Clinical, myopathological, and genetic features of two Chinese families with Andersen-Tawil syndrome.

Purpose: To explore the clinical, muscle pathological, and pathogenic gene mutation characteristics of Andersen-Tawil Syndrome (ATS) and enhance the understanding of ATS among clinical practitioners. Methods: Retrospective analysis of clinical data and muscle pathology of two ATS families, along with genetic testing for probands and some family members. Results: In Family 1, spanning four generations, four individuals were affected, while Family 2 had two affected individuals across four generations. All six patients in both families experienced onset in childhood, presenting with periodic paralysis, arrhythmias, and craniofacial skeletal abnormalities. In Family 1, the proband's periodic paralysis was more triggered by low temperature and exercise, occurring several times a year, lasting 4-7 days. All three adult patients in Family 1 had a history of hypokalemia, and the frequency and severity of attacks were reduced after regular oral potassium supplement therapy. Two adult females in Family 1 experienced limb weakness triggered by stress, exertion, and premenstrual period, with milder symptoms than the proband. In Family 2, the proband's periodic paralysis typically occurred the day after excessive exertion, with a frequency of approximately 2-3 months. Two years prior, the proband developed arrhythmias without palpitations or chest tightness. The proband's brother experienced intermittent limb weakness during adolescence, remained untreated, and had sudden death at age 40. Physical examination revealed characteristic features in Family 1 and both probands: small mandible, wide eye spacing, and fifth-digit clinodactyly. Four adult patients were shorter in stature, while the growth status of a pediatric patient was indeterminate. Supplementary tests showed a history of hypokalemia during muscle weakness episodes in Family 1, while Family 2 patients had normal potassium levels during episodes. The long exercise tests were positive in both probands. Muscle MRI showed no significant abnormalities, but muscle pathology revealed rimmed vacuoles and tubular aggregates. Genetic testing identified KCNJ2 gene mutations in two probands and some of their family members, with c.407C > T (p.S136F) heterozygous mutation in Family 1 and c.652C > T (p.R218W) heterozygous mutation in Family 2. Conclusion: Among the clinical symptoms of the patients with Andersen-Tawil Syndrome in this study, not everyone exhibits the full triad of signs: periodic paralysis is the most common initial symptom, craniofacial and digit skeletal abnormalities are characteristic signs, and ventricular arrhythmias pose the most serious potential risk. Given that these typical symptoms were observed in 5 out of 6 patients, clinicians should pay special attention to these typical symptoms, and patients with these symptoms should be followed up over time. Muscle biopsy May reveal pathological changes such as tubular aggregates, but genetic testing for KCNJ gene mutations remains a crucial diagnostic criterion for this syndrome.

Efficacy and safety of PD-1 inhibitors plus anti-angiogenesis tyrosine kinase inhibitors with or without transarterial chemo(embolization) for unresectable hepatocellular carcinoma: a meta-analysis.

Background: The triple combination of programmed cell death protein-1 (PD-1) inhibitors plus anti-angiogenesis tyrosine kinase inhibitors (TKIs) with or without transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) enhance the effect of treatment for unresectable hepatocellular carcinoma (uHCC). The present study compared the efficacy and safety of PD-1 plus TKI with or without transarterial chemo(embolization) for uHCC. Methods: The meta-analysis was conducted using data acquired from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials.gov from the inception date to December 2023. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs) were used to measure the pooled effect. In addition, subgroup analysis was conducted to determine the specific patient population that benefited. Results: The OS (HR = 0.47; 95% CI: 0.39-0.56, P <  0.05), PFS (HR = 0.52; 95% CI: 0.45-0.60, P < 0.05), and ORR (RR = 1.94; 95% CI: 1.60-2.35, P < 0.05) were significantly better in TACE/HAIC+TKI+PD-1(TACE/HAIC TP) group than TKI+PD-1(TP) group. The incidence of AEs was acceptable. Conclusion: The triple therapy of TACE/HAIC TP had better efficacy for uHCC than TP, with acceptable security. Systematic review registration: PROSPERO, identifier CRD42023475953.

Analysis of the Haematological Phenotype and Molecular Characteristics of Rare Abnormal Haemoglobin.

BACKGROUND: Haemoglobinopathy refers to a group of common monogenic inherited conditions associated with variations in the haemoglobin molecule; however, there is relatively limited reporting on abnormal haemoglobinopathy in the Chinese population, especially rare abnormal haemoglobin (Hb). The aim of this study was to explore the clinical characteristics of haemoglobinopathy to supplement data for the epidemiological investigation of Hb variants in Guangdong province of China. METHODS: Peripheral blood was collected from five patients (including a family) for Complete blood count, Hb electrophoresis, High-performance liquid chromatography analysis and degenerative globin body testing. Hb variants were further analysed by PCR and DNA sequencing. RESULTS: The research subjects were diagnosed with different types of abnormal Hb. The blood routine of the Hb Fukuyama (HBB:c.232C>T) diagnosed individual showed microcytic hypochromic anaemia, with a lower Hb level (64 g/L), mean corpuscular volume (MCV) of 71.5 fL and mean corpuscular haemoglobin (MCH) of 21.5 pg. Individuals diagnosed with Hb Port Phillip (HBA2:c.275T>C) exhibit a MCH level that is slightly below average, at 26.4 pg. The Hb Saint Etienne (HBB:c.279C>G) diagnosed individual showed macrocytic hypochromic anaemia, and the proband had a low Hb level (116 g/L), MCV of 102.2 fL and MCH of 29.4 pg. CONCLUSION: We confirmed the presence of Hb Fukuyama (HBB:c.232C>T) in China for the first time. Three rare patients with the Hb Saint Etienne (HBB:c.279C>G) phenotype and one patient with Hb Port Phillip (HBA2:c.275T>C) phenotype were included. Our research enriches the gene mutation map of haemoglobinopathy in Guangdong province and improves the detection system of haemoglobinopathy for population prevention and eugenics.

Prognostic nomogram for the patency of wrist autologous arteriovenous fistula in first year.

Autologous arteriovenous fistula (AVF) is preferred in hemodialysis patients. Maintaining its patency is a critical problem. This study aimed to create a nomogram model for predicting 1-year primary patency of AVF. Consequently, a total of 414 patients were retrospectively enrolled and randomly allocated to training and validation cohorts. Risk factors were identified by multivariable logistic regression and used to create a nomogram model. Performance of the model was evaluated by receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test, and calibration curve. The results suggested that diameter of cephalic vein, low-density lipoprotein, glycosylated hemoglobin (%), and C-reactive protein were risk factors which could predict the patency of AVF. Area under ROC curves for training and validation cohorts were 0.771 and 0.794, respectively. Calibration ability was satisfactory in both cohorts. Therefore, present nomogram model could predict the 1-year primary patency of AVF.

Efficacy and safety of transarterial chemoembolization plus lenvatinib combined with PD-1 inhibitors versus transarterial chemoembolization plus lenvatinib for unresectable hepatocellular carcinoma: a meta-analysis.

Background: Locoregional treatment combined with systemic therapy is expected to play a synergistic anticancer role. We conducted this systemic meta-analysis to examine the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib with or without programmed cell death protein-1 (PD-1) inhibitors (TLP group) compared with TACE + lenvatinib (TL group) for unresectable hepatocellular carcinoma (uHCC). Methods: From the inception date to April 2024, the data from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials. gov were used for meta-analysis. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CI) were used to measure the pooled effect. Results: This study included 10 retrospective cohort studies, including 1128 patients. The OS (HR=0.51; 95% CI: 0.43-0.60, P < 0.05), PFS (HR=0.52; 95% CI: 0.45-0.61, P < 0.05), ORR (RR = 1.58; 95% CI: 1.37-1.83; P < 0.05) and DCR (RR = 1.31; 95% CI: 1.20-1.43; P < 0.05) were significantly higher in TLP group than in the TL group. The incidence of AEs was acceptable. Prognostic factor analysis identified that ECOG PS (1/0), Child-Pugh class (B/A), BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for OS. BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for PFS. Conclusion: The TLP group had better efficacy for uHCC than that of the TL group, with acceptable safety. Systematic review registration: PROSPERO, identifier (CRD42023420093).

One-Step Self-Assembled WO3/rGO Microspheres Photoanode Assembled Efficient Photocatalytic Fuel Cells for Simultaneous Organic Pollutant Degradation and Electricity Generation.

Photocatalytic fuel cells (PFCs) present a promising and environmentally friendly approach to simultaneously treat organic pollutants in wastewater and electricity generation. The development of photoanodes with high light absorption and carrier mobility is essential for enhancing the performance of PFCs but remains challenging. Herein, a one-step self-assembly strategy was adopted to develop flower-like WO3/rGO microspheres for PFC devices. Attributed to the abundant surface-active sites, enhanced light harvesting, and efficient separation of photogenerated charge carriers, the WO3/rGO photoanode demonstrated superior rhodamine B (RhB) degradation rate (90% in 2 h), maximum power density (4.74 µW/cm2), and maximum photocurrent density (0.096 mA/cm2), 1.4, 2.4, and 4.0 times higher than the corresponding pure WO3 photoanode, respectively. Density functional theory (DFT) calculations reveal that the built-in electric field formed between the interface of WO3 and rGO promotes the transfer of photogenerated electrons from WO3 to rGO, thus exerting a significant impact on improving the migration and separation of photoinduced charge carriers. Moreover, by combining experimental and theoretical results, a complete PFC operation mechanism for the PFC system was proposed. This study focuses on the strategy of constructing rGO-doped photocatalysts to enhance the interfacial charge transfer mechanism, providing a promising approach for the development of high-performance photoanodes in PFC systems.

Clinical Effectiveness and Safety of Transarterial Chemoembolization: Hepatic Artery Infusion Chemotherapy Plus Tyrosine Kinase Inhibitors With or Without Programmed Cell Death Protein-1 Inhibitors for Unresectable Hepatocellular Carcinoma-A Retrospective Study.

BACKGROUND: Locoregional treatment with transarterial chemoembolization (TACE) or hepatic artery infusion chemotherapy (HAIC) and systemic targeted immunotherapy with tyrosine kinase inhibitors (TKI) and programmed cell death protein-1 (PD-1) inhibitors in the treatment of unresectable hepatocellular carcinoma (uHCC) have achieved promising efficacy. The retrospective study aimed to evaluate the efficacy and safety of TACE and HAIC plus TKI with or without PD-1 for uHCC. PATIENTS AND METHODS: From November 2020 to February 2024, the data of 44 patients who received TACE-HAIC + TKI + PD-1 (THKP group) and 34 patients who received TACE-HAIC + TKI (THK group) were retrospectively analyzed. Primary outcomes were overall survival (OS) and progress-free survival (PFS), and secondary outcomes were objective response rate (ORR), disease control rate (DCR), conversion rates, and adverse events (AEs). RESULTS: A total of 78 patients were recruited in our single-center study. The patients in THKP group had prolonged median OS [25 months, 95% confidence interval (CI) 24.0-26.0 vs 18 months, 95% CI 16.1-19.9; p = 0.000278], median PFS [16 months, 95% CI 14.1-17.9 vs 12 months 95% CI 9.6-14.4; p = 0.004] and higher ORR (38.6% vs 23.5%, p = 0. 156) and DCR (88.6% vs 64.7%, p = 0.011) compared with those in THK group. Multivariate analysis showed that treatment option and alpha-fetoprotein (AFP) level were independent prognostic factors of OS and PFS. The frequency of AEs were similar between the two groups. CONCLUSIONS: The THKP group had better efficacy for uHCC than the THK group, with acceptable safety.

Structures reveal how SGLT inhibitors work.

Sodium glucose cotransporters (SGLTs) transport glucose against its concentration gradient by harnessing the electrochemical potential gradient of sodium ions. SGLT inhibitors are widely prescribed to treat diabetes and other conditions. Recent structural studies have uncovered how chemically diverse SGLT inhibitors bind and inhibit the transporter at the atomic level.

H2-Promoted Benign Coke Strategy for Dimethyl Ether Carbonylation with Long-Term Stability and High Activity.

Zeolite-catalyzed dimethyl ether (DME) carbonylation provides a novel route to producing methyl acetate (MeOAc). Mordenite (MOR) has drawn significant interest because of its remarkable MeOAc selectivity in DME carbonylation, albeit with limited catalytic stability. Herein, novel MOR-based DME carbonylation catalysts, distinguished by long-term stability and high activity were successfully developed, based on an H2-promoted benign coke strategy. Both the H2 cofeeds and the presence of metal species with hydrogenation capability are demonstrated to be crucial for the regulation of coke depositions. The coke deposits can potentially cover the acid sites in the 12-MR main channels, thereby mitigating the occurrence of undesirable methanol-to-hydrocarbon side reactions. Meanwhile, the elimination of ultralarge coke species under the assistance of H2 and Cu species could ensure smooth mass transfer within the catalyst, contributing to its remarkable catalytic performance. The most highlighted DME carbonylation performance was achieved on coke-mediated CuZn-HMOR with a high MeOAc yield of 0.4-0.5 g·gcat-1·h-1 for over 520 h (over 50× enhancement versus HMOR), exhibiting promising industrial application potential. The current strategy is expected to inspire further research into zeolite-catalyzed reactions, which could be potentially improved by the presence of benign coke.

Protective effect of empagliflozin against palmitate-induced lipotoxicity through AMPK in H9c2 cells.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as novel cardioprotective agents. However, their direct impact on cardiomyocyte injury is yet to be studied. In this work, we investigate the underlying molecular mechanisms of empagliflozin (EMPA), an SGLT2 inhibitor, in mitigating palmitate (PA)-induced cardiomyocyte injury in H9c2 cells. We found that EMPA significantly attenuated PA-induced impairments in insulin sensitivity, ER stress, inflammatory cytokine gene expression, and cellular apoptosis. Additionally, EMPA elevated AMP levels, activated the AMPK pathway, and increased carnitine palmitoyl transferase1 (CPT1) gene expression, which collectively enhanced fatty acid oxidation and reduced stress signals. This study reveals a novel mechanism of EMPA's protective effects against PA-induced cardiomyocyte injury, providing new therapeutic insights into EMPA as a cardioprotective agent.

Causal association of epigenetic aging and osteoporosis: a bidirectional Mendelian randomization study.

BACKGROUND: The relationship between aging and osteoporosis is well established. However, the relationship between the body's physiological age, i.e. epigenetic age, and osteoporosis is not known. Our goal is to analyze the bidirectional causal relationship between epigenetic clocks and osteoporosis using a bidirectional Mendelian randomization study. METHODS: We used SNPs closely associated with GrimAge, Hannum, PhenoAge, and HorvathAge in epigenetic age and SNPs closely associated with femoral neck bone mineral density, lumbar spine bone mineral density, and forearm bone mineral density as instrumental variables, respectively, using the inverse variance weighting method and several other MR methods to assess the bidirectional causal relationship between epigenetic age and osteoporosis. RESULT: There was no evidence of a clear causal relationship of epigenetic age (GrimAge, Hannum, PhenoAge, and HorvathAge) on femoral neck bone mineral density, lumbar spine bone mineral density, and forearm bone mineral density. In reverse Mendelian randomization analysis showed a significant causal effect of lumbar spine bone mineral density on GrimAge: odds ratio (OR) = 0.692, 95% confidence interval (CI) = (0.538-0.890), p = 0.004. The results suggest that a decrease in lumbar spine bone mineral density promotes an acceleration of GrimAge. CONCLUSION: There was no significant bidirectional causal relationship between epigenetic age and osteoporosis A decrease in lumbar spine bone density may lead to an acceleration of the epigenetic clock "GrimAge". Our study provides partial evidence for a bidirectional causal effect between epigenetic age and Osteoporosis.

Study on creep characteristics and component model of saline soil in hexi corridor.

Accurate mastery of the creep characteristics of unsaturated saline soil is extremely important for the long-term stability and safe operation of all types of buildings. In this paper, the research object focused on the saline soil of the Zhangye area, Hexi corridor. The indoor triaxial CU creep test was carried out by means of graded loading to study the creep characteristics of saline soil under different salt content and loading stress. The Merchant and Burgers models were used to predict the creep behavior of the saline soils, and the predicted results were compared with the experimental values. The results showed that the triaxial creep curve of saline soil developed in stage III. Namely, transient creep stage, deceleration creep stage and steady-state creep stage. The creep deformation increases with the increase of salt content and loading stress. The stress-strain isochronous curve has non-linear growth, and the cluster of curves develops from dense to sparse after increasing to long-term strength (100∼150 kPa). The parameters of the Merchant and Burgers model vary with salt content and loading stress, and the creep curve predicted by the Burgers model is closer to the test value.

Apocynin exerts cytoprotective effects on dexamethasone-induced osteoblasts by inhibiting oxidative stress through the Nrf2 signalling pathway.

Steroid-induced femoral head necrosis (SIFHN) is a serious clinical complication that is caused by prolonged or excessive use of glucocorticoids (GCs). Osteoblast apoptosis and osteogenic differentiation dysfunction caused by GC-induced oxidative stress and mitochondrial impairment are strongly implicated in SIFHN. Apocynin (APO) is a kind of acetophenone extracted from an herb. In recent years, APO has received much attention for its antiapoptotic and antioxidant properties. This study aimed to investigate whether APO could protect against SIFHN and explore the mechanism. In our study, low-dose APO had no toxic effects on osteoblasts and restored dexamethasone (Dex)-treated osteoblasts by improving survival, inhibiting OS and restoring mitochondrial dysfunction. Mechanistically, APO alleviated Dex-induced osteoblast injury by activating the Nrf2 pathway, and the use of ML385 to block Nrf2 significantly eliminated the protective effect of APO. In addition, APO could reduce the formation of empty lacunae, restore bone mass and promote the expression of Nrf2 in SIFHN rats. In conclusion, APO protects osteoblasts from Dex-induced oxidative stress and mitochondrial dysfunction through activation of the Nrf2 pathway and may be a beneficial drug for the treatment of SIFHN.

Design and Synthesis of Bistetrazole-Based Energetic Salts Bearing the Nitrogen-Rich Fused Ring.

A series of bistetrazole-based energetic salts bearing a nitrogen-rich fused ring were designed and synthesized. Among them, compounds 4-10 showed good detonation properties and excellent thermostability. By treating nitrogen-rich fused ring 3 with concentrated hydrochloric acid, a new type of Dimroth rearrangement was observed that afforded compound 12 efficiently. This new transformation herein constitutes a valuable addition to the Dimroth rearrangement.

Causal relationships between COVID-19 and osteoporosis: a two-sample Mendelian randomization study in European population.

Introduction: The causal relationship between Coronavirus disease 2019 (COVID-19) and osteoporosis (OP) remains uncertain. We aimed to assess the effect of COVID-19 severity (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, and severe COVID-19) on OP by a two-sample Mendelian randomization (MR) study. Methods: We conducted a two-sample MR analysis using publicly available genome-wide association study (GWAS) data. Inverse variance weighting (IVW) was used as the main analysis method. Four complementary methods were used for our MR analysis, which included the MR-Egger regression method, the weighted median method, the simple mode method, and the weighted mode method. We utilized the MR-Egger intercept test and MR pleiotropy residual sum and outlier (MR-PRESSO) global test to identify the presence of horizontal pleiotropy. Cochran's Q statistics were employed to assess the existence of instrument heterogeneity. We conducted a sensitivity analysis using the leave-one-out method. Results: The primary results of IVW showed that COVID-19 severity was not statistically related to OP (SARS-CoV-2 infection: OR (95% CI) = 0.998 (0.995 ~ 1.001), p = 0.201403; COVID-19 hospitalization: OR (95% CI) =1.001 (0.999 ~ 1.003), p = 0.504735; severe COVID-19: OR (95% CI) = 1.000 (0.998 ~ 1.001), p = 0.965383). In addition, the MR-Egger regression, weighted median, simple mode and weighted mode methods showed consistent results. The results were robust under all sensitivity analyses. Conclusion: The results of the MR analysis provide preliminary evidence that a genetic causal link between the severity of COVID-19 and OP may be absent.

A numerical study of the hemodynamic behavior and gas transport in cardiovascular systems with severe cardiac or cardiopulmonary failure supported by venoarterial extracorporeal membrane oxygenation.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been extensively demonstrated as an effective means of bridge-to-destination in the treatment of patients with severe ventricular failure or cardiopulmonary failure. However, appropriate selection of candidates and management of patients during Extracorporeal membrane oxygenation (ECMO) support remain challenging in clinical practice, due partly to insufficient understanding of the complex influences of extracorporeal membrane oxygenation support on the native cardiovascular system. In addition, questions remain as to how central and peripheral venoarterial extracorporeal membrane oxygenation modalities differ with respect to their hemodynamic impact and effectiveness of compensatory oxygen supply to end-organs. In this work, we developed a computational model to quantitatively address the hemodynamic interaction between the extracorporeal membrane oxygenation and cardiovascular systems and associated gas transport. Model-based numerical simulations were performed for cardiovascular systems with severe cardiac or cardiopulmonary failure and supported by central or peripheral venoarterial extracorporeal membrane oxygenation. Obtained results revealed that: 1) central and peripheral venoarterial extracorporeal membrane oxygenation modalities had a comparable capacity for elevating arterial blood pressure and delivering oxygenated blood to important organs/tissues, but induced differential changes of blood flow waveforms in some arteries; 2) increasing the rotation speed of extracorporeal membrane oxygenation pump (ω) could effectively improve arterial blood oxygenation, with the efficiency being especially high when ω was low and cardiopulmonary failure was severe; 3) blood oxygen indices (i.e., oxygen saturation and partial pressure) monitored at the right radial artery could be taken as surrogates for diagnosing potential hypoxemia in other arteries irrespective of the modality of extracorporeal membrane oxygenation; and 4) Left ventricular (LV) overloading could occur when ω was high, but the threshold of ω for inducing clinically significant left ventricular overloading depended strongly on the residual cardiac function. In summary, the study demonstrated the differential hemodynamic influences while comparable oxygen delivery performance of the central and peripheral venoarterial extracorporeal membrane oxygenation modalities in the management of patients with severe cardiac or cardiopulmonary failure and elucidated how the status of arterial blood oxygenation and severity of left ventricular overloading change in response to variations in ω. These model-based findings may serve as theoretical references for guiding the application of venoarterial extracorporeal membrane oxygenation or interpreting in vivo measurements in clinical practice.

Efficient hydrodeoxygenation of methyl levulinate into pentanoic biofuels over Ru/USY catalysts.

Catalytic hydrodeoxygenation of neat methyl levulinate into pentanoic biofuels is one of the pivotal reactions in biomass valorization. A combined pentanoic acid/methyl pentanoate yield of 92% can be achieved for Ru/USY with a Si/Al ratio of 15 at 220 °C and 40 bar H2. The superior performance of Ru/USY-15 for the efficient production of pentanoic biofuels is attributed to the optimal site balance between the Ru species and strong acid sites (ca. 1 : 5).

Structures of human SGLT in the occluded state reveal conformational changes during sugar transport.

Sodium-Glucose Cotransporters (SGLT) mediate the uphill uptake of extracellular sugars and play fundamental roles in sugar metabolism. Although their structures in inward-open and outward-open conformations are emerging from structural studies, the trajectory of how SGLTs transit from the outward-facing to the inward-facing conformation remains unknown. Here, we present the cryo-EM structures of human SGLT1 and SGLT2 in the substrate-bound state. Both structures show an occluded conformation, with not only the extracellular gate but also the intracellular gate tightly sealed. The sugar substrate are caged inside a cavity surrounded by TM1, TM2, TM3, TM6, TM7, and TM10. Further structural analysis reveals the conformational changes associated with the binding and release of substrates. These structures fill a gap in our understanding of the structural mechanisms of SGLT transporters.

Design and Analysis of a Fluid-Filled RF MEMS Switch.

In the present study, a fluid-filled RF MEMS (Radio Frequency Micro-Electro-Mechanical Systems) switch is proposed and designed. In the analysis of the operating principle of the proposed switch, air, water, glycerol and silicone oil were adopted as filling dielectric to simulate and research the influence of the insulating liquid on the drive voltage, impact velocity, response time, and switching capacity of the RF MEMS switch. The results show that by filling the switch with insulating liquid, the driving voltage can be effectively reduced, while the impact velocity of the upper plate to the lower plate is also reduced. The high dielectric constant of the filling medium leads to a lower switching capacitance ratio, which affects the performance of the switch to some extent. By comparing the threshold voltage, impact velocity, capacitance ratio, and insertion loss of the switch filled with different media with the filling media of air, water, glycerol, and silicone oil, silicone oil was finally selected as the liquid filling medium for the switch. The results show that the threshold voltage is 26.55 V after filling with silicone oil, which is 43% lower under the same air-encapsulated switching conditions. When the trigger voltage is 30.02 V, the response time is 10.12 µs and the impact speed is only 0.35 m/s. The frequency 0-20 GHz switch works well, and the insertion loss is 0.84 dB. To a certain extent, it provides a reference value for the fabrication of RF MEMS switches.

Identification and Validation of Hub Genes in the Stenosis of Arteriovenous Fistula.

Arteriovenous fistula (AVF) is the most widely used hemodialysis vascular access in China. However, stenosis of the AVF limits its use. The mechanism of AVF stenosis is currently unknown. Therefore, the purpose of our study was to explore the mechanisms of AVF stenosis. In this study, we identified the differentially expressed genes (DEGs) based on the Gene Expression Omnibus (GEO) dataset (GSE39488) between venous segments of AVF and normal veins. A protein-protein interaction (PPI) network was constructed to identify hub genes of AVF stenosis. Finally, six hub genes (FOS, NR4A2, EGR2, CXCR4, ATF3, and SERPINE1) were found. Combined with the results of the PPI network analysis and literature search, FOS and NR4A2 were selected as the target genes for further investigation. We validated the bioinformatic results via reverse transcription PCR (RT-PCR) and Western blot analyses on human and rat samples. The expression levels of the mRNA and protein of FOS and NR4A2 were upregulated in both human and rat samples. In summary, we found that FOS may play an important role in AVF stenosis, which could be a potential therapeutic target of AVF stenosis.