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Bcl-2 family proteins play key roles in the intrinsic apoptosis pathway in platelets, with both pro- and antiapoptotic protein expressions regulating survival during ex vivo storage. We detected a significant decrease in antiapoptotic Bcl-xL and increase in proapoptotic Bak expression on the third day of storage and as a result the ratio of Bak:Bcl-xL also decreased. Moreover, we identified an interaction between Bcl-xL and Bak. These shifts corresponded with activation of the apoptotic pathway, suggesting these proteins might play an important role in platelet survival. We then performed bioinformatic analysis to gain insight into protein expression regulation during storage. This identified a potential binding site of the microRNA (miRNA) let-7b in the 3ʹ-UTR of the Bcl-xL gene, which we confirmed by a dual-luciferase reporter assay. We also determined that let-7b was upregulated during platelet storage, and let-7b transfection influenced Bcl-xL and Bak protein, but not mRNA, expression. Together, these data suggest that only posttranscriptional mechanisms are available for regulating gene expression in anucleate platelets.

Selector is considered as a promising solution to solve sneak-path current for high-density 3-Dimensional (3D) memories. However, bidirectional selector with fast speed and long lifetime is still extremely needed. In this work, 2D material of graphene oxide containing epoxide, hydroxyl and carboxyl (-COOH, -OH, >C=O) is assembled with HfO2 to form a flexible bi-layer selector. Interestingly, the selector exhibits excellent uniformity, fast switching speed (~160 ns) and remarkable endurance of ~5×108 cycles. Moreover, no performance degradation is observed for more than 103 times with the bending radii ranging from 40 mm to 20 mm. The high uniformity and excellent endurance may be attributed to the insulating interface layer at the HfO2/GO interface, which plays a vital role on the connection/disrupt of conductive filament (CF). Thus, the incorporation of GO into HfO2 selector may be a feasible way to achieve a promising HfO2-based selector, which have potential applications in high-density 3D integration for flexible electronics.

Sepsis is a heterogeneous syndrome caused by a dysregulated host response during the process of infection. Neutrophils are involved in the development of sepsis due to their essential role in host defense. COVID-19 is a viral sepsis. Disfunction of neutrophils in sepsis has been described in previous studies, however, little is known about the role of microRNA-let-7b (miR-let-7b), toll-like receptor 4 (TLR4), and nuclear factor kappa B (NF-κB) activity in neutrophils and how they participate in the development of sepsis. In this study, we investigated the regulatory pathway of miR-let-7b/TLR4/NF-κB in neutrophils. We also explored the downstream cytokines released by neutrophils following miR-let-7b treatment and its therapeutic effects in cecal ligation and puncture (CLP)-induced septic mice. Six-to-eight-week-old male C57BL/6 mice underwent CLP following treatment with miR-let-7b agomir. Survival (n=10), changes in liver and lungs histopathology (n=4), circulating neutrophil counts (n=4), the liver-body weight ratio (n=4–7), and the lung wet-to-dry ratio (n=5–6) were recorded. We found that overexpression of miR-let-7b could significantly down-regulate the expression of human-derived neutrophilic TLR4 at a post-transcriptional level, a decreased level of proinflammatory factors including interleukin-6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), and an upregulation of anti-inflammatory factor IL-10 in vitro. After miR-let-7b agomir treatment in vivo, neutrophil recruitment was inhibited and thus the injuries of liver and lungs in CLP-induced septic mice were alleviated (p=0.01 and p=0.04, respectively), less weight loss was reduced, and survival in septic mice was also significantly improved (p=0.013). Our study suggested that miR-let-7b could be a potential target of sepsis.

Previous research has found ankle proprioception to be impaired in people with Parkinson's disease (PD). However, the relationship between ankle proprioception and functional mobility in people with PD has not been fully investigated. The purpose of this study was to examine whether ankle proprioception is related to the functional mobility of people with PD. Forty-two participants with mild to moderate PD volunteered. Ankle proprioceptive acuity was measured in standing, by using active movement extent discrimination assessment (AMEDA). Functional mobility measures included the timed-up-and-go test (TUG), 30 s sit-to-stand test (30s-STS) and 10-meter walking test (10MWT). Step length and step cadence were recorded during the 10MWT. No significant correlation was found between ankle proprioceptive discrimination scores and any mobility performance measure in people with PD (−0.20 0.05). However, ankle proprioception scores were significantly correlated with step length (r = 0.38, p < 0.05) and step cadence (r = −0.30, p < 0.05), and were significantly and negatively correlated with the stage of modified Hoehn and Yahr (rho = −0.53, p < 0.01). The lack of relationship between ankle proprioceptive acuity and functional mobility in PD suggests that people with PD may be more limited by reduced sensorimotor integration or may rely more on other sensory input, rather than ankle proprioception, to achieve functional mobility, a finding consistent with sensory reweighting theory. In addition, poorer ankle proprioceptive acuity was associated with decreased step length and increased step cadence, suggesting that the shuffling gait observed in PD may be related to impaired ankle proprioception, which has important clinical implications for gait retraining in people with PD. Given that ankle proprioception was significantly and negatively correlated with the stage of modified Hoehn and Yahr, it may warrant being used as an objective biomarker to monitor the progression of PD.

Background. Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in adults, causing high morbidity and mortality worldwide. In recent years, the prevalence of T2DM has been increasing significantly, and genome-wide association studies (GWAS) have shown that KCNQ1 significantly increases the risk of T2DM. Objective. To find large-scale evidence on whether the KCNQ1rs2237892C⟶T gene polymorphism is associated with T2DM susceptibility. Methods. A comprehensive review of the Chinese and English literature on the association of T2DM with KCNQ1rs2237892 is published by PubMed and Baidu Academic. The included literature was part or all of the studied loci which were evaluated for association with T2DM. Forest plots were made of the included literature to analyze the association of KCNQ1 with polymorphisms of the studied loci, and funnel plots and Egger’s test were used to evaluate the publication bias of the selected included literature. Results. Ten case-control studies including a total of 7027 cases and 8208 controls met our inclusion criteria. Allele (C allele frequency distribution) (OR: 1.19; 95% CI: 0.87,1.62; P

Background. Diabetes is one of the common chronic diseases in which susceptibility is determined by a combination of genetic and environmental factors, and more than 90% of diabetic patients are diabetes mellitus type 2 (T2DM). The existing studies on the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes are inconsistent across populations. Aim. We aim to explore the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes in different populations. Methods. We examined all studies before June 12, 2021, that associated CDKAL1 rs10946398 with T2DM. Heterogeneity was assessed by meta-analysis of allelic inheritance models (A vs. C), dominant inheritance models (AA vs. AC+CC), and recessive inheritance model (AA+AC vs. CC); I2 was used to assess the heterogeneity (if I20.05 indicates that there is no publication bias). Results. Fourteen data totaling 30288 subjects, including 19272 controls and 11016 patients with T2DM, met our inclusion criteria. In the Asian population, the differences were statistically significant (p0.01). In the non-Asian population, the differences were statistically significant (p

We propose a multiband asymmetric acoustic absorption and reflection system constructed from a waveguide and multi-order resonators with different radiant modes. Theoretical and experimental results confirm that the coupling of the dark and bright modes at each resonant frequency enables multiband high-efficiency absorption requiring only two functional units. More interestingly, we demonstrate a hybrid multiband asymmetric system based on customized multi-mode pairs. One side of the hybrid multiband system almost completely absorbs the lower frequency incident sound waves while reflecting the higher frequency ones; conversely, the other side effectively reflects the lower frequency ones and absorbs the higher frequency ones. Our design showcases the flexibility of customized multiband asymmetric absorption and also provides an approach for the design of bidirectional wave-manipulation devices. [ABSTRACT FROM AUTHOR]

As an effective means to improve quality of life and prevent diseases, the demand for probiotics and related products has increased in recent years. However, it is still unclear whether a particular probiotic strain will have similar beneficial effects on healthy adults from different regions. In this study, the probiotic Lactobacillus casei Zhang (LCZ) was consumed by healthy adults from six different Asian regions and the changes in gut microbiota were compared using PacBio single molecule, real-time (SMRT) sequencing technology based on samples collected before, during and after consumption of LCZ. Our results reveal that the effect of LCZ consumption on individuals was closely related to the composition of that individual’s basal gut microbiota. A Gut Microbiota Variability Index (GMVI) was proposed to quantitatively compare the effects of LCZ on human gut microecology. Subjects from Xinjiang and Singapore regions had the highest and lowest GMVI, respectively. In general, consumption of LCZ increased the relative abundance of certain beneficial bacteria such as Lactobacillus, Roseburia, Coprococcus and Eubacterium rectale, while it inhibited growth of certain harmful bacteria such as Blautia and Ralstonia pickettii. In addition, consumption of LCZ was responsible for the conversion of some participants from Prevotella copri/Faecalibacterium prausnitzii (PF) enterotype to Faecalibacterium prausnitzii/Bacteroides dorei (FB) enterotype and consistently increased the abundance of lactic acid bacteria in the gut. It also increased/enhanced phosphate metabolic modules, amino acid transport systems, and isoleucine biosynthesis, but conversely decreased lipopolysaccharide biosynthesis. These changes could have health benefits for healthy adults.

Background: Quantitative flow ratio (QFR) is a novel angiography derived fractional flow reserve (FFR) technique. However, its diagnostic accuracy has only be validated in native coronary lesions but not in vessels after bioresorbable scaffold (BRS) implantation. This study aims to evaluate the diagnostic accuracy of residual QFR in coronary vessels immediately post-BRS implantation. Methods: This is a retrospective, two center, validation cohort study. 73 stable angina patients who received at least one de novo lesion of an everolimus eluting stent (EES)/BRS implantation with subsequent residual FFR assessment were screened. Patients with aorta-ostial stenoses, bridge vessels at the distal segment of targeted vessels, acute coronary syndrome, previous coronary artery bypass grafting, age

Matrix converters have many advantages, including high-efficiency, single-stage AC/AC energy conversion, bidirectional power flow, a near-unity input power factor, sinusoidal three-phase input currents, and sinusoidal three-phase output currents. However, matrix converters have 360 Hz voltage pulsations at the virtual DC-bus, which produce input harmonic currents and output harmonic currents, which cause unsatisfactory responses. To solve the problem of the input harmonic currents, a systematic design of an input three-phase current modulation method and an input three-phase AC filter that uses two different design methods are proposed. In addition, to improve dynamic responses, two predictive speed controllers are investigated and compared, and a predictive current controller is studied to reduce the output harmonic currents. A digital signal processor and an FPGA are used to execute the control algorithms. Several experimental results validate the theoretical analysis and show that the proposed methods effectively improve the power quality of the PMSM drive system and its input power-source quality.

Objective This study was performed to explore the relationship between various clinical factors and the prognosis of limb osteosarcoma. Methods We retrospectively analyzed the clinical data of 336 patients with limb osteosarcoma treated from June 2000 to August 2016 at 7 Chinese cancer centers. Data on the patients’ clinical condition, treatment method, complications, recurrences, metastasis, and prognosis were collected and analyzed. Kaplan–Meier analysis and Cox regression models were used to analyze the data. Results The patients comprised 204 males and 132 females ranging in age from 6 to 74 years (average, 21.1 years). The overall 3- and 5-year survival rates were 65.0% and 55.0%, respectively. The 5-year overall survival rate was 64.0% with standard chemotherapy and 45.6% with non-standard chemotherapy. Cox regression analysis demonstrated that standard chemotherapy, surgery, recurrence, and metastasis were independent factors associated with the prognosis of limb osteosarcoma. Conclusion The survival of patients with limb osteosarcoma can be significantly improved by combining standard chemotherapy and surgery. The overall survival rate can also be improved by adding methotrexate to doxorubicin–cisplatin–ifosfamide triple chemotherapy.

Detection of characteristic species released from over-heated PVC cables may enable early warning of electrical fire. This work identified the major volatile species for over-heated PVC cables, and verified their potential as fire signatures with metal oxide gas sensors. Semi-volatile Dioctyl phthalate (DOP) and 2-Ethylhexanol (2-EH) were found to be ubiquitously present in the cable vapors as major species. Detection of these species and the vapors of overheated cables was accomplished with a metal oxide gas sensor. The response of the gas sensor to the cable vapors resulted mainly from DOP and 2-EH, demonstrating them as effective signature gases for over-heated PVC cables. A gas sensor based on SnO2 nanofibers was prepared with greatly enhanced response to the signature gases. Large-scale simulation tests showed that the nanofiber gas sensor could effectively detect the cable overheating at an early stage.

The blindness caused by cornea diseases has exacerbated many patients all over the world. The disadvantages of using donor corneas may cause challenges to recovering eye sight. Developing artificial corneas with biocompatibility may provide another option to recover blindness. The techniques of making individual artificial corneas that fit the biometric parameters for each person can be used to help these patients effectively. In this study, artificial corneas with different shapes (spherical, aspherical, and biconic shapes) are designed and they could be made by two different hydrogel polymers that form an interpenetrating polymer network for their excellent mechanical strength. Two designed cases for the artificial corneas are considered in the simulations: to optimize the artificial cornea for patients who still wear glasses and to assume that the patient does not wear glasses after transplanting with the optimized artificial cornea. The results show that the artificial corneas can efficiently decrease the imaging blur. Increasing asphericity of the current designed artificial corneas can be helpful for the imaging corrections. The differences in the optical performance of the optimized artificial corneas by using different materials are small. It is found that the optimized artificial cornea can reduce the high order aberrations for the second case.

The matrix converter-based IPMSM drive has 360 Hz virtual DC-bus voltage variations which produce severe stator harmonic currents. To solve this problem, a speed-loop classical periodic controller and two current-loop periodic controllers, including a classical periodic controller and a selective harmonic controller, are proposed in this paper. By using the proposed methods, the harmonic currents are obviously reduced and the speed responses of the IPMSM are clearly improved. A detailed analysis is discussed. A digital signal processor, type SH7237, manufactured by Renesas Electronics Corporation is used for the control algorithms. Experimental results show that those proposed periodic controllers reduce up to nearly 32% of the total harmonic distortion at the stator currents, and also apparently improve the transient, tracking, and repetitive load disturbance speed responses.

DC circuit breaker (DCCB) systems with a DC reactor in series are normally equipped in the voltage-sourced-converter-based multi-terminal DC (VSC–MTDC) systems for DC fault clearance. However, it is revealed that the use of DC reactors could undermine the system damping and deteriorate the system stability. In this paper, a controller based on hybrid sensitivity is proposed to improve the stability of power system and realize the power symmetry of multi-terminal systems. Firstly, based on a generalized MTDC small-signal model, an eigenvalue analysis is performed to provide deep insight into the stability issue imposed by DC reactors. Furthermore, a local controller based on hybrid sensitivity was proposed, and on this basis, a global controller was designed to solve asymmetrical power flow. Finally, a four-terminal VSC–MTDC model was built in Simulink to evaluate the performance of DC-PSS. Simulation results verify the effectiveness of the proposed controller in stabilizing MTDC systems and symmetrizing of power flow.