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Hao Zhang,1,* Linling Ju,2,* Peipei Hu,3,* Jun Ye,4 Canlin Yang,1 Junxing Huang1 1Department of Oncology, Taizhou People’s Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, 225300, Jiangsu, People’s Republic of China; 2Nantong Institute of Liver Diseases, Nantong Third People’s Hospital, Nantong University, Nantong, 226000, Jiangsu, People’s Republic of China; 3Department of Pain Medicine, Nantong Hospital of Traditional Chinese Medicine, Nantong Hospital Affiliated to Nanjing University of Chinese Medicine, Nantong, 226000, Jiangsu, People’s Republic of China; 4Institute of Clinical Medicine, Taizhou People’s Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, 225300, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junxing HuangDepartment of Oncology, Taizhou People’s Hospital Affiliated to Nanjing University of Chinese Medicine, 366 Taihu Road, Taizhou, 225300, Jiangsu, People’s Republic of ChinaEmail hjxtz@sina.cnBackground: Circular RNAs (circRNAs) have recently been verified to have multiple biological functions and participate in diverse biological processes in different malignant tumors, including esophageal squamous cell carcinoma (ESCC). Nonetheless, the function of circular RNA 0014715 (hsa_circ_0014715, circ_0014715) in ESCC has not been described.Materials and Methods: We investigated clinical data from sixty-seven patients undergoing surgery for esophageal cancer. The clinical data were collected. And we analyzed the correlation between the clinical characteristics of these patients and the expression of circ_0014715. Besides, we explored the expression of circ_0014715 in ESCC cell lines. We used cell counting kit-8, colony formation, transwell assay, and flow cytometry to detect changes in cell proliferation, migration, apoptosis, and cell cycle progression.Results: We found that circ_0014715 was highly expressed in esophageal squamous cell carcinoma tissues and cell lines. The correlation analysis of clinicopathological features and gene expression revealed that high expression of circ_0014715 was related to nerve invasion, vascular invasion, more advanced tumor-node-metastasis (TNM) stage and poor differentiation grade. Receiver operating characteristic (ROC) curves revealed that circ_0014715 might have diagnostic value for ESCC. Experiments with cultured cells showed that knockdown of circ_0014715 significantly restrained cell proliferation, migration, invasion, wound healing and accelerated cell apoptosis. And cell cycle arrest at G2 phase was observed via flow cytometry. Overexpression of circ_0014715 caused the opposite effects. Collectively, these studies show that circ_0014715 is closely connected with the pathogenesis and development of ESCC. The excess expression of circ_0014715 may have promoting effects on the progression of esophageal cell carcinoma.Conclusion: Our finding revealed that circ_0014715 promoted tumor growth and cell proliferation. All of these suggest that targeting circ_0014715 has potential therapeutic value in the treatment of ESCC.Keywords: circular RNA 0014715, circular RNAs, esophageal squamous cell carcinoma, biological characteristics, cell proliferation

Background Although several measures have been taken to control hand foot and mouth disease (HFMD) and herpangina (HA), these two diseases have been prevalent in China for 10 years with high incidence. We suspected that adults’ inapparent infection might be the cause of the continued prevalence of HFMD/HA infection in mainland China. Methods To explore the role of adults (especially caregivers) in the transmission process of HFMD/HA among children, 330 HFMD/HA cases and 330 healthy children (controls) were selected for a case–control study. Then, data were analyzed by logistic regression. Results Single-variable analyses revealed that caregivers who tested positive for enterovirus was a significant risk factor of HFMD/HA transmission to children (adjusted odds ratio (OR) = 9.22; 95% CI, 1.16 to 73.23). In the final multivariable model, caregiver behavior, such as cooling children’s food with mouth (OR = 1.85; 95% CI, 1.11 to 3.08) and feeding children with their own tableware (OR = 2.19; 95% CI, 1.07 to 4.45), significantly increased the risk of transmitting HFMD/HA to children. On the contrary, washing hands before feeding children reduced such risk. Conclusions These results implied that the caregivers might be the infectious source or carriers of enterovirus. Therefore, preventing or treating the caregivers’ enterovirus infection and improving their hygiene habits, especially when they are in contact with children, could provide a breakthrough for the effective control of HFMD/HA.

Background Home quarantine as a non-pharmaceutical measure is a key strategy for preventing the spread of hand, foot, and mouth disease (HFMD) and herpangina (HA). However, the status of home quarantine remains unclear. This study aimed to provide a theoretical basis for the prevention and control of the HFMD and HA by investigating the situation and determining the factors influencing home quarantine in children with HFMD or HA. Methods The convenience sampling method was used in this cross-sectional study involving parents whose children suffered from HFMD or HA in 2019. An online questionnaire tool was used to collect demographic information, socioeconomic status, clinical factors, sources of advice, and details of home quarantine. Logistic regression analysis was used to explore the factors influencing of home quarantine. Results A total of 3145 parents answered the electronic questionnaire; among them, 317 had children diagnosed with HFMD or HA in 2019. After quality control, 298 questionnaires were included in the analysis. The whole compliance rate of home quarantine for HFMD and HA was 59.1%. Results of multivariate logistic regression analysis indicated that having grandparents as the primary caregiver (OR = 2.53, 95% CI: 1.20–5.43) was a risk factor of home-quarantine noncompliance, whereas doctor's notification (OR = 0.35, 95% CI: 0.18–0.67) and advice from parents of other infected children (OR = 0.53, 95% CI: 0.31–0.91) can increase the compliance with home quarantine. Conclusions Home-quarantine measures for HFMD and HA were not well implemented. The caregivers, doctor's notification, and advice from parents of other infected children were associated with home-quarantine compliance. Corresponding measures should be taken to regulate home quarantine.

Previous studies suggested an association between female fertility and body size, but most of these studies were from Western countries and focused mainly on obesity. This study investigated the association between preconception body mass index (BMI) and time to pregnancy (TTP) in women planning to conceive from Shanghai, China. A total of 1,182 women aged 24-46 years were recruited from the Shanghai Birth Cohort between 2013 and 2015 and were followed up for 12 months. Preconception BMI was categorized as underweight, normal weight, and overweight/obesity according to the Chinese classification of BMI. Fecundability (FOR) and infertility (IOR) odds ratios were estimated using Cox (n = 1,092) and Logistic (n = 820) regression models, respectively. We found no differences in fecundability between underweight and overweight/obese women and normal-weight women. Furthermore, underweight and overweight/obese women did not have a higher risk of infertility compared with normal-weight women. Our findings suggest that non-optimal preconception BMI does not appear to influence female fecundability and infertility in Chinese women. These results should be interpreted with caution as they may be applicable only to women with demographic and anthropometric characteristics similar to our study population. Our findings need to be confirmed in other populations.

International audience; Significance: The vast majority of autoimmune diseases are polygenic, and causal loci uncovered by genetic-mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this missing heritability include rare meaningful variants, rare copy number variations or deletions, epistasis, epigenetics, disease heterogeneity, and rare or infrequent variants that segregate within individual families (even within monozygotic twins). Here we demonstrate that experimental models of spontaneous autoimmune diseases may be invaluable tools to map rare germline variants impacting disease susceptibility traits. We identified a variant of the dual-specificity phosphatase 10 encoding gene that accelerates disease in an autoimmune type 1 diabetes model, the nonobese diabetic mouse.Abstract: Insulin-dependent or type 1 diabetes (T1D) is a polygenic autoimmune disease. In humans, more than 60 loci carrying common variants that confer disease susceptibility have been identified by genome-wide association studies, with a low individual risk contribution for most variants excepting those of the major histocompatibility complex (MHC) region (40 to 50% of risk); hence the importance of missing heritability due in part to rare variants. Nonobese diabetic (NOD) mice recapitulate major features of the human disease including genetic aspects with a key role for the MHC haplotype and a series of Idd loci. Here we mapped in NOD mice rare variants arising from genetic drift and significantly impacting disease risk. To that aim we established by selective breeding two sublines of NOD mice from our inbred NOD/Nck colony exhibiting a significant difference in T1D incidence. Whole-genome sequencing of high (H)- and low (L)-incidence sublines (NOD/NckH and NOD/NckL) revealed a limited number of subline-specific variants. Treating age of diabetes onset as a quantitative trait in automated meiotic mapping (AMM), enhanced susceptibility in NOD/NckH mice was unambiguously attributed to a recessive missense mutation of Dusp10, which encodes a dual specificity phosphatase. The causative effect of the mutation was verified by targeting Dusp10 with CRISPR-Cas9 in NOD/NckL mice, a manipulation that significantly increased disease incidence. The Dusp10 mutation resulted in islet cell down-regulation of type I interferon signature genes, which may exert protective effects against autoimmune aggression. De novo mutations akin to rare human susceptibility variants can alter the T1D phenotype.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of cisplatin, which is characterized by intolerable paresthesia, burning, and hyperalgesia, and severely impacts the life quality of patients. However, no clearly potent drug has been found for clinical medication due to its undefined mechanism. Corydalis Saxicola Bunting, a traditional Chinese medicine, has been proven to work well in anti-inflammation, blood circulations improvement, hemostasis, and analgesia. This study was designed to observe the effects of Corydalis saxicola Bunting total alkaloids (CSBTA) on cisplatin-induced neuropathic pain and to explore its potential mechanisms. In this study, the rats received intraperitoneal injection of 2[Formula: see text]mg/kg cisplatin twice a week for five weeks. Meanwhile, oral administration of low (30[Formula: see text]mg/kg)-, medium (60[Formula: see text]mg/kg)- and high (120[Formula: see text]mg/kg)-dose CSBTA were given daily for five weeks. By using Von-frey hair, heat radiant and [Formula: see text]C cold acetone, we found that CSBTA could obviously relieve cisplatin-induced mechanical, heat, and cold hyperalgesia. It has been verified that cisplatin-induced peripheral neuropathy is related to intraepidermal nerve fibers loss and activation of inflammation downstream. Our research found that Tumor necrosis factor-alpha (TNF-[Formula: see text]), Interleukin-1beta (IL-1[Formula: see text]), and Prostaglandin E2 (PGE2) were significantly increased by 10 intraperitoneal injections of cisplatin, and such pro-inflammation cytokines could be reduced via CSBTA administration. Besides, in the cisplatin model group, the neuronal structures of dorsal root ganglia (DRG) were severely damaged and the loss of intraepidermal nerve fibers occurred; but in the CSBTA administration groups, all above pathological changes were improved. Moreover, CSBTA could normalize the overexpression levels of p-p38 and Transient receptor potential vanilloid receptor (TRPV1) induced by cisplatin in DRG, trigeminal ganglion (TG), spinal cord, and foot of rats. In summary, we considered that CSBTA exerted its therapeutic effects by ameliorating neuronal damages, improving intraepidermal nerve fiber (IENF) loss, and inhibiting inflammation-induced p38 phosphorylation to block TRPV1 activation. These findings were the first to confirm the analgesic effect of CSBTA on CIPN and suggested a novel strategy for treating CIPN in clinic.

Previous studies suggested that thyroid function in the first trimester of gestation played an important role in fetal growth. However, limited clinical data are available to support this relationship in the second trimester of gestation.We examined the relationship of maternal thyroid function parameters in early second trimester of gestation with birth outcomes in China.Participating 5016 mother-infant pairs were recruited from the Songjiang District Maternity and Infant Hospital, Shanghai, China, between July and December 2016. Linear regression assessed the associations of thyroid hormones with birthweight. Logistic regression tested the correlations between thyroid hormones and low birthweight, macrosomia, small for gestational age , and large for gestational age infants. Maternal serum TSH, TT3, TT4, FT3, and FT4 concentrations were measured in 16-20 weeks of gestation.TT3 and FT3 were positively associated with birthweight, while TT4 and FT4 were negatively associated with birthweight, respectively. Furthermore, higher TT3 and FT3 were associated with increased risks of LGA infants (OR = 1.48, 95% CI: 1.15-1.9; OR = 1.22, 95% CI: 1.01-1.46), respectively. Higher TT3 was associated with an increased risk of macrosomic infants (OR = 1.35, 95% CI: 1.04-1.74). In contrast, higher FT4 was associated with decreased risks of LGA (OR = 0.87, 95% CI: 0.81-0.93) and macrosomic infants (OR = 0.90, 95% CI: 0.84-0.96), respectively. No associations were found between TSH and any of the outcomes.TT3 and FT3 were positively associated with fetal growth, while TT4 and FT4 were negatively associated with fetal growth. Our findings suggested that thyroid function in early second trimester of gestation is a potential risk factor for abnormal fetal growth.

Vaccination is a key strategy to prevent the pandemic caused by the coronavirus disease 2019 (COVID-19). This study aims to investigate the willingness of Chinese adults to be vaccinated against COVID-19 and further explore the factors that may affect their willingness. We used a self-design anonymous questionnaire to conduct an online survey via the Sojump. A total of 1009 valid questionnaires were analyzed. The age of the participants ranged from 18 to 74. Among them, 609 (60.4%, 95%CI: 57.4–63.4%) were willing to receive the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Logistic regression analysis results showed that the age of 30–49 (OR = 2.042, 95%CI: 1.098–3.799), universities and colleges education (OR = 1.873, 95% CI = 1.016–3.451), master degree or above education (OR = 1.885, 95%CI = 1.367–2.599), previous influenza vaccination history (OR = 2.176, 95%CI: 1.474–3.211), trust in the effectiveness of the vaccine (OR = 6.419, 95%CI: 3.717–11.086), and close attention to the latest news of the vaccine (OR = 1.601, 95%CI: 1.046–2.449) were facilitative factors that affected their willingness to be vaccinated. More than half of the adults in China would be willing to receive a SARS-CoV-2 vaccine. Middle-aged people with higher education, those who had been vaccinated against influenza, and those who believed that COVID-19 vaccine was effective and paid close attention to it were more willing to be vaccinated. Our findings can provide reference for the implementation of vaccination and the prevention of COVID-19 in China. More studies are needed after the vaccine is launched.

Objectives: This study aimed to compare the risk of infection of children with that of adults and to explore risk factors of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by following up close contacts of COVID-19 patients. Method: The retrospective cohort study was performed among close contacts of index cases diagnosed with COVID-19 in Guangzhou, China. Demographic characteristics, clinical symptoms and exposure information were extracted. Logistic regression analysis was employed to explore the risk factors. The restricted cubic spline was conducted to examine to the dose-response relationship between age and SARS-CoV-2 infection. Results: The secondary attack rate (SAR) was 4.4% in 1,344 close contacts. The group of household contacts (17.2%) had the highest SAR. The rare-frequency contact (p < 0.001) and moderate-frequency contact (p < 0.001) were associated with lower risk of infection. Exposure to index cases with dry cough symptoms was associated with infection in close contacts (p = 0.004). Compared with children, adults had a significantly increased risk of infection (p = 0.014). There is a linear positive correlation between age and infection (p = 0.001). Conclusions: Children are probably less susceptible to COVID-19. Close contacts with frequent contact with patients and those exposed to patients with cough symptoms are associated with an increased risk of infection.

Metastatic bone pain is characterized by insufferable bone pain and abnormal bone structure. A major goal of bone cancer treatment is to ameliorate osteolytic lesion induced by tumor cells. Corydalis saxicola Bunting total alkaloids (CSBTA), the alkaloid compounds extracted from the root of C. saxicola Bunting, have been shown to possess anticancer and analgesic properties. In this study, we aimed to verify whether CSBTA could relieve cancer induced bone pain and inhibit osteoclastogenesis. The in vivo results showed that CSBTA ameliorated Walker 256 induced bone pain and osteoporosis in rats. Histopathological changes also supported that CSBTA inhibited Walker 256 cell-mediated osteolysis. Further in vitro analysis confirmed that CSBTA reduced the expression of RANKL and downregulate the level of RANKL/OPG ratio in breast cancer cells. Moreover, CSBTA could inhibit osteoclastogenesis by suppressing RANKL-induced NF-κB and c-Fos/NFATc1 pathways. Collectively, this study demonstrated that CSBTA could attenuate cancer induced bone pain via a novel mechanism. Therefore, CSBTA might be a promising candidate drug for metastatic bone pain patients.

Here we report the isolation by selective breeding of two sublines of Non-Obese Diabetic (NOD) mice exhibiting a significant difference in the incidence of autoimmune type 1 diabetes (T1D). Whole genome sequencing of the NOD/NckH (high T1D incidence) and NOD/NckL (low T1D incidence) revealed the presence of a limited number of variants specific to each subline. Treating the age of T1D onset as a quantitative trait and using automated meiotic mapping (AMM), enhanced susceptibility in the NOD/NckH subline was unambiguously attributed to a recessive allele of Dusp10 which encodes a dual specificity phosphatase. The causative effect of the mutation was verified with a high level of confidence by targeting Dusp10 with CRISPR/Cas9 in NOD/NckL mice: in these animals a higher incidence of diabetes was observed. Expression of wild-type Dusp10 correlated with higher levels of surface PD-L1 in the islets of NOD/NckL mice.

Background: Animal studies suggest that pesticide exposure elicits endocrine changes, increases embryo implantation failure, and decreases litter size. However, only a few epidemiological studies have evaluated the effects of pesticides on the outcomes of in vitro fertilization (IVF) pregnancies. Objectives: This study examined the associations between preconception organophosphate pesticides (OP) exposure and pregnancy outcomes among women undergoing IVF in a Chinese population. Methods: This study included 522 women with infertility who underwent IVF. Women were recruited from a prospective study, the China National Birth Cohort (CNBC), from Shanghai, China, between July 2017 and December 2018. Demographic and clinical information were collected from medical records and through questionnaires. Preconception exposure to OP was assessed by measuring six nonspecific dialkylphosphate (DAP) metabolites [diethylthiophosphate (DETP), diethylphosphate (DEP), diethyldithiophosphate (DEDTP), dimethylthiophosphate (DMTP), dimethylphosphate (DMP), dimethyldithiophosphate (DMDTP)] in urine samples collected at recruitment. Generalized estimating equation (GEE) models were used to evaluate the associations between OP and pregnancy outcomes. Results: Compared with women in the lowest quartile (Q1) of individual DEP and Σ4DAP (the sum of DMP, DMTP, DEP, and DETP), women in the highest quartile (Q4) had lower odds of successful implantation, clinical pregnancy, and live birth, and most of the negative trends were significant (p-trends

Huoxuezhitong capsule (HXZT, activating blood circulation and relieving pain capsule), has been applied for osteoarthritis since 1974. It consists of Angelica sinensis (Oliv.) Diels, Panax notoginseng (Burkill) F. H. Chen ex C. H., Boswellia sacra, Borneol, Eupolyphaga sinensis Walker, Pyritum. However, the direct effects of HXZT on osteoarthritis and the underlying mechanisms were poorly understood. In this study, we aimed to explore the analgesia effect of HXZT on MIA-induced osteoarthritis rat and the underlying mechanisms. The analgesia and anti-inflammatory effect of HXZT on osteoarthritis in vivo were tested by the arthritis model rats induced by monosodium iodoacetate (MIA).. Mechanistic studies confirmed that HXZT could inhibit the activation of NF-κB and down-regulate the mRNA expression of related inflammatory factors in LPS-induced RAW264.7 and ATDC5 cells. Furtherly, in LPS-induced RAW264.7 cells, HXZT could suppress NF-κB via inhibiting PI3K/Akt pathway. Taken together, HXZT capsule could ameliorate MIA-induced osteoarthritis of rats through suppressing PI3K/ Akt/ NF-κB pathway.

Silver (Ag) nanoparticles (NPs) are well known for their antibacterial properties. However, concerns have been raised on their possible toxicity to humans. This work is aimed to understand molecular interactions between Ag NPs and model mammalian cell membranes. Sum frequency generation (SFG) vibrational spectroscopy was used to study such interactions, supplemented by attenuated total reflectance–Fourier transform infrared spectroscopy (ATR–FTIR). Based on the SFG and ATR–FTIR results, it was found that Ag NPs could induce flip-flop of substrate supported lipid bilayers serving as model mammalian cell membranes. The Ag NPs could accumulate onto the model cell membrane and may aggregate. The Ag NP–model cell membrane interactions depend on the Ag NP solution concentration. At low Ag NP solution concentration, lipid flip-flop was observed. At higher Ag NP concentrations, Ag NPs caused lipid flip-flop faster and might aggregate. Therefore, the lipid flip-flop rates and Ag NP accumulation/aggregation rates are directly related to the Ag NP concentration of the subphase in contact with the lipid bilayer.

Context: It is reported that NTCP (sodium taurocholate cotransporting polypeptide) gene polymorphisms are associated with spontaneous clearance of hepatitis B virus (HBV), but the results are contradictory. Therefore, the current meta-analysis aimed at systematically clarifying the association between NTCP gene polymorphisms and spontaneous clearance of HBV in Asia. Evidence Acquisition: PubMed, Embase, Web of Science, Scopus, China National Knowledge Infrastructure and China Wanfang Data were searched systematically for articles published before 09 August 2019. Results: A total of nine case-control studies were finally included in the current meta-analysis. The pooled results indicated that the NTCP gene rs2296651 A allele is a protective factor for spontaneous clearance of HBV (GG vs. GA+AA: odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.58 - 0.93; GG vs. GA: OR = 0.74, 95%CI = 0.59 - 0.93; G vs. A allele: OR = 0.74, 95%CI = 0.58 - 0.94). Conclusions: NTCP gene rs2296651 polymorphism is correlated with spontaneous clearance of HBV, while NTCP gene rs4646287 and rs7154439 variants are not associated with persistent HBV susceptibility.

Background Spinal cord injury (SCI) is a common type of injury, and about half of patients affected by SCI will suffer from neuropathic pain within a year after injury. However, the treatment effect of neuropathic pain is far from satisfactory. Our study attempted to reveal whether salvianolic acid B (SalB) could relieve the neuropathic pain caused by SCI in mice by inhibiting the Toll-like receptor 4 (TLR4)/Myeloid differentiation factor 88 (MyD88) pathway. Methods The mice were randomly divided into a sham group, model group, high-dose treatment group, and low-dose treatment group. The high- and low-dose groups received varying doses of SalB after modeling. Results The increase of pain sensitivity was evaluated by detecting paw withdrawal mechanical threshold and withdrawal thermal latency. Messenger RNA and protein expression levels of TLR4 and myD88 were detected by using quantitative reverse-transcription polymerase chain reaction and western blot, respectively. Compared with the model group, there was a significant reduction in paw withdrawal mechanical threshold and withdrawal thermal latency after SalB treatment. Conclusions SalB reduced the release of tumor necrosis factor-α and substance P by inhibiting the TLR4/MyD88 pathway in the SCI mouse model. This not only resulted in lower pain, but also contributed to long-term relief of mechanical hyperalgesia.

Epidemiological studies have reported association of urinary 3-phenoxybenzoic acid (3-PBA), a major metabolite of pyrethroid insecticides (PYRs), with respiratory disease. However, knowledge regarding its effect on pulmonary function in susceptible children is limited. This study aimed to assess the associations between environmental 3-PBA concentrations and pulmonary function in children aged 6–17 years. Using data on 1174 children aged 6–17 years from the U.S. National Health and Nutrition Examination Survey (NHANES) 2007–2012, the exposure to PYRs was assessed by measuring urinary 3-PBA concentrations and pulmonary function was assessed by spirometry. Multivariable linear regression and generalized linear models (GLMs) were used to examine the associations between 3-PBA concentrations and pulmonary function in children, controlling for confounders. We found that 3-PBA concentrations were inversely associated with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) in the pediatric population (p-trends

Surface modification of nanoparticles (NPs) has been reported to play a significant role in determining their interactions with cell membranes. In this research, the interactions between carboxyl- or amine-functionalized Au NPs and model mammalian cell membranes were investigated by a nonlinear optical spectroscopic technique, sum frequency generation (SFG) vibrational spectroscopy, supplemented by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. To test the effects of surface composition on the NP–membrane interactions, we altered the ratio of different functional groups on the NP surfaces to create NPs with varied surface chemistry. In this study, a substrate-supported 1,2-distearoyl-d70-sn-glycero-3-phosphocholine (d70-DSPC or dDSPC)/1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) lipid bilayer was used as a model cell membrane. It was found that the interactions between the Au NPs and the lipid bilayer induced the lipid bilayer to flip-flop. A higher surface coverage o...

A coupled within-(immunological) and between-host (epidemiological) dynamic model was developed which is about the spreading of drugsensitive HIV strain and drug-resistant HIV strain in men who have sex with men (MSM) population. The within-host model was nested within the betweenhost model by linking the dynamics of the within-host model to the additional host mortality and transmission rate of the infection. The existences of equilibria and their stabilities were found, as well as the thresholds RS and RR for the two different strains of the nested model. Some simulations about the spreading of the two HIV strains in Beijing MSM population were given. Our results show that the drug-resistant strain will increase quite fast in this population and both strains can coexist, which will make a big pressure for China's "Four-Free-One-Care Policy".

The interactions between nanoparticles (NPs) and cells are of huge interest because NPs have been extensively researched for biomedical applications. For the cellular entry of NPs, it remains unclear how the cell membrane molecules respond to the exposure of NPs due to a lack of appropriate surface/interface-sensitive techniques to study NP-cell membrane interactions in situ in real time. In this study, sum frequency generation (SFG) vibrational spectroscopy was employed to examine the interactions between lipid bilayers (serving as model mammalian cell membranes) and Au NPs of four different sizes with the same mass, or the same NP number, or the same NP surface area. It was found that lipid flip-flop was induced by Au NPs of all four sizes. Interestingly, the lipid flip-flop rate was found to increase as the Au NP size increased with respect to the same particle number or the same NP surface area. However, the induced lipid flip-flop rate was the same for Au NPs with different sizes with the same mass, which was interpreted by the same "effective surface contact area" between Au NPs and the model cell membrane. We believe that this study provided the first direct observation of the lipid flip-flop induced by the interactions between Au NPs and the model mammalian cell membrane.

Di-(2-ethylhexyl) phthalate (DEHP) has been considered as a widespread environmental persistent organic pollutant and its potential concern on human health is raised by previous studies. In particular, children are more likely to be exposed to DEHP through gastrointestinal route and consequently are more susceptible to DEHP hazards. Some reports have uncovered a positive association between DEHP exposure and an increased prevalence of allergic diseases in infants and juveniles. Allergy is a hypersensitive reaction rooted in imbalanced humoral immunity. T follicular helper cell (Tfh), an important CD4(+) Th cell subset, until recently has been identified as a key player in humoral immune response by modifying B cells functions. Tfh cells are therefore perceived as the therapeutic target of immune disorders. In the present study, focusing on the newly confirmed Tfh cells, we examined the effects of DEHP on humoral immunity and investigated the underlying mechanisms. Using ovalbumin (OVA) sensitization weanling mice model under the condition of gastrointestinal exposure to DEHP, we found that DEHP acted as an immunoadjuvant to augment OVA-specific IgE and IgG1 production, amplified germinal center formation in lymphoid nodule, as well as stimulated the expansion of CD4(+)CXCR5(+)ICOS(+)/CD4(+)CXCR5(+)PD-1(+) Tfh cells and CD19(+)CD138(+)GL7(+) plasma cells. Based on the results of immune adoptive transfusion, DEHP-related anaphylactic response was ascribed to Tfh cells hyperfunction directly. We further proved that DEHP gavage together with OVA sensitization adjuvantly promoted the synthesis of cytokines IL-21 and IL-4 and the expression of transcription factors Bcl-6 and c-Maf in Tfh cells. In conclusion, our study demonstrates that DEHP has adjuvant toxic effects on Tfh cells by synthesizing an excess of cytokines IL-21 and IL-4 via over-expression of transcription factors Bcl-6 and c-Maf, leading to an increasing secretion of allergy-related IgE and IgG1.

Background To project the impact of partner reduction on preventing new HIV infections among men who have sex with men (MSM) under varying conditions of enhanced HIV testing and treatment (T&T) and condom use in Beijing, China. Methods and findings A complex network model was fitted to predict the number of new HIV infections averted from 2014 to 2023 under four scenarios of sexual behavior risk reduction (S)—S1: Male sexual partners decrease (reduced by a random value m from 1–50) while condom use increases (risk constant p is a random value between 0.2 and 1]); S2: Both sexual partners and condom use decrease (m 1, 50; p 1, 1.8); S3: Sexual partners reduce (m 1, 10) while condom use increases or decreases (p 0.2, 1.8); S4: Only MSM with ≥100 male sexual partners reduce their partners (m 1, 50) while condom use increases (p 0.2, 1). HIV prevalence will reach 23.2% by 2023 among Beijing MSM if T&T remains at the 2013 level. The three most influential factors are: T&T coverage; partner reduction (m); and the background risk (p). Under scenarios 1–4 of sexual behavioral changes with enhanced T&T interventions, the cumulative HIV new infections prevented over the 10 years will be 46.8% for S1 (interquartile range [IQR] 32.4%, 60.1%); 29.7% for S2 (IQR 18.0%, 41.4%), 23.2% for S3 (IQR 12.2%, 37.0%) and 11.6% for S4 (IQR 4.0%, 26.6%), respectively. The reproduction number R0 could drop below 1 if there were a substantial reduction of male sexual partners and/or expanded condom use. Conclusion Partner reduction is a vital factor within HIV combination interventions to reduce HIV incidence among Beijing MSM, with substantial additional benefits derived from condom use. T&T without substantial partner reduction and increased condom use is less promising unless its implementation were extremely (and improbably) efficient.