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Abstract Yoga is effective in binge eating disorder (BED) treatment, but it does not seem effective enough to improve low physical fitness. In contrast, high-intensity interval training (HIIT) is effective in improving physical fitness but has never been studied in the context of BED. In the study, 47 young inactive females with mild to moderate BED were recruited and randomly assigned to a HIIT group (HIIT), a Yoga group (YG), or a control group (CG; age, 19.47 ± 0.74, 19.69 ± 0.874, and 19.44 ± 0.63 years; BMI, 21.07 ± 1.66, 21.95 ± 2.67, and 20.68 ± 2.61 kg/m2, respectively). The intervention groups participated in 8-week specific exercises, while the CG maintained their usual daily activity. Before and after the training, participants were evaluated for BED using the binge eating scale (BES) and for physical fitness. The obtained data were compared within groups and between groups, and a correlation analysis between BES and physical fitness parameters was performed. After the training, the YG presented significant improvements in BES (− 20.25%, p = 0.006, η p 2 = 0.408), fat mass (FM, − 3.13%, p = 0.033, η p 2 = 0.269), and maximal oxygen consumption (VO2max, 11.51%, p = 0.000, η p 2 = 0.601), whereas the HIIT showed significant improvements in body weight (BW, − 1.78%, p = 0.006, η p 2 = 0.433), FM (− 3.94%, p = 0.033, η p 2 = 0.285), and BMI (− 1.80%, p = 0.006, η p 2 = 0.428), but not in BES. Comparisons between groups revealed that both HIIT and YG had significantly higher VO2max levels than CG (HIIT 12.82%, p = 0.006, η p 2 = 0.088; YG: 11.90%, p = 0.009, η p 2 = 0.088) with no difference between HIIT and YG. Additionally, YG presented significantly lower BES than both HIIT (15.45%, p = 0.02, η p 2 = 0.03) and CG (11.91%, p = 0.022, η p 2 = 0.03). In conclusion, Yoga is an effective treatment for BED, but HIIT is not, despite its high efficacy in improving physical fitness.

Zimbabwe, located in Southern Africa, faces a significant public health challenge due to schistosomiasis. We investigated this issue with emphasis on risk prediction of schistosomiasis for the entire population. To this end, we reviewed available data on schistosomiasis in Zimbabwe from a literature search covering the 1980-2022 period considering the potential impact of 26 environmental and socioeconomic variables obtained from public sources. We studied the population requiring praziquantel with regard to whether or not mass drug administration (MDA) had been regularly applied. Three machine-learning algorithms were tested for their ability to predict the prevalence of schistosomiasis in Zimbabwe based on the mean absolute error (MAE), the root mean squared error (RMSE) and the coefficient of determination (R2). The findings revealed different roles of the 26 factors with respect to transmission and there were particular variations between Schistosoma haematobium and S. mansoni infections. We found that the top-five correlation factors, such as the past (rather than current) time, unsettled MDA implementation, constrained economy, high rainfall during the warmest season, and high annual precipitation were closely associated with higher S. haematobium prevalence, while lower elevation, high rainfall during the warmest season, steeper slope, past (rather than current) time, and higher minimum temperature in the coldest month were rather related to higher S. mansoni prevalence. The random forest (RF) algorithm was considered as the formal best model construction method, with MAE = 0.108; RMSE = 0.143; and R2 = 0.517 for S. haematobium, and with the corresponding figures for S. mansoni being 0.053; 0.082; and 0.458. Based on this optimal model, the current total schistosomiasis prevalence in Zimbabwe under MDA implementation was 19.8%, with that of S. haematobium at 13.8% and that of S. mansoni at 7.1%, requiring annual MDA based on a population of 3,003,928. Without MDA, the current total schistosomiasis prevalence would be 23.2%, that of S. haematobium 17.1% and that of S. mansoni prevalence at 7.4%, requiring annual MDA based on a population of 3,521,466. The study reveals that MDA alone is insufficient for schistosomiasis elimination, especially that due to S. mansoni. This study predicts a moderate prevalence of schistosomiasis in Zimbabwe, with its elimination requiring comprehensive control measures beyond the currently used strategies, including health education, snail control, population surveillance and environmental management.

AbstractIn this study, seventeen isobavachalcone (IBC) derivatives (1–17) were synthesised, and evaluated for their cytotoxic activity against three human lung cancer cell lines. Among these derivatives, compound 16 displayed the most potent cytotoxic activity against H1975 and A549 cells, with IC50 values of 4.35 and 14.21 μM, respectively. Compared with IBC, compound 16 exhibited up to 4.11-fold enhancement of cytotoxic activity on human non-small cell lung cancer H1975 cells. In addition, we found that compound 16 suppressed H1975 cells via inducing apoptosis and necroptosis. The initial mechanism of compound 16 induced cell death in H1975 cells involves the increasing of Bax/Bcl-2 ratio and Cyt C protein level, down-regulating of Akt protein level, and cleaving caspase-9 and -3 induced apoptosis; the up-regulation of RIP3, p-RIP3, MLKL, and p-MLKL levels induced necroptosis. Moreover, compound 16 also caused mitochondrial dysfunction, thereby decreasing cellular ATP levels, and resulting in excessive reactive oxygen species (ROS) accumulation.

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

In order to explore the effect of alloying on the microstructures and mechanical properties of AlCoCrFeNi2.1 eutectic high-entropy alloys (EHEAs), 0.1, 0.2, and 0.3 at.% V, Mo, and B were added to the AlCoCrFeNi2.1 alloy in this work. The effects of the elements and contents on the phase composition, microstructures, mechanical properties, and fracture mechanism were investigated. The results showed that the crystal structures of the AlCoCrFeNi2.1 EHEAs remained unchanged, and the alloys were still composed of FCC and BCC structures, whose content varied with the addition of alloying elements. After alloying, the aggregation of Co, Cr, Al, and Ni elements remained unchanged, and the V and Mo were distributed in both dendritic and interdendritic phases. The tensile strengths of the alloys all exceeded 1000 MPa when the V and Mo elements were added, and the Mo0.2 alloy had the highest tensile strength, of 1346.3 MPa, and fracture elongation, of 24.6%. The alloys with the addition of V and Mo elements showed a mixed ductile and brittle fracture, while the B-containing alloy presented a cleavage fracture. The fracture mechanism of Mo0.2 alloy is mainly crack propagation in the BCC lamellae, and the FCC dendritic lamellae exhibit the characteristics of plastic deformation.

Objective Acute respiratory infections are a major global public health concern. However, there are few epidemiological studies investigating pathogens associated with respiratory tract infections in Guizhou Province, China. Methods We collected 17,850 blood samples from Guizhou Provincial People’s Hospital between November 2018 and May 2023 to investigate the epidemiological characteristics of respiratory pathogens and their spread during the SARS-CoV-2 epidemic in Guizhou Province. Results We identified influenza virus and Mycoplasma pneumoniae as the predominant pathogens involved in acute respiratory infections in the study area. Immunoglobulin M positivity for respiratory syncytial virus, influenza virus, and M. pneumoniae showed a strong correlation with the clinical diagnosis of pneumonia. Seasonal epidemic patterns were observed for influenza A and B viruses. Following the SARS-CoV-2 outbreak, there was a significant decrease in the positive rates for most respiratory pathogens, particularly influenza A and B, Legionella pneumophila , and respiratory syncytial virus. Conclusion This retrospective study contributes to the epidemiological evidence regarding respiratory pathogens in Guizhou Province, thereby enhancing the surveillance network for respiratory pathogens in China and providing valuable guidance for local hospitals.

Abstract Objective To investigate the risk factors associated with the peripheral venous catheter-related complication and infection in children with bronchopneumonia. Methods A total of 185 patients were divided into case group (n = 114) and control group (n = 71) according to the presence of catheter-related infection and complications related to indwelling needle. We performed a multivariate logistic regression analysis to explore the risk factors associated with the infection. Results Age was divided into 4 categories (0 6). The case group had a higher percentage of patients with 0

In this study, 21 new honokiol derivatives were synthesised, and their anti-cancer properties were investigated. Among these, compound 1g exhibited the most potent cytotoxic activity against human nasopharyngeal carcinoma CNE-2Z cells, human gastric cancer SGC7901 cells, human breast cancer MCF-7 cells, and mouse leydig testicular cancer I-10 lines with IC50 values of 6.04, 7.17, 6.83, and 5.30 μM, respectively. Compared to the parental compound, 1g displayed up to 5.18-fold enhancement of the cytotoxic effect on CNE-2Z cells. We further demonstrated that 1g inhibited cell growth, suppressed migration and invasion, and induced apoptosis of CNE-2Z cells by down-regulating HIF-1α, MMP-2, MMP-9, Bcl-2, Akt and up-regulating Bax protein levels. Transfection of CNE-2Z cells with HIF-1α siRNA reduced cell migration and invasion. In addition, in vivo experiments confirmed that 1g inhibited tumour growth in CNE-2Z cell-xenografted nude mice with low toxicity. Thus, our data suggested that 1g was a potent and safe lead compound for nasopharyngeal carcinoma therapy.

Abstract Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC‐CMs) have the potential to be a therapeutic option for myocardium restoration. However, hiPSC‐CMs of varying maturation and transplantation routes exhibit different reactivity and therapeutic effects. We previously demonstrated that the saponin+ compound induces more mature hiPSC‐CMs. The safety and efficacy of multi‐route transplantation of saponin+ compound‐induced hiPSC‐CMs in a nonhuman primate with myocardial infarction will be investigated for the first time in this study. Our findings indicate that optimized hiPSC‐CMs transplanted via intramyocardial and intravenous routes may affect myocardial functions by homing or mitochondrial transfer to the damaged myocardium to play a direct therapeutic role as well as indirect beneficial roles via anti‐apoptotic and pro‐angiogenesis mechanisms mediated by different paracrine growth factors. Due to significant mural thrombosis, higher mortality, and unilateral renal shrinkage, intracoronary transplantation of hiPSC‐CMs requires closer attention to anticoagulation and caution in clinical use. Collectively, our data strongly indicated that intramyocardial transplantation of hiPSC‐CMs is the ideal technique for clinical application; multiple cell transfers are recommended to achieve steady and protracted efficacy because intravenous transplantation's potency fluctuates. Thus, our study offers a rationale for choosing a therapeutic cell therapy and the best transplantation strategy for optimally induced hiPSC‐CMs.

Objective: This study was aimed to explore the role of AhR in the neurotoxicity of adult zebrafish induced by three typical bisphenol compounds (BPA, BPS, TBBPA) at environmentally relevant doses. Methods: The adult zebrafish were randomly divided into solvent control group (DMSO) and AhR inhibitor CH223191 (CH) group (0.05 μmol/L), bisphenol exposure groups (10, 100, 1000 nmol/L) and combined exposure groups (0.05 μmol/L CH and 1000 nmol/L bisphenol compounds). Each tank contained 8 fish (4 male and 4 female), and two parallel tanks were set synchronously. After 30 days of exposure, zebrafish were put on ice plate for anesthesia, weighed and measured for body length, and dissected for brain tissue. The gene expression was detected by RT-qPCR, and the activities of antioxidant enzymes were detected by commercial kits. SPSS 26.0 was used to analyze the data. Additionally, GO, KEGG and principal component analysis (PCA) were carried out. Results: Compared with the solvent control group, there were no significant differences in body weight and length among the exposed groups. In general, exposure to bisphenol compounds could affect the expression of Ahr2 and AhR target genes (cyp1a1, cyp1a2, and cyp1c1), key genes of neural function (elavl3, gfap, mbp, syn2a, gap43, Zn5, shha, and ache), oxidative stress related genes (nrf2, gpx1a, gstp1/gstp1.2, gstp2/gstp1.1, sod1, sod2, and cat), and the activities of antioxidant enzymes (SOD, CAT and GSH-Px/GPX) in zebrafish brain tissue to some extent. Compared with the groups exposed to bisphenols alone, CH could antagonize the above interference effects caused by bisphenols to some extent. Therefore, the toxic effects of BPA, BPS and TBBPA might be produced through similar mechanisms. Conclusion: Environmentally related doses of bisphenols (BPA, BPS, TBBPA) could disturb the expression of key molecules of oxidative stress and neural function through activating the AhR signaling pathway, and ultimately lead to neurotoxicity.

In order to analyze the shear mechanism of the steel-fiber high-strength concrete corbels, a calculation model for the shear bearing capacity of steel-fiber-reinforced high-strength concrete corbels was proposed based on the modified compression field theory. Considering the existence of residual tensile stress in steel-fiber-reinforced concrete at crack locations, the cracked steel-fiber-reinforced concrete was treated as a continuous material. The constitutive relation of cracked steel-fiber-reinforced concrete and the local stress equilibrium equation were modified. It was compared with the results of 34 steel-fiber high-strength concrete corbels, including those in this paper. The predicted results were compared with the experimental values and the predictions of the Fattuhi model, Campione model, and Russo model to validate the rationality of the proposed model. The results revealed that the mean value between the experimental values and the predicted results of the proposed model is 1.104, with a variance of 0.003, showing good agreement. The proposed model can accurately predict the shear bearing capacity of steel-fiber-reinforced high-strength concrete corbels.

A Gram-negative, aerobic, rod-shaped, motile bacterium with multi-flagella, strain RST, was isolated from bacterial wilt of tobacco in Yuxi city of Yunnan province, China. The strain contains the major fatty acids of C16:0, summed feature 3 (C16:1ω7c and/or C16:1ω6c), and summed feature 8 (C18:1ω7c and/or C18:1ω6c). The polar lipid profile of strain RST consists of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and unidentified aminophospholipid. Strain RST contains ubiquinones Q-7 and Q-8. 16S rRNA gene sequence (1,407 bp) analysis showed that strain RST is closely related to members of the genus Ralstonia and shares the highest sequence identities with R. pseudosolanacearum LMG 9673T (99.50%), R. syzygii subsp. indonesiensis LMG 27703T (99.50%), R. solanacearum LMG 2299T (99.28%), and R. syzygii subsp. celebesensis LMG 27706T (99.21%). The 16S rRNA gene sequence identities between strain RST and other members of the genus Ralstonia were below 98.00%. Genome sequencing yielded a genome size of 5.61 Mbp and a G + C content of 67.1 mol%. The genomic comparison showed average nucleotide identity (ANIb) values between strain RST and R. pseudosolanacearum LMG 9673T, R. solanacearum LMG 2299T, and R. syzygii subsp. indonesiensis UQRS 627T of 95.23, 89.43, and 91.41%, respectively, and the corresponding digital DNA–DNA hybridization (dDDH) values (yielded by formula 2) were 66.20, 44.80, and 47.50%, respectively. In addition, strains belonging to R. solanacearum phylotype I shared both ANIb and dDDH with strain RST above the species cut-off values of 96 and 70%, respectively. The ANIb and dDDH values between the genome sequences from 12 strains of R. solanacearum phylotype III (Current R. pseudosolanacearum) and those of strain RST were below the species cut-off values. Based on these data, we concluded that strains of phylotype I, including RST, represent a novel species of the genus Ralstonia, for which the name Ralstonia nicotianae sp. nov. is proposed. The type strain of Ralstonia nicotianae sp. nov. is RST (=GDMCC 1.3533T = JCM 35814T).

Abstract Background Alveolar recruitment maneuvers (ARMs) is an important part of lung-protective ventilation strategies (LPVSs), but the optimal duration and interval Remain unclear. Methods Patients:252 patients who underwent holmium laser lithotripsy surgery and meet inclusion criteria were included and randomized into three groups based on the duration and frequency of ARMs (Regular, one 30 s ARM (RARMs); Improved and intermittent, three 10s ARMs (IARMs); and Control (C), no ARMs).Interventions: Groups R and I received ARMs at 20 cmH2O pressures every 30 min. All patients received the same anesthesia and mechanical ventilation. Measurements:Outcomes included heart rate and mean arterial pressure changes during ARMs and postoperative pulmonary complications (PPCs) within the first 7 postoperative days. Main results Incidences of PPCs in groups R(7.1%) and I (5.0%)were slightly lower than those in group C (8.9%).This indicated the potential to reduce lung injury. Heart rate and mean arterial pressure fluctuations during ARMs were significantly higher in groups R and I than in group C (P

As a transfer member at the discontinuous place of vertical load, the deep beam has a complex stress mechanism and many influencing factors, such as compressive strength of concrete, shear span ratio, and reinforcement ratio. At the same time, the stress analysis principle of traditional shallow beams is no longer applicable to the design and calculation of deep-beam structure. The main purpose of this paper was to use the strut-and-tie model to analyze its stress mechanism, and to verify the applicability of the model. Nine high-strength concrete deep-beam specimens with longitudinal reinforcement with an anchor plate of the same size were tested by two-point concentrated loading method. The effects of shear span ratio (0.3, 0.6, and 0.9), longitudinal reinforcement ratio (0.67%, 1.05%, and 1.25%), horizontal reinforcement ratio (0.33%, 0.45%, and 0.50%), and stirrup reinforcement ratio (0.25%, 0.33%, and 0.50%) on the failure mode, deflection curve, characteristic load, crack width, steel bar, and concrete strain of the specimens were analyzed. The results showed that the failure mode of deep-beam specimens was diagonal compression failure. The normal section cracking load was about 15 to 20% of the ultimate load, and the inclined section cracking load was about 30~40% of the ultimate load. The shear span ratio increased from 0.3 to 0.9, and the bearing capacity decreased by 32.9%. When the longitudinal reinforcement ratio increased from 0.67% to 1.25%, the ultimate load increased by 42.6%. The shear span ratio and longitudinal reinforcement ratio have a significant effect on the bearing capacity of the high-strength concrete deep beams with longitudinal reinforcement with an anchor plate. The shear capacity of nine high-strength concrete deep-beam specimens with longitudinal reinforcement with an anchor plate was calculated by national standards, and the results were compared with the calculation results of the Tan–Tang model, the Tan–Cheng model, SSTM, and SSSTM. The analysis showed that the softened strut-and-tie model takes into account the softening effect of compressive concrete, and is a more accurate mechanical model, which can be applied to predict the shear capacity of high-strength concrete deep-beam members with longitudinal reinforcement with an anchor plate.

Meloidogyne vitis is a new root-knot nematode parasitic on grape root in Yunnan Province, China. In order to establish a rapid, reliable and specific molecular detection method for M. vitis, the species-specific primers were designed with rDNA-ITS (ribosomal DNA internal transcribed spacer) gene fragment as the target. The reaction system was optimized and the reliability, specificity and sensitivity of primer were testified, therefore, a rapid PCR detection method for M. vitis was established. The result showed that the optimal annealing temperature of the primers was 53°C, which was suitable for the detection of different life stages of M. vitis. Specificity test showed that the specific fragment size of 174 bp was obtained from M. vitis, but other five non-target nematodes did not have any amplification bands, thus effectively distinguish M. vitis and the other five species, and could specifically detect the M. vitis from mixed populations. Sensitivity test showed that this PCR technique could detect the DNA of a single second-stage juvenile (J2) and 10−4 female. Futhermore, this PCR technique could be used to detect directly M. vitis from soil samples. The rapid, sensitive and specific PCR molecular detection technique could be used for the direct identification of a single J2 of M. vitis and the detection of M. vitis in mixed nematode populations and the detection of two J2s or one male in 0.5 g soil samples, which will provide technical support for the investigation of the occurrence and damage of M. vitis and the formulation of efficient green control strategies.

Background: Schistosomiasis is a parasitic disease caused by hematodes of genus Schistosoma. This review evaluated the available nucleic acid amplification techniques for diagnosing S. mansoni infections in humans, intermediate host snails, and presumed rodent reservoirs. Methods: Sensitivity, specificity, diagnostic odds ratio (DOR), and 95% CI were calculated based on available literature. The potential of PCR, nPCR, PCR-ELISA, qPCR, and LAMP was compared for diagnosing S. mansoni infections. Results: A total of 546 published records were identified. Quality assessment by QUADAS-2 revealed an uncertain risk in most studies, and 21 references were included in the final. For human samples, the four nucleic acid amplification techniques showed an overall sensitivity of 89.79% (95% CI: 83.92%-93.67%), specificity of 87.70% (95% CI: 72.60%-95.05%), and DOR of 37.73 (95% CI: 21.79-65.33). LAMP showed the highest sensitivity, followed by PCR-ELISA, PCR, and qPCR, while this order was almost reversed for specificity; qPCR had the highest AUC. For rodent samples, qPCR showed modest sensitivity (68.75%, 95% CI: 43.32%-86.36%) and high specificity (92.45%, 95% CI: 19.94%-99.83%). For snail samples, PCR and nPCR assays showed high sensitivity of 90.06% (95% CI: 84.39%-93.82%) and specificity of 85.51% (95% CI: 54.39%-96.69%). Conclusion: Nucleic acid amplification techniques had high diagnostic potential for identifying S. mansoni infections in humans.

Malaria and schistosomiasis are highly prevalent in Burkina Faso, whereas China has successfully eliminated malaria as well as schistosomiasis as a public health problem. To implement the China-Africa health cooperation initiative, a series of activities were launched since 2019 to enhance understanding and cooperation among malaria and schistosomiasis professionals in China and Burkina Faso. This study described the achievements of the First Virtual Symposium of China-Burkina Faso Cooperation on Schistosomiasis and Malaria Control. Pre- and post-test questionnaires were employed to study the knowledge changes of participants regarding malaria and schistosomiasis control and elimination, explore capacity-building priorities, and identify potential challenges. Chi-squared statistics were used to compare the differences between sub-groups, and p value

Electrocatalytic CO2 reduction reaction (CO2RR) is one of the effective means to realize CO2 resource utilization. Among the high-efficiency metal-based catalysts, Cu is a star material profiting from its ability for CO2 reduction into valuable hydrocarbon products. However, due to the difficulty in activating CO2 and regulating intermediate adsorption/desorption properties, the CO2RR activity and selectivity of Cu-based catalysts still cannot meet the requirements of industrial applications. The design of Cu-based bimetallic catalysts is a potential strategy because the introduction of the second metal can well promote the activation of CO2 and break the linear scaling relationship in intermediate adsorption/desorption. In this review, the synergistic enhancements of Cu-based bimetals on CO2 activation and intermediate adsorption/desorption are analyzed in detail, including the advantages caused by the morphology of Cu-based bimetallic catalysts, the local electric field effect induced by the special nanoneedle structure, the interface engineering (strain effect, atomic arrangement, interface regulation), and other particular effects (electronic effect and tandem effect). Finally, the challenges and perspectives on the development of Cu-based bimetallic catalysts for CO2 reduction are proposed.

Infection with helminths can modulate the host immune response, which ultimately shape morbidity and mortality of the associated diseases. We studied key cytokines for essential immune response in sera from 229 southeastern China individuals infected with Clonorchis sinensis and 60 individuals without C. sinensis infection, and measured serum specific IgG and IgE against worms in these people. Individuals infected with C. sinensis had significantly higher antigen-specific IgG and IgE levels, which were positively correlated with egg counts in feces. However, less enhancement of IgE antibody was observed in females when compared to males with similar infection levels. C. sinensis infection caused diminished Th1 cytokines (IL-1β, IL-2, IL-12p70, IFN-γ and TNF-α), Th2 cytokine (IL-4), as well as Th17 cytokine (IL-17A) in sera, which showed decreasing trend by infection intensity. Notably, these phenotypes were more significant in females than those in males. Although C. sinensis infection is associated with the development of hepatobiliary diseases, there was no significant correlation between the dampened cytokine profiles and the hepatobiliary morbidities. Our study indicates C. sinensis infection is strongly related to the immune suppression in human. Sex differences shape the immune milieus of clonorchiasis. This study provides a better understanding of how worms affect immune responses and cause a long-term immune alternation in humans with C. sinensis infection.

According to the shear capacity test results of six steel-fiber-reinforced high-strength concrete (SFHSC) corbels with welded-anchorage longitudinal reinforcement under concentrated load, the effects of shear span ratio and steel fiber volume fraction on the failure mode, cracking load and ultimate load of corbel specimens were analyzed. On the basis of experimental research, the shear transfer mechanism of corbel structure was discussed. Then, a modified softened strut-and-tie model (MSSTM), composed of the diagonal and horizontal mechanisms, was proposed, for steel-fiber-reinforced high-strength concrete corbels. The contributions of concrete, steel fiber and horizontal stirrups to the shear bearing capacity of the corbels were clarified. A calculation method for the shear bearing capacity of steel-fiber-reinforced high-strength concrete corbels was established and was simplified on this basis. The calculation results of the model were compared with the test values and calculation results of the GB50010-2010 code, the ACI318-19 code, the EN 1992-1-1 code and the CSA A23.3-19 code. The results showed that the concrete corbel with small shear span ratio mainly has two typical failure modes: shear failure and diagonal compression failure. With the increase in shear span ratio, the shear capacity of corbels decreases. Steel fiber can improve the ductility of a reinforced concrete corbel, but has little effect on the failure mode of the diagonal section. The calculated values of the national codes were lower than the experimental values, and the results were conservative. The theoretical calculation values of the shear capacity calculation model of the corbels were close to the experimental results. In addition, the model has a clear mechanical concept considering the tensile properties of steel-fiber-reinforced high-strength concrete and the influence of horizontal stirrups, which can reasonably reflect the shear transfer mechanism of corbels.

On the basis of the test results of nine steel-fiber high-strength concrete corbel specimens subjected to a vertical load, the influence of the steel fiber content on the shear performance of corbels was analyzed. The softened strut-and-tie model (SSTM) was used to analyze the shear strength of steel-fiber high-strength concrete corbels, taking into consideration the shear contribution of steel fibers. A calculation model for the shear strength of steel-fiber high-strength concrete corbels is proposed, and a database for 26 steel-fiber high-strength concrete corbels was created by using the model. The results obtained according to the codes ACI318-19, EC2, CSA A23.3-19 and the softened strut-and-tie model were compared with the experimental values to verify the rationality of the model. The findings showed that steel fiber can effectively limit the crack width and improve the crack morphology. The overall average value of the ratio between the experimental and the predicted strengths of the model was 1.082, and the variance was 0.004. The values predicted with the proposed calculation model were closer to the experimental values than those calculated according to the codes. This study provides a definite mechanical model that can reveal the shear mechanism of steel-fiber high-strength concrete. It can reasonably predict the shear strength of steel-fiber high-strength concrete corbels.

As short cantilever members, corbels are mainly used to transfer eccentric loads to columns. Because of the discontinuity of load and geometric structure, corbels cannot be analyzed and designed using the method based on beam theory. Nine steel-fiber-reinforced high-strength concrete (SFRHSC) corbels were tested. The width of the corbels was 200 mm, the cross-section height of the corbel column was 450 mm, and the cantilever end height was 200 mm. The shear span/depth ratios considered were 0.2, 0.3, and 0.4; the longitudinal reinforcement ratios were 0.55%, 0.75%, and 0.98%; the stirrup reinforcement ratios were 0.39%, 0.52%, and 0.785%; and the steel fiber volume ratios were 0, 0.75%, and 1.5%. According to the test results, this paper discusses the failure process and failure mode of corbel specimens with a small shear span/depth ratio and analyzes the effects of variables such as shear span/depth ratio, longitudinal reinforcement ratio, stirrup reinforcement ratio, and steel fiber volume content on the shear capacity of corbels. The shear capacity of corbels is significantly affected by the shear span/depth ratio, followed by the longitudinal reinforcement ratio and the stirrup reinforcement ratio. Moreover, it is shown that steel fibers have little impact on the failure mode and ultimate load of corbels, but can enhance the crack resistance of corbels. In addition, the bearing capacities of these corbels were calculated by Chinese code GB 50010-2010 and further compared with ACI 318-19 code, EN 1992-1-1:2004 code, and CSA A23.3-19 code, which adopt the strut-and-tie model. The results indicate that the calculation results by the empirical formula in the Chinese code are close to the corresponding test results, while the calculation method based on the strut-and-tie model of a clear mechanical concept yields conservative results, and hence the related parameter values must be further modified.

Abstract Background The Regional Network for Asian Schistosomiasis and Other Helminth Zoonoses (RNAS+) was established in 1998, which has developed close partnerships with Asian countries endemic for schistosomiasis and other helminthiasis in Asia. RNAS+ has provided an ideal regional platform for policy-makers, practitioners and researchers on the prevention, control and research of parasitic diseases in Asian countries. China, one of the initiating countries, has provided significant technical and financial support to the regional network. However, its roles and contributions have not been explored so far. The purpose of this study was to assess China's contributions on the supporting of RNAS+ development. Methods An assessment research framework was developed to evaluate China’s contributions to RNAS+ in four aspects, including capacity building, funding support, coordination, and cooperation. An anonymous web-based questionnaire was designed to acquire respondents’ basic information, and information on China’s contributions, challenges and recommendations for RNAS+development. Each participant scored from 0 to 10 to assess China’s contribution: “0” represents no contribution, and “10” represents 100% contribution. Participants who included their e-mail address in the 2017–2019 RNAS+ annual workshops were invited to participate in the assessment. Results Of 71 participants enrolled, 41 responded to the survey. 37 (37/41, 90.24%) of them were from RNAS+ member countries, while the other 4 (4/41, 9.76%) were international observers. Most of the respondents (38/41, 92.68%) were familiar with RNAS+. Respondents reported that China’s contributions mainly focused on improving capacity building, providing funding support, coordination responsibility, and joint application of cooperation programs on RNAS+ development. The average scores of China’s contributions in the above four fields were 8.92, 8.64, 8.75, and 8.67, respectively, with an overall assessment score of 8.81 (10 for a maximum score). The challenge of RNAS+ included the lack of sustainable funding, skills, etc. and most participants expressed their continual need of China’s support. Conclusions This survey showed that China has played an important role in the development of RNAS+ since its establishment. This network-type organization for disease control and research can yet be regarded as a great potential pattern for China to enhance regional cooperation. These findings can be used to promote future cooperation between China and other RNAS+ member countries.

Abstract This study focuses on the immunoregulatory effects of chicken TRIM25 on the replication of subgroup A of avian leukosis virus (ALV-A) and the MDA5-mediated type I interferon response. The ALV-A-SDAU09C1 strain was inoculated into DF1 cells and 1-day-old SPF chickens, and the expression of TRIM25 was detected at different time points after inoculation. A recombinant overexpression plasmid containing the chicken TRIM25 gene (TRIM25-GFP) was constructed and transfected into DF1 cells to analyse the effects of the overexpression of chicken TRIM25 on the replication of ALV-A and the expression of MDA5, MAVS and IFN-β. A small interfering RNA targeting chicken TRIM25 (TRIM25-siRNA) was prepared and transfected into DF1 cells to assess the effects of the knockdown of chicken TRIM25 on the replication of ALV-A and the expression of MDA5, MAVS and IFN-β. The results showed that chicken TRIM25 was significantly upregulated at all time points both in ALV-A-infected cells and in ALV-A-infected chickens. Overexpression of chicken TRIM25 in DF1 cells dramatically decreased the antigenic titres of ALV-A in the cell supernatant and upregulated the relative expression of MDA5, MAVS and IFN-β induced by ALV-A or by poly(I:C); in contrast, knockdown of chicken TRIM25 significantly increased the antigenic titres of ALV-A and downregulated the relative expression of MDA5, MAVS and IFN-β. It can be concluded that chicken TRIM25 can inhibit the replication of ALV-A and upregulate the MDA5 receptor-mediated type I interferon response in chickens. This study can help improve the understanding of the antiviral activities of chicken TRIM25 and enrich the knowledge of antiviral responses in chickens.

There is growing concern about adverse effects of bisphenol A alternatives including bisphenol B (BPB) due to their estrogenic activity. However, limited data are available concerning the influences of BPB on male reproductive development in vertebrates, especially in amphibians, which are believed to be susceptible to estrogenic chemicals. The present study investigated the effects of 10, 100 and 1000 nM BPB (2.42, 24.2 and 242 μg/L) on testis development in Xenopus laevis, a model amphibian species for studying gonadal feminization. We found that exposure to BPB from stages 45/46 to 52 resulted in down-regulation of testis-biased gene expression and up-regulation of ovary-biased gene and vitellogenin (vtgb1) expression in gonad-mesonephros complexes (GMCs) of tadpoles at stage 52, coupled with suppressed cell proliferation in testes and reduced gonadal metameres, resembling the effects of 17ß-estradiol. Moreover, an estrogen receptor (ER) antagonist ICI 182780 antagonized BPB-caused up-regulation of ovary-biased gene and vtgb1 expression to some degree, indicating that the effects of BPB on X. laevis testis differentiation could be partly mediated by ER. All observations demonstrate that early exposure to BPB inhibited testis differentiation and exerted certain feminizing effects during gonadal differentiation. When exposure was extended to post-metamorphosis, testes exhibited histological and morphological abnormalities including segmented, discontinuous and fragmented shapes, besides altered sex-dimorphic gene expression. Notably, most of BPB-caused alterations were not concentration-dependent, but the lowest concentration indeed exerted significant effects. Overall, our study for the first time reveals that low concentrations of BPB can disrupt testis differentiation partly due to its estrogenic activity and subsequently cause testicular dysgenesis after metamorphosis, highlighting its reproductive risk to amphibians and other vertebrates including humans. Our finding also implies that estrogenic chemicals-caused testis differentiation inhibition at tadpole stages could predict later testicular dysgenesis after metamorphosis, meaning a possibility of early detection of abnormal testis development caused by estrogenic chemicals.

This study aimed to investigate the effects of perfluorooctanesulfonic acid (PFOS) exposure on glucose-stimulated insulin secretion (GSIS) of rat insulinoma (INS-1) cells and the potential protective effects of procyanidins (PC). The effects of PFOS and/or PC on GSIS of INS-1 cells were investigated after 48 h of exposure (protein level: insulin; gene level: glucose transporter 2 (Glut2), glucokinase (Gck), and insulin). Subsequently, the effects of exposure on the intracellular reactive oxygen species (ROS) activity were measured. Compared to the control group, PFOS exposure (12.5, 25, and 50 μM) for 48 h had no significant effect on the viability of INS-1 cells. PFOS exposure (50 μM) could reduce the level of insulin secretion and reduce the relative mRNA expression levels of Glut2, Gck, and insulin. It is worth noting that PC could partially reverse the damaging effect caused by PFOS. Significantly, there was an increase in ROS after exposure to PFOS and a decline after PC intervention. PFOS could affect the normal physiological function of GSIS in INS-1 cells. PC, a plant natural product, could effectively alleviate the damage caused by PFOS by inhibiting ROS activity.

Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.

In epithelial cells Zeb1 is involved in the epithelial to mesenchymal transition. In this study, the authors show in a mouse model of breast cancer, that Zeb1 expression in stromal cells is required for tumour formation and metastasis.

Clonorchis sinensis infection is highly prevalent in Asia. Diverse hepatobiliary morbidity has been documented for C. sinensis infection. This study aimed to assess the association between C. sinensis infection and hepatobiliary morbidity, taking into consideration of the control, confounders and infection intensity. A cross-sectional community survey was implemented in Hengxian county, southeastern China. Helminth infections were detected by fecal examination. Physical examination and abdominal ultrasonography were then conducted. After excluding confounding effects from gender, age and alcohol drinking, quantitative association between C. sinensis infection and hepatobiliary morbidity was assessed, and the effect from infection intensity was also evaluated, through adjusted odds ratio (aOR) and 95% confidence intervals (95% CI). 696 villagers older than 10 years were enrolled. The prevalence and infection intensity of C. sinensis were higher in male, elder people and the individuals consuming alcohol. Light C. sinensis infection was associated with the increase of diarrhoea (aOR: 2.2, 95% CI: 1.1-4.5). C. sinensis infection was associated with the increase of fatty liver (aOR: 2.7, 95% CI: 1.4-5.2), and the effect was similar in different infection intensities. Moderate C. sinensis infection was associated with the increase of gallbladder stone (aOR: 3.0, 95% CI: 1.1-8.6), while moderate and heavy infections with the increase of intrahepatic bile duct dilatation (aOR: 2.2, 95% CI: 1.0-4.9 and aOR: 4.3, 95% CI: 1.9-9.9, respectively). C. sinensis infection had an effect on the development of periductal fibrosis (aOR: 3.2, 95% CI: 2.1-4.9), which showed increasing trend by infection intensity. The length and width of gallbladder in those with C. sinensis infection were enlarged, especially in those over 30 years old. C. sinensis infection is significantly associated with hepatobiliary morbidity. The occurrence of some morbidity was strongly related to the infection intensity. Awareness on harm of clonorchiasis should be raised both for policy-makers and villagers to adopt effective interventions.

ABSTRACT Activation of cyclic GMP-AMP (cGAMP) synthase (cGAS) plays a critical role in antiviral responses to many DNA viruses. Sensing of cytosolic DNA by cGAS results in synthesis of the endogenous second messenger cGAMP that activates stimulator of interferon genes (STING) in infected cells. Critically, cGAMP can also propagate antiviral responses to uninfected cells through intercellular transfer, although the modalities of this transfer between epithelial and immune cells remain poorly defined. We demonstrate here that cGAMP-producing epithelial cells can transactivate STING in cocultured macrophages through direct cGAMP transfer. cGAMP transfer was reliant upon connexin expression by epithelial cells and pharmacological inhibition of connexins blunted STING-dependent transactivation of the macrophage compartment. Macrophage transactivation by cGAMP contributed to a positive-feedback loop amplifying antiviral responses, significantly protecting uninfected epithelial cells against viral infection. Collectively, our findings constitute the first direct evidence of a connexin-dependent cGAMP transfer to macrophages by epithelial cells, to amplify antiviral responses. IMPORTANCE Recent studies suggest that extracellular cGAMP can be taken up by macrophages to engage STING through several mechanisms. Our work demonstrates that connexin-dependent communication between epithelial cells and macrophages plays a significant role in the amplification of antiviral responses mediated by cGAMP and suggests that pharmacological strategies aimed at modulating connexins may have therapeutic applications to control antiviral responses in humans.

Age-related macular degeneration(ARMD)is one of the major senile blinding eye diseases in the world. Among them, wet age-related macular degeneration(wARMD)causes severe visual impairment. In our country, age-related degenerative diseases pose a serious medical burden as the population tends to age. With the deep research of wARMD risk factors by domestic and foreign scholars, the prevention and control of wARMD has become an important research topic. Therefore, by studying the risk factors of wARMD and taking effective preventive measures, it is expected to reduce the incidence of wARMD and delay the development of the disease. This article reviews the research progress of wARMD risk factors.

Abstract Background Clonorchiasis ranks among the most important food-borne parasitic diseases in China. However, due to low compliance to traditional fecal examination techniques in the general population and medical personnel, immunodiagnosis is expected. This study evaluated, in parallel, the performance of four immunodiagnostic kits detecting clonorchiasis in China. Results A bank with 475 sera was established in this study. Except for the low performance of the kit detecting IgM, the other three kits detecting IgG showed sensitivities ranging from 81.51% (194/238) to 99.16% (236/238). Higher sensitivity was presented in heavy infection intensity [89.47% (68/76) to 100% (76/76)]. Among the four kits, the overall specificity varied from 73.42% (174/237) to 87.34% (207/237). It was observed that the specificity was lower in the sera of the participants living in clonorchiasis-endemic areas but without any parasite infection [67.5% (81/120) to 90% (108/120)], as compared to those from the non-endemic area [94% (47/50) to 98% (49/50)]. The cross-reaction rate varied from 14.93% (10/67) to 31.34% (21/67). Youden’s index was -0.022, 0.689, 0.726, and 0.802 for kits T1, T2, T3 and T4, respectively. Repeatability was high in all four kits. Conclusions Three immunodiagnosis kits targeting IgG antibody had high performance on detecting chronic Clonorchis sinensis infection, but that detecting IgM antibody had not. The kits detecting IgG antibody also showed high sensitivity in heavy infection intensity. Research on immunological diagnosis of clonorchiasis is expected to be strengthened to improve the sensitivity in light infection and specificity.

The morbidity and mortality caused by the globally prevalent human respiratory pathogen respiratory syncytial virus (RSV) approaches that world-wide of influenza. We previously demonstrated that the RSV matrix (M) protein shuttles, in signal-dependent fashion, between host cell nucleus and cytoplasm, and that this trafficking is central to RSV replication and assembly. Here we analyze in detail the nuclear role of M for the first time using a range of novel approaches, including quantitative analysis of de novo cell transcription in situ in the presence or absence of RSV infection or M ectopic expression, as well as in situ DNA binding. We show that M, dependent on amino acids 110–183, inhibits host cell transcription in RSV-infected cells as well as cells transfected to express M, with a clear correlation between nuclear levels of M and the degree of transcriptional inhibition. Analysis of bacterially expressed M protein and derivatives thereof mutated in key residues within M’s RNA binding domain indicates that M can bind to DNA as well as RNA in a cell-free system. Parallel results for point-mutated M derivatives implicate arginine 170 and lysine 172, in contrast to other basic residues such as lysine 121 and 130, as critically important residues for inhibition of transcription and DNA binding both in situ and in vitro. Importantly, recombinant RSV carrying arginine 170/lysine 172 mutations shows attenuated infectivity in cultured cells and in an animal model, concomitant with altered inflammatory responses. These findings define an RSV M-chromatin interface critical for host transcriptional inhibition in infection, with important implications for anti-RSV therapeutic development.

Ginkgo biloba L. has been used in traditional Chinese medicine (TCM) for thousands of years. However, the anti-cancer properties of ginkgolic acids (GAS) isolated from G. biloba have not been investigated in human nasopharyngeal carcinoma cells. In this study, GAS exhibited an inhibitory effect on the ATPase activity of heat shock protein 90 (Hsp90) and anti-proliferative activities against four human cancer cell lines, with IC50 values ranging from 14.91 to 23.81 μg·mL−1. In vivo experiments confirmed that GAS inhibited tumor growth in CNE-2Z cell-xenografted nude mice with low hepatotoxicity. We further demonstrated that GAS suppressed migration and invasion and induced the apoptosis of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (MMP-2, MMP-9, Her-2, c-Raf, Akt, and Bcl-2). Together, GAS are new Hsp90 inhibitors by binding to Hsp90 (hydrogen bond and hydrophobic interaction). Thus, GAS from G. biloba might represent promising Hsp90 inhibitors for the development of anti-nasopharyngeal carcinoma agents.

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 μM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.

A new series of mollugin-1,2,3-triazole derivatives were synthesized using a copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of corresponding O-propargylated mollugin with aryl azides. All the compounds were evaluated for their cytotoxicity on five human cancer cell lines (HL-60, A549, SMMC-7721, SW480, and MCF-7) using MTS assays. Among the synthesized series, most of them showed cytotoxicity and most of all, compounds 14 and 17 exhibited significant cytotoxicity of all five cancer cell lines.

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 μM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 μM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.

Background: Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus. Methods: This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of