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A novel nano-hydroxyapatite/bamboo fiber (n-HA/BF) composite membrane was obtained by a simple casting technique. The membrane forming mechanism and the effects of different forming membrane methods, drying methods and n-HA amounts on the properties of n-HA/BF composite membrane were investigated by Fourier Transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), contact angle, electromechanical universal tester, in vitro soaking in simulated body fluid (SBF) and in vitro cell culture experiment. The results demonstrated that the dispersity of n-HA nanoparticles in BF matix was not affected by the prepartion condition, however, the morphologies of membrane was determined by the different preparation conditions owing to different hydrogen bond shrinkage. Moreover, the hydrophilicity of the composite membrane was improved under the condition of the membrane formation in oven, freeze drying and high addition content of n-HA, and the mechanical properties of composite membrane depended on n-HA content. In vitro soaking behavior indicated that the degradability and bone-like apatite deposition could be controlled by different preparation conditions. And the cell proliferation experiment showed that the n-HA/BF composite membranes obtained under different preparation conditions were all non-toxic. The above results indicated that the casting technique could be used to prepare n-HA/BF composite membrane, and the properties of the composite membrane could be controlled by adopting different preparation conditions, which would have a great promising as guide bone tissue regeneration (GBR) membrane, and the study would provide a new application for BF in biomedical field.

Rheumatoid wrist arthritis is a chronic autoimmune disease, resulting in joint deformity and functional impairment. We aimed to compare the wrist synovial ultrasound indices and serum vascular endothelial growth factor (VEGF) level in patients with RA before and after treatment, and to explore the correlation between the two.Forty patients with RA in wrist underwent ultrasound examination to determine wrist synovial thickness, synovial blood flow grade, and synovial artery resistive index (RI) before and after treatment. The serum level of VEGF was detected by enzyme-linked immunosorbent assay. Correlation between synovial ultrasound indices and serum VEGF level was assessed.Pre-treatment synovial thickness, synovial artery RI, and serum VEGF level were 8.60 ± 2.82 mm, 0.62 ± 0.07, and 419.49 ± 19.27 pg/mL, respectively. The corresponding post-treatment levels were 4.05 ± 1.89 mm, 0.83 ± 0.10, and 199.30 ± 16.18 pg/mL. Pre-treatment distribution of synovial blood flow grades was as follows: grade 0, nil; grade I, 1 case; grade II, 17 cases; grade III, 22 cases. The post-treatment distribution was as follows: grade 0, 6 cases; grade I, 23 cases; grade II, 11 cases; and grade III, nil. There were significant differences between pre- and post-treatment wrist synovial thickness, artery RI, and blood flow grading. Wrist synovial thickness and synovial blood flow grade showed a strong positive correlation with serum VEGF level (P 0.01). There was strong negative correlation between wrist synovial artery RI and serum VEGF level (P 0.01).The strong correlation between wrist synovial ultrasound indicators and serum VEGF may be clinically useful for diagnosis and therapy.

Objectives Myocarditis, a health-threatening heart disease, is attracting increasing attention. This systematic study was conducted to study the prevalence of disease through the trends of incidence, mortality, disability-adjusted life years (DALYs) over the last 30 years, which would be helpful for the policymakers to better the choices for reasonable decisions. Methods The global, regional, and national burdens of myocarditis from 1990–2019 were analyzed by using the 2019 Global Burden of Disease (GBD) database. This study on myocarditis produced new findings according to age, sex, and Social-Demographic Index (SDI) by investigating DALYs, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and corresponding estimated annual percentage change (EAPC). Results The number of myocarditis incidence increased by 62.19%, from 780,410 cases in 1990 to 1,265,770 cases in 2019. The ASIR decreased by 4.42% (95%CI, from -0.26% to -0.21%) over the past 30 years. The number of deaths from myocarditis increased by 65.40% from 19,618 in 1990 to 324,490 in 2019, but the ASDR was relatively stable over the investigated period. ASDR increased in low-middle SDI regions (EAPC=0.48; 95%CI, 0.24 to 0.72) and decreased in low SDI regions (EAPC=-0.97; 95%CI, from -1.05 to -0.89). The age-standardized DALY rate decreased by 1.19% (95%CI, from -1.33% to -1.04%) per year. Conclusions Globally, the ASIR and DALY for myocarditis decreased and the ASDR was stable over the past 30 years. The risk of incidences and death cases increased with age. Measures should be taken to control the risk of myocarditis in high-burden regions. Medical supplies should be improved in the high-middle SDI regions and middle SDI regions to reduce the deaths from myocarditis in these regions.

Multiple myeloma (MM) remains incurable due to relapse, although the use of proteasome inhibitors, immunomodulatory drugs, CD38-targeting antibodies, and autologous stem cell transplantation (auto-SCT) significantly improve the clinical outcomes of patients with newly diagnosed MM. In recent years, the introduction of chimeric antigen receptor T-cell (CAR T-cell) therapy has brought hope to patients with refractory and relapsed MM. The graft-versus-myeloma effect of allogeneic SCT provides the possibility for curing a subset of MM patients. In this review, we summarize the recent advances and challenges of cellular immunotherapies for MM, focusing on auto-SCT, allogeneic SCT, and CAR T-cell approaches. We also discuss future directions, and propose a specific algorithm for cellular therapies for MM and probability of minimal residual disease-directed therapy.

In this work, 0.94(K0.48Na0.52)0.935Li0.065NbO3–0.06BaZrO3 (abbreviated as KNLN–0.06BZ) lead-free ceramics were prepared by conventional sintering (CS) and three-step sintering (TSS). The effects of sintering process on the microstructure and piezoelectric properties of ceramics were systematically studied. The result showed that, the ceramic prepared by TSS obtained higher density and better electrical properties compared to the ceramic prepared by CS. As we all know, the formation of defects will have a pinning effect on the domain switching. According to the results of impedance spectroscopy analysis, the ceramics prepared by TSS have fewer oxygen vacancies, which will make domain switching easier at an applied electric field, resulting in more excellent piezoelectric activity. The ceramics prepared by TSS with different sintering conditions showed different properties, but multiple phases may coexist in all ceramic samples according to the analysis of XRD, and the domain can adequately switch at an external electric field due to lower energy barrier at the phase boundary, resulting in high piezoelectric properties of ceramics. Hence, when the sintering condition was 1050 °C/0 min–1150 °C/5 min–1070 °C/20 h, the ceramic samples exhibited an optimal performance of ρ = 4.51 g/cm3, d33 ~ 258 pC/N, kp ~ 0.35, and TC ~ 328 oC. This superior result manifests that the KNLN–0.06BZ ceramic prepared by TSS is a promising ceramic for industrial application.

SummaryWe performed a retrospective analysis to investigate dynamic peri-hematopoietic stem cell transplantation (HSCT) minimal/measurable residual disease (MRD) on outcomes in patients with T-cell acute lymphoblastic leukemia (T-ALL). A total of 271 patients were enrolled and classified into three groups: unchanged negative MRD pre- and post-HSCT group (group A), post-MRD non-increase group (group B), and post-MRD increase group (group C). The patients in group B and group C experienced a higher cumulative incidence of relapse (CIR) (42% vs. 71% vs. 16%, Pvs. 21% vs. 70%, Pvs. 28% vs. 72%, Pvs. 12% vs. 8%, P=0.752). Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR (HR=2.392, 95% CI, 1.816–3.151, PPPversus-host disease (GVHD). This risk scoring system could better distinguish CIR (c=0.730) than that for pre-HSCT MRD (c=0.562), post-HSCT MRD (c=0.616) and pre- and post-MRD dynamics (c=0.648). Our results confirm the outcome predictive value of dynamic peri-HSCT MRD either alone or in combination with other variables for patients with T-ALL.

To obtain nano-hydroxyapatite/poly(lactide-co-glycolide) (n-HA/PLGA) nanocomposite with superior mechanical properties, here, lignin was chosen to surface-modify for n-HA through co-precipitation method. The different reaction conditions of reaction time, phosphorus source, and the lignin addition amount were studied by fourier transformation infrared spectra, X-ray diffraction, the intuitionistic dispersion experiment, transmission electron microscope and thermal gravimetric analysis. The reaction mechanism and the best appropriate reaction condition were obtained. More importantly, the results of electromechanical universal tester, scanning electron microscope, differential scanning calorimetric analyzer, polarized optical microscopy and dynamic mechanical analysis confirmed that the obtained n-HA could greatly increase the mechanical strength of PLGA, owing to the excellent dispersion and promotion crystallization effect. Moreover, in vitro cell culture experimental results indicated that the n-HA surface-modified by lignin was favorable to improve the cell biocompatibility of PLGA. The study suggested that the introduction of lignin was a novel method to acquire a highly dispersed n-HA, which would provide a new idea to achieve the n-HA/PLGA nanocomposite as bone materials in future, and it would pave the way towards a new application of lignin in biomedical field.

The successive discoveries of the cage-like D2d B40−/0 and C3/C2 B39− mark the onset of borospherene chemistry. Based on extensive global minimum searches and first-principles theory calculations, we predict herein the possible existence of the axially chiral cage-like C2 B38+ (1/1′) and C2 B382+ (3/3′) which are novel aromatic members of the borospherene family featuring a B21 boron triple-chain on the waist and four B6 hexagonal holes on the cage surface. Detailed bonding analyses show that the B38+ (1) and B382+ (3) possess 12 and 11 delocalized π bonds over a σ-skeleton, respectively, following the universal bonding pattern of σ + π double delocalization of the borospherene family. Extensive molecular dynamics simulations indicate that both B38+ (1) and B382+ (3) are dynamically stable at 700 K. The IR, Raman, and UV–vis spectra of these cluster cations are computationally simulated to facilitate their future spectral characterizations.

To obtain an ideal guided bone tissue regeneration (GBR) membrane, carboxylated bamboo fiber (BF) was designed to be introduced into the chitosan/nano-hydroxyapatite (CS/n-HA) system by ionic crosslinking to fabricate a novel BF/CS/n-HA composite membranes with different weight ratios. The formation mechanism of the BF/CS/n-HA ternary composite membrane and the effect of BF different contents on the BF/CS/n-HA composite membranes were studied by Fourier Transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), electromechanical universal tester, in vitro soaking in simulated body fluid (SBF). Results demonstrated that CS and modified BF would be ionic crosslinked by electrostatic interaction to form a three dimensional polyelectrolyte structure, meanwhile, n-HA was loaded in the polyelectrolyte structure by hydrogen bonding, which ensured the modified BF/CS/n-HA composite membranes to possess excellent tensile strength, compared to the CS/n-HA and untreated BF/CS/n-HA composite membrane. Moreover, the weight ratio of the modified BF/CS/n-HA of 2:6:2 displayed the highest tensile strength, whose tensile strength was improved by over two folds than that of CS/n-HA composite membrane owing to the most suitable proportion. In addition, in vitro simulated body fluids soaking results indicated that the modified BF/CS/n-HA composite membranes presented different degradation rates and could promote the apatite to deposit by investigating the weight loss, water absorption rate, SEM morphology observation and tensile strength reduce. All results revealed that the ionic crosslinking of carboxylated BF and CS was conducive to fabricate BF/CS/n-HA composite membrane with higher mechanical property, more suitable degradation and better bioactivity, in contrast with the CS/n-HA and untreated BF/CS/n-HA composite membranes, which had a great promising to obtain more satisfactory GBR membrane, moreover, the study would provide a new application for natural BF in the biomedical membrane field. In this manuscript, carboxylated bamboo fiber (BF) was designed to be introduced into the chitosan/nano-hydroxyapatite (CS/n-HA) system to fabricate a novel BF/CS/n-HA composite membranes with different weight ratios. The formation mechanism of the BF/CS/n-HA ternary composite membrane and the effect of modified BF different contents on the BF/CS/n-HA composite membranes were studied, and the main purpose of the study was to explore the feasibility of preparing the new BF/CS/n-HA composite membrane by ionic crosslinking. Results revealed that the ionic crosslinking of carboxylated BF and CS played an essential role in fabricating BF/CS/n-HA composite membrane with higher mechanical properties, more suitable degradation and better bioactivity. The study proved that the carboxylated BF/CS/n-HA composite membrane fabricated by ionic crosslinking had a great potential in obtaining more satisfactory GBR membrane in contrast with the CS/n-HA and untreated BF/CS/n-HA composite membranes, which would open up a new application for natural BF in the biomedical membrane field.

BackgroundBursaphelenchus xylophilusis the causal agent of pine wilt disease (PWD) that has caused enormous ecological and economic losses in China. The mechanism in the interaction between nematodes and pine remains unclear. Plant parasitic nematodes (PPNs) secrete effectors into host plant tissues. However, it is poorly studied that role of effector in the infection of pine wood nematode (PWN).ResultsWe cloned, characterized and functionally validated theB. xylophiluseffector BxML1, containing an MD-2-related lipid-recognition (ML) domain. This protein inhibits immune responses triggered by the molecular pattern BxCDP1 ofB. xylophilus. An insitu hybridization assay demonstrated that BxML1 was expressed mainly in the dorsal glands and intestine ofB. xylophilus. Subcellular localization analysis showed the presence of BxML1 in the cytoplasm and nucleus. Furthermore, number ofB. xylophilusand morbidity of pine were significantly reduced inPinus thunbergiiinfected withB. xylophiluswhen BxML was silenced. Using yeast two-hybrid (Y2H) and coimmunoprecipitation (CoIP) assays, we found that the BxML1 interacts with cyclophilin protein PtCyP1 inP. thunbergii.ConclusionsThis study illustrated that BxML1 plays a critical role in theB. xylophilus–plant interaction and virulence ofB. xylophilus.

Moderate autophagy can remove damaged proteins and organelles. In some inflammatory diseases, autophagy plays a protective role by inhibiting the NOD-like receptor family pyrin domain containing 3(NLRP3). (Pro)renin receptor (PRR, or ATP6AP2) is a critical component of the V-ATPase required for autophagy. It remains controversial about ATP6AP2 in the pathological process. The impact of ATP6AP2 on NLRP3 inflammasome and autophagic flux remains unknown under pressure overload stress. This research explores the potential link between ATP6AP2, autophagic flux, and NLRP3. There was upregulation of ATP6AP2 from 5-day post-TAC, and this expression remained at a high level until 8-weeks post-TAC in wild mice. Meanwhile, autophagic flux switched from early compensatory activation to blocking in the heart failure phase. NLRP3 activation can be seen at 8-week post-TAC. Adenovirus-mediated knockdown of ATP6AP2(shR-ATP6AP2) accelerated the progress of heart failure. After TAC was induced, shR-ATP6AP2 significantly deteriorated heart function and fibrosis compared with the shR-Scr group. Meanwhile, there was an elevated expression of NLRP3 and autophagic flux blockage. A transgenic mouse(Tg) with cardio-restricted ATP6AP2/(P)RR overexpression was constructed. Although high expression in cardiac tissue, there were no spontaneous functional abnormalities under the basal state. Cardiac function, fibrosis, hypertrophy remained identical to the control TAC group. However, SQSTM1/P62 was reduced, which indicated the relief of autophagic flux blockage. Further, Neonatal rat ventricular myocyte (NRVMs) transfected with shR-ATP6AP2 showed more susceptibility than sh-Scr NRVMs to phenylephrine-induced cell death. More reactive oxygen species (ROS) or mito-ROS accumulated in the shR-ATP6AP2 group when phenylephrine stimulation. Blocking NLRP3 activation in vivo partly rescued cardiac dysfunction and fibrosis. In conclusion, ATP6AP2 upregulation is a compensatory response to pressure overload. If not effectively compensated, it compromises autophagic flux, leads to dysfunctional mitochondria accumulation, further produces ROS to activate NLRP3, eventually accelerates heart failure.

Background Human-human (HH) interaction mediated by machines (e.g., robots or passive sensorized devices), which we call human-machine-human (HMH) interaction, has been studied with increasing interest in the last decade. The use of machines allows the implementation of different forms of audiovisual and/or physical interaction in dyadic tasks. HMH interaction between two partners can improve the dyad’s ability to accomplish a joint motor task (task performance) beyond either partner’s ability to perform the task solo. It can also be used to more efficiently train an individual to improve their solo task performance (individual motor learning). We review recent research on the impact of HMH interaction on task performance and individual motor learning in the context of motor control and rehabilitation, and we propose future research directions in this area. Methods A systematic search was performed on the Scopus, IEEE Xplore, and PubMed databases. The search query was designed to find studies that involve HMH interaction in motor control and rehabilitation settings. Studies that do not investigate the effect of changing the interaction conditions were filtered out. Thirty-one studies met our inclusion criteria and were used in the qualitative synthesis. Results Studies are analyzed based on their results related to the effects of interaction type (e.g., audiovisual communication and/or physical interaction), interaction mode (collaborative, cooperative, co-active, and competitive), and partner characteristics. Visuo-physical interaction generally results in better dyadic task performance than visual interaction alone. In cases where the physical interaction between humans is described by a spring, there are conflicting results as to the effect of the stiffness of the spring. In terms of partner characteristics, having a more skilled partner improves dyadic task performance more than having a less skilled partner. However, conflicting results were observed in terms of individual motor learning. Conclusions Although it is difficult to draw clear conclusions as to which interaction type, mode, or partner characteristic may lead to optimal task performance or individual motor learning, these results show the possibility for improved outcomes through HMH interaction. Future work that focuses on selecting the optimal personalized interaction conditions and exploring their impact on rehabilitation settings may facilitate the transition of HMH training protocols to clinical implementations.