a median delay interval of 32 days (IQR 24-82 days). Phylogenetic analysis of culture-positive patients revealed that most of them shared a small genetic distance (≤12 SNPs), with three separate genetic clusters (including one MDR-TB genomic cluster), indicating the recent transmission of Mycobacterium tuberculosis strains. Conclusion: This combination of field investigation and WGS analysis revealed the transmission of three TB outbreaks in schools. Reinforced implementation is needed to improve timely case finding and reduce diagnosis delay in routine TB control in the school population.

Mechanisms of OCT4 on 3,5,3'-Tri-iodothyronine and FSH-induced Granulosa Cell Development in Female Mice.

Octamer-binding transcription factor 4 (OCT4) regulates the pluripotency of stem cells and also plays important roles in granulosa cells growth, which is regulated by follicle-stimulating hormone (FSH). Thyroid hormone (TH) is important for the development and maturation of follicles and the maintenance of various endocrine functions. Although 3,5,3'-triiodothyronine (T3) enhances the effects of FSH on the regulation of the growth of granulosa cells and development of follicles, it is unclear whether and, if so, how TH combines with FSH to regulate OCT4 expression in granulosa cells during the preantral to early antral transition stage. Our results showed that T3 enhanced FSH-induced OCT4 expression. However, T3/FSH-induced cellular growth was reduced by OCT4 small interfering RNA. OCT4 knockdown significantly increased the number of apoptotic cell. Moreover, T3 combined with FSH to increase estrogen receptor ß (ERß) expression but did not significantly affect estrogen receptor α expression. ERß knockdown dramatically decreased T3/FSH-induced OCT4 expression and cell development and increased cell apoptosis. The phosphoinositide 3-kinases/protein kinase B pathway was involved in hormones inducing OCT4 and ERß expressions. Furthermore, the hormones regulating OCT4 and ERß expressions were regulated by cytochrome P450 lanosterol 14a-demethylase (CYP51), a key enzyme in sterol and steroid biosynthesis. T3 and FSH cotreatment potentiated cellular development by upregulating OCT4 expression, which is mediated by CYP51 and ERß. These regulatory processes are mediated by the phosphoinositide 3-kinase/protein kinase B signaling pathway. These findings suggest that OCT4 mediates the T3 and FSH-induced development of follicles.

Effects of Levistilide A on Hemorheology and Endothelial Cell Injury in Rats with Blood Stasis.

BACKGROUND: Vascular endothelial cell injury is not only the initiating factor of cardiovascular and cerebrovascular diseases but also the essence of blood stasis. Levistilide A (LA), a natural component isolated from the traditional Chinese herb, Ligusticum chuanxiong Hort, has traditional effects on improving blood circulation and removing stasis. In this study, the effects and potential mechanisms of LA in the rat model of blood stasis and the mechanism in endothelial cell injury have been explored. MATERIALS AND METHODS: In this experiment, the effects of LA on the model of acute blood stasis in rats were explored. The blood samples were collected for the measurement of coagulation and hemorheological indices, and the carotid arteries were also excised from rats for hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). In addition, the improvement effects of LA on the H2O2-induced human umbilical vein endothelial cell (HUVEC) injury model were evaluated. And the cell viability detection was conducted by the CCK8 assay, and the pathway-related protein expressions were detected by western blotting. RESULTS: In vivo, compared with the model group, the treatment of LA (10 mg/kg) could reduce the FIB (fibrinogen) content (P < 0.01), increase the INR (international normalized ratio) and PT (prothrombin time) (P < 0.01), and reduce the plasma viscosity (P < 0.05) and whole blood viscosities of low, medium, and high shear rates in the blood of blood stasis model rats (P < 0.01). In vitro, the cell viability in the LA-pretreated group was higher than that of the model group (P < 0.05). The expression levels of PI3K, AKT, and eNOs in the LA-pretreated group were increased (P < 0.01) as compared to the model group. CONCLUSION: These findings demonstrated that LA has the ability to improve blood hypercoagulation and blood viscosity, and enhance the viability of cells. It is more likely that it exerts a protective effect on the endothelial cell through the PI3K-AKT-eNOs pathway. These results indicate LA will be a potential candidate to cure blood stasis with endothelial cell injury.

FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer.

Human papillomavirus (HPV)-mediated cervical carcinogenesis is a multistep progressing from persistent infection, precancerous lesion to cervical cancer (CCa). Although molecular alterations driven by viral oncoproteins are necessary in cervical carcinogenesis, the key regulators behind the multistep process remain not well understood. It is pivotal to identify the key genes involved in the process for early diagnosis and treatment of this disease. Here we analyzed the mRNA expression profiles in cervical samples including normal, cervical intraepithelial neoplasia (CIN), and CCa. A co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to reveal the crucial modules in the dynamic process from HPV infection to CCa development. Furthermore, the differentially expressed genes (DEGs) that could distinguish all stages of progression of CCa were screened. The key genes involved in HPV-CCa were identified. It was found that the genes involved in DNA replication/repair and cell cycle were upregulated in CIN compared with normal control, and sustained in CCa, accompanied by substantial metabolic shifts. We found that upregulated fibronectin type III domain-containing 3B (FNDC3B) and downregulated bisphosphoglycerate mutase (BPGM) could differentiate all stages of CCa progression. In patients with CCa, a higher expression of FNDC3B or lower expression of BPGM was closely correlated with a shorter overall survival (OS) and disease-free survival (DFS). A receiver operating characteristic (ROC) analysis of CIN and CCa showed that FNDC3B had the highest sensitivity and specificity for predicting CCa development. Taken together, the current data showed that FNDC3B and BPGM were key genes involved in HPV-mediated transformation from normal epithelium to precancerous lesions and CCa.

An innovative strategy for synchronous treatment of combined heavy metal and organic pollutants through polysaccharide gel encapsulating S2.

In many industrial fields, treatment of composite contaminations involving inorganic heavy metal ions and organic pollutants simultaneously remains a tremendous challenge. In this paper, an innovative strategy based on the gelation process of Sodium Alginate (SA) was proposed for synchronous treatment of composite pollutants. Through a pre-gelation step, SA gel balls encapsulated with S2- (SA/S2- gel) were formed and immersed into polluted solutions containing Pb2+/Cd2+ and Cd2+/dye. The removal efficiency of Pb2+/Cd2+ by SA/S2- gel were both increased compared with pure SA gel. The adsorbed Pb2+/Cd2+ was in-situ transformed into PbS/CdS quantum dots (QDs) possessing photo-catalytic activity, which induced the degradation of dyes under UV irradiation. In this respect, the proposed SA/S2- system might provide a high-performance and energy-saving way for comprehensive treatment of inorganic heavy metal and organic industrial pollutants.

[Epidemiological survey on clonorchiasis sinensis in an endemic area of South Hunan Province].

OBJECTIVE: To make an epidemiological investigation on clonorchiasis sinensis and relevant factors in the south of Hunan Province. METHODS: One village from each of Lengshuitan District and Qiyang County was selected for the survey from November to December in 2006. Stool samples from villagers were collected and examined by modified Kato-Katz method. Questionnairing was performed for relevant knowledge and attitude among residents. The infection rate in animal reservoirs and intermediate hosts were detected. RESULTS: A total of 586 cases with Clonorchis sinensis infection were found from 777 people with a prevalence of 75.4%. The average egg density was 451 eggs per gram (EPG) feces. Light, moderate and heavy infections occupied 85.5% (501/586), 14.0% (82/586), and 0.5% (3/586) respectively. Prevalence in males and females was 76.9% (316/411) and 73.8% (270/366) respectively with no significant difference (chi2 = 1.013, P > 0.05). Infections were found in all age groups, with the highest prevalence in the group of 70 to 79 years (85.7%, 30/35). By occupations, the prevalence was 82.5% (447/542) in peasants, 79.3% (42/53) in doctors, 73.7% (28/38) in teachers, and 73.5% (25/34) in local cadres. The infection rate was 17.4% (29/167) and 7.4% (2/27) in Parafossarulus seriatulus and Alocinma longicornis, and 69.2% (9/13) and 5.3% (1/19) in Carassius auratus and Cyprinus carpios respectively. Adult worms were found in all 3 dogs dissected. Over 80% inhabitants did not know that this disease can be acquired by eating raw fish. 95.6% (153/160) of the farmers and 56.7% (349/616) of the students had a history of eating raw fish. The water was contaminated with C. sinensis eggs by using untreated feces as fertilizer for farming and by scrubbing pail latrines in the ponds. CONCLUSION: The prevalence of clonorchiasis in human population is high in Lengshuitan District and Qiyang County of Hunan Province. Eating raw fish and using untreated feces as fertilizer are the most important epidemiological factors of the disease.