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Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by declines in cognitive and functional severities. This research utilized the Clinical Dementia Rating (CDR) to assess the influence of tilavonemab on these deteriorations., Methods: Longitudinal Item Response Theory (IRT) models were employed to analyze CDR domains in early-stage AD patients. Both unidimensional and multidimensional models were contrasted to elucidate the trajectories of cognitive and functional severities., Results: We observed significant temporal increases in both cognitive and functional severities, with the cognitive severity deteriorating at a quicker rate. Tilavonemab did not demonstrate a statistically significant effect on the progression in either severity. Furthermore, a significant positive association was identified between the baselines and progression rates of both severities., Discussion: While tilavonemab failed to mitigate impairment progression, our multidimensional IRT analysis illuminated the interconnected progression of cognitive and functional declines in AD, suggesting a comprehensive perspective on disease trajectories., Highlights: Utilized longitudinal Item Response Theory (IRT) models to analyze the Clinical Dementia Rating (CDR) domains in early-stage Alzheimer's disease (AD) patients, comparing unidimensional and multidimensional models.Observed significant temporal increases in both cognitive and functional severities, with cognitive severity deteriorating at a faster rate, while tilavonemab showed no statistically significant effect on either domain's progression.Found a significant positive association between the baseline severities and their progression rates, indicating interconnected progression patterns of cognitive and functional declines in AD.Introduced the application of multidimensional longitudinal IRT models to provide a comprehensive perspective on the trajectories of cognitive and functional severities in early AD, suggesting new avenues for future research including the inclusion of time-dependent random effects and data-driven IRT models., Competing Interests: The authors have no potential conflicts of interest to report. Author disclosures are available in the supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Porcine circovirus (PCV) typically causes severe immune suppression in pigs, leading to mixed clinical infections with various pathogens that can cause significant harm to the pig industry. PCV has four subgenotypes, with PCV4 being an emerging virus that requires investigation due to its potential for epidemic outbreaks. Therefore, there is a need to develop a method that can detect all four PCV strains simultaneously. In this study, four pairs of specific primers and TaqMan probes were designed based on the conserved sequence of the PCV1-4 ORF2 gene to establish a PCV1-4 TaqMan multiplex real-time quantitative PCR method. The novel method was compared to six commercial testing kits for its efficacy. Then, a total of 595 mixed samples of spleen and lymph node collected from 12 districts in Chengdu from July to December 2021 were tested using the novel method. The results showed that the novel PCV1-4 TaqMan multiplex real-time quantitative PCR detection method has satisfied specificity, sensitivity, and repeatability. The positive rates of PCV1, PCV2, and PCV3 in Chengdu were 2.18%, 31.60%, and 15.29%, respectively, while no positive PCV4 was detected. The mixed infection rate of PCV2 and PCV3 was 5.21%. Our novel method may be as a potential method for PCV1-4 detection. Currently, PCV2 is the main epidemic PCV subtype in Chengdu, while the potential threat of PCV4 should also be considered., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mi, Huang, Zhuo, Li, Yue, Zhong, Li, Zhong, Liu, Peng, Zhu, Zhou and Zhou.)

Objective: Femoral neck fractures (FNFs) are among the most common fractures in elderly individuals. Surgery is the main treatment for FNFs, and osteonecrosis of the femoral head (ONFH) is one of the unacceptable complications. This study aimed to assess both the clinical and radiological outcomes in patients with FNFs treated with three parallel cannulated screws and to identify relationship between screws position and ONFH., Patients and Methods: A total of 100 patients who were treated with closed reduction and fixed with 3 parallel cannulated screws met the inclusion criteria between January 2014 and December 2020 at authors' institution. The follow-up duration, age, sex, affected side, and injury-to-surgery interval were collected; the neck-shaft angle of both hips, screw-apex distance (SAD) and the tip-apex distance (TAD)were measured; and the Garden classification, quality of reduction and presence of ONFH were evaluated., Results: The sample consisted of 37 males and 63 females, with 60 left and 40 right hips affected. The mean age of patients was 54.93 ± 12.24 years, and the mean follow-up was 56.3 ± 13.38 months. The overall incidence of ONFH was 13%. No significant difference was observed in the incidence of ONFH by affected side, age, fracture displacement, injury-to-surgery interval, neck-shaft angle deviation, or reduction quality. The SAD was significantly shorter in ONFH patients than in normal patients for all three screws (p = 0.02, 0.02, and 0.01, respectively)., Conclusions: The short SAD of all screws is associated with femoral head necrosis of FNFs treated with 3 cannulated screws. The short SAD indicated that screws malpositioning in the weight-bearing area of the femoral head, potentially harming the blood supply and compromising the anchorage of the primary compressive trabeculae in this region., (© 2024. The Author(s).)

Technology innovation is the key driving force in achieving economic transformation and development. Financial development and the expansion of higher education can promote technological progress primarily by easing financing constraints and improving the level of human capital. This study examines the impact of financial development and higher education expansion on green technology innovation. It conducts an empirical analysis by constructing a linear panel model and a nonlinear threshold model. The present study sample is based on the urban panel data of China from 2003-2019. (1) Financial development can significantly promote the expansion of higher education. (2) The expansion of higher education can improve energy and environment-based technological progress. (3) Financial development can both directly and indirectly promote green technology evolution by expanding higher education. The joint financial development and higher education expansion can significantly empower green technology innovation. (4) In the process of promoting green technology innovation, financial development has a non-linear influence on it, with higher education as the threshold. The effect of financial development on green technology innovation varies according to the degree of higher education. Based on these findings, we put forward policy proposals for green technology innovation to promote economic transformation and development in China., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The phenomenon of climate change has become a global challenge that affects human activities in many ways. Exploring the sustainability and innovativeness of digital education is an important reference for the further implementation of science and education strategies and positive effects on climate change mitigation. This study designed two questionnaires for basic and tertiary education to address variability in education and collected 523 samples for basic education and 412 samples for tertiary education respectively. Using digital teaching practices and digital teaching quality as mediators, structural equation modelling (SEM) was used to examine the impact of digital education on sustainability and innovation in education. Research shows that digital teaching and learning in basic and higher education can significantly contribute to the two-way development of educational sustainability and innovation, through digital teaching and learning practices. Digital teaching practice and digital teaching quality in higher education play a complete mediating role, while basic education only plays a partial mediating role. Higher education emphasizes digital teaching and learning practice processes and teaching quality, and most students hope that online teaching and learning can be further integrated with offline education to form a new model of education. This study will help government departments understand the pedagogical reality of digital education at a deeper level and provide ideas for the subsequent sustainable development and educational innovation of digital teaching. It can also provide new ideas for climate change mitigation and sustainable development., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

In order to improve the detection performance of surface-enhanced Raman scattering (SERS), a low-cost Au@Ag nanorods (Au@Ag NRs) substrate with a good SERS enhancement effect was developed and applied to the detection of malachite green (MG) in aquaculture water and crayfish. By comparing the SERS signal enhancement effect of five kinds of Au@Ag NRs substrates with different silver layer thickness on 4-mercaptobenzoic acid (4-MBA) solution, it was found that the substrate prepared with 100 µL AgNO 3 had the smallest aspect ratio (3.27) and the thickest Ag layer (4.1 nm). However, it showed a good signal enhancement effect, and achieved a detection of 4-MBA as low as 1 × 10 -11 M, which was 8.7 times higher than that of the AuNRs substrate. In addition, the Au@Ag NRs substrate developed in this study was used for SRES detection of MG in crayfish; its detection limit was 1.58 × 10 -9 M. The developed Au@Ag NRs sensor had the advantages of stable SERS signal, uniform size and low cost, which provided a new tool for SERS signal enhancement and highly sensitive SERS detection method development.

Background: Periprosthetic fractures (PPFs) is one of the major causes of failure of hip arthroplasty with cementless stem; however, studies on the incidence and risk factors of PPFs after cementless hemiarthroplasty for femoral neck fractures (FNFs) are lacking., Methods: This retrospective study included patients who underwent cementless bipolar hemiarthroplasty for displaced intracapsular FNFs. The demographic data were reviewed, Dorr classification was used to describe morphology of the femur, radiological parameters were measured including stem-shaft angle, canal fill ratio (CFR), canal flare index (CFI), morphologic cortical index (MCI), canal calcar ratio (CCR), and vertical and horizontal femoral offset., Results: The sample comprised 10 men and 46 women (affected hip: left, 38; right, 18). The mean patient age was 82.82±10.61 (range, 69-93) years, and the mean hemiarthroplasty to PPFs time was 26.28±14.04 (range, 6.54-47.77) months. Seven (12.28%) patients had PPFs. A significant relationship was found between the incidence of PPF and CFR (p = 0.012), patients had a significantly smaller femoral stem CFR (0.76%±0.11%) than controls (0.85%±0.09%). The PPFs group had a significant shorter and unreestablished vertical femoral offset (p = 0.048)., Conclusions: A smaller femoral stem CFR associated with a potentially unacceptably high PPFs risk in uncemented hemiarthroplasty for displaced FNFs may result from mismatched prosthesis and bone dimensions in the elderly population, especially when accompanied by a poorly reestablished vertical femoral offset. With increasing evidence of the benefits of cemented fixation, a cemented stem for the treatment of displaced intracapsular FNFs is recommended for such a elderly frail population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Green innovation is an important way to realize the "double carbon" target, but financial support is necessary and important. This paper uses the multi-period difference-in-difference method to estimate the impact of city commercial banks on city green innovation. The data sample is the panel data of 285 prefecture-level cities in China from 2003 to 2019. Based on the empirical results, it can be concluded that city commercial banks can significantly promote green innovation, but have no significant contribution to the unbiased technological progress expressed by total factor productivity, i.e., overall innovation, while indicating that they are more efficient in promoting green innovation than overall innovation. This finding is still valid after a series of robustness, placebo, and parallel trend tests. After considering the moderating effect of environmental regulations, we find that market-incentive environmental regulation has a significant moderating effect on green innovation promotion, whereas command-control environmental regulation does not. On this basis, we propose policy recommendations to promote the development of city commercial banks; strengthen green innovation in central and western China, be both rigid and flexible in their approach to environmental regulation; and improve legal regulations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Following a Chinese saying: To be rich, roads first, high-speed rail (HSR) opening and station construction are indispensable for economic developing. Probing the nexus between HSR, as a vital part of modern transportation system, and local tourism development provides a scan for reviving tourism and gaining low-carbon transition after COVID-19 pandemic. Drawing on prefecture-level panel data, this study takes difference-in-difference and instrument variable methods to detect the overall and heterogeneous effects of HSR connection on cities' tourism development. The results showed that HSR connection had an overall positive effect on cities' domestic tourist arrivals. The heterogeneity of the effect from HSR to tourism development appears to be that central and western cities, non-resource-based cities, and small cities benefited more from the opening of HSR. From a dynamic perspective, HSR connection promoted local tourism development in the 0 and 1 year of HSR opening but failed to show a positive effect in the long term. Hence, the study proposed some adjustments for evaluating the efficiency of HSR with consideration for the tourism effect, redesigning the system of HSR with consideration for local heterogeneity, and optimizing the HSR environment. These measures can optimize China's HSR management and the design of HSR systems., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fecal microbiota transplantation (FMT) is a potential treatment for many intestinal diseases. In dogs, FMT has been shown to have positive regulation effects in treating Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), canine parvovirus (CPV) enteritis, acute diarrhea (AD), and acute hemorrhagic diarrhea syndrome (AHDS). FMT involves transplanting the functional components of a donor's feces into the gastrointestinal tract of the recipient. The effective components of FMT not only include commensal bacteria, but also include viruses, fungi, bacterial metabolites, and immunoglobulin A (IgA) from the donor feces. By affecting microbiota and regulating host immunity, these components can help the recipient to restore their microbial community, improve their intestinal barrier, and induce anti-inflammation in their intestines, thereby affecting the development of diseases. In addition to the above components, mucin proteins and intestinal epithelial cells (IECs) may be functional ingredients in FMT as well. In addition to the abovementioned indications, FMT is also thought to be useful in treating some other diseases in dogs. Consequently, when preparing FMT fecal material, it is important to preserve the functional components involved. Meanwhile, appropriate fecal material delivery methods should be chosen according to the mechanisms these components act by in FMT.

Enterovirus 71 (EV71) is the major pathogen causing fatal neurological complications of hand, foot, and mouth disease (HFMD) in young children. Currently no effective antiviral therapy is available. In the present study, we found that natural compound Berberine (BBR) displayed potent inhibitory effects on EV71 replication in various neural cells (IC 50 of 2.79-4.03 μM). In a newborn mouse model of lethal EV71 infection, Berberine at 2-5 mg/kg markedly reduced mortality and clinical scores. Consistently, the replication of EV71 and pathological changes were attenuated in various infected organs including brain and lung with BBR treatment. Interestingly, EV71 infection in the brain mainly localized in the peripheral zone of brainstem and largely in astrocytes. Primary culture of astrocytes from newborn mouse brain confirmed the efficient EV71 replication that was mostly inhibited by BBR treatment at 5 μM. Further investigations revealed remarkably elevated cellular reactive oxygen species (ROS) levels that coincided with EV71 replication in primary cultured astrocytes and various cell lines. BBR largely abolished the virus-elevated ROS production and greatly diminished EV71 replication by up-regulating NFE2 like bZIP transcription factor 2 (Nrf2) via the kelch like ECH associated protein 1 (Keap)-Nrf2 axis. The nuclear localization of Nrf2 and expression of downstream antioxidant enzymes heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were increased significantly by BBR treatment. Collectively, our findings revealed that BBR prevents lethal EV71 neurological infection via inhibiting virus replication through regulating Keap-Nrf2 axis and ROS generation in astrocytes of brainstem, thus providing a potential antiviral treatment for severe EV71 infection associated with neurological complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cui, Wang, Yang, Zhou, Wang, Wang and Ma.)

With the internationalization and financial development, it is urgent to explore the effect of foreign direct investment on green economy under the context of multiple environmental regulations. By using the provincial panel data in the period of 2000-2016, the paper adopts the System Generalized Method of Moments and threshold models to detect the moderating effect of diversified environmental regulation on the nexus between foreign direct investment and green growth in China. The empirical results reveal that foreign direct investment has direct positive spillovers on China's green growth and supports the "pollution halo" hypothesis. There is a threshold effect of command-and-control regulation that exists in foreign direct investment's spillovers to green growth. Stricter command-and-control regulation can stimulate foreign direct investment's spillovers on green growth in China; however, market-based and informal regulations fail to. Some suggestions are proposed for constructing a matched and compatible policy system of foreign direct investment, environment protection, and economic growth by adjusting the intensity, tools, and enforcement of corresponding policies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To compare the effectiveness of posterior malleolus fractures treated by plate and screw internal fixation through posterolateral approach., Methods: The clinical data of 95 patients with posterior malleolus fractures who were admitted between January 2016 and December 2019 and met the selection criteria were retrospectively analysed. They were divided into plate group (44 cases, treated with posterolateral plate internal fixation) and screw group (51 cases, treated with posterolateral screw internal fixation) according to different treatment methods. There was no significant difference in general data between the two groups of patients such as age, gender, cause of injury, side of injury, ankle fracture or injury classification, time from injury to operation, and percentage of posterior ankle fracture area to the distal tibia articular surface ( P >0.05). The operation time, hospital stay, fracture healing time, and surgical complications were compared between the two groups. Imaging examinations (X-ray film, CT scan and reconstruction) were used to assess the reduction quality of ankle fracture, articular congruity, and re-displacement in ankle fracture. At last follow-up, the pain visual analogue scale (VAS) score was used to evaluate the patients' pain, and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score was used to evaluate ankle joint function., Results: Patients in both groups were followed up 6-30 months, with an average of 18.2 months. The operation time of the plate group was significantly longer than that of the screw group ( U =-2.040, P =0.041); there was no significant difference in hospital stay between the two groups ( U =-1.068, P =0.285). Incision swelling occurred in 2 cases in the plate group, sural nerve injury in 3 cases, and traumatic arthritis in 2 cases during follow-up. In the screw group, there were 1, 2, and 2 cases, respectively. The incidence of complications in the two groups (15.9% vs. 9.8%) was not significantly different ( P =0.372). All patients who underwent tibiofibular screw fixation underwent the removal of the tibiofibular screw before taking full weight bearing at 12 weeks after operation, and there was no screw fracture and retention. During the follow-up, there was no infection, re-displacement of fracture, delayed bone union or nonunion, and there was no significant difference in fracture healing time between the two groups ( t =0.345, P =0.731). There was no significant difference between the two groups of reduction quality of ankle fracture and articular congruity evaluation results ( P >0.05). At last follow-up, there was no significant difference in VAS score, AOFAS ankle-hindfoot score and evaluation grade between the two groups ( P >0.05)., Conclusion: Both the plate and screw internal fixation through posterolateral approach can achieve satisfied effectiveness in the treatment of posterior ankle fractures with maintenance of fracture reduction, and recovery of ankle joint function. The screw internal fixation has the advantages of minimal invasion and shorter operation time.

Background: Pancreatic cancer is a malignant tumor and ranks the sixth in incidence among cancers. Circular RNA (circRNA) has been reported to regulate the progression of pancreatic cancer. However, the effects of circ-membrane bound O-acyltransferase domain containing 2 (circ-MBOAT2) on regulating pancreatic cancer process were unclear., Methods: The expression levels of circ-MBOAT2, microRNA-433-3p (miR-433-3p) and glutamic-oxaloacetic transaminase 1 (GOT1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). GOT1 protein expression was determined by western blot analysis. Cell proliferation was illustrated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and cell colony formation assay. Cell apoptosis was demonstrated by flow cytometry analysis. Cell invasion and migration were investigated by transwell invasion and wound-healing assays. Glutamine catabolism was explained by detecting glutamine consumption, alpha ketoglutarate (α-KG) production and glutamate production. In vivo assay was performed to illustrate the impacts of circ-MBOAT2 silencing on tumor formation in vivo. The binding relationship between miR-433-3p and circ-MBOAT2 or GOT1 was predicted by circinteractome or starbase online databases, and identified by dual-luciferase reporter assay., Results: Circ-MBOAT2 and GOT1 expression were significantly upregulated, while miR-433-3p expression was downregulated in pancreatic cancer tissues and cells compared with normal pancreatic tissues or cells. Circ-MBOAT2 silencing repressed cell proliferation, migration, invasion and glutamine catabolism, whereas promoted cell apoptosis in pancreatic cancer. Additionally, circ-MBOAT2 acted as a sponge of miR-433-3p, which was found to be associate with GOT1. MiR-433-3p inhibitors hindered circ-MBOAT2 silencing-mediated impacts on pancreatic cancer progression and glutamine catabolism. Furthermore, circ-MBOAT2 silencing repressed tumor formation in vivo., Conclusion: Circ-MBOAT2 modulated tumor development and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer. This finding suggests that circ-MBOAT2 may be a therapeutic target for pancreatic cancer.

Chronic hepatitis B is caused by prolonged infection with the hepatitis B virus (HBV), which can substantially increase the risk of developing liver disease. Despite the development of preventive vaccines against HBV, a therapeutic vaccine inducing an effective antibody response still remains elusive. The preS1 domain of the large HBV surface protein is the major viral attachment site on hepatocytes and thus offers a therapeutic target; however, its poor immunogenicity limits clinical translation. Here, we design a ferritin nanoparticle vaccine that can deliver preS1 to specific myeloid cells, including SIGNR1 + dendritic cells (which activate T follicular helper cells) and lymphatic sinus-associated SIGNR1 + macrophages (which can activate B cells). This nanoparticle vaccine induces a high-level and persistent anti-preS1 response that results in efficient viral clearance and partial serological conversion in a chronic HBV mouse model, offering a promising translatable vaccination strategy for the functional cure of chronic hepatitis B.

Backgroud: The osteotomy of the posterolateral overhanging part (PLOP) of the greater trochanter via posterior approach has been used for the hip arthroplasty for decades with good results. However, the osteotomy method remains undefined and the precise adjacent structures around PLOP have not been reported. The purpose of this study was to present a modified PLOP osteotomy approach and perform a detailed study of the topographic and surgical anatomy of the PLOP., Methods: The peri-PLOP soft tissue and the bony parameters were measured using 10 cadavers with 20 hips and 20 skeletal hip specimens, respectively., Results: A 1.8-cm vertical osteotomy did not jeopardize the femoral neck, and a 1.8-cm wide bone block did not damage the insertions of the short external rotators. The average distances between the most distal branch of the superior gluteal nerve/artery and the 1.8-cm point of the greater trochanter were 5.70 ± 0.66 cm and 6.33 ± 0.56 cm, respectively., Conclusion: For osteotomy of the PLOP, we suggested that the width of the upper side from the lateral to medial greater trochanter should be 1.8 cm, depth of vertical osteotomy should be 1.8 cm, and length of the posterior edge should be 4 cm. Obturator externus tendon should be kept within the bone block of osteotomy. The proximal extension of the gluteus medius muscle split should be limited to 5.5 cm at the 1.8 cm-point of the greater trochanter., Level of Evidence: Prospective comparative study Level II.

Background: Continued debate exists on the management of displaced 3- or 4-part proximal humeral fractures. Only a few studies have compared the efficacy of proximal humeral locking plates (PHLPs) for treating anatomic neck fractures (ANFs) and surgical neck fractures (SNFs)., Methods: The medical data of 31 consecutive patients with displaced 4-part proximal humeral fractures treated with PHLPs between May 2013 and April 2015 were reviewed retrospectively. We divided the patients into the ANF and SNF groups and assessed the neck-shaft angle (NSA), sum of the screw tip-articular surface distance, and other parameters postoperatively at 3 days and at 12 months using shoulder radiographs. The Constant-Murley scores were assessed at 3 days, 12 months, and last follow-up., Results: The ANF group had a significantly lower mean age and significantly greater mean operative duration, estimated blood loss, and rate of bone grafting. Full or partial osteonecrosis of the humeral head developed in 7 patients and 1 patient in the ANF and SNF groups, respectively. Screw cutout and/or pullout complications occurred in 8 cases in the ANF group but not in the SNF group. In the ANF group, the values for NSA and the sum of the screw tip-articular surface distance changed significantly from 3 days to 12 months postoperatively. There were no significant correlations among the tested parameters., Conclusion: ANFs resulted in more complications at a younger age than SNFs. ANF treatment using PHLPs is more prone to a decreased NSA and humeral head osteonecrosis and has poorer clinical outcomes than SNF treatment using PHLPs., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Recently, tumor neoantigens have been attractive for development of personal therapeutic vaccines. However, how to instantly deliver multiple neoantigens for efficient anti-tumor immunity is still challenging. Here, we established a SpyCatcher-modified ferritin nanoparticle platform, which permits convenient and stable covalent conjugation with tumor specific antigens containing SpyTag in a click-link manner. These ferritin nanoparticles are rapidly drained to lymph nodes and target dendritic cells, especially CD8α + population, upon subcutaneous immunization. Ferritin nanoparticles carrying HPV16 oncogene E7 peptide antigen or MC38 tumor derived mutant neoantigens elicit about 2-3 folds enhanced antigen-specific cytotoxic T lymphocyte (CTL) response than soluble peptide antigens and significantly suppress the growth of E7-related or MC38 tumors. The anti-tumor effect was further enhanced in combination with PD-1 checkpoint blockade. Together, our study provides a ferritin nanoparticle-based, SpyTag/SpyCatcher-enabled click vaccine platform, especially for personalized tumor immunotherapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To observe the effect of stromal vascular fraction cells (SVFs) from rat fat tissue combined with sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2) in promoting the lumbar fusion in rat model., Methods: SVFs were harvested from subcutaneous fat of bilateral inguinal region of 4-month-old rat through the collagenase I digestion. The sustained release carrier was prepared via covalent bond of the rhBMP-2 and β-tricalcium phosphate (β-TCP) by the biominetic apatite coating process. The sustained release effect was measured by BCA method. Thirty-two rats were selected to establish the posterolateral lumbar fusion model and were divided into 4 groups, 8 rats each group. The decalcified bone matrix (DBX) scaffold+PBS, DBX scaffold+rhBMP-2/β-TCP sustained release carrier, DBX scaffold+SVFs, and DBX scaffold+rhBMP-2/β-TCP sustained release carrier+SVFs were implanted in groups A, B, C, and D respectively. X-ray films, manual spine palpation, and high-resolution micro-CT were used to evaluate spinal fusion at 8 weeks after operation; bone mineral density (BMD) and bone volume fraction were analyzed; the new bone formation was evaluated by HE staining and Masson's trichrome staining, osteocalcin (OCN) was detected by immunohistochemical staining., Results: The cumulative release amount of rhBMP-2 was about 40% at 2 weeks, indicating sustained release effect of rhBMP-2; while the control group was almost released within 2 weeks. At 8 weeks, the combination of manual spine palpation, X-ray, and micro-CT evaluation showed that group D had the strongest bone formation (100%, 8/8), followed by group B (75%, 6/8), group C (37.5%, 3/8), and group A (12.5%, 1/8). Micro-CT analysis showed BMD and bone volume fraction were significantly higher in group D than groups A, B, and C ( P <0.05), and in group B than groups A and C ( P <0.05). HE staining, Masson's trichrome staining, and immunohistochemistry staining for OCN staining exhibited a large number of cartilage cells with bone matrix deposition, and an active osteogenic process similar to the mineralization of long bones in group D. The bone formation of group B was weaker than that of group D, and there was no effective new bone formation in groups A and C., Conclusion: The combination of sustained release of rhBMP-2 and freshly SVFs can significantly promote spinal fusion in rat model, providing a theoretical basis for further clinical applications.

To explore the fact that minimal invasive osteosynthesis surgery could promote patient rehabilitate quickly. Patients needed to remove fracture fixation plates and screws in clavicle/femur/tibia and fibular bones were totally divided into two groups (conventional surgery group and minimal invasive surgery group). The operation time, intra-operative blood loose, post-operation 48 hours analgesic need, VAS score of 24-hours and 72-hours post-operation, post operation incision healing conditions, incision infection, patients' satisfaction about incision scar, and resting days were measured. Patients in the minimal invasive surgery group were satisfied with their scar condition than the conventional surgery group. There were no much difference between conventional surgery group and minimal invasive surgery group in operation time (46.3±10.2 minutes Vs 48.0±11.8 minutes) (P>0.05) and the blood lose in these two groups were 4 ml Vs 47.4±20.1 ml (P>0.05), respectively. There were no screws broken in both groups and all the implants were removed out successfully. Remove four limb fracture fixation implant with minimal invasive surgery is good for patients' early rehabilitation.

Objective: The fungi diversity in the guts of five sub-adult giant pandas was analyzed., Method: We analyzed the fungal internal transcribed spacer sequences (ITS) using restriction fragment length polymorphism (RFLP). ITS regions were amplified with fungal universal primers to construct ITS clone libraries. The fingerprints were analyzed by restriction fragment length polymorphism using the Hha I and Hae III enzymes. The cloned PCR products were analyzed by sequencing and diversities were demonstrated by phylogenetic tree., Results: The gut fungi of 5 sub-adult giant pandas were mainly composed of Ascomycota (average of 46.24%), Basidiomycota ( average of 15.79%), unclassified (average of 29.14%), uncultured fungus (average of 8.83% ). Ascomycota was mainly composed of Saccharomycetes (average of 63.74%) and Dothideomycetes ( average of 35.91%); Basidiomycota was mainly composed of Tremellomycetes (average of 65.80%) and Microbotryomycetes (average of 33.15%). Four classes were mainly composed of Candida and Debaryomyces; Pleosporales and Myriangium; Cystofilobasidium and Trichosporon; Leucosporidium, and Leucosporidiella, whereas the proportions were different for each sample., Conclusion: Fungal flora existing in the intestines of sub-adult giant pandas expand our knowledge on the structure of the giant panda gut microbes and also help us to further study whether fungal flora can help giant pandas digest high-fiber foods.

Tetracyclines have been widely used in bone histomorphometry to label new bone formation and apposition rate. However, most studies of tetracyclines have also shown their strong inhibitory action on osteoclasts and their effects on osteoblast activities as well. To even obtain the in-depth understanding on this issue, we have reviewed related studies in "Pubmed" by searching the keywords "tetracyclines and osteoclast", "tetracyclines and osteoblast", which retrieved 118 and 162 related documents, respectively. Among these papers, some described the application of tetracyclines as fluorescent marker in bone histomorphometry, while others discussed their role in protection of bone metabolism partly through inhibiting osteoclastogenesis or bone resorption and through enhancing osteogenesis. Based on the above mentioned, it seems that tetracyclines used as bone labeling markers may affect the results of bone histomorphometry to some extent. To even confirm the effect of tetracyclines on bones cells (osteoblast, osteoclast) and in vivo bone remodeling, related research work has been performed in our research team which indicated quite different results in vivo and in vitro. Therefore, the influence of tetracyclines on bones may differ in terms of different conditions which need to be further elucidated.