The molecular basis of spinocerebellar ataxia type 48 caused by a de novo mutation in the ubiquitin ligase CHIP.

The spinocerebellar ataxias (SCAs) are a class of incurable diseases characterized by degeneration of the cerebellum that results in movement disorder. Recently, a new heritable form of SCA, spinocerebellar ataxia type 48 (SCA48), was attributed to dominant mutations in STIP1 homology and U box-containing 1 (STUB1); however, little is known about how these mutations cause SCA48. STUB1 encodes for the protein C terminus of Hsc70 interacting protein (CHIP), an E3 ubiquitin ligase. CHIP is known to regulate proteostasis by recruiting chaperones via a N-terminal tetratricopeptide repeat domain and recruiting E2 ubiquitin-conjugating enzymes via a C-terminal U-box domain. These interactions allow CHIP to mediate the ubiquitination of chaperone-bound, misfolded proteins to promote their degradation via the proteasome. Here we have identified a novel, de novo mutation in STUB1 in a patient with SCA48 encoding for an A52G point mutation in the tetratricopeptide repeat domain of CHIP. Utilizing an array of biophysical, biochemical, and cellular assays, we demonstrate that the CHIPA52G point mutant retains E3-ligase activity but has decreased affinity for chaperones. We further show that this mutant decreases cellular fitness in response to certain cellular stressors and induces neurodegeneration in a transgenic Caenorhabditis elegans model of SCA48. Together, our data identify the A52G mutant as a cause of SCA48 and provide molecular insight into how mutations in STUB1 cause SCA48.

[Clinical application value of modified Lee grading system to evaluate the degree of foraminal stenosis in patients with intervertebral foraminal lumbar disc herniation].

Objective: To investigate the clinical application value of the modified Lee grading system (abbreviated as the modified system) in evaluating the degree of intervertebral foraminal stenosis(IFS) in patients with foraminal lumbar disc herniations(FLDH). Methods: MRI data of 83 patients with FLDH-IFS (34 patients in the operation group and 49 patients in the conservative group) in Yantai Affiliated Hospital of Binzhou Medical University and Yantai Yantaishan Hospital from March 2018 to February 2021 were retrospectively collected. There were 43 males and 40 females, ranged from 34 to 82 years old, with an average of (61±10) years. MRI images of selected patients were independently evaluated and recorded by two radiologists in a blind method, using both the Lee grading system (abbreviated as Lee system) and the modified system, respectively and each method was evaluated twice. The difference between the evaluation level of the two systems, and the agreement of observer assessments of the two systems were compared, and the correlation between the evaluation level of the two grading systems and the clinical treatment modalities was analyzed. Results: The percentage of nongrade 3 (grade 0-2) patients with effective conservative treatment according to the two grading systems was 94.6 % (139/147) and 64.2 % (170/265), respectively. The percentage of grade 3 patients requiring surgical treatment according to the two grading systems was 69.2 % (128/185) and 61.2 % (41/67), respectively. There was a statistically significant difference between the evaluation levels of the modified system and the Lee system (Z=-5.16, P=0.001). In the Lee system, the intra-observer observation consistency Kappa values of the two radiologists were 0.735 and 0.542, respectively, which were highly and moderately consistent; and the inter-observer observation consistency Kappa values were 0.426-0.521, which were moderate consistency. In the modified system, the intra-observer consistency Kappa values of the two radiologists were 0.900 and 0.921, respectively, and the consistency was almost completely consistent; and the inter-observer consistency Kappa values were 0.783-0.861, which were highly consistent or almost completely consistent. Lee system and clinical treatment modalities was correlative (rs=0.39,P<0.001), and modified system and clinical treatment modalities was correlative (rs=0.61,P<0.001). Conclusion: According to FLDH-IFS, the modified system can comprehensively and accurately grade, with high reliability and reproducibility. The evaluation level has a more significant correlation with clinical treatment modalities.

[Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study].

Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

[Effect of China Children's Asthma Action Plan on exercise in school-age children with bronchial asthma].

Objective: To investigate the effect of China Children's Asthma Action Plan (CCAAP) on the exercise status of school-age children with asthma. Methods: We included 400 school-age asthmatic children as research objects from CCAAP asthma management platform of the Affiliated Hospital of Qingdao University during March 1, 2018 to February 28, 2021 by simple random sampling method. The questionnaires of basic information and international physical activity were applied through WeChat or face to face investigation to collect the basic information and exercise status of the object. There were 346 valid questionnaires included in the study to compare the differences in exercise status and incidence of exercise-related asthma-like symptoms between the good and poor CCAAP application groups. Results: There were 232 (67.05%) and 114 (32.95%) cases in good and poor CCAAP application group, respectively. Age, female proportion and BMI of good CCAAP application group were (8±2) years, 47.0% (109/232) and (19.79±2.32) kg/m2, respectively, no statistic difference comparing to poor CCAAP application group [(8±2) years, 46.5% (53/114) and (19.87±2.43) kg/m2, respectively] (all P values>0.05). In good CCAAP application group, 30.18% (70/232) achieved the standard of moderate (high) intensity exercise per day, no statistic difference comparing to poor CCAAP application group [29.82% (34/112)] (P=0.947); 31.90% (74/232) participated in high-intensity exercise per week, higher than that of poor CCAAP application group [17.54% (20/112)] (P=0.005); incidence of exercise-related asthma-like symptoms was 19.83% (46/232), lower than that of poor CCAAP application group [29.82% (34/112)] (P=0.038). Conclusion: CCAAP promotes the exercise of school-age children with asthma.

The Effects of ß-Pinene, a Pine Needle Oil Monoterpene, on Adenovirus Type 3.

The mechanisms of the inhibitory action of ß-pinene, a pine needle oil monoterpene, on human adenovirus type 3 were studied using cytopathic inhibition test, MTT test, atomic force and laser confocal microscopy. ß-Pinene inhibited the viruses stronger that the reference antiviral medication ribavirin (p<0.05). Inhibition of viral cytopathic effect (CPE) increased with increasing the concentration of ß-pinene, which attested to direct elimination of adenovirus type 3. During viral reproduction phase, ß-pinene significantly inhibited proliferation of adenovirus type 3. Typical signs of adenoviral CPE as cell swelling and rounding were less pronounced in comparison with the control (ribavirin treatment). In addition, elevation of ß-pinene concentration significantly increased the cell survival rate (p<0.05). Laser confocal microscopy showed that fluorescence intensity in the ß-pinene group was significantly lower than in the control group (p<0.01), which was consistent with the results of MTT test, thereby providing additional arguments that ß-pinene affects the virus during the absorption phase. Thus, ß-pinene directly inactivates adenovirus type 3 and impedes its invasion into the cells, but produces no protective effects on cells. Understanding the mode of action of such monoterpenes as ß-pinene is of great importance for the development of new antiviral drugs.

A Mendelian randomization study on the role of serum parathyroid hormone and 25-hydroxyvitamin D in osteoarthritis.

OBJECTIVE: Serum parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D] have been demonstrated to be associated with pathogenesis and progression of osteoarthritis (OA). This study aimed to determine the potential causal relationship between serum PTH and 25(OH)D levels and risk of OA. DESIGN: We applied the two-sample Mendelian randomization (MR) approach to estimate the causal roles of serum PTH and 25(OH)D on OA. The instrumental variables for serum PTH and 25(OH)D were derived from two large genome-wide association studies (GWAS), which included 29,155 and 79,366 individuals, respectively. Summary-level data for overall, hip and knee OA were extracted from a GWAS meta-analysis, including 455,221 individuals. All participants included in this study were from the European population. RESULTS: An inverse association was observed between serum PTH levels and risk of OA (random-effects: Effect = 0.71; 95% CI: 0.54 to 0.92; fixed-effects: Effect = 0.71; 95% CI: 0.61 to 0.82). Stratified by site, serum PTH levels were found to be inversely associated with knee OA (random-effects: Effect = 0.53; 95% CI: 0.41 to 0.68; fixed-effects: Effect = 0.53; 95% CI: 0.41 to 0.68). However, there was no evidence of the causal effect of serum 25(OH)D levels on OA. CONCLUSIONS: The present study indicates an inverse causal relationship between serum PTH concentrations and development of OA. Moreover, a site-specific association was also observed between serum PTH levels and knee OA. The potential mechanisms by which serum PTH affects OA need to be further investigated.

Management of cN0 papillary thyroid microcarcinoma patients according to risk-scoring model for central lymph node metastasis and predictors of recurrence.

BACKGROUND: The role of routine prophylactic central neck dissection (pCND) in clinically lymph node-negative (cN0) papillary thyroid microcarcinoma (PTMC) patients remains controversial. This retrospective study aimed to identify the clinical and pathologic factors of central lymph node metastasis (CLNM) and recurrence in PTMC patients. METHODS: A total of 371 cN0 PTMC patients from two hospitals were retrospectively analyzed. All patients underwent thyroidectomy plus pCND between January 2010 and January 2018. Clinicopathological features were collected, univariate and multivariate analyses were performed to determine the risk factors of CLNM. A scoring model was constructed on the basis of the results of independent risk factors of CLNM. The Cox proportional hazards model was used to analyze the risk factors of recurrence. RESULTS: CLNM occurred in 123 (33.2%) patients. Multivariate analysis showed male, tumor size > 0.75 cm, multifocality, extrathyroidal extension (ETE) and tumor in the middle/lower pole were independent risk predictors of CLNM (P < 0.05). A seven-point risk-scoring model was established to predict the stratified CLNM in cN0 PTMC patients. Multivariate Cox regression model showed ETE, vascular invasion and CLNM were independent risk predictors of recurrence (P < 0.05). CONCLUSION: Our study suggested that routine pCND should be performed for cN0 PTMC patients with score ≥ 3 according to the risk-scoring model. Moreover, patients with risk factors of recurrence should consider more complete treatment and more frequent follow-up.

Total tumor diameter: the neglected value in papillary thyroid microcarcinoma.

BACKGROUND: Tumor multifocality is not uncommon in papillary thyroid carcinoma (PTC), especially in micro-PTC. However, assessing the size of the largest tumor may underestimate effect of additional foci. We aimed to investigate the effect of total tumor diameter (TTD) on clinicopathological features of micro-PTC. METHODS: Data from 442 patients who underwent thyroidectomy with cervical lymph node dissection for PTC were retrospectively analyzed. Patients were classified into subgroups according to multifocality and TTD. The relationships of clinicopathological features among these groups were analyzed. RESULTS: Multifocality was observed in 119 patients (26.9%). TTD > 1 cm and presence of extrathyroidal extension (ETE) were significantly higher in multifocal tumors compared to unifocal tumor (P < 0.001, P = 0.016, respectively). When comparing multifocal micro-PTC with TTD > 1 cm to those with unifocal micro-PTC or multifocal micro-PTC with TTD ≤ 1 cm, the proportions of cases with ETE, central lymph node metastasis (CLNM), and lateral lymph node metastasis (LLNM) were significantly higher (all P < 0.05). There was no significant difference in terms of these parameters between multifocal micro-PTC with TTD > 1 cm and macro-PTC or multifocal macro-PTC. The risk of CLNM was 2.056 (P = 0.044) times higher in multifocal micro-PTC with TTD > 1 cm than in unifocal micro-PTC. CONCLUSION: For multifocal micro-PTC, TTD can better assess the aggressiveness of the tumor. Multifocal micro-PTC with TTD > 1 cm was more aggressive than unifocal micro-PTC or multifocal micro-PTC with TTD ≤ 1 cm.

[Analysis of short-term and long-term clinical outcomes in patients with acute myocardial infarction after one year of coronary stent implantation].

Objective: To observe in-hospital and 1-year prognosis of patients with acute myocardial infarction after one year of coronary stent implantation. Methods: From January 2015 to February 2018, 329 patients with acute myocardial infarction (AMI) after 1 year of coronary artery stent implantation were enrolled and received coronary angiography. These patients were divided into two groups (very late stent thrombosis (VLST) group and denovo group) according to whether the occurrence of acute myocardial infarction was due to stent thrombosis (ST), and in-hospital and long-term (1 year) outcomes were compared between the two groups. The primary end points included cardiac death and recurrent acute myocardial infarction. The secondary study end points included target lesion revascularization (TLR), re-stent thrombosis, heart failure, and stroke. Results: In total, 72.9% of patients with AMI after one year of coronary stent implantation were caused by VLST. There were no significant differences of both primary and secondary end-point events between the two groups during in-hospital period (3.3% vs 3.4%, P=0.987; 5.4% vs 4.5%, P=0.956). After a mean follow-up of 1 year, there were no significant differences of the primary end-point events between the two groups. The secondary end-point events and TLR incidence were higher in the VLST group (16.3% vs 6.7%, P=0.026; 9.6% vs 2.2%, P=0.026). Kaplan and Meier survival analysis showed that there were no significant differences of the 1-year cumulative non-primary and non-secondary end-point survival rates between the two groups (P=0.124 and 0.004, respectively). COX regression analysis showed that heart function ≥Ⅲ level (Killip's) and VLST were independent predictive risk factors for end-point events, while postprocedural thrombolysis in myocardial infarction (TIMI) flow grade 3 was an independent protective factor. Conclusion: In-hospital end points show no significant differences between VLST and denovo groups patients. However, the VLST group patients have a poor prognosis and a higher proportion of TLR after 1 year follow-up. The patients with heart function ≥Ⅲ level (Killip's) or VLST have a poor prognosis, while the patients with postprocedural TIMI flow grade 3 have a good prognosis.

[Analysis of misdiagnosis causes of suprasellar arachnoid cysts].

Objective: To investigate the causes of misdiagnosis of suprasellar arachnoid cysts, analyze its characteristics and put forward the diagnostic basis and differential points. Methods: The clinical data fo 97 cases of suprasellar arachnoid cysts diagnosed and treated in the neurosurgery department of Beijing Tiantan Hospital and Hebei General Hospital from March 2015 to March 2019 were analyzed retrospectively. All patients underwent CT and MRI scans with obstructive hydrocephalus. 13 cases were misdiagnosed, including 7 males and 6 females. First visit age 1-31 years old, with an average age of 6.3 years. There were 10 patients younger than 6 years old. The remaining 15-year-old patients, 31-year-old patients and 26-year-old patients each have one case. 11 cases were misdiagnosed as obstructive hydrocephalus, 2 cases as cystic craniopharyngioma. Results: 13 cases were misdiagnosed and mistreated, 11 cases were treated with intraventricular and abdominal shunt, 9 cases were treated with neuroendoscopy and recovered well. One cases of intracranial hematomas underwent craniotomy again, the hematomas were removed again and the bone slise were decompressed. One case had fissured stable after shunt. There were no operative deaths and no complications in this group. After endoscopic reoperation, CT and/or MRI scans showed that the ventricle narrowed in varying degrees, some of them returned to normal size and the flow of cerebrospinal fluid (cerebrospinal fluid) was unobstruct at the end of magnetic resonance cerebrospinal fluid angiography (MRI) fistula after endoscopic reoperation. Conclusions: The incidence of suprasellar arachnoid cysts is low, it is rare in clinic and it is easy to misdiagnose and mistreate. At present, it is recognized that the best treatment methods are partial resection of endoscope cyst wall, cyst ventricle fistula and third ventricle floor fisthla.

[Isolated biceps tenodesis by double row for pulley lesions].

Objective: To explore clinical outcome of isolated arthroscopic biceps tenodesis by double row for pulley lesions. Methods: Forty-nine patients with pulley lesions were treated from July 2017 to June 2018 in the Department of Sport Medicine, the Affiliated Zhongshan Hospital of Dalian University by isolated arthroscopic biceps tenodesis by double row. Patients were divided into 2 groups according to the intraoperative damage of the pulley system. In group A, there were 16 patients with isolated superior glenohumeral ligament/coracohumeral ligament (SGHL/CHL) complex lesions, including 9 males and 7 females, aged (55±6) years. In group B, there were 33 patients (15 males and 18 females, aged (57±8) years) with SGHL/CHL complex and adjacent supraspinatus tendon and/or subscapularis tendon articular-side partly tears. Patients in two groups were treated with different isolated arthroscopic biceps tenodesis by double row. Constant-Murley shoulder score and pain visual analogue scale (VAS) score were assessed before operation and 3, 6, 12 months after the operation. Postoperative complications were also recorded in two groups. The t test was used to compare the quantitative data within and between two groups. Results: All 49 patients were followed up for 12 to 24 months with an average of (17±6) months. The first-stage healing was achieved in all incisions in the two groups. No surgical complications related to revision, infection, Popeye syndrome and cramping pain were observed in either group. There was 1 case treated by secondary arthroscopy for retrauma in group B. The Constant-Murley shoulder score in group A before the operation was 46±10, and it was increased to 89±9 at the 12 months post operation(t=-22.637, P<0.05); and it was 39±10 and 87±8 before and 12 months after the operation respectively in group B (t=-44.849, P<0.05). The VAS scores in the two groups were both decreased significantly at the 12 months post operation when compared with those before the operation (0.68±0.70 vs 5.25±0.27 and 0.72±0.83 vs 5.69±0.84, respectively) (t=29.007, 37.079, both P<0.05). Conclusion: Isolated arthroscopic biceps tenodesis by double row can relieve pain, recover functions of shoulder joint effectively, and achieve a satisfactory outcome in the treatment of pulley lesions.

[Comparison of graft vessel versus native vessel strategies for late saphenous vein graft disease after coronary artery bypass grafting].

Objective: To compare clinical efficacy of interventional treatment with graft vessel and native coronary artery for patients with late saphenous vein grafts disease(SVGD) after coronary artery bypass grafting (CABG). Methods: A total of 1 608 patients underwent CABG in Tianjin Chest from March 2014 to December 2017 were screened. During the follow-up period, 165 hospitalized patients with recurrence of angina pectoris within one year after CABG, who had at least one narrow vein graft(≥50%) confirmed by the coronary angiography were enrolled. According to the results of angiography and surgeon's clinical experiences, the patients received interventional treatment to vein grafts(grafts group, n=53) or native coronary vessels(native group, n=112). The operation success rate, mortality and incidence of serious complications after interventional treatment in two groups at the time of hospitalization were compared.And the incidence of major adverse cardiovascular events(MACE) in two groups at one year after discharge were also compared. Kaplan-Meier survival curve was used to compare the cumulative event-free survival rates. The risk factors for the MACE in the patients with late SVGD and treated by interventional therapy were analyzed by Cox regression analysis. Results: A total of 165 patients were included for analysis, including 98 males(59.4%). The age was (64.2±7.1) years old. The follow-up time was 12 (8, 12) months. In the grafts group, operation success rate was 90.57%(48/53), and 3 cases(5.66%) suffered from serious complications after interventional treatment, 2 cases(3.77%) died. For native group the operation success rate was 88.39%(99/112), and 7(6.25%) cases suffered from serious complications after interventional treatment, and no deaths. The operation success rate and the incidences of serious complications after interventional treatment in two groups had no statistically significant difference(both P>0.05). The mortality in hospital of native group was lower than that in grafts group(P<0.05). Within 12 months after discharge, there was no statistically significant difference in incidence of MACE of two groups (11.32%(6/53) vs. 10.71%(12/112), P>0.05). Survival analysis showed that the cumulative event-free survival rates in two groups were 73.58% (39/53) and 66.13%(74/112), and there was no statistically significant difference (P>0.05). Cox regression analysis showed acute coronary syndrome (HR=41.203, 95%CI 4.859-349.361, P<0.01), and peripheral vascular diseases (HR=2.808, 95%CI 1.067-7.393, P<0.05) were the risk factors of the MACE for the patients treated by interventional therapy with late SVGD. Conclusion: For the patients with late SVGD after CABG, the success rate of intervention with vein grafts and own coronary vessels are both high with satisfactory safety.The in-hospital mortality of interventional therapy in own coronary vessels is lower than in graft vessel. Patients with acute coronary syndrome and peripheral vascular disease have a poor prognosis.

Anomalous Thermoelectric Effects of ZrTe_{5} in and beyond the Quantum Limit.

Thermoelectric effects are more sensitive and promising probes to topological properties of emergent materials, but much less addressed compared to other physical properties. We study the thermoelectric effects of ZrTe_{5} in a magnetic field. The presence of the nontrivial electrons leads to the anomalous Nernst effect and quasilinear field dependence of thermopower below the quantum limit. In the strong-field quantum limit, both the thermopower and Nernst signal exhibit exotic peaks. At higher magnetic fields, the Nernst signal has a sign reversal at a critical field where the thermopower approaches zero. We propose that these anomalous behaviors can be attributed to the gap closing of the zeroth Landau bands in topological materials with the band inversion. Our understanding to the anomalous thermoelectric properties in ZrTe_{5} opens a new avenue for exploring Dirac physics in topological materials.

Suspended low-loss germanium waveguides for the longwave infrared.

Germanium is a material of high interest for mid-infrared (MIR) integrated photonics due to its complementary metal-oxide-semiconductor (CMOS) compatibility and its wide transparency window covering the 2-15 µm spectral region exceeding the 4 and 8 µm limit of the silicon-on-insulator platform and Si material, respectively. In this Letter, we report suspended germanium waveguides operating at a wavelength of 7.67 µm with a propagation loss of 2.6±0.3 dB/cm. To the best of our knowledge, this is the first demonstration of low-loss suspended germanium waveguides at such a long wavelength. Suspension of the waveguide is achieved by defining holes alongside the core providing access to the buried oxide layer and the underlying Si layer so that they can be wet etched using hydrofluoric acid and tetramethylammonium hydroxide, respectively. Our MIR waveguides create a new path toward long wavelength sensing in the fingerprint region.

Suspended silicon waveguides for long-wave infrared wavelengths.

In this Letter, we report suspended silicon waveguides operating at a wavelength of 7.67 µm with a propagation loss of 3.1±0.3 dB/cm. To our knowledge, this is the first demonstration of low-loss silicon waveguides at such a long wavelength, with loss comparable to other platforms that use more exotic materials. The suspended Si waveguide core is supported by a sub-wavelength grating that provides lateral optical confinement while also allowing access to the buried oxide layer so that it can be wet etched using hydrofluoric acid. We also demonstrate low-loss waveguide bends and s-bends.

Parametric Study and Optimization of Flow Characteristics of Wire-Nonparallel Plate-Type Electrostatic Air Accelerators.

Wire and nonparallel plate electrode-type electrostatic air accelerators have attracted significant interest. The physical process involved in using accelerators is complicated. Moreover, mechanisms are unclear, especially for accelerators with double- and multiwire electrodes. In this study, the two-dimensional (2D) model of a wire-nonparallel plate-type accelerator validated by experiments is established with a finite element method. Onset voltage, average current, and outlet average velocity are analyzed with respect to different parameters. Onset voltage is derived by the proposed quadratic regression extrapolation method. Moreover, current is affected by interference and discharge effects, while velocity is also influenced by the suction effect. For the single-wire electrode, high wind speed can be obtained by either increasing channel slope or placing the wire near the entry section. For the double-wire electrode, velocity can be further increased when one of the wires is placed near the inlet and the distance between the two wires is widened. Comparatively, the velocity of the three-wire electrode is higher with larger gaps between wires and stronger discharge effect. The highest velocity is obtained by the four-wire electrode. Comparisons indicate that higher velocity can be obtained with weaker interference effect, stronger suction effect, and intensified discharge effect. Optimum parameter combinations are considered by the Taguchi method. Consequently, velocity can be enhanced by more than 39% after optimization compared with the reference design.

[Virtual planning and 3D printing modeling for mandibular reconstruction with fibula free flap].

Objective: To evaluate the use of virtual planning and 3D printing modeling in mandibular reconstruction and compare the operation time and surgical outcome of this technique with conventional method. Methods: Between June 2013 and June 2017, A total of 18 patients underwent the mandibular reconstruction with fibula free flap in the Affiliated Hospital of Qingdao University.Among 18 patients, there were 11 males and 7 females with an average age of 36.5 years (21-73 years). Nine patients underwent vascularized fibula flap mandibular reconstruction using virtual planning and 3D printing modeling.Titanium plates were pre-bent using the models and cutting guides which were used for osteotomies.Another 9 patients who underwent mandibular reconstruction using fibula flap without aid of virtual planning and 3D printing models were selected as control group. The operation time was recorded and compared in two groups. Accuracy of reconstruction was measured by superimposing the preoperative image onto the postoperative image of mandible. The selected bony landmark, distance and angle were measured. Results: The mean total operation time were 4.7-6.2(5.5±0.5) h in computer-assisted group and 5.6-7.5(6.6±0.7) h in conventional group, respectively. The operation time was shorter in computer-assisted group. The difference between the preoperative and postoperative intercondylar distances, intergonial angle distances, anteroposterior distances were(2.6±1.4)vs(4.4±1.6)mm, (2.9±1.2)vs(4.7±1.7)mm, (4.2±1.4) vs(5.9±1.8)mm in the computer-assisted and conventional group, respectively. The differences between the preoperative and postoperative mandible were smaller in the computer-assisted group. Conclusions: Virtual planning and 3D printing modeling have the potential to increase mandibular reconstruction accuracy and reduce operation time. We believe that this technology for mandibular reconstruction in selected patients can significantly improve the quality of reconstruction.

Gq-activated fibroblasts induce cardiomyocyte action potential prolongation and automaticity in a three-dimensional microtissue environment.

Cardiac fibroblasts (CFs) are known to regulate cardiomyocyte (CM) function in vivo and in two-dimensional in vitro cultures. This study examined the effect of CF activation on the regulation of CM electrical activity in a three-dimensional (3-D) microtissue environment. Using a scaffold-free 3-D platform with interspersed neonatal rat ventricular CMs and CFs, Gq-mediated signaling was selectively enhanced in CFs by Gαq adenoviral infection before coseeding with CMs in nonadhesive hydrogels. After 3 days, the microtissues were analyzed by signaling assay, histological staining, quantitative PCR, Western blots, optical mapping with voltage- or Ca2+-sensitive dyes, and microelectrode recordings of CF resting membrane potential (RMPCF). Enhanced Gq signaling in CFs increased microtissue size and profibrotic and prohypertrophic markers. Expression of constitutively active Gαq in CFs prolonged CM action potential duration (by 33%) and rise time (by 31%), prolonged Ca2+ transient duration (by 98%) and rise time (by 65%), and caused abnormal electrical activity based on depolarization-induced automaticity. Constitutive Gq activation in CFs also depolarized RMPCF from -33 to -20 mV and increased connexin 43 and connexin 45 expression. Computational modeling confers that elevated RMPCF and increased cell-cell coupling between CMs and CFs in a 3-D environment could lead to automaticity. In conclusion, our data demonstrate that CF activation alone is capable of altering action potential and Ca2+ transient characteristics of CMs, leading to proarrhythmic electrical activity. Our results also emphasize the importance of a 3-D environment where cell-cell interactions are prevalent, underscoring that CF activation in 3-D tissue plays a significant role in modulating CM electrophysiology and arrhythmias.NEW & NOTEWORTHY In a three-dimensional microtissue model, which lowers baseline activation of cardiac fibroblasts but enables cell-cell, paracrine, and cell-extracellular matrix interactions, we demonstrate that selective cardiac fibroblast activation by enhanced Gq signaling, a pathophysiological trigger in the diseased heart, modulates cardiomyocyte electrical activity, leading to proarrhythmogenic automaticity.

Expression patterns of HENMT1 and PIWIL1 in human testis: implications for transposon expression.

This study aimed to define the expression patterns of HENMT1 and PIWI proteins in human testis and investigate their association with transposon expression, infertility sub-type or development of testicular germ cell tumours (TGCTs). Testis biopsies showing normal spermatogenesis were used to identify normal localisation patterns of HENMT1 and PIWIL1 by immunolocalisation and RT-PCR after laser microdissection. 222 testis biopsies representing normal spermatogenesis, hypospermatogenesis, spermatogenic arrests, Sertoli cell-only (SCO) tumours and TGCTs were analysed by RT-qPCR for expression of HENMT1/PIWIL1/PIWIL2/PIWIL3/PIWIL4 and LINE-1 Additionally, HENMT1-overexpressing TCam2 seminoma cell lines were analysed for the same parameters by RT-qPCR. We found that HENMT1 and PIWIL1 are coexpressed in pachytene spermatocytes and spermatids. Expression of HENMT1, PIWIL1 and PIWIL2 was mainly dependent on germ cell content but low levels of expression were also detected in some SCO samples. Levels of HENMT1, PIWIL1 and PIWIL2 expression were low in TGCT. Samples with HENMT1, PIWIL2 and PIWIL4 expression showed significantly (P < 0.05) lower transposon expression compared to samples without expression in the same histological group. HENMT1-overexpressing TCam2 cells showed lower LINE-1 expression than empty vector-transfected control lines. Our findings support that the transposon-regulating function of the piRNA pathway found in the mouse is conserved in adult human testis. HENMT1 and PIWI proteins are expressed in a germ-cell-specific manner and required for transposon control.

Ancestral whole-genome duplication in the marine chelicerate horseshoe crabs.

This corrects the article DOI: 10.1038/hdy.2015.89.