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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Roles of different n-3/n-6 PUFA ratios in ovarian cell development and steroidogenesis in PCOS rats.

Polycystic ovary syndrome (PCOS) is a complex and common endocrine disorder characterized by hyperandrogenism, which is accompanied by follicle growth arrest at the small antral stage, minimal granulosa cell proliferation, and chronic anovulation. Polyunsaturated fatty acids (PUFAs) are necessary for the body's metabolism, growth and development. Although PUFAs play an important role in the regulation of female reproduction, their role in ovarian development in PCOS is still unclear. The present study was conducted to investigate the effects of different ratios of n-3/n-6 PUFAs (omega-3/omega-6) on ovary development in PCOS rats. Serum levels of reproductive hormones and enzymes related to steroidogenesis were assessed. The results indicated that PUFAs (n-3/n-6: 1/15) significantly increased ovarian weight and improved the ovarian structure although they had no significant effect on body weight in PCOS rats. Meanwhile, apoptosis was attenuated accompanied by increased cell proliferation by PUFAs (n-3/n-6: 1/15). Moreover, serum levels of hormones (FSH and E2) were also significantly increased by PUFAs (n-3/n-6: 1/15) accompanied by decreased T levels. To investigate whether PUFAs regulate the expression of enzymes related to hormone synthesis, western blotting was used to determine the protein levels of CYP51, CYP19, StAR and 3ß-HSD. The results showed that PUFAs significantly increased the protein levels of all of these enzymes. These results indicate that PUFAs enhance the reproductive performance of PCOS by increasing the expression of steroidogenesis enzymes, which are related to hormone secretion and ovarian functions. These findings provide evidence that a balanced n-3/n-6 PUFA ratio is beneficial for PCOS reproduction.

Effect of hypothyroidism on CYP51 and FSHR expression in rat ovary.

Although thyroid hormone (TH) plays important roles in regulating ovarian development, the mechanism are still unclear. Cytochrome P450 lanosterol 14α-demethylase (CYP51) is a key enzyme in sterols and steroids biosynthesis that involved in folliculogenesis and oocyte maturation, which is regulated by follicle stimulating hormone (FSH). However, the effect of TH on CYP51 expression in ovarian cells is unclear. The objective of this study was to determine the effects of TH on CYP51 in rat ovary. Hypothyroidism rats were induced by 6-propyl-2-thiouracil (PTU), genes expressions in ovary were analyzed by Western blot or qRT-PCR. The data showed that CYP51 was significantly decreased in hypothyroidism, which was accompanied by the down-regulation of mRNA level. Meanwhile, similar tendency was also showed in FSHR expression in hypothyroidism. To evaluate the effect of the gonadotropin on CYP51 and FSHR expression in ovarian cells in vivo, hypo rats were injected subcutaneously with equine chorionic gonadotropin (eCG) respectively. The results showed that eCG reversed CYP51 and FSHR expression in hypo group. Moreover, FSH-induced CYP51 expression was meditated by FSHR. In addition, serum concentration of FSH and E2 were also decreased in hypothyroidism, and E2 was up-regulated by eCG treatment. These results indicate that hypothyroidism changes CYP51 and FSHR expression in ovary, which are regulated by gonadotropin. Moreover, genes changes in ovary are at least partially attributed to steroids biosynthesis.

Minocycline inhibits microglial activation and alleviates depressive-like behaviors in male adolescent mice subjected to maternal separation.

Exposure to early adversity increases vulnerability to psychiatric disorders in later life. Microglia-mediated inflammation has been linked to psychopathology, so such inflammation may be a target for treating depression. Using a model of depression involving adolescent male C57BL/6J mice subjected to maternal separation, we explored whether using minocycline to mitigate inflammation can alleviate depression-like behaviors. Between postnatal days 1 and 14, male mice were separated from their mothers for 3 h per day. Minocycline (20 mg/kg) was administered intraperitoneally once daily for 2 weeks starting one week after weaning. Then the male mice were subjected to a second stress for 2 weeks. Results from the sucrose preference test, forced swimming test, and open field test showed that maternal separation did not obviously alter behavior of the male mice, but it did increase the risk of depression-like behaviors following a second stress. This increased risk disappeared if minocycline was given preemptively before the second stress. Maternal separation and second stress up-regulated pro-inflammatory markers and down-regulated anti-inflammatory markers in the hippocampus, and they activated microglia and promoted pro-inflammatory transitions in microglia. All these effects were reversed by minocycline. These changes in inflammatory processes correlated with changes in neurogenesis and BDNF expression in the hippocampus. Our results in this mouse model suggest the potential of minocycline for treating psychiatric disorders induced by early adversity.

Generation and Stability of Size-Adjustable Bulk Nanobubbles Based on Periodic Pressure Change.

Recently, bulk nanobubbles have attracted intensive attention due to the unique physicochemical properties and important potential applications in various fields. In this study, periodic pressure change was introduced to generate bulk nanobubbles. N2 nanobubbles with bimodal distribution and excellent stabilization were fabricated in nitrogen-saturated water solution. O2 and CO2 nanobubbles have also been created using this method and both have good stability. The influence of the action time of periodic pressure change on the generated N2 nanobubbles size was studied. It was interestingly found that, the size of the formed nanobubbles decreases with the increase of action time under constant frequency, which could be explained by the difference in the shrinkage and growth rate under different pressure conditions, thereby size-adjustable nanobubbles can be formed by regulating operating time. This study might provide valuable methodology for further investigations about properties and performances of bulk nanobubbles.