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In this study, we used the whole-exome sequencing (WES) approach to obtain genomic profiles from 92 marrow samples of myelodysplastic syndrome (MDS) patients before haematopoietic stem cell transplantation. We identified 129 mutations in 45 driver genes. Fifty-five patients (59.8%) carried at least 1 driver mutation. The splicing factor U2AF1 was the most frequently mutated in the cohort (21 cases, 23%), followed by BCOR (9 cases, 10%), ASXL1 (8 cases, 9%), TET2 (6 cases, 7%), NPM1 (5 cases, 5%), RUNX1 (5 cases, 5%), and SETBP1 (5 cases, 5%). WES also identified 49 possible oncogenic variants in six genes (PIEZO1, LOXHD1, MYH13, DNAH5, DPH1, and USH2A) that were associated with overall survival (OS) or relapse-free survival (RFS) in MDS after transplantation. Multivariate analysis showed mutations in DNAH5 and USH2A to be independent risk factors for OS. Mutations in DNAH5 and LOXHD1 were risk factors for worse RFS. The Molecular International Prognostic Scoring System retained its independent prognostic significance for RFS after multivariate analysis., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Cordyceps cicadae is recognized for its medicinal properties, attributed to bioactive constituents like polysaccharides and adenosine, which have been shown to improve kidney and liver functions and possess anti-tumor properties. Rho GTPase activating proteins (Rho GAPs) serve as inhibitory regulators of Rho GTPases in eukaryotic cells by accelerating the GTP hydrolysis of Rho GTPases, leading to their inactivation. In this study, we explored the function of the CcRga8 gene in C. cicadae, which encodes a Rho-type GTPase activating protein. Our study found that the knockout of CcRga8 resulted in a decrease in polysaccharide levels and an increase in adenosine concentration. Furthermore, the mutants exhibited altered spore yield and morphology, fruiting body development, decreased infectivity, reduced resistance to hyperosmotic stress, oxidative conditions, and cell wall inhibitors. These findings suggest that CcRga8 plays a crucial role in the development, stress response, and bioactive compound production of C. cicadae., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bacterial cellulose (BC) hydrogel is renowned in the field of tissue engineering for its high biocompatibility, excellent mechanical strength, and eco-friendliness. Herein, we present a biomimetic mineralization method for preparing BC/hydroxyapatite (HAP) composite hydrogel scaffolds with different mineralization time and ion concentration of the mineralized solution. Spherical HAP reinforcement enhanced bone mineralization, thereby imparting increased bioactivity to BC matrix materials. Subsequently, platelet-rich plasma (PRP) was introduced into the scaffold. The PRP-loaded hydrogel enhanced the release of growth factors, which promoted cell adhesion, growth, and bone healing. After 3 weeks of MC3T3-E1 cell-induced osteogenesis, PRP positively affected cell differentiation in BC/HAP@PRP scaffolds. Overall, these scaffolds exhibited excellent biocompatibility, mineralized nodule formation, and controlled release in vitro, demonstrating great potential for application in bone tissue repair., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Food-related functional substances with biological activity serve as a crucial material foundation for achieving precision nutrition, which has gained increasing attraction in regulating physiological functions, preventing chronic diseases, and maintaining human health. Nutritional substances typically include bioactive proteins, peptides, polysaccharides, polyphenols, functional lipids, carotenoids, probiotics, vitamins, saponins, and terpenes. These functional substances play an essential role in precise nutrition. This chapter introduces and summarizes typical functional substances to demonstrate the challenges in precision nutrition for their stability, solubility, and bioavailability. The current status of delivery systems of functional substances is described to give an insight into the development of desirable characteristics, such as food grade status, high loading capacity, site targeting, and controlled release capacity. Finally, the applications of food-borne delivery systems of functional substances for precision nutrition are emphasized to meet the requirement for precision nutrition during nutritional intervention for chronic diseases., (Copyright © 2024. Published by Elsevier Inc.)

Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent. We reviewed 108 patients with hematological diseases including acute leukemia, myelodysplastic syndrome, aplastic anemia, and others who received allogeneic hematopoietic stem cell transplantation (HSCT) from January 2019 through December 2020. After multivariable logistic regression, we found that splenomegaly (odds ratio [OR] = 26.98, p  < .001) and JAK mutation (OR = 17.32, p  = .024) were independent risk factors for PTR. During the period of transplantation, patients in the PTR group had a significantly higher platelet transfusion demand, which was reflected in the increased number of platelet transfusions (10.23 ± 6.696 vs. 5.06 ± 1.904, p  < .001). After multivariate adjustment, PTR turned out to be independently associated with worse overall survival (hazard ratio = 2.794, 95% confidence interval = 1.083-7.207, p  = .034). In conclusion, we found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. A history of PTR prior to allo-HSCT indicates a poor prognosis.

Background and Objective: Calcaneal Sanders type II or III fractures are highly disabling with significant burden. Surgical treatment modalities include open reduction and internal fixation (ORIF) techniques and a variety of minimally invasive surgical (MIS) approaches. ORIF techniques are associated with complications and traditional MIS techniques need extensive intraoperative fluoroscopic procedures. The present study aims to investigate the effects of three different minimally invasive internal fixation (MIIF) techniques used to treat Sanders type II intra-articular calcaneal fractures using finite element analyses., Methods: A 64-row spiral computed tomography scan was used to observe the calcaneus of a healthy adult. The scanning data were imported into Mimics in a DICOM format. Using a new model of a Sanders type II-B intra-articular calcaneal fracture, three minimally invasive techniques were simulated. Technique A involved fixation using an isolated minimally invasive locking plate; Technique B used a minimally invasive locking plate with one medial support screw; and Technique C simulated a screw fixation technique using four 4.0-mm screws. After simulating a 640-N load on the subtalar facet, the maximum displacement and von Mises stress of fragments and implants were recorded to evaluate the biomechanical stability of different fixation techniques using finite element analyses., Results: After stress loading, the maximum displacements of the fragments and implants were located at the sustentaculum tali and the tip of sustentaculum tali screw, respectively, in the three techniques; however, among the three techniques, Technique B had better results for displacement of both. The maximum von Mises stress on the fragments was < 56 Mpa, and stress on the implants using the three techniques was less than the yield strength, with Technique C having the least stress., Conclusion: All three techniques were successful in providing a stable fixation for Sanders type II intra-articular calcaneal fractures, while the minimally invasive calcaneal locking plate with medial support screw fixation approach exhibited greater stability, leading to improved enhancement for the facet fragment; however, screw fixation dispersed the stress more effectively than the other two techniques., (© 2023. The Author(s).)

Hepatitis B virus (HBV) infection is a noteworthy cause of liver diseases, especially cirrhosis and hepatocellular carcinomas. However, the interaction between the host and HBV has not been fully elucidated. Peptide YY (PYY) is a 36-amino-acid gastrointestinal hormone that is mainly involved in the regulation of the human digestive system. This study found that PYY expression was reduced in HBV-expressing hepatocytes and HBV patients. Overexpression of PYY could significantly inhibit HBV RNA, DNA levels, and the secretion of HBsAg. In addition, PYY inhibits HBV RNA dependent on transcription through reducing the activities of CP/Enh I/II, SP1 and SP2. Meanwhile, PYY blocks HBV replication independent on core, polymerase protein and ε structure of pregenomic RNA. These results suggest that PYY can impair HBV replication by suppressing viral promoters/enhancers in hepatocytes. Our data shed light on a novel role for PYY as anti-HBV restriction factor., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chronic ankle instability (CAI) is a common sequela following an acute lateral ankle sprain (LAS). To treat an acute LAS more effectively and efficiently, it is important to identify patients at substantial risk for developing CAI. This study identifies magnetic resonance imaging (MRI) manifestations for predicting CAI development after a first episode of LAS and explores appropriate clinical indications for ordering MRI scans for these patients., Methods: All patients with a first-episode LAS who received plain radiograph and MRI scanning within the first 2 weeks after LAS from December 1, 2017 to December 1, 2019 were identified. Data were collected using the Cumberland Ankle Instability Tool at final follow-up. Demographic and other related clinical variables, including age, sex, body mass index, and treatment were also recorded. Univariable and multivariable analyses were performed successively to identify risk factors for CAI after first-episode LAS., Results: A total 131 out of 362 patients with a mean follow-up of 3.0 ± 0.6 years (mean ± SD; 2.0-4.1 years) developed CAI after first-episode LAS. According to multivariable regression, development of CAI after first-episode LAS was associated with 5 prognostic factors: age (odds ratio (OR) = 0.96, 95% confidence interval (95%CI): 0.93-1.00, p = 0.032); body mass index (OR = 1.09, 95%CI: 1.02-1.17, p = 0.009); posterior talofibular ligament injury (OR = 2.17, 95%CI: 1.05-4.48, p = 0.035); large bone marrow lesion of the talus (OR = 2.69, 95%CI: 1.30-5.58, p = 0.008), and Grade 2 effusion of the tibiotalar joint (OR = 2.61, 95%CI: 1.39-4.89, p = 0.003). When patients had at least 1 positive clinical finding in the 10-m walk test, anterior drawer test, or inversion tilt test, they had a 90.2% sensitivity and 77.4% specificity in terms of detecting at least 1 prognostic factor by MRI., Conclusion: MRI scanning is valuable in predicting CAI after first-episode LAS for those patients with at least 1 positive clinical finding in the 10-m walk test, anterior drawer test, and inversion tilt test. Further prospective and large-scale studies are necessary for validation., (Copyright © 2023. Production and hosting by Elsevier B.V.)

In this work, the effects of konjac glucomannan (KGM) concentrations on microstructure, gel properties, stability and digestibility of water-in-oil-in-water emulsion gels stabilized by polyglycerol polyricinoleate and whey protein isolate were investigated. Visual appearance indicated that a non-layered double emulsion gel was formed when KGM increased to 0.75%. Emulsion gels with 1.5% KGM showed the highest encapsulation, freeze-thaw and photochemical stability due to the formation of the smallest droplets, which were supported by microscopic observations. Moreover, the addition of KGM improved water holding capacity, rheological and texture properties of emulsion gels. Particularly, at 1.5% or 1.75% KGM, color and potential of hydrogen showed the most stable level after 14 days of storage. During in vitro digestion, KGM delayed the hydrolysis of protein and oil droplets, and then improved the bioavailability of grape seed proanthocyanidin. These results promoted the application of KGM in emulsion gels and the encapsulation of nutraceuticals., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023. Published by Elsevier Ltd.)

The damage or degeneration of spiral ganglion neurons (SGNs) can impair the auditory signals transduction from hair cells to the central auditory system, and cause significant hearing loss. Herein, a new form of bioactive hydrogel incorporating topological graphene oxide (GO) and TEMPO-oxidized bacterial cellulose (GO/TOBC hydrogel) was developed to provide a favorable microenvironment for SGN neurite outgrowth. As the network structure of lamellar interspersed fiber cross-linked by GO/TOBC hydrogels well simulated the structure and morphology of ECM, with the controllable hydrophilic property and appropriate Young's modulus well met those requirements of SGNs microenvironment, the GO/TOBC hybrid matrix exhibited great potential to promote the growth of SGNs. The quantitative real-time PCR result confirmed that the GO/TOBC hydrogel can significantly accelerate the development of growth cones and filopodia, by increasing the mRNA expression levels of diap3, fscn2, and integrin β1. These results suggest that GO/TOBC hydrogel scaffolds have the potential to be used to construct biomimetic nerve grafts for repairing or replacing nerve defects., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Platelet transfusion refractoriness (PTR) remains an intractable issue in clinical practice, and is common in hematological patients. At present, it is believed that both immune and non-immune factors play a role. We conducted a meta-analysis of various risk factors which may contribute to PTR., Methods: PubMed, Embase, Cochrane library, and Web of Science were selected as research database platforms. Citations included were further assessed for quality and bias using the Newcastle-Ottawa Scale. All analyses were performed using Review Manager Version 5.4 and STATA 16.0., Results: The preliminary search revealed 1069 publications, and 17 (5929 patients in total) were ultimately included in the quantitative analysis. The following variables were associated with the occurrence of PTR: fever (OR = 2.26, 95%CI 2.00-2.55, p < 0.00001), bleeding (OR = 2.10, 95%CI 1.36-3.24, p = 0.0008), female sex (OR = 2.06, 95%CI 1.13-3.75, p = 0.02), antibiotic use (OR = 2.94, 95%CI 1.54-5.59, p = 0.001), and infection (OR = 2.19, 95%CI 1.20-4.03, p = 0.01). Antibodies involved in immune activation were a higher risk factor (OR = 4.17, 95%CI 2.36-7.36, p < 0.00001), and splenomegaly was nearly significant (OR = 1.73, 95%CI 0.97-3.07, p = 0.06)., Conclusions: We identified some important risk factors for PTR, but further research is needed to identify the many other possible elements that may contribute to or mediate PTR., (© 2023. Japanese Society of Hematology.)

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy. Several studies have demonstrated the efficacy of caplacizumab in iTTP. However, the effect on different populations remains controversial. Therefore, we performed a systematic review and meta-analysis to assess the effectiveness and safety of caplacizumab for treating iTTP., Materials and Methods: We searched PubMed, Embase, and the Cochrane Library for studies until 24 March 2023. Participants were hospitalized patients with iTTP. Interventions included caplacizumab versus placebo or standard of care (SOC). Outcomes assessed included all-cause mortality, exacerbation, relapse, refractory, time-to-platelet-count-recovery, length of TPE and hospital stay, bleeding, and thrombosis., Results: A total of 1119 patients from eight studies were subjected to meta-analysis. The results of the meta-analysis showed that iTTP patients treated with caplacizumab achieved a reduction in mortality (RR 0.38, 95% CI: 0.19-0.75), exacerbation (RR 0.29, 95% CI: 0.14-0.61) and refractory (RR 0.50, 95% CI: 0.31-0.81). Besides, adding caplacizumab to SOC was associated with a shorten time-to-platelet-count-recovery (MD - 2.31, 95% CI: -3.86 to -0.77) and length of TPE (MD - 4.61, 95% CI: -6.20 to -3.02). In terms of safety, the bleeding rate was higher in the caplacizumab group (RR 1.57, 95% CI: 1.21-2.02), while there was no significant difference in hospital stay and thrombosis between the two groups., Conclusions: Caplacizumab is an effective treatment for patients with iTTP, especially in reducing all-cause mortality, exacerbations, refractoriness, and the time-to-platelet-count-recovery. Although the risk of bleeding may be increased, it is generally modest and manageable.

Background: DNA methylation is a form of epigenetic modification that regulates gene expression. However, there are limited data on the comprehensive analysis of DNA methylation regulated gene mutations (DMRGM) in acute myeloid leukemia (AML) mainly referring to DNA methyltransferase 3α (DNMT3A), isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2), and Tet methylcytidine dioxygenase 2 (TET2)., Results: A retrospective study of the clinical characteristics and gene mutations in 843 newly diagnosed non-M3 AML patients was conducted between January 2016 and August 2019. 29.7% (250/843) of patients presented with DMRGM. It was characterized by older age, higher white blood cell count, and higher platelet count (P < 0.05). DMRGM frequently coexisted with FLT3-ITD, NPM1, FLT3-TKD, and RUNX1 mutations (P < 0.05). The CR/CRi rate was only 60.3% in DMRGM patients, significantly lower than in non-DMRGM patients (71.0%, P = 0.014). In addition to being associated with poor overall survival (OS), DMRGM was also an independent risk factor for relapse-free survival (RFS) (HR: 1.467, 95% CI: 1.030-2.090, P = 0.034). Furthermore, OS worsened with an increasing burden of DMRGM. Patients with DMRGM may be benefit from hypomethylating drugs, and the unfavorable prognosis of DMRGM can be overcome by hematopoietic stem cell transplantation (HSCT). For external validation, the BeatAML database was downloaded, and a significant association between DMRGM and OS was confirmed (P < 0.05)., Conclusion: Our study provides an overview of DMRGM in AML patients, which was identified as a risk factor for poor prognosis., (© 2023. The Author(s).)

Purpose: The aim of this study was to evaluate the relation between anteromedial ankle osteophytes (AMAO) and anteromedial ankle impingement (AMAI) in chronic lateral ankle instability (CLAI) through visualization and quantification., Methods: Forty-three patients with unilateral CLAI between September 2018 and March 2020 accepted arthroscopic repair of an anterior talofibular ligament (ATFL) and were split into two groups: AMAI (AMAI including intraoperative AMAO resection) and pure CLAI (with AMAO but without AMAI, no AMAO resection). The AMAO protrusion lengths in each direction were measured and compared after all of the ankles were reconstructed. All patients were assessed preoperatively and at 2-year follow-up with ankle dorsiflexion, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and visual analog scale (VAS) score., Results: Intelligent analysis showed that a large extent of osteophytes was found at the dorsomedial surface of the talar neck in AMAI group. The upper and inner bound protrusion distances of AMAO in AMAI group were greater than in the pure CLAI group. There was no significant difference in anterior bound protrusion distance of AMAO between the two groups. Preoperatively, the ankle dorsiflexion of AMAI group (7.6 ± 1.4°) was considerably lower than that of pure CLAI group (22.4 ± 1.9°) (p < 0.001). When compared to the pure CLAI group, the AMAI group had a substantially worse AOFAS score (62.2 ± 6.7 vs 71.1 ± 9.1; p < 0.001) and VAS score (6.0 ± 1.0 vs 4.9 ± 0.8; p < 0.05). However, there was no significant difference in postoperative ankle dorsiflexion, AOFAS score, or VAS score between the two groups., Conclusion: AMAO is formed mostly on the dorsomedial surface of the talar neck in CLAI with AMAI, and the upper and inner bound protrusion lengths of AMAO were shown to be significantly correlated with the existence of AMAI in CLAI., (© 2023. The Author(s).)

Introduction: Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe hematopoietic stem cell transplantation complication with high mortality and a poor patient prognosis. The pathogenesis of TA-TMA is not yet clear. In previous studies, the conclusions of different centers remain controversial. We conducted a systematic review and meta-analysis of nine selected risk factors that might be associated with the onset of TA-TMA., Materials and Methods: PubMed databases were searched from their inception up to 15 September 2021, for relevant studies. The articles included unprocessed data related to one or more of the risk factors discussed in this meta-analysis, including recipient gender, donor type, graft source, pretreatment, infection, aGVHD, diagnosis, total body irradiation (TBI), and CMV infection. The outcome is the incidence rate (IR) of TA-TMA., Results and Conclusions: According to the sixteen articles included, risk factors included in this Meta-analysis included gender, unrelated donor source (95% CI: 1.29-2.01), graft source from peripheral blood stem cell (PBSC)(95% CI: 0.48-0.97), RIC/NMA, class II-IV aGVHD (95% CI: 2.22-4.78), nonmalignant disease, TBI. However, inconsistent diagnostic criteria for TA-TMA and the limited number of studies have an impact on the results of the study. More prospective cohort studies and More accurate diagnostic criteria are needed.

Purpose: Appropriate pre-transplant strategies in patients with myelodysplastic syndromes (MDS) remain challenging. We sought to assess the effect of different pre-transplant therapies and transplantation interval times on patient prognosis., Methods: We retrospectively analysed clinical data for 371 consecutive MDS patients after myeloablative transplantation between 2007 and 2019., Results: The median age of the patients was 38 years (range, 12-64 years). A total of 114 patients (31%) received supportive care (SC), 108 (29%) hypomethylating agents (HMAs), and 149 (40%) chemotherapy-based therapy before transplantation. In patients who received HMA or SC, there was no significant difference in overall survival (OS; P=0.151) or relapse-free survival (RFS; P=0.330), except that HMA-treated patients had a lower rate of non-relapse mortality (5-year NRM: 18% vs. 32%, P=0.035). However, compared with patients who received HMA, those who received chemotherapy-based therapy had a lower 5-year OS rate (56% vs. 69%, P=0.020) and a slightly higher 5-year NRM rate (28% vs. 18%, P=0.067). Compared to the delayed transplant group (transplant interval ≥6 months), the early transplant group (transplant interval <6 months) had a superior 5-year OS (66% vs. 51%, P=0.001) and a lower 5-year cumulative incidence of NRM (22% vs. 36%, P=0.001)., Conclusion: The findings of the study indicate that receiving an appropriate pre-transplant strategy (SC/HMA + <6 months) significantly improves OS and decreases NRM in MDS patients after myeloablative transplantation., 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 © 2023 Wang, Wang, Qi, Li, Chu, Qiu, Fu, Tang, Ruan, Wu and Han.)

The NLR family CARD domain containing 3 (NLRC3) gene has been reported to have a crucial effect on immunity, inflammation, and tumorigenesis. However, the clinical relevance of NLRC3 in lung adenocarcinoma (LUAD) remains unclear. This study analyzed both RNA sequencing data and corresponding clinical outcomes obtained from public databases to identify (i) NLRC3 as a tumor suppressor in LUAD and (ii) its predictive value for the likelihood of patient responsiveness to immunotherapy. The results showed that NLRC3 expression was reduced in LUAD and was lower in advanced-stage tumors. Additionally, reduced NLRC3 expression was correlated with worse patient prognosis. The protein level of NLRC3 was also observed to have prognostic significance. Moreover, downregulation of NLRC3 was found to suppress the chemotaxis and infiltration of antitumor lymphocyte subpopulations as well as natural killer cells. Mechanistic analysis indicated that NLRC3 may be involved in immune infiltration by regulating chemokines and their receptors in LUAD. Furthermore, NLRC3 functions as a molecular switch in macrophages, whereby it mediates the polarization of M1 macrophages. Patients with high NLRC3 expression were also found to exhibit a more promising response to immunotherapy. In conclusion, NLRC3 could serve as a potential prognostic biomarker for LUAD, help predict the immunotherapeutic response of patients, and guide personalized strategies for the treatment of LUAD., (© 2023. The Author(s).)

Objectives: With positive outcomes recorded, the mixed reality (MR) technology has lately become popular in orthopedic surgery. However, there are few studies that specifically address the utility of MR in talocalcaneal coalitions (TCC) resection. Our goal in this retrospective study is to assess certain data while examining the viability of using MR to treat TCC resection., Methods: Six consecutive patients with TCC diagnosed by computed tomography (CT) for which nonoperative therapy had failed and MR system assisted TCC resection were included in this study from March 2021 to December 2021. The feasibility and accuracy of TCC resection were assessed by post-operation radiography. The American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score and visual analog scale (VAS) score were used to assess the recovery condition and pain level pre- and post-operation., Results: The surgeon can accurately resect the TCC according to the preoperatively determined range by superimposing the holographic model with the actual anatomy of the TCC using an MR system. Additionally, no additional x-ray was necessary while operating. Mean follow-up was 10.3 months, with a minimum of 6 months. There is a significant difference between the preoperative AOFAS score of 53.4 ± 3.8 and the 6-month follow-up AOFAS score of 97.3 ± 2.2 ( p  < 0.05). There is also a significant difference between the preoperative VAS score of 8.1 ± 0.7 and the 6-month follow-up VAS score of 1.7 ± 0.4 ( p  < 0.05). All individuals had clinical subtalar mobility without stiffness following surgery., Conclusion: While the TCC resection operation is being performed, the application of MR technology is practicable, effective, and radiation-free, giving surgeons satisfactory support., 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., (© 2023 Zhang, Wang, Li, Fu, Gu and Shi.)

Purpose: The common disease hallux valgus results in foot discomfort and dysfunction. Less soft tissue damage and faster wound healing have made minimally invasive surgery (MIS) more popular. However, little research has compared the fixation results of minimally invasive chevron-akin (MICA) osteotomy thus far. In this study, the clinical and radiographic results of MICA with first metatarsal single- or dual-screw fixation are being examined., Methods: A total of 107 feet of 103 patients with mild to moderate symptomatic hallux valgus treated MICA from January 2018 to June 2020 were retrospective evaluated, with at least 12-months follow-up. 51 patients underwent single-screw fixation procedures and 52 patients received dual-screw fixation procedures. Patients were assessed preoperatively and at the final follow-up with radiographic measurements [hallux valgus angle (HVA), intermetatarsal angle (IMA) and distal metatarsal articular angle (DMAA)] and clinical scores (american orthopaedic foot and ankle society (AOFAS) forefoot score, visual analog scale (VAS) and Manchester-Oxford Foot Questionnaire (MOxFQ) scores). The coughlin satisfaction scores were also obtained., Results: Both groups showed significantly improved HVA, IMA and DMAA at the final follow-up ( P  < 0.001). Regarding clinical outcomes, the AOFAS, VAS and MOxFQ in two categories also significantly improved postoperatively ( P  < 0.001). There was no obvious difference in the clinical and radiographic outcomes between the two groups (HVA, P  = 0.833; IMA, P  = 0.073; DMAA, P  = 0.35; AOFAS, P  = 0.48; VAS, P  = 0.86; MOxFQ, P  = 0.87). However, the single-screw fixation group showed significantly lower operation time and less number of intraoperative fluoroscopy ( P  < 0.001). No serious complications were observed in either group. The single-screw fixation technique saves at least $1,086 compared with the dual-screw group., Conclusion: At the final follow-up, both the single- and dual-screw fixation groups had comparable good to excellent clinical and radiographic outcomes, as well as a similar incidence of complications. Additionally, the single-screw fixation group reduces overall surgical costs, number of intraoperative fluoroscopy and operational time., 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. The reviewer CG declared a shared parent affiliation with the authors to the handling editor at the time of review., (© 2023 Li, Zhang, Fu, Wang, Yang and Shi.)

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) is a fatal post-transplant complication. It has a high mortality rate and worse prognosis, but treatment strategies remain controversial. We screened 6 out of 3453 studies on the treatment of TA-TMA. These investigations compared 5 treatment strategies with a network meta-analysis approach. The final outcome was the proportion of patients who responded to these therapies. There were significant differences in response rates for each treatment. Achieving analysis through direct and indirect evidence in the rank probabilities shows that rTM (recombinant human soluble thrombomodulin) is most likely to be rank 1 (64.98%), Eculizumab intervention rank 2 (48.66%), ISM (immunosuppression manipulation) rank 3 (32.24%), TPE (therapeutic plasma exchange) intervention rank 4 (69.56%), and supportive care intervention rank 5 (70.20%). Eculizumab and ISM have significantly higher efficacy than supportive care (odds ratio (OR): 18.04, 18.21 respectively); and TPE having lower efficacy than all other TA-TMA therapies exception to supportive care. In our study, rTM and Eculizumab may be the best choice when treating TA-TMA., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Because of the rising prevalence of anterior talofibular ligament (ATFL) damage, there is a considerable interest in developing innovative techniques to improve the biological healing response of ATFL. Platelet-rich plasma (PRP) includes several growth factors linked to a favorable healing response, however none of the studies involved both quality evaluation and clinical results to evaluate this treatment. Purpose: To determine the clinical results of PRP injections into the ATFL in lateral ankle sprain (LAS) patients, as well as the quality of the ATFL based on radiographic outcomes. Methods: Patients with clinically confirmed grade II LAS for the first time ( n = 83) were examined. The clinical outcomes of three types of injection methods were evaluated: none, once within 48 h after the sprain, and once more 4 weeks later after first injection. PRP was injected into the tear site of the ATFL using ultrasound guidance, and all ankles were immobilized for 2 weeks. The American Orthopedic Foot and Ankle Score (AOFAS) ankle-hindfoot scale and the Visual Analogue Scale (VAS) were used to assess the results at 2, 6, 8, 24, and 48 weeks of follow-up. The signal/noise ratio (SNR) value of Magnetic Resonance Imaging (MRI)-based ATFL signal intensity can disclose ATFL quality. The ATFL SNR results were then assessed 8, 24 and 48 weeks following the first injection to compare ATFL quality. Results: The PRP injection groups outperformed the control group in terms of clinical outcomes, and the two injections group outperformed other groups in terms of pain reduction and functional outcome at 8 weeks. The clinical results of all groups were comparable at 6 and 12 months follow-up. ATFL SNR findings improved significantly across all groups over time. At the same follow-up time, the PRP injection groups outperformed the control group, and the best SNR result showed in the two injections group at the final follow-up. Conclusion: PRP injection helped relieve early symptoms of LAS, although all patients saw a similar development after 6 months. The two PRP injections group produced considerably better clinical results and quality of the ATFL in short-term follow-up., 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 Zhang, Wang, Li, Fu, Gu and Shi.)

Background and Objectives: Platelets are affected by many factors, such as infectious or aseptic inflammation, and different inflammatory states may induce either thrombocytopenia or thrombocytosis. Tumor necrosis factor α (TNFα) is an important inflammatory cytokine that has been shown to affect the activity of hematopoietic stem cells. However, its role in megakaryocyte (MK) development and platelet production remains largely unknown. This study aimed to investigate the effects of TNFα on MK and platelet generation., Methods and Results: The ex vivo study with human CD34 + cells demonstrated that TNFα differentially modulated commitment toward the MK lineage. Specifically, a low concentration of 0.5 ng/ml TNFα promoted MK maturation, proplatelet formation, and platelet production, whereas a high concentration of 10 ng/ml or more TNFα exhibited a substantial inhibitory effect on MK and platelet production. The distinct effect of TNFα on MKs was mainly dependent on TNFα receptor 1. TNFα differentially regulated the MAPK-ERK1/2 signaling pathway and the cytoskeletal proteins cofilin and MLC2. The in vivo study with Balb/c mice indicated that low-dose or high-dose TNFα administration differentially affected short-term platelet recovery after bone marrow transplantation., Conclusions: Our study revealed distinct roles for TNFα in megakaryopoiesis and thrombopoiesis and may provide new insights regarding the treatment for platelet disorders., (© 2022 International Society on Thrombosis and Haemostasis.)

Background: Arthroscopic microfracture for osteochondral lesion of the talus (OLT) has shown good functional outcomes in the short and long term., Purpose: To investigate 5-year radiographic and clinical outcomes after arthroscopic microfracture in treatment of OLT and the effectiveness of adjunct therapies including platelet-rich plasma (PRP) and hyaluronic acid (HA)., Study Design: Cohort study; Level of evidence, 2., Methods: We prospectively enrolled 432 patients who underwent arthroscopic microfracture for OLT from May 1, 2011, to May 31, 2015. Magnetic resonance imaging (MRI) and weightbearing radiographs were performed annually after the initial surgery. The MOCART (magnetic resonance observation of cartilage repair tissue) score was used to evaluate the structure of the repaired cartilage on MRI, and patient-reported outcomes (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale [AOFAS] and the Foot and Ankle Outcome Score) were collected annually. The primary outcome measure was 5-year AOFAS score. We recorded baseline characteristics including age, body mass index (BMI), and lesion size, and other potentially related factors including number of PRP/HA injection and change in BMI from baseline., Results: Included were 355 patients, all with minimum 5-year follow-up data. The overall reoperation rate was 9.0% (32 of 355). According to multivariable analysis, 5-year AOFAS scores were associated with number of PRP injections (correlation coefficient, 3.12 [95% CI, 2.36 to 3.89]; P < .001), BMI at baseline (correlation coefficient, -0.222 [95% CI, -0.363 to -0.082]; P = .002), and mean BMI change from baseline (correlation coefficient, -1.15 [95% CI, -1.32 to -0.98]; P < .001). When comparing number of PRP injections (0, 1-2, or ≥3), we found that patients who had serial PRP injection (≥3 with at least a 3-month interval between injections) had diminished functional and radiographic deterioration over time., Conclusion: Arthroscopic microfracture improved patient-reported and structural outcomes for patients with OLT at 5 years after surgery. Serial PRP injections and reduction in BMI from baseline were able to slow radiographic and functional deterioration. Future trials regarding the combination of microfracture and PRP in treatment of OLT should focus on the efficacy of longer term, intra-articular, serial injections of PRP instead of single injections., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by Ningxia Hui Autonomous Region Key R&D Program (2020BCH01001), Shanghai Science and Technology Innovation Action Plan (20025800200), and Shanghai Municipal Technical and Scientific Commission (19441902400). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane protein epsin3 (EPN3) negatively regulates the expression of HBV RNA. EPN3 expression was induced by transfection of an HBV replicon plasmid, and reduced HBV-RNA level in hepatic cell lines and murine livers hydrodynamically injected with the HBV replicon plasmid. Viral RNA reduction by EPN3 was dependent on transcription, and independent from epsilon structure of viral RNA. Viral RNA reduction by overexpression of p53 or IFN-α treatment, was attenuated by knockdown of EPN3, suggesting its role downstream of IFN-α and p53. Taken together, this study demonstrates the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed., (Copyright © 2022 Li, Wang, Zhou, Fu, Zhang, Sun, Yang, Bai, Dai, Xu, Cui, Zhao, Zhang, Wang, Li, Muramatsu, Wakae and Liu.)

Prolonged isolated thrombocytopenia (PT) is a common complication affecting the outcome of stem cell transplantation. In this study, we undertook a real-world study of 303 myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT) between December 2007 and June 2018. 28.4% of MDS patients suffered from PT after HSCT. Survival analysis indicated that PT was associated with worse overall survival (OS) in MDS patients. The 2-year and 5-year OS in MDS patients with PT after HSCT were 49% and 47%, significantly worse than that of 68% and 60% in patients without PT (P=0.005). For RFS, patients with PT did not have an increased risk of disease relapse (P=0.964). After multivariate adjustment, PT was proved to be the independent risk factor associated with the worse OS (HR 1.49, 95% CI 1.00-2.21, P =0.048). We further analyzed risk factors associated with the occurrence of PT in MDS patients. Multiple logistic regression identified grade II-IV aGVHD, extensive chronic GVHD, hemorrhagic cystitis, and CMV activation as significant risk factors for developing PT. Among these variables, the Odds Ratio (OR) of grade II-IV aGVHD was the highest (P =0.001, OR: 2.65, 95% CI: 1.51-4.64). These data indicated the prognostic value of PT in MDS after HSCT. The identification of risk factors for PT may help improve patient management and lead to the design of effective treatment strategies., 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 Wang, Qi, Li, Chu, Qiu, Fu, Tang, Ruan, Wu and Han.)

ITP is a common autoimmune bleeding disorder with elusive pathogenesis. Our study was implemented to profile the plasma metabolic alterations of patients diagnosed with ITP, aiming at exploring the potential novel biomarkers and partial mechanism of ITP. The metabolomic analysis of plasma samples was conducted using GC-MS on 98 ITP patients and 30 healthy controls (HCs). Age and gender matched samples were selected to enter the training set or test set respectively. OPLS-DA, t-test with FDR correction and ROC analyses were employed to screen out and evaluate the differential metabolites. Possible pathways were enriched based on metabolomics pathway analysis (MetPA). A total of 85 metabolites were investigated in our study and 17 differential metabolites with diagnostic potential were identified between ITP patients and HCs. MetPA showed that the metabolic disorders of ITP patients were mainly related to phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and glyoxylate and dicarboxylate metabolism. Additionally, we discriminated 6 differential metabolites and 5 enriched pathways in predicting the resistance to glucocorticoids in chronic ITP patients. The distinct metabolites discovered in our study could become novel biomarkers for the auxiliary diagnosis and prognosis prediction of ITP. Besides, the dysregulated pathways might contribute to the development of ITP., 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 Zhang, Wu, Zhou, Qi, Zhang, Li, Wang, Ruan and Han.)

Background: Relapse is the leading cause of death from myeloid malignancies after allogeneic hematopoietic stem cell transplantation (HSCT). Azacitidine has gained attention in recent years in the prophylaxis of relapsed refractory hematologic malignancies. This study evaluated the efficacy of AZA in preventing relapse after HSCT in patients with myeloid malignancies., Methods: A systematic review and meta-analysis of all available cohort studies were performed regarding the application of AZA for prophylaxis of relapse after HSCT for advanced MDS and AML. Databases were searched for relevant studies. Endpoints included 2-year relapse rate, survival, relapse-related mortality, as well as the incidence of graft-versus-host disease (GVHD)., Results: A total of 444 patients from 13 studies were included in this analysis. The pooled estimate of the cumulative incidence of relapse after two years in enrolled patients was 25% (95% confidence interval [CI], 18%-33%). The pooled estimates of 2-year survival probabilities were 65% (95% CI, 50%-79%). The pooled cumulative incidence of relapse-related mortality was 28% (95% CI, 22%-34%). The pooled estimated incidence of acute and chronic GVHD, respectively, were 28% (95% CI, 22%-34%) and 38% (95% CI, 27%-49%)., Conclusion: AZA administration is efficacious for relapse prevention after HSCT in myeloid malignancies.

Background: The high success rate, minimal invasion, and safety of subtalar arthroereisis (SA) have made it a primary mode of surgical management for pediatric flexible flatfoot. The HyProCure procedure is a new surgery for SA, However, very few available studies reported the therapeutic effects of the HyProCure procedure, especially in pediatric flexible flatfoot. The main aim of the present study was to investigate the clinical and radiological outcomes of the HyProCure procedure for pediatric flexible flatfoot and analyze the risk factors for therapeutic outcomes and sinus tarsi pain., Methods: In this retrospective cohort study, 69 pediatric flexible flatfoot patients (107 feet) who underwent the HyProCure procedure were included between July 2015 and September 2020. All patients underwent the HyProCure procedure with or without gastrocnemius recession. The Maryland foot score (MFS), visual analog scale (VAS), radiographic data, and complications were assessed at a minimum 1-year follow-up and statistically analyzed., Results: The mean follow-up was 35.9 months (range, 13-73 months). At the last follow-up, VAS (0.64 ± 1.16) was significantly lower than the preoperative VAS (4.06 ± 1.43) ( p < 0.001); MFS (90.39 ± 12.10) was significantly higher than the preoperative MFS (71.36 ± 10.25) ( p < 0.001). The AP talar-second metatarsal angle (T2MT angle) significantly decreased from 17.0 ± 5.4° preoperatively to 11.4 ± 5.2° at the last follow-up ( p < 0.001). The lateral talar-first metatarsal angle (Meary's angle) significantly decreased from 13.8 ± 6.4° preoperatively to 6.3 ± 5.0° at the last follow-up ( p < 0.001). The calcaneal declination angle (Pitch angle) significantly increased from 13.5 ± 4.9° preoperatively to 14.8 ± 4.4° at the last follow-up ( p < 0.001). Logistic regression analysis indicated that patients with a longer distance from the tail end of the implant exceeding the longitudinal talar bisection line had 275.8% greater odds of MFS < 90. Yet, no risk factors were found in connection with sinus tarsi pain., Conclusions: The HyProCure procedure for pediatric flexible flatfoot achieved satisfactory curative effects with a low complication rate; implant depth was associated with unsatisfactory postoperative outcome., 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 Chen, Jiang, Fu, Wang, Su, Mei, Xue, Zou, Li and Shi.)

Thrombocytopenia is a tough complication after hematopoietic stem cell transplantation (HSCT) with elusive pathogenesis and lack of well-established therapies. Thrombopoietin receptor agonists (TPO-RAs) have been used for thrombocytopenia post HSCT in recent years, but the outcomes remain debatable. We conducted this meta-analysis and systematic-review to evaluate the efficacy and safety of TPO-RAs for platelet recovery after HSCT. We searched PubMed, EMBASE, and Cochrane databases for studies on the application of TPO-RAs (eltrombopag and romiplostim) in the settings of primary or secondary thrombocytopenia after HSCT by 17 March 2021. Efficacy outcomes included response rate and survival rate, and adverse events were also evaluated. A total of 19 studies involving 378 patients were included. The pooled response rate was 73% (95%CI: 68-78%), which was significantly higher than recombinant human thrombopoietin (rhTPO) (27.8%). The pooled survival rate was 66% (95%CI: 54-77%), and infection was found to be the main cause of death. In addition, the pooled rate of adverse events was 3% (95%CI: 1-7%), with no severe adverse events reported. TPO-RAs could effectively and safely promote the recovery of platelets in patients after HSCT.

Background: Complement activation plays an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed to evaluate the relationship between mesangial C3 deposition and histologic lesions and to investigate the role of mesangial C3 deposition and serum C3 reduction in predicting renal outcome in IgAN children., Methods: We performed a retrospective cohort study in children with biopsy-proven IgAN. Mesangial C3 deposition (< 2+ vs. ≥ 2+) was detected by the immunofluorescence. Histopathologic kidney grades were determined by the Oxford classification. A decreased serum C3 concentration (hypoC3) was defined when C3 < 90 mg/dl. The endpoint was composite kidney outcome with either a 30% decline in glomerular filtration rates from baseline or kidney failure during the follow-up period., Results: A total of 98 children were analyzed. Mesangial hypercellularity (M) was an independent factor associated with mesangial C3 deposition (HR 3.267; 95% CI 1.028-10.389; P = 0.045). After a median follow-up period of 25 months (interquartile range 18-36 months), 6 (6.1%) children reached the endpoint. Compared with other children, a significantly higher proportion of children with composite kidney outcomes had mesangial C3 deposition ≥ 2+ and hypoC3 (3.4% versus 27.3%, P = 0.002). After adjustment for clinicopathologic risk factors, mesangial C3 deposition ≥ 2+ and hypoC3 were associated with renal outcome (HR 9.772; 95% CI 1.264-75.518; P = 0.029)., Conclusion: Mesangial C3 deposition was associated with M in IgAN. Mesangial C3 deposition and hypoC3 were risk factors for renal outcome in children with IgAN.

Introduction: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of inotuzumab ozogamicin (INO) in patients with relapsed/refractory acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL)., Materials and Methods: Databases (PubMed, EMBASE, and Cochrane databases) were searched through April 4, 2020. Outcome measures of efficacy covered complete remission (CR) rates and minimal residual disease response rates. Safety was evaluated by hepatic venous obstructive disease/sinus obstructive syndrome and grade ≥ 3 hematologic adverse events. We also evaluated the quality of enrolled studies by the Newcastle-Ottawa Quality Assessment Scale., Results: A total of 12 studies involving 644 patients were included. The summary estimates of the CR and minimal residual disease response rates for patients with ALL were 67% (95% confidence interval [CI], 61%-73%) and 45% (95% CI, 37%-53%) of patients with NHL. The pooled CR rate was 28% (95% CI, 15%-47%). Thrombocytopenia and neutropenia were the most common adverse events. In patients receiving INO, venous obstructive disease/sinus obstructive syndrome, grade ≥ 3 thrombocytopenic events, grade ≥ 3 neutropenic events of the pooled estimated incidence were 8% (95% CI, 5%-14%), 29% (95% CI, 20%-39%), and 48% (95% CI, 38%-57%)., Conclusions: According to our study, INO was effective in the treatment of relapsed/refractory ALL and NHL with limited adverse effects. High-quality randomized controlled trials and extensive follow-up are pending to confirm and update the results of this analysis in the future., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAV-N) are related diseases. Galactose-deficient IgA1 (Gd-IgA1) plays an important role in the pathology of IgAV-N and IgAN, so we aim to compare the serum levels of Gd-IgA1 in Chinese pediatric patients with IgAN, IgAV-N, and IgAV., Methods: We retrospectively enrolled 52 patients with IgAN, 57 patients with IgAV-N, 26 patients with IgAV, and 40 healthy children. The serum levels of Gd-IgA1 were measured at the time of biopsy using a lectin-based ELISA method., Results: Gd-IgA1 levels in IgAV-N patients and IgAN patients were higher than in healthy controls (303.94 ± 39.37 U/ml, 314.91 ± 47.79 U/ml vs. 273.57 ± 48.29 U/ml, P < 0.001), and Gd-IgA1 levels in IgAV-N patients were higher than in IgAV patients (303.94 ± 39/ml vs. 286. 21 ± 38.81 U/ml, P = 0.059), but the latter result is not statistically significant. The Gd-IgA1 levels in IgAV patients were comparable with those in healthy controls (286.21 ± 38.81 U/ml vs. 273.57 ± 48.29 U/ml, P = 0.267). Among the four groups, we did not observe significant correlations of Gd-IgA1 levels with eGFR, proteinuria, or the MEST-C score., Conclusion: Serum Gd-IgA1 maybe involved in the pathogenesis of the IgAV-N and IgAN. However, we found no statistically significant correlation between Gd-IgA1 levels and clinical and pathological features.

High-performance dielectric nanomaterials have received increasing attention due to their important applications in the field of energy storage. Among various dielectric materials, polymer nanocomposite is one of the most promising candidates. However, the problems of environmental pollution caused by polymer-based dielectric materials have been extensively studied in recent years, which need to be solved urgently, leading to the search for new biodegradable dielectric materials. Herein, we report composite materials based on biodegradable and renewable chitin and molybdenum disulfide (MoS 2 ) nanosheets for the first time. The MoS 2 nanosheets were first fabricated by glycerol/urea system and then KOH/urea aqueous solution was used to directly dissolve chitin at low temperature together with the dispersion of the MoS 2 nanosheets in a simple green process. The two-dimensional MoS 2 nanosheets possess high polarization strength, and a large specific surface area can enhance the interfacial polarization with chitin; meanwhile, it can serve as a charge breakdown barrier to hinder the propagation of electrical tree branches. The results also show that the dielectric constant and breakdown strength of the chitin/MoS 2 nanocomposites were increased, while the dielectric loss remained low. When the MoS 2 content was 5 wt %, the charge and discharge efficiencies of the composite film were more than 80%, and the breakdown strength also reached 350 MV m -1 , thus resulting in a high discharge energy density of 4.91 J cm -3 , which was more than twice of the neat chitin (2.17 J cm -3 ). Furthermore, the nanocomposite films exhibited good thermal stability. Therefore, these chitin-based nanocomposite films are promising as high-performance biomass-based dielectric capacitors.

We report the light-induced modification of catalytic selectivity for photoelectrochemical CO 2 reduction in aqueous media using copper (Cu) nanoparticles dispersed onto p-type nickel oxide (p-NiO) photocathodes. Optical excitation of Cu nanoparticles generates hot electrons available for driving CO 2 reduction on the Cu surface, while charge separation is accomplished by hot-hole injection from the Cu nanoparticles into the underlying p-NiO support. Photoelectrochemical studies demonstrate that optical excitation of plasmonic Cu/p-NiO photocathodes imparts increased selectivity for CO 2 reduction over hydrogen evolution in aqueous electrolytes. Specifically, we observed that plasmon-driven CO 2 reduction increased the production of carbon monoxide and formate, while simultaneously reducing the evolution of hydrogen. Our results demonstrate an optical route toward steering the selectivity of artificial photosynthetic systems with plasmon-driven photocathodes for photoelectrochemical CO 2 reduction in aqueous media.

Electrochemical reduction of CO 2 to CO offers a promising strategy for regulating the global carbon cycle and providing feedstock for the chemical industry. Understanding the origin that determines the faradaic efficiency (FE) of reduction of CO 2 to CO is critical for developing a highly efficient electrocatalyst. Here, by constructing a single-atom Ni catalyst on nitrogen-doped winged carbon nanofiber (NiSA-NWC), we find that the single-atom Ni catalyst possesses the maximum CO FE of over 95% at -1.6 V vs Ag/AgCl, which is about 30% higher than the standard Ni nanoparticles on the same support. The Tafel analysis reveals that the single-atom Ni catalyst has a preferred reduction of CO 2 to CO and a slower rate for the hydrogen evolution reaction. We propose that the domination of singular Ni 1+ electronic states and limited hydrogen atom adsorption sites on the single-atom Ni catalyst lead to the observed high FE for CO 2 reduction to CO.

Background: There is controversy over whether IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) are the same diseases. This study focuses on the clinicopathological comparison between HSPN and IgAN in children., Methods: Children with IgAN and HSPN who had a diagnostic renal biopsy were enrolled. This study collected the clinical data of patients at biopsy, re-evaluated the pathological lesions of patients according to the Oxford Classification (MEST-C), and made a retrospective comparison between IgAN and HSPN on different stratifications of the course (Tc) and proteinuria., Results: A total of 142 children with IgAN and 57 children with HSPN were enrolled. Various stratification showed the same result, which suggested that IgAN showed more mesangial proliferation (M). HSPN showed more segmental glomerulosclerosis in the Tc > 12 m group than IgAN (S 60.0% vs. 9.10%, P = 0.008). In the non-nephrotic-range and nephrotic-range proteinuria group, there were no significant differences in MEST-C scores between IgAN and HSPN., Conclusion: M is more common in IgAN. HSPN had more S than IgAN over the course of more than 12 months. These results indicate the differences in the pathogenesis in IgAN and HSPN. We propose early biopsy and active treatment of HSPN within 12 months to delay the development of chronic lesions.

Brain ischemia, including cerebral ischemia and cerebrovascular ischemia, leads to poor oxygen supply or cerebral hypoxia, and causes brain tissue death or cerebral infarction/ischemic stroke. The troxerutin and cerebroprotein hydrolysate injection (TCHI), is widely applied in China to improve blood supply in ischemic brain tissues and to enhance neuroprotective effects in clinical practice. However, the benefits and detailed underlying mechanism elaborating the effectiveness of TCHI in cerebrovascular diseases require further investigation. Therefore, in the present study, experimental in vivo and in vitro models were employed to investigate the potential mechanisms of TCHI on cerebral ischemic injury. The results demonstrated that TCHI increased the lactate dehydrogenase levels in the brain homogenate and conversely decreased lactic acid levels. TCHI was further observed to significantly increase superoxide dismutase activity and decrease malondialdehyde levels in ischemic brain tissues. In addition, TCHI significantly induced vascular maturation processes, including proliferation, adhesion, migration and tube formation in cultured human umbilical vein endothelial cells. Additionally, TCHI significantly stimulated microvessel formation in the rat aortic ring and chick chorioallantoic membrane assays. Taken together, these results provided strong evidence that TCHI stimulated angiogenesis at multiple steps, and indicated that TCHI attenuated cerebral ischemic damage through the amelioration of oxidative stress and promotion of angiogenesis.

Industrial scale catalytic chemical synthesis demands both high reaction rates and high product yields. In exothermic chemical reactions, these conflicting objectives require a complex balance of optimized catalysts, high temperatures, high pressures, and multiple recycling steps, as in the energy-intensive Haber-Bosch process for ammonia synthesis. Here we report that illumination of a conventional ruthenium-based catalyst produces ammonia with high reaction rates and high conversion yields. Indeed, using continuous wave light-emitting diodes that simulate concentrated solar illumination, ammonia is copiously produced without any external heating or elevated pressures. The possibility of nonthermal plasmonic effects are excluded by carefully comparing the catalytic activity under direct and indirect illumination. Instead, thermal gradients, created and controlled by photothermal heating of the illuminated catalyst surface, are shown to be responsible for the high reaction rates and conversion yields. This nonisothermal environment enhances both by balancing the conflicting requirements of kinetics and thermodynamics, heralding the use of optically controlled thermal gradients as a universal, scalable strategy for the catalysis of many exothermic chemical reactions.

Background: Rhodomyrtone is one of the main active compounds derived from Rhodomyrtus tomentosa, which belongs to the Myrtaceae family. In the current study, we investigated the properties of rhodomyrtone as a potential drug candidate for the treatment of stress-caused depression., Methods: We assessed the function of rhodomyrtone in chronic unpredictable mild stress, a well-validated depression model in mice. Depression-like behavior tests, including a sucrose performance test, social interaction test, and forced swimming test, were used to validate the antidepressant effects of rhodomyrtone. The Morris water maze was used to evaluate the mice's learning and memory ability. Spine density, glycogen synthase kinase-3β, brain-derived neurotrophic factor, postsynaptic density protein 95, and apoptosis-associated protein were detected to reveal the underlying mechanism., Results: Rhodomyrtone was found to prevent source consumption decrease, decreased social behaviors, and increase immobility in the forced swimming test, suggesting a protective effect of rhodomyrtone against depression-like behaviors. Additionally, rhodomyrtone prevented the impairment of spatial memory in mice exposed to chronic unpredictable mild stress. Rhodomyrtone administration also reversed dendritic spine density defects in chronic unpredictable mild stress. Furthermore, rhodomyrtone inhibited the increase of glycogen synthase kinase-3β activity and reversed the decrease of brain-derived neurotrophic factor and postsynaptic density protein 95 in chronic unpredictable mild stress mice. Elevated expression of apoptosis-associated protein Bax and cleaved-caspase 3 was also reversed by rhodomyrtone treatment., Conclusions: These results suggested that the antidepressant effect of rhodomyrtone involves the regulation of neurogenesis, neuronal survival, and synaptic plasticity in the hippocampus.

Estradiol (E2) is a prime culprit for enhancing the progression of female hormone‑related cancers. Bone marrow‑derived cells (BMDCs) have been found to play a pivotal role in tumor growth. Estrogen receptors (ERs) are also found on certain subtypes of BMDCs, in addition to endothelial cells (ECs) and certain tumor cells. However, the role of BMDCs in E2‑induced tumor biology is still unclear. Thus, the effects of E2 on ER‑negative 4T1 breast cancer growth, the mobilization and recruitment of BMDCs, and interactions among BMDCs, ECs, and 4T1 cells were investigated. The results showed that E2 potentiated 4T1 tumor growth and angiogenesis in mice subjected to sham operation, ovariectomy (OVX), or OVX and E2 replacement treatment. E2 supplementation in mice with OVX upregulated the transcription of stromal cell‑derived factor‑1 (SDF‑1) mRNA in tumor tissues and enhanced the recruitment of BMDCs into tumor tissues in vivo. E2 deficiency significantly decreased proangiogenic CXCR4+, β3+, Sca‑1+ and CXCR4+β3+ BMDCs circulating in the peripheral blood. Cell‑based system analyses showed that E2 augmented the transcription of β3 mRNA in ECs, increased the adhesion of BMDCs to ECs. In addition, E2 enhanced the BMDC‑induced EC proliferation and migration, the BMDC‑induced 4T1 proliferation and the 4T1‑stimulated EC proliferation in addition to enhancing the proliferation of tumor cells and the migration of ECs in vitro. Therefore, E2 enhanced the growth of breast tumors by stimulating tumor cells and ECs directly, as well as by increasing proangiogenic BMDC mobilization and recruitment leading to augmentation of the tumor and EC functions indirectly by cell proliferation assay. These findings reveal a separate mechanism via which E2 promotes the growth of female hormone‑dependent tumors, which may be useful in explorations of new therapies for related cancers.

The electrodeposition of graphene has drawn considerable attention due to its appealing applications for sensors, supercapacitors and lithium-ion batteries. However, there are still some limitations in the current electrodeposition methods for graphene. Here, we present a novel electrodeposition method for the direct deposition of reduced graphene oxide (rGO) with chitosan. In this method, a 2-hydroxypropyltrimethylammonium chloride-based chitosan-modified rGO material was prepared. This material disperses homogenously in the chitosan solution, forming a deposition solution with good dispersion stability. Subsequently, the modified rGO material was deposited on an electrode through codeposition with chitosan, based on the coordination deposition method. After electrodeposition, the homogeneous, deposited rGO/chitosan films can be generated on copper or silver electrodes or substrates. The electrodeposition method allows for the convenient and controlled creation of rGO/chitosan nanocomposite coatings and films of different shapes and thickness. It also introduces a new method of creating films, as they can be peeled completely from the electrodes. Moreover, this method allows for a rGO/chitosan film to be deposited directly onto an electrode, which can then be used for electrochemical detection.

In plasmon-enhanced heterogeneous catalysis, illumination accelerates reaction rates by generating hot carriers and hot surfaces in the constituent nanostructured metals. In order to understand how photogenerated carriers enhance the nonthermal reaction rate, the effects of photothermal heating and thermal gradients in the catalyst bed must be confidently and quantitatively characterized. This is a challenging task considering the conflating effects of light absorption, heat transport, and reaction energetics. Here, we introduce a methodology to distinguish the thermal and nonthermal contributions from plasmon-enhanced catalysts, demonstrated by illuminated rhodium nanoparticles on oxide supports to catalyze the CO 2 methanation reaction. By simultaneously measuring the total reaction rate and the temperature gradient of the catalyst bed, the effective thermal reaction rate may be extracted. The residual nonthermal rate of the plasmon-enhanced reaction is found to grow with a superlinear dependence on illumination intensity, and its apparent quantum efficiency reaches ∼46% on a Rh/TiO 2 catalyst at a surface temperature of 350 °C. Heat and light are shown to work synergistically in these reactions: the higher the temperature, the higher the overall nonthermal efficiency in plasmon-enhanced catalysis.

Photocatalysis has not found widespread industrial adoption, in spite of decades of active research, because the challenges associated with catalyst illumination and turnover outweigh the touted advantages of replacing heat with light. A demonstration that light can control product selectivity in complex chemical reactions could prove to be transformative. Here, we show how the recently demonstrated plasmonic behaviour of rhodium nanoparticles profoundly improves their already excellent catalytic properties by simultaneously reducing the activation energy and selectively producing a desired but kinetically unfavourable product for the important carbon dioxide hydrogenation reaction. Methane is almost exclusively produced when rhodium nanoparticles are mildly illuminated as hot electrons are injected into the anti-bonding orbital of a critical intermediate, while carbon monoxide and methane are equally produced without illumination. The reduced activation energy and super-linear dependence on light intensity cause the unheated photocatalytic methane production rate to exceed the thermocatalytic rate at 350 °C.

Granulocyte-macrophage colony-stimulating factor has been widely used as an adjuvant therapy for cancer patients exhibiting myelosuppression induced by chemotherapy or radiotherapy. However, the effects of granulocyte-macrophage colony-stimulating factor on tumor growth, as well as its precise mechanism, are still controversial due to inconsistent evidence. This study investigated the effect of exogenous granulocyte-macrophage colony-stimulating factor on the growth of B16 melanoma, S180 sarcoma, and U14 cervical carcinoma in mice. The angiogenesis and recruitment of bone-marrow-derived cells were analyzed in tumor tissues. Interactions among granulocyte-macrophage colony-stimulating factor, bone-marrow-derived cells, and B16 tumor cells were investigated in vitro. Proangiogenic types of bone-marrow-derived cells in blood were assessed both in vivo and in vitro. The results showed that granulocyte-macrophage colony-stimulating factor markedly facilitated the growth of B16 and S180 tumors, but not U14 tumors. Granulocyte-macrophage colony-stimulating factor increased the densities of blood vessels and the number of bone-marrow-derived cells in B16 tumor tissues. The granulocyte-macrophage colony-stimulating factor-induced enhancement of tumor cell proliferation was mediated by bone-marrow-derived cells in vitro. Meanwhile, a distinct synergistic effect on endothelial cell function between granulocyte-macrophage colony-stimulating factor and bone-marrow-derived cells was observed. After separating two types of bone-marrow-derived cells, granulocyte-macrophage colony-stimulating factor-induced enhancement of tumor growth and angiogenesis in vivo was mediated by proangiogenic cells in granulocytes, but not monocytes, with CD11b + , vascular endothelial growth factor receptor 2, and C-X-C chemokine receptor 4 granulocytes possibly involved. These data suggest that granulocyte-macrophage colony-stimulating factor contributes to the growth and angiogenesis of certain types of tumor, and these mechanisms are probably mediated by proangiogenic cells in granulocytes. Applying granulocyte-macrophage colony-stimulating factor may attenuate the antitumor effects of chemotherapy and radiotherapy in certain types of tumor.