Reactive oxygen species (ROS) are important in osteoporosis development. Oxidative stress induces apoptosis of osteoblasts and arrest of their differentiation. Both Danshensu (DSS) and hydrogen sulfide (H2S) produce significant antioxidant effect in various systems. In this study, we synthesized SDSS, a novel H2S-releasing compound derived from DSS, and studied its antioxidant effect in an H2O2-induced MC3T3-E1 osteoblastic cell injury model. We first characterized the H2S releasing property of SDSS in both in vivo and in vitro models. HPLC chromatogram showed that intravenous injection of SDSS in adult rats released ADT-OH, a well proved H2S sustained-release moiety, within several minutes in the rat plasma. Using an H2S selective fluorescent probe, we further confirmed that SDSS released H2S in MC3T3-E1 osteoblastic cells. Biological studies revealed that SDSS had no significant toxic effect but produced protective effects against H2O2-induced MC3T3-E1 cell apoptosis. SDSS also reversed the arrest of cell differentiation caused by H2O2 treatment. This was caused by the stimulatory effect of SDSS on bone sialoprotein, runt-related transcription factor 2, collagen expression, alkaline phosphatase activity, and bone nodule formation. Further studies revealed that SDSS reversed the reduced superoxide dismutase activity and glutathione content, and the increased ROS production in H2O2 treated cells. In addition, SDSS significantly attenuated H2O2-induced activation of p38-, ERK1/2-, and JNK-MAPKs. SDSS also stimulated phosphatidylinositol 3-kinase/Akt signaling pathway. Blockade of this pathway attenuated the cytoprotective effect of SDSS. In conclusion, SDSS protects MC3T3-E1 cells against H2O2-induced apoptosis by suppressing oxidative stress, inhibiting MAPKs, and activating the phosphatidylinositol 3-kinase/Akt pathway.

It has been a long-standing question as to whether the interaction between gall-forming insects and their host plants is merely parasitic or whether it may also benefit the host. On its host Rhus chinensis, the aphid Schlechtendalia chinensis induces the formation of closed galls, referred to as horned galls. Typically, mature aphid populations comprise thousands of individuals, which is sufficient to cause the accumulation of high CO2 levels in galls (on average 8-fold higher and up to 16 times than atmospheric levels). Large aphid populations also excrete significant amounts of honeydew, a waste product high in sugars. Based on 13C isotope tracing and genomic analyses, we showed that aphid-derived carbon found in CO2 and honeydew was recycled in gall tissues via photosynthesis and glycometabolism. These results indicated that the aphid-gall system evolved in a manner that allowed nutrient recycling, where the gall provides nutrients to the growing aphid population, and in turn, aphid-derived carbon metabolites provide a resource for the growth of the gall. The metabolic efficiency of this self-circulating system indicates that the input needed from the host plant to maintain aphid population growth less than previously thought and possibly minimal. Aside from the recycling of nutrients, we also found that gall metabolites were transported to other parts of the host plant and is particularly beneficial for leaves growing adjacent to the gall. Taken together, galls in the S. chinensis-Rhus chinensis system are highly specialized structures that serve as a metabolic and nutrient exchange hub that benefits both the aphid and its host plant. As such, host plants provide both shelter and nutrients to protect and sustain aphid populations, and in return, aphid-derived metabolites are channeled back to the host plant and thus provide a certain degree of "metabolic compensation" for their caloric and structural needs.

Characterizing the breeding sites of Culex pipiens complex is of major importance for the control of West Nile disease and other related diseases. However, little information is available about the characteristics and associated factors of the breeding sites of the Cx. pipiens complex in Lhasa, a representative high-altitude region in Southwestern China. In this study, a cross-sectional study concerning the breeding site characteristics and associated factors of the Cx. pipiens complex was carried out in Lhasa, Tibet from 2013-2016. Chi-square analysis and binary logistic regression analysis were applied to identify the key factors associated with the presence of Cx. pipiens complex larvae. Using a standard dipping method, 184 water bodies were examined and Cx. pipiens complex larvae were observed in 36 (19.57%) of them. There were significant differences in the composition of Cx. pipiens complex larvae among the breeding site stability (χ2 = 19.08, p = 0.00) and presence or absence of predators (χ2 = 6.986, p = 0.008). Binary logistic regression analysis indicated that breeding site stability and presence or absence of predators were significantly associated with the presence of Cx. pipiens complex larvae in Chengguan District, Lhasa. Relatively permanent water bodies such as water bodies along river fringes, ponds and puddles, and water bodies with no predators should be paid more attention for future Cx. pipiens complex larvae abatement campaigns in Lhasa, China.

Diabetic retinopathy is a multifactorial microvascular complication, and its pathogenesis hasn't been fully elucidated. The irreversible oxidation of cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) was increased in the type 1 diabetic retinal vasculature. SERCA2 C674S knock-in (SKI) mouse line that half of C674 was replaced by serine 674 (S674) was used to study the effect of C674 inactivation on retinopathy. Compared with wild type (WT) mice, SKI mice had increased number of acellular capillaries and pericyte loss similar to those in type 1 diabetic WT mice. In the retina of SKI mice, pro-apoptotic proteins and intracellular Ca2+-dependent signaling pathways increased, while anti-apoptotic proteins and vessel density decreased. In endothelial cells, C674 inactivation increased the expression of pro-apoptotic proteins, damaged mitochondria, and induced cell apoptosis. These results suggest that a possible mechanism of retinopathy induced by type 1 diabetes is the interruption of calcium homeostasis in the retina by oxidation of C674. C674 is a key to maintain retinal health. Its inactivation can cause retinopathy similar to type 1 diabetes by promoting apoptosis. SERCA2 might be a potential target for the prevention and treatment of diabetic retinopathy.

Background: Malaria is endemic in Sierra Leone, with stable and perennial transmission in all parts of the country. At present, the main prevention and control measures for mosquito vectors here involve insecticide treated nets (ITN) and indoor residual spraying (IRS). The most recent entomological surveillance was conducted prior to the civil war, between 1990 and 1994. Therefore, a new entomological surveillance required to support targeted malaria control strategies. Methods:Anopheles mosquitoes were collected between June and December 2019 using the light trap method. On these, we conducted species identification, analyzed seasonal fluctuation and Plasmodium infection rate, and monitored insecticide resistance. Results: Surveillance of seasonal fluctuation showed that there were two peak of Anopheles density in July (mean 13.67 mosquitoes/trap/night) and October (mean 13.00 mosquitoes/trap/night). Meanwhile, the lowest Anopheles density was seen in early September. Ninety-one representatives of Anopheles gambiae s.l. were selected and identified as An. coluzzii (n = 35) and An. gambiae s.s. (n = 56) using PCR. An. coluzzii and An. gambiae s.s. were found to be heterozygous resistant to the knockdown resistance (kdr) L1014F mutation (100%). Meanwhile, the East African mutation (kdr L1014S) was absent in the tested mosquitoes. Three mosquitoes that tested positive for the parasite, had an individual Plasmodium falciparum infection rate of 12.50, 16.67, and 14.29%. The sampling dates of positive mosquitoes were distributed in the two periods of peak Anopheles mosquito density. Conclusion: This study identified the dominant Anopheles species in Freetown as An. gambiae while the predominant species within the An. gambiae complex was An. gambiae sensu stricto. Surveillance of seasonal fluctuations and high P. falciparum infection rates in Anopheles indicate that the alternation of drought and rainy seasons from June to July, and from October to November, are the key periods for malaria control and prevention in Freetown, Sierra Leone. The high frequency of kdr allele mutations in An. gambiae calls for close monitoring of vector susceptibility to insecticides and tracing of resistance mechanisms in order to develop more effective vector control measures and strategies.

Dengue virus serotype 4 (DENV 4) has had a relatively low prevalence worldwide for decades; however, likely due to data paucity, no study has investigated the epidemiology and evolutionary dynamics of DENV 4 genotype I (DENV 4-I). This study aims to understand the diversity, epidemiology and dynamics of DENV 4-I. We collected 404 full length DENV4-1 envelope (E) gene sequences from 14 countries using two sources: Yunnan Province in China (15 strains during 2013-2016) and GenBank (489 strains up to 2018-01-11). Conducting phylogenetic and phylogeographical analyses, we estimated the virus spread, population dynamics, and selection pressures using different statistical analysis methods (substitution saturation, likelihood mapping, Bayesian coalescent inference, and maximum likelihood estimation). Our results show that during the last 60 years (1956-2016), DENV 4-I was present in mainland and maritime Southeast Asia, the Indian subcontinent, the southern provinces of China, parts of Brazil and Australia. The recent spread of DENV 4-I likely originated in the Philippines and later spread to Thailand. From Thailand, it spread to adjacent countries and eventually the Indian subcontinent. Apparently diverging around years 1957, 1963, 1976 and 1990, the different Clades (Clade I-V) were defined. The mean overall evolution rate of DENV 4-I was 9.74 (95% HPD: 8.68-10.82) × 10-4 nucleotide substitutions/site/year. The most recent common ancestor for DENV 4-I traces back to 1956. While the demographic history of DENV 4-I fluctuated, peaks appeared around 1982 and 2006. While purifying selection dominated the majority of E-gene evolution of DENV 4-I, positive selection characterized Clade III (Vietnam). DENV 4-I evolved in situ in Southeast Asia and the Indian subcontinent. Thailand and Indian acted as the main and secondary virus distribution hubs globally and regionally. Our phylogenetic analysis highlights the need for strengthened regional cooperation on surveillance and sharing of sample sequences to improve global dengue control and cross-border transmission prevention efforts.

Most chemotherapeutic agents for leukemia are DNA damaging agents. However, DNA lesions can be repaired by activities of DNA repair systems. Increasing evidence have shown that enhanced DNA damage repair capacity contributes to chemotherapy resistance in leukemia cells. Thus, targeting DNA repair mechanisms is a promising strategy for novel leukemia treatment. SIRT1 expressions were downregulated by lentivirus-delivered SIRT1 shRNA in myeloid leukemia cells. SIRT1 mRNA and protein levels were analyzed by real-time PCR and Western blot, respectively. Flow cytometry was carried out to analyze cell cycle progression, apoptosis and DNA damage repair efficiency. DNA damage levels were assessed by alkaline comet assay, and H2AX phosphorylation was analyzed by immunoblotting and immunofluorescence. A mouse leukemia model was established by transplanting lentivirus-infected K562 cells containing SIRT1 shRNA into sublethally irradiated NOD/SCID mice, and tumorigenesis was evaluated by detecting tumor weights and mice survival. SIRT1 expressions were upregulated in myeloid leukemic patients. Downregulation of SIRT1 by RNAi promoted etoposide-induced DNA damage in myeloid leukemia cells accompanied by reduced NHEJ activity, and increased Ku70 acetylation. Furthermore, SIRT1 knockdown resulted in cell cycle arrest, induction of apoptosis and reduction of K562 cell proliferation accompanied by enhanced p53 and FOXO1 acetylation in K562 cells after etoposide treatment. Importantly, SIRT1 downregulation reduced the tumorigenesis ability of K562 cells in mouse xenografts following chemotherapy treatment. These results revealed that SIRT1 promotes the NHEJ repair pathway by deacetylating Ku70 in K562 cells, suggesting that SIRT1 is a novel therapeutic target for treating myeloid leukemia.

Lysine acetylation (Kac) is an important post-translational modification (PTM) of proteins in all organisms, but its functions have not been extensively explored in filamentous fungi. In this study, a Tandem Mass Tag (TMT) labelling lysine acetylome was constructed, and differentially modified Kac proteins were quantified during mycoparasitism and vegetative growth in the biocontrol fungus Clonostachys chloroleuca 67-1, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1448 Kac sites were detected on 740 Kac proteins, among which 126 sites on 103 proteins were differentially regulated. Systematic bioinformatics analyses indicate that the modified Kac proteins were from multiple subcellular localizations and involved in diverse functions including chromatin assembly, glycometabolism and redox activities. All Kac sites were characterized by 10 motifs, including the novel CxxKac motif. The results suggest that Kac proteins may have effects of broadly regulating protein interaction networks during C. chloroleuca parasitism to Sclerotinia sclerotiorum sclerotia. This is the first report of a correlation between Kac events and the biocontrol activity of C. chloroleuca. Our findings provide insight into the molecular mechanisms underlying C. chloroleuca control of plant fungal pathogens regulated by Kac proteins.

Plant-specific TCP transcription factors play vital roles in the controlling of growth, development, and the stress response processes. Extensive researches have been carried out in numerous species, however, there hasn't been any information available about TCP genes in sweet potato (Ipomoea batatas L.). In this study, a genome-wide analysis of TCP genes was carried out to explore the evolution and function in sweet potato. Altogether, 18 IbTCPs were identified and cloned. The expression profiles of the IbTCPs differed dramatically in different organs or different stages of leaf development. Furthermore, four CIN-clade IbTCP genes contained miR319-binding sites. Blocking IbmiR319 significantly increased the expression level of IbTCP11/17 and resulted in a decreased photosynthetic rate due to the change in leaf submicroscopic structure, indicating the significance of IbmiR319-targeted IbTCPs in leaf anatomical morphology. A systematic analyzation on the characterization of the IbTCPs together with the primary functions in leaf anatomical morphology were conducted to afford a basis for further study of the IbmiR319/IbTCP module in association with leaf anatomical morphology in sweet potato.

Although mammals are a well-studied group of animals, making accurate field identification of small mammals is still complex because of morphological variation across developmental stages, color variation of pelages, and often damaged osteological and dental characteristics. In 2008, small mammals were collected for an epidemiological study of a spotted fever outbreak in Hainan, China. Ten species of small mammals were identified by morphological characters in the field, most using pelage color characters only. The study is extended here, in order to assess whether DNA barcoding would be suitable as an identification tool in these small mammals. Barcode clusters showed some incongruence with morphospecies, especially for some species of Rattus and Niviventer, so molecular delineation was carried out with an expanded dataset of combined cytochrome b (Cyt-b) and cytochrome c oxidase subunit I (COI) sequences. COI sequences were successfully amplified from 83% of collected mammals, but failed in all specimens of Suncus murinus, which were thus excluded in DNA barcoding analysis. Of note, ten molecular taxonomic units were found from samples of nine morphologically identified species. Accordingly, 11 species of small mammals were present in the investigated areas, including four Rattus species, three Niviventer species, Callosciurus erythraeus, Neohylomys hainanensis, Tupaia belangeri, and Suncus murinus. Based on the results of the phylogenetic and molecular delineation analyses, the systematic status of some rodent species should be redefined. R. rattus hainanicus and R. rattus sladeni are synonyms of R. andamanensis. R. losea from China and Southeast Asia comprises two independent species: R. losea and R. sakeratensis. Finally, the taxonomic status of three putative species of Niviventer should be further confirmed according to morphological, molecular and ecological characters.

Ovarian cancer is one of the most lethal malignancies, with a 1.9% mortality rate worldwide. The dysregulation of the FEN1 gene and miR-4324 has been associated with cancer progression. However, the relationship between miR-4324 and-FEN1 requires further investigation.

Lung cancer is one of the main threats to human health. Survival of patients with lung cancer depends on timely detection and diagnosis. Among the genetic irregularities that control cancer development and progression, there are microRNAs (miRNAs/miRs). The present study aimed to investigate the expression patterns of miR-200a-3p and transcription factor GATA-6 (GATA6) in peripheral blood of patients with non-small cell lung cancer (NSCLC) and their clinical significance. The expression patterns of miR-200a-3p and GATA6 in the peripheral blood of patients with NSCLC and healthy subjects were measured via reverse transcription-quantitative PCR. The correlation between GATA6/miR-200a-3p expression and their diagnostic efficacy were analyzed by receiver operating characteristic curve analysis. The association between miR-200a-3p/GATA6 expression with the patient clinicopathological characteristics, and their correlation with carcinoembryonic antigen (CEA), neuron specific enolase (NSE) and squamous cell carcinoma antigen (SCCAg) were evaluated. The cumulative survival rate was examined, and whether miR-200a-3p and GATA6 expression levels were independently correlated with the prognosis of NSCLC was analyzed using multivariate logistic regression model. The results demonstrated that the expression of miR-200a-3p was high and that of GATA6 was low in the peripheral blood of patients with NSCLC, and both exhibited high clinical diagnostic efficacy. miR-200a-3p was revealed to target GATA6 by dual-luciferase assay. miR-200a-3p in the peripheral blood was correlated with TNM stage, lymph node metastasis and distal metastasis, while GATA6 in the peripheral blood was correlated with TNM stage and lymph node metastasis. miR-200a-3p and GATA6 were positively correlated with CEA and SCCAg, but not with NSE. High expression of miR-200a-3p and low expression of GATA6 predicted poor prognosis in patients with NSCLC. After adjusting for TNM stage, lymph node metastasis, distance metastasis, GATA6, CEA, NSE and SCCAg in the logistic regression model, it was indicated that the high expression of miR-200a-3p increased the risk of death in patients with NSCLC. Collectively, it was revealed that miR-200a-3p and GATA6 were abnormally expressed in the peripheral blood of patients with NSCLC. Serum levels of miR-200a-3p >1.475 and GATA6 <1.195 may assist the early diagnosis of NSCLC. GATA6 may function in NSCLC as a miR-200a-3p target, which may provide a future reference for NSCLC early diagnosis and treatment.

In China, Guangdong and Yunnan are the two most dengue-affected provinces. This study aimed to compare the epidemiological characteristics of dengue fever in Guangdong and Yunnan during 2004-2018.

Long noncoding RNAs play essential roles in colon cancer tumorigenesis. This study aimed to explore the potential function and molecular mechanisms of LINC00961 in colon cancer. qPCR results showed that LINC00961 was downregulated in colon cancer cells and tissues. Functional assays demonstrated that LINC00961 suppressed the migration and invasion of colon cancer cells in vitro. LINC00961 functioned as an endogenous sponge for miR-223-3p in colon cancer cells. SOX11 was confirmed as a target gene of miR-223-3p. The effect of miR-223-3p on colon cancer cells was then investigated. MiR-223-3p inhibition enhanced their migration and invasion. The effect of SOX11 on colon cancer cells was studied. SOX11 overexpression inhibited the invasion of colon cancer cells. LINC00961 acted as an anti-oncogene and upregulated SOX11 expression by functioning as a miR-223-3p sponge. This research revealed the molecular mechanism of LINC00961 in colon cancer. LINC00961 might act as a potential diagnostic biomarker and therapeutic target for further clinical treatments.

Aedes albopictus is naturally infected with Wolbachia spp., maternally transmitted bacteria that influence the reproduction of hosts. However, little is known regarding the prevalence of infection, multiple infection status, and the relationship between Wolbachia density and dengue outbreaks in different regions. Here, we assessed Wolbachia infection in natural populations of Ae. albopictus in China and compared Wolbachia density between regions with similar climates, without dengue and with either imported or local dengue.

Climate change may lead to emerging and re-emerging infectious diseases and pose public health challenges to human health and the already overloaded healthcare system. It is therefore important to review current knowledge and identify further directions in China, the largest developing country in the world.

Probiotic bacteria can induce immune regulation or immune tolerance in patients with allergic diseases, but the underlying mechanisms are still unclear. There has been a growing interest in the use of beneficial bacteria for allergic diseases recently. This study aimed at exploring whether Clostridium butyricum CGMCC0313-1 (C. butyricum) can reduce β-lactoglobulin(BLG)-induced intestinal anaphylaxis in a murine model of food allergy.

It is necessary to identify the relationship between neck circumference and cardiovascular risk factors in patients with hypertension.Patients with hypertension treated in our hospital were included. The height, weight, neck circumference, waist circumference, fasting blood glucose, 2 h blood glucose (2hPPG), density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and glycated hemoglobin (HbA1c) were analyzed and compared.A total of 2860 patients with hypertension were included. There were significant differences between male and female patients in the neck circumference, waist circumference, fasting blood glucose, Total cholesterol, triacylglycerol, HDL-C, LDL-C, diabetes, metabolic syndrome, dyslipidemia, drinking and smoking (all P < .05); the neck circumference was positively correlated with waist circumference, body mass index (BMI), fasting blood glucose, 2hPPG, HbA1c, triacylglycerol and LDL-C (all P < .05), and negatively correlated with HDL-C (P = .014); as the neck circumference increases, the risk of hypertension, diabetes, metabolic syndrome, abdominal obesity, and dyslipidemia increases accordingly (all P < .05); the area under curve (AUC) was 0.827 and 0.812, and the neck circumference of 37.8 and 33.9 cm was the best cut-off point for male and female patients, respectively.Neck circumference is closely related to cardiovascular risk factors in patients with hypertension, which should be promoted in the screening of cardiovascular diseases.

To investigate the relationship between climate variables, East Asian summer monsoon (EASM) and large outbreaks of dengue in China.

Flap structure-specific endonuclease 1 (FEN1) is one of the enzymes that involve in Eukaryotic DNA replication and repair. Recent studies have proved that FEN1 is highly over-expressed in various types of cancer cells and is a drug target. However, a limited number of FEN1 inhibitors has been identified and approved. Herein, we investigate the catalytic activity of FEN1, and propose a substrate-based inhibitor. As a consequence, one of the phosphorothioate-modified substrates is proved to exhibit the most efficient inhibitory effect in our in vitro examinations. A novelly-designed substrate-based FEN1 inhibitor was accordingly constructed and determined a remarkable IC50 value.