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Abstract Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.

Epstein–Barr virus (EBV) infection has been related to multiple epithelial cancers and lymphomas. Current efforts in developing a prophylactic EBV vaccine have focused on inducing neutralizing antibodies. However, given the lifelong and persistent nature of EBV infection following primary infection, it is rationalized that an ideal vaccine should elicit both humoral and cellular immune responses targeting multiple stages of the EBV lifecycle. This study used a DNA vector and a TianTan vaccinia virus to express key EBV antigens, including BZLF1, EBNA1, EBNA3B, and gH/gL, to generate multi-antigen vaccines. The multi-antigen vaccine expressing all four antigens and the multi-antigen vaccine expressing BZLF1, EBNA1, and EBNA3B showed comparable protection effects and prevented 100% and 80% of humanized mice, respectively, from EBV-induced fatal B cell lymphoma by activating BZLF1, EBNA1, and EBNA3B specific T cell. The vaccine expressing lytic protein BZLF1 elicited stronger T cell responses and conferred superior protection compared to vaccines targeting single latent EBNA1 or EBNA3B. The vaccine solely expressing gH/gL exhibited no T cell protective effects in our humanized mice model. Our study implicates the potential of EBV vaccines that induce potent cellular responses targeting both latent and lytic phases of the EBV life cycle in the prevention of EBV-induced B cell lymphoma.

Abstract Background CircRNAs participate in the development of hepatocellular carcinoma (HCC). This work aims to explore the key tumor promoting circRNA as a gene therapy target. Methods The differentially expressed gene circRNAs in HCC tumor tissues was identified by mining GSE121714 dataset. EdU staining, wound healing, transwell invasion assay, TUNEL staining and western blotting examined proliferation, migration, invasion, apoptosis and epithelial mesenchymal transition (EMT). Xenograft mouse model and orthotopic transplantation tumor mouse model were constructed to verify the role of hsa_circ_001726 in growth and metastasis of HCC. The relationship among CCT2, E2F6, hsa_circ_001726, miR-671-5p and PRMT9 was identified by RNA-fluorescence in situ hybridization, luciferase reporter assay and RNA Immunoprecipitation. Results Eleven differentially expressed circRNAs were found in HCC tumors. Among them, hsa_circ_001726 was highly expressed in HCC tumors and cells, which was transcribed from CCT2. As a transcription factor of CCT2, E2F6 knockdown inactivated CCT2 promoter and reduced hsa_circ_001726 expression. Moreover, hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway. Additionally, hsa_circ_001726 deficiency repressed malignant phenotypes of HCC cells, including proliferation, migration, invasion, EMT and apoptosis. In vivo, hsa_circ_001726 deficiency reduced tumor growth and lung metastasis of HCC in xenograft mouse models and orthotopic transplantation tumor mouse models. Conclusion Hsa_circ_001726 functioned as an oncogene in HCC, which was derived from CCT2 and regulated by E2F6. Hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway, thereby accelerating malignant phenotypes of HCC. Therefore, targeting hsa_circ_001726 may be a new avenue for HCC treatment.

Abstract Background The hepatitis B virus X (HBx) protein is an established cause of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Whether arginine methylation regulates ferroptosis involved in HBx-induced HCC progression has not been reported. This study aimed to explore whether HBx-regulated protein arginine methyltransferase 9 (PRMT9) mediates the involvement of ferroptosis in the development of HCC. Methods and results HBx inhibited ferroptosis through promoting PRMT9 expression in HCC cells. PRMT9 suppressed ferroptosis to accelerate HCC progression in vivo. PRMT9 targeted HSPA8 and enhanced arginine methylation of HSPA8 at R76 and R100 to regulate ferroptosis in HCC. HSPA8 overexpression altered the transcriptome profile of HepG2 cells, in particular, ferroptosis and immune-related pathways were significantly enriched by differentially expressed genes, including CD44. HSPA8 overexpression up-regulated CD44 expression and knockdown of CD44 significantly reversed the inhibition of ferroptosis caused by PRMT9 overexpression. Conclusions In conclusion, HBx/PRMT9/HSPA8/CD44 axis is a vital signal pathway regulating ferroptosis in HCC cells. This study provides new opportunities and targets for the treatment of HBV-induced HCC. Graphical Abstract

The accuracy of sampling of gas components has a significant impact on the measurement of various performance parameters in the combustion chamber of an aero-engine. In order to investigate the effect of the probe geometry of a six-point gas sampling probe on sampling accuracy in supersonic gas flow, a three-dimensional probe gas flow characteristic solution model is established through numerical simulation methods of components of transport and fluid–solid coupling. Probes with three angles of 28°, 30°, and 32° and an optimized conical probe are constructed. The sampling accuracy of the probes with different geometries is compared and evaluated by the deviation of the component volume fraction before and after sampling and the resulting combustion efficiency error. This paper presents a set of calculation methods for solving the relative deviation of volume fraction by an iterative method based on the ideal gas law and the Redlich–Kwong equation (R-K equation). The method is designed to solve the exact component volume fraction problem in the simulation calculation. The study results demonstrate that the 28° and optimized conical probes improve sampling accuracy more effectively than the original 30° structure. The deviation of the volume fractions of the two structures is less than 1.7%, and the combustion efficiency error is less than 0.09%. The developed iterative calculation method can significantly reduce the theoretical calculation error to less than 0.06%. The experimental data of the test bench are in good agreement with the simulation results, thereby demonstrating the reliability and accuracy of the sampling probe following structural optimization.

Background: Closed reduction is the preferred treatment for distal radius fractures. However, it requires a multiple experienced medical staff and manually maintaining stable traction is difficult. Additionally, doctors cannot assess the reduction status of a fracture in real-time through radiographic images, which may lead to improper reduction. Furthermore, post-fracture complications such as joint adhesion, stiffness, and impaired mobility pose a challenge for the doctors. So it is necessary to optimize the treatment process of the distal radius fracture through technological means.Methods: A robot-assisted closed reduction and rehabilitation system, which could assist doctors throughout the entire process of reduction, fixation, and rehabilitation of distal radius fractures, was developed. A mechanical system, composed of two grippers and a cooperative robotic arm, was used to grasp and tract the affected limb. A doctor controlled the robot through a joystick console and Windows application program. A biplane radiographic device was integrated into the system, which is not only convenient for doctors to view radiographic images of the fracture at any time but also for them to select the rotation axis of the wrist on the images before reduction and rehabilitation. Important information including the anteroposterior and lateral radiographic data and force and position parameters during the reduction and rehabilitation process were displayed on a graphic user interface.Results: Experimental results showed that the proposed robotic system can meet the technical requirements for the reduction and rehabilitation of distal radius fractures, all the rotation angles could be achieved, a maximum force of more than 50 N could be achieved in all traction directions, and the error in selecting the wrist joint rotation axis line using radiographic images was less than 5 mm.Conclusion: The developed robot-assisted system was shown to be suitable for closed reduction and rehabilitation of distal radius fractures, contributing a potential improvement in the quality of the procedures.

Epstein–Barr virus (EBV) is the first reported human oncogenic virus and infects more than 95% of the human population worldwide. EBV latent infection in B lymphocytes is essential for viral persistence. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into B cells. The C-type lectin domain (CTLD) of gp42 plays a key role in receptor binding and is the major target of neutralizing antibodies. Here, we isolated two rabbit antibodies, 1A7 and 6G7, targeting gp42 CTLD with potent neutralizing activity against B cell infection. Antibody 6G7 efficiently protects humanized mice from lethal EBV challenge and EBV-induced lymphoma. Neutralizing epitopes targeted by antibodies 1A7 and 6G7 are distinct and novel. Antibody 6G7 blocks gp42 binding to B cell surface and both 1A7 and 6G7 inhibit membrane fusion with B cells. Furthermore, 1A7- and 6G7-like antibodies in immunized sera are major contributors to B cell neutralization. This study demonstrates that anti-gp42 neutralizing antibodies are effective in inhibiting EBV infection and sheds light on the design of gp42-based vaccines and therapeutics.

Purpose: We report an unusual case of severe proptosis during phacoemulsification in a 58-year-old female with a history of Crohn's disease, bilateral chronic panuveitis, prior bilateral central retinal vein occlusion, and uncontrolled steroid-associated ocular hypertension requiring bilateral Ahmed glaucoma drainage device (GDD) implantation with pars plana tube placement. Observations: During phacoemulsification of the right eye, the patient developed significant proptosis. Following lid speculum removal and mechanical eyelid manipulation, the proptosis resolved within 20 minutes without requiring a lateral canthotomy. The patient had no permanent visual complications. Conclusions and Importance: The likely pathophysiology of intraoperative proptosis in this case was accumulation of fluid in the retrobulbar space due to a functioning Ahmed tube shunt with the tube placed in the vitreous cavity. To avoid this complication, concurrent cataract surgery may be considered for patients with pars plana tube placement GDD surgery.

Epstein-Barr Virus (EBV) is closely linked to nasopharyngeal carcinoma (NPC), notably prevalent in southern China. Although type II latency of EBV plays a crucial role in the development of NPC, some lytic genes and intermittent reactivation are also critical for viral propagation and tumor progression. Since T cell-mediated immunity is effective in targeted killing of EBV-positive cells, it is important to identify EBV-derived peptides presented by highly prevalent human leukocyte antigen class I (HLA-I) molecules throughout the EBV life cycle. Here, we constructed an EBV-positive NPC cell model to evaluate the presentation of EBV lytic phase peptides on streptavidin-tagged specific HLA-I molecules. Utilizing a mass spectrometry (LC-MS/MS)-based immunopeptidomic approach, we characterized eleven novel EBV peptides as well as two previously identified peptides. Furthermore, we determined these peptides were immunogenic and could stimulate PBMCs from EBV VCA/NA-IgA positive donors in an NPC endemic southern Chinese population. Overall, this work demonstrates that highly prevalent HLA-I-specific EBV peptides can be captured and functionally presented to elicit immune responses in an in vitro model, which provides insight into the epitopes presented during EBV lytic cycle and reactivation. It expands the range of viral targets for potential NPC early diagnosis and treatment.

Abstract Epstein-Barr virus (EBV), a γ-herpesvirus, is the first identified oncogenic virus, which establishes permanent infection in humans. EBV causes infectious mononucleosis and is also tightly linked to many malignant diseases. Various vaccine formulations underwent testing in different animals or in humans. However, none of them was able to prevent EBV infection and no vaccine has been approved to date. Current efforts focus on antigen selection, combination, and design to improve the efficacy of vaccines. EBV glycoproteins such as gH/gL, gp42, and gB show excellent immunogenicity in preclinical studies compared to the previously favored gp350 antigen. Combinations of multiple EBV proteins in various vaccine designs become more attractive approaches considering the complex life cycle and complicated infection mechanisms of EBV. Besides, rationally designed vaccines such as virus-like particles (VLPs) and protein scaffold-based vaccines elicited more potent immune responses than soluble antigens. In addition, humanized mice, rabbits, as well as nonhuman primates that can be infected by EBV significantly aid vaccine development. Innovative vaccine design approaches, including polymer-based nanoparticles, the development of effective adjuvants, and antibody-guided vaccine design, will further enhance the immunogenicity of vaccine candidates. In this review, we will summarize (i) the disease burden caused by EBV and the necessity of developing an EBV vaccine; (ii) previous EBV vaccine studies and available animal models; (iii) future trends of EBV vaccines, including activation of cellular immune responses, novel immunogen design, heterologous prime-boost approach, induction of mucosal immunity, application of nanoparticle delivery system, and modern adjuvant development.

Abstract Background Epstein-Barr virus (EBV) is a wide-spread human herpesvirus that is highly associated with infectious mononucleosis and several malignancies. Evaluation of EBV neutralizing antibody titers is important for serological studies, vaccine development and monoclonal antibody screening. The traditional method based on antibody inhibition of EBV transformation of B cells is very time-consuming. A more practical flow cytometry-based (FCM) approach to evaluate neutralizing titers is not amenable to achieving high-throughput evaluation of large-scale samples. A high-throughput approach is urgently needed. Results Here, we present a rapid and high-throughput method based on high content imaging system (HCIS) analysis. EBV titers determined by the HCIS-based assay were similar to those obtained by the FCM-based assay. Neutralizing titers of sera and monoclonal antibodies measured by the HCIS-based assay strongly correlated with titers measured by the FCM-based assay. HCIS assays showed a strong correlation between B cell infection neutralizing titers and the anti-gp350 IgG titers in healthy EBV carriers and monkey sera. Finally, anti-gHgL IgG titers from sera of healthy EBV carriers significantly correlated with epithelial cell infection neutralizing titers. Conclusions This HCIS-based assay is a high-throughput assay to determine viral titers and evaluate neutralizing potentials of sera and monoclonal antibodies. This HCIS-based assay will aid the development of vaccines and therapeutic monoclonal antibody against EBV.

ObjectiveThis meta-analysis aims to evaluate the efficacy and safety of autologous platelet-rich plasma (PRP) administration in reducing adhesion recurrence and improving pregnancy outcomes in patients with intrauterine adhesion (IUA).MethodsWe conducted a comprehensive search of Pubmed, Embase, the Cochrane Library, Web of Science, Scopus, and China National Knowledge Internet (CNKI) from inception to February 10, 2023, without any language or regional restrictions. We used random-effects models to assess odds ratios (OR) and weight mean differences (WMD) with 95% confidence intervals (CI).ResultsOur meta-analysis included a total of 730 patients from 10 clinical studies (6 RCTs and 4 non-RCTs). The results showed that PRP administration significantly increased endometrial thickness (WMD = 0.79, 95% CI: 0.40–1.19; P < 0.001; I2 = 0.0%), menstrual volume (WMD = 2.96, 95% CI = 2.30–3.61; P < 0.001; I2 = 0.0%), and days of menstruation (WMD = 1.13, 95% CI = 0.86–1.41; P < 0.001; I2 = 0.0%). Additionally, the clinical pregnancy rate was also improved (OR = 1.82, 95% CI: 1.19-2.78; P = 0.006; I2 = 0.0%). However, there was insufficient evidence to reach a conclusion regarding the effects of PRP on the recurrence rate of moderate to severe IUA, changes in AFS scores, miscarriage rate, and live birth rate.ConclusionsOur analysis confirms that autologous PRP is an effective treatment for IUA. However, the limited sample size suggests that the results should be interpreted with caution. Therefore, larger and well-designed studies are necessary in the future to confirm these findings and explore the optimal PRP dosing regimens further.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023391115.

As a physical analysis method, susceptibility not only predicts the probability of failure of a structure under different hazard levels but also prevents disasters induced by structural damage due to vulnerable members. To study the susceptibility of steel clarification tank under earthquake action, this study analyzes the dynamic response of steel clarification tank under near-field impulse, near-field no impulse, and far-field ground shaking, derives IDA curve clusters by incremental dynamic analysis method, and conducts related studies to analyze the susceptibility of clarification tank structures through susceptibility curves. The results of the study show that the probability of failure of the clarification tank under different ground shaking intensities is different. The probability of liquid wave height transcendence of the clarification tank under seismic action is the largest, the probability of liquid wave height transcendence of the clarification tank under near-field pulsed seismic action is the second, the probability of liquid wave height transcendence of the clarification tank under near-field nonpulsed seismic action is the smallest, and the probability of transcendence occurs similarly in near-field pulsed and far-field seismic actions.

The stress at the support structure of the clarification tank is large, which will have a certain impact on the whole clarification tank structure. The typical stress concentration phenomenon will cause structural damage and serious harm to the steel clarification tank itself. In order to study the influence of the bearing plate on the seismic response of steel clarification tank, this paper analyzes the dynamic response of the clarification tank by setting different thickness bearing plates at the connection between the steel column and the structure body of the steel clarification tank. Based on the displacement, stress, and liquid sloshing height of the steel clarification tank, the thickness of the bearing plate is obtained. The results show that the maximum stress of the steel clarification tank under different seismic waves decreases with the increase of the thickness of the bearing plate. The thickness of the bearing plate has a certain influence on the maximum displacement of the clarification tank structure, but the increase in the thickness of the bearing plate does not necessarily reduce the maximum displacement. Different bearing plate thicknesses have no effect on the position of displacement, and the maximum displacement occurs at the top of the outer wall.

IntroductionSubjective tinnitus is a common and intractable ear disease. The effectiveness of acupuncture in the treatment of subjective tinnitus has been confirmed, but its mechanism of action is not clear. The structures of the amygdala (AMYG) are mainly closely related to emotion in the human brain. This study aimed to investigate the changes in functional connectivity (FC) of AMYG in subjective tinnitus to elucidate the neural mechanism of acupuncture.MethodsCorrelation scale scores of 26 patients with subjective tinnitus were collected, including Tinnitus Evaluation Questionnaire (TEQ), Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS). Meanwhile, rs-fMRI data were collected before and after acupuncture treatment in the patients, and in healthy controls (HC) matching the patient's gender and age. Then, AMYG was selected as region of interest to perform FC analysis. Finally, FC patterns of AMYG were first compared between patients with subjective tinnitus and HC, and then within subjects pre-acupuncture and post-acupuncture. Simple linear regression models between correlation scale scores and FC-values were established as well.ResultsAcupuncture treatment relieved the severity of tinnitus. With the acupuncture treatment, the total THI score, TEQ score, and VSA score of patients were significantly lower than before (p < 0.05). Compared with HC, FC of tinnitus patients between AMYG and right inferior temporal gyrus and right precuneus significantly decreased before acupuncture (voxel p < 0.001, cluster p < 0.05, corrected with GRF), while FC of tinnitus patients between AMYG and left superior frontal gyrus and right superior temporal gyrus significantly decreased after acupuncture treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). FC of tinnitus patients between the AMYG and right superior frontal gyrus and left paracingulate gyrus showed significant decrease after acupuncture treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). Besides, the linear regression models of the effect of THI on FC and VAS on FC performed were statistically significant (p < 0.05).DiscussionThe findings demonstrate that acupuncture can decrease FC of AMYG, which could be positively correlated with the relief of tinnitus symptoms. This result suggests that acupuncture stimulation can effectively relieve the severity of tinnitus by decreasing FC of AMYG in subjective tinnitus patients.

Abstract Through active involvement in UNESCO’s ICH (Intangible Cultural Heritage) programme, China has developed its own framework to support traditional making practices. To examine the ‘characteristics’ of heritage crafts preservation in China, we undertook empirical research in the Yellow River basin. Our research involved in-depth observations and key informant interviews with a range of highly accomplished craftspeople who have inherited their particular expertise from their family and have been officially designated ICH Inheritors. Through our qualitative research with inheritors, a businessperson and a government official, we identified various support mechanisms employed by the Chinese government that aim to protect traditional culture while also recognising outstanding individuals. We also found that ICH Inheritors play an important role in raising cultural awareness and enhancing cultural confidence through their creative activities and making practices, craft businesses and transfer of expertise. Based on the findings, potential areas where designers may collaborate with inheritors were identified.

With the rapid progress of artificial intelligence, various perception networks were constructed to enable Internet of Things (IoT) applications, thereby imposing formidable challenges to communication bandwidth and information security. Memristors, which exhibit powerful analog computing capabilities, emerged as a promising solution expected to address these challenges by enabling the development of the next-generation high-speed digital compressed sensing (CS) technologies for edge computing. However, the mechanisms and fundamental properties of memristors for achieving CS remain unclear, and the underlying principles for selecting different implementation methods based on various application scenarios have yet to be elucidated. A comprehensive overview of memristor-based CS techniques is currently lacking. In this article, we systematically presented CS requirements on device performance and hardware implementation. The relevant models were analyzed and discussed from the mechanism level to elaborate the memristor CS system scientifically. In addition, the method of deploying CS hardware using the powerful signal processing capabilities and unique performance of memristors was further reviewed. Subsequently, the potential of memristors in all-in-one compression and encryption was anticipated. Finally, existing challenges and future outlooks for memristor-based CS systems were discussed.

Abstract This study aimed to investigate the contribution of renal dysfunction to enhanced hyperuricemia prevalence in older people. A cohort of 13,288 Chinese people aged between 40 and 95 years were recruited from January to May 2019. Serum uric acid concentration and estimated glomerular filtration rate [eGFR] were measured. The associations between age or eGFR and serum uric acid or hyperuricemia were analyzed using linear or binary logistic regression adjusting for risk factors. Uric acid concentration and prevalence of hyperuricemia were greater in older participants. Adjustment for reduced renal function (eGFR

The Epstein–Barr virus (EBV) is the first reported oncogenic herpesvirus that establishes persistent infection in B lymphocytes in 95% of adults worldwide. Glycoprotein B (gB) plays a predominant role in the fusion of the viral envelope with the host cell membrane. Hence, it is of great significance to isolate gB-specific fusion-inhibiting neutralizing antibodies (NAbs). AMMO5 is the only gB NAb but fails to antagonize B-cell infection. It is essential to isolate potent NAbs that can completely block EBV infection of B cells. Using hybridoma technology and neutralization assay, we isolate two gB NAbs 8A9 and 8C12 that are capable of completely neutralizing B-cell infection in vitro. In addition, 8A9 shows cross-reactivity with rhesus lymphocryptovirus (rhLCV) gB. Competitive binding experiments demonstrate that 8A9 and 8C12 recognize novel epitopes that are different from the AMMO5 epitope. The epitopes of 8A9 and 8C12 are mapped to gB D-II, and the AMMO5 epitope is located precisely at gB aa 410–419. We find that 8A9 and 8C12 significantly inhibit gB-derived membrane fusion using a virus-free fusion assay. In summary, this study identifies two gB-specific NAbs that potently block EBV infection of B cells. Our work highlights the importance of gB D-II as a predominant neutralizing epitope, and aids in the rational design of therapeutics or vaccines based on gB.

Acupuncture is recommended for the relief of chronic tinnitus in traditional Chinese medicine, but the underlying neural mechanism remains unclear. The human brain is a dynamic system, and it’s unclear about acupuncture’s effects on the dynamic functional connectivity (DFC) of chronic tinnitus. Therefore, this study based on resting-state functional magnetic resonance imaging (fMRI) investigates abnormal DFC in chronic tinnitus patients and the neural activity change evoked by acupuncture treatment for tinnitus. In this study, 17 chronic tinnitus patients and 22 age- and sex-matched normal subjects were recruited, and their tinnitus-related scales and hearing levels were collected. The fMRI data were measured before and after acupuncture, and then sliding-window and k-means clustering methods were used to calculate DFC and perform clustering analysis, respectively. We found that, compared with the normal subjects, chronic tinnitus patients had higher temporal variability of DFC between the supplementary motor area and medial part of the superior frontal gyrus, and it positively correlated with hearing loss. Clustering analysis showed higher transition probability (TP) between connection states in chronic tinnitus patients, and it was positively correlated with tinnitus severity. Furthermore, the findings showed that acupuncture treatment might improve tinnitus. DFC between the posterior cingulate gyrus and angular gyrus in chronic tinnitus patients after acupuncture showed significantly decreased, and it positively correlated with the improvement of tinnitus. Clustering analysis showed that acupuncture treatment might promote chronic tinnitus patients under lower DFC state, and it also positively correlated with the improvement of tinnitus. This study suggests that acupuncture as an alternative therapy method might decrease the tinnitus severity by decreasing the time variability of DFC in chronic tinnitus patients.

Helicoverpa armigera is a polyphagous destructive lepidopteran pest with strong Bacillus thuringiensis (Bt) resistance. Cholesterol, a vital component for insect growth, can only be obtained from food, and its transfer and metabolism are regulated by sterol carrier protein-2 (SCP-2). This study examined whether H. armigera SCP-2 (HaSCP-2) gene expression, involved in cholesterol absorption, can be silenced by nanocarrier fluorescent nanoparticle-RNA interference (FNP-RNAi) by larval feeding and whether the silencing affected H. armigera development. Fluorescence microscopy showed that nanoparticle-siRNA was distributed in Ha cells and the larval midgut. FNP-HaSCP-2 siRNA suppressed HaSCP-2 expression by 52.5% in H.armigera Ha cells. FNP can effectively help deliver siRNA into cells, protect siRNA, and is not affected by serum. FNP-siRNA in vivo biological assays showed that HaSCP-2 transcript levels were inhibited by 70.19%, 68.16%, and 67.66% in 3rd, 4th, and 5th instar larvae, leading to a decrease in the cholesterol level in the larval and prepupal fatbodies. The pupation rate and adult emergence were reduced to 26.0% and 56.52%, respectively. This study demonstrated that FNP could deliver siRNA to cells and improve siRNA knockdown efficiency. HaSCP-2 knockdown by FNP-siRNA in vivo hindered H. armigera growth and development. FNP could enhance RNAi efficiency to achieve pest control by SCP-2-targeted FNP-RNAi.

Objective: To compare the cumulative live birth rates (cLBRs) after the first assisted reproductive technology (ART) cycle using flexible gonadotropin releasing hormone (GnRH)-antagonist protocol vs. standard long GnRH agonist protocol for controlled ovarian stimulation (COS) in infertile women with different ages and ovarian reserve.Methods: Women who underwent ART treatment at our center between June 1st, 2015 and December 31st, 2018 were screened. Among them, only women who underwent their first COS cycle with flexible GnRH antagonist protocol or standard long GnRH agonist protocol were included in this study. The main outcome measurement was cLBR.Results: A total of 4,402 patients were eligible for the analysis, of whom, 2,762 patients used the GnRH agonist protocol and 1,640 patients used the GnRH antagonist protocol. The cLBRs of women in the antagonist protocol group and long agonist protocol group were 45.3 and 50.0%, respectively. Subgroup multivariable regression analysis showed that, in patients with low ovarian reserve (AFC ≤ 7), the cLBR was significantly lower in the antagonist group than in the long agonist protocol group [OR (95% CI) 0.62 (0.41, 0.94)], which effect was more robust in younger patients (24), the cLBR was higher in cycles with antagonist protocol than with the long agonist protocol [OR (95% CI) 1.43 (0.96, 2.12)], and the effect was of statistical significance in younger patients (< 30 y) [OR (95% CI) 1.78 (1.07, 2.96)].Conclusion: The present study suggests that the flexible GnRH antagonist protocol might not be suitable for patients with low ovarian reserve (AFC ≤ 7) or patients aged over 40 years. However, flexible GnRH antagonist protocol might be strongly recommended for patients under 30 years old and with high ovarian reserve (AFC > 24). For the rest groups of patients in the present cohort, antagonist protocol was slightly favored because it had lower OHSS in general and in patients with poly-cystic ovarian syndrome (PCOS) according to previous publications.

Rainfall seepage changes the mechanical properties of loess masses. Considering fluid-solid coupling, the calculation model of a loess tunnel is established according to the finite element method (FEM). Based on porous media seepage theory and rainfall infiltration depth theory and considering the infiltrated depth of the loess surface for different rainfall intensities over a certain period, the stability of a loess tunnel under different rainfall amounts and loess cover thicknesses is studied using the dynamic finite element static strength reduction method. The results show that under the same rainfall intensity, the safety factor increases with the depth of the tunnel; the safety factor of the loess tunnel with the same loess cover thickness decreases with increasing infiltration depth. The plastic strain is mainly distributed on both sides of the vault and the arch feet. The stability of the loess tunnel is directly related to the loess cover thickness and rainfall seepage.

Epstein–Barr virus (EBV) is the first reported oncogenic virus and infects more than 90% of adults worldwide. EBV can establish a latent infection in B lymphocytes which is essential for persistence and transmission. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into a B cell. The N-terminal region of gp42 plays a key role in binding to gH/gL and triggering subsequent membrane fusion. However, no antibody has been reported to recognize this region and the immunogenicity of gp42 N-domain remains unknown. In the present study, we have generated a panel of nine mAbs against the gp42 N-terminal region (six mAbs to gp42-44-61aa and three mAbs to gp42-67-81aa). These mAbs show excellent binding activity and recognize different key residues locating on the gp42 N-domain. Among the nine mAbs, 4H7, 4H8 and 11G10 cross-react with rhLCV-gp42 while other mAbs specifically recognize EBV-gp42. Our newly obtained mAbs provide a useful tool for investigating the gp42 function and viral infection mechanism of γ-Herpesvirus. Furthermore, we assess the immunogenicity of the gp42 N-terminal region using the HBc149 particle as a carrier protein. The chimeric VLPs can induce high antibody titers and elicit neutralizing humoral responses to block EBV infection. More rational and effective designs are required to promote the gp42-N terminal region to become an epitope-based vaccine.

Humanized mouse models are used as comprehensive small-animal models of EBV infection. Previously, infectious doses of EBV used in vivo have been determined mainly on the basis of TD50 (50% transforming dose), which is a time-consuming process. Here, we determined infectious doses of Akata-EBV-GFP using green Raji units (GRUs), and characterized dose-dependent effects in humanized mice. We defined two outcomes in vivo, including an infection model and a lymphoma model, following inoculation with low or high doses of Akata-EBV-GFP, respectively. Inoculation with a low dose induced primary B cells to become lymphoblastoid cell lines in vitro, and caused latent infection in humanized mice. In contrast, a high dose of Akata-EBV-GFP resulted in primary B cells death in vitro, and fatal B cell lymphomas in vivo. Following infection with high doses, the frequency of CD19+ B cells decreased, whereas the percentage of CD8+ T cells increased in peripheral blood and the spleen. At such doses, a small part of activated CD8+ T cells was EBV-specific CD8+ T cells. Thus, GRUs quantitation of Akata-EBV-GFP is an effective way to quantify infectious doses to study pathologies, immune response, and to assess (in vivo) the neutralizing activity of antibodies raised by immunization against EBV.

KCNQ1 has been identified as a susceptibility gene of type 2 diabetes mellitus (T2DM) in Asian populations through genome-wide association studies. However, studies on the association between gene polymorphism of KCNQ1 and T2DM complications remain unclear. To further analyze the association between different alleles at the single nucleotide polymorphism (SNP) rs2237892 within KCNQ1 and TD2M and its complications, we conducted a case-control study in a Chinese Han population. The C allele of rs2237892 variant contributed to susceptibility to T2DM (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.20–1.75). Genotypes CT (OR, 1.97; 95% CI, 1.24–3.15) and CC (OR, 2.49; 95% CI, 1.57–3.95) were associated with an increased risk of T2DM. Multivariate regression analysis was performed with adjustment of age, gender, and body mass index. We found that systolic blood pressure (P = 0.015), prevalence of hypertension (P = 0.037), and risk of macrovascular disease (OR, 2.10; CI, 1.00–4.45) were significantly higher in subjects with the CC genotype than in the combined population with genotype either CT or TT. Therefore, our data support that KCNQ1 is associated with an increased risk for T2DM and might contribute to the higher incidence of hypertension and macrovascular complications in patients with T2DM carrying the risk allele C though it needs further to be confirmed in a larger population.