High expression circRALGPS2 in atretic follicle induces chicken granulosa cell apoptosis and autophagy via encoding a new protein

Background The reproductive performance of chickens mainly depends on the development of follicles.Abnor-mal follicle development can lead to decreased reproductive performance and even ovarian disease among chick-ens.Chicken is the only non-human animal with a high incidence of spontaneous ovarian cancer.In recent years,the involvement of circRNAs in follicle development and atresia regulation has been confirmed.Results In the present study,we used healthy and atretic chicken follicles for circRNA RNC-seq.The results showed differential expression of circRALGPS2.It was then confirmed that circRALGPS2 can translate into a protein,named cir-cRALGPS2-212aa,which has IRES activity.Next,we found that circRALGPS2-212aa promotes apoptosis and autophagy in chicken granulosa cells by forming a complex with PARP1 and HMGB1.Conclusions Our results revealed that circRALGPS2 can regulate chicken granulosa cell apoptosis and autophagy through the circRALGPS2-212aa/PARP1/HMGB1 axis.

Gga-miRNA-181-5p family facilitates chicken myogenesis via targeting TGFBR1 to block TGF-βsignaling

MicroRNAs(miRNAs)have been demonstrated to control chicken skeletal muscle growth,however,the potential function of the miR-181-5p family in chicken myogenesis remains largely unknown.Here,our study identified the two chicken(Gallus gallus;Gga)miR-181-5p family members widely expressed in various tissues,specifically miR-181a-5p and miR-181b-5p.Besides,the breast muscles of fast-growing broilers expressed higher levels of miR-181a-5p and miR-181b-5p than those of slow-growing layers.Functionally,miR-181a-5p and miR-181b-5p both promote the expression level of myogenic factors including myogenin(MyoG),myogenic differentiation 1(MyoD1),and myosin heavy chain(MyHC),meanwhile accelerating the myotube formation of skeletal muscle satellite cells(SMSCs).Mechanistically,miR-181a-5p and miR-181b-5p directly bind to the 3′untranslated region(UTR)of the transforming growth factor beta receptor 1(TGFBR1)mRNA,further reducing the expression of TGFBR1.TGFBR1 is a key Transforming growth factor beta(TGF-β)signaling transduction receptor and had a negative function in muscle cell differentiation.Furthermore,knockdown of TGFBR1 facilitated the expression of chicken myogenic factors,boosted myotube formation,and decreased the SMAD family member 2/3(SMAD2/3)phosphorylation in chicken SMSCs.SMAD2/3 are downstream of TGF-βsignaling,and miR-181a-5p and miR-181b-5p could reduce the expression of TGFBR1 to further diminish the SMAD2/3 phosphorylation.Our findings revealed that the miR-181-5p family targets TGFBR1 to break the TGF-βsignaling transduction,which resulted in promoting chicken skeletal muscle development.

Development of a stable attenuated double-mutant of tobacco mosaic virus for cross-protection

Tobacco(Nicotiana tabacum)and tomato(Solanum lycopersicum)are two major economic crops in China.Tobacco mosaic virus(TMV;genus Tobamovirus)is the most prevalent virus infecting both crops.Currently,some widely cultivated tobacco and tomato cultivars are susceptible to TMV and there is no effective strategy to control this virus.Cross-protection can be a safe and environmentally friendly strategy to prevent viral diseases.However,stable attenuated TMV mutants are scarce.In this study,we found that the substitutions in the replicase p126,arginine at position 196(R^(196))with aspartic acid(D),glutamic acid at position 614(E^(614))with glycine(G),serine at position 643(S^(643))with phenylalanine(F),or D at position 730(D^(730))with S,significantly reduced the virulence and replication of TMV.However,only the mutation of S^(643) to F reduced the RNA silencing suppression activity of TMV p126.A double-mutant TMV-E614G-S643F induced no visible symptom and was genetically stable through six successive passages in tobacco plants.Furthermore,our results showed that TMV-E614G-S643F double-mutant could provide effective protection against the wild-type TMV infection in tobacco and tomato plants.This study reports a promising mild mutant for cross-protection to control TMV in tobacco and tomato plants.

An Image Fingerprint and Attention Mechanism Based Load Estimation Algorithm for Electric Power System

With the rapid development of electric power systems,load estimation plays an important role in system operation and planning.Usually,load estimation techniques contain traditional,time series,regression analysis-based,and machine learning-based estimation.Since the machine learning-based method can lead to better performance,in this paper,a deep learning-based load estimation algorithm using image fingerprint and attention mechanism is proposed.First,an image fingerprint construction is proposed for training data.After the data preprocessing,the training data matrix is constructed by the cyclic shift and cubic spline interpolation.Then,the linear mapping and the gray-color transformation method are proposed to form the color image fingerprint.Second,a convolutional neural network(CNN)combined with an attentionmechanism is proposed for training performance improvement.At last,an experiment is carried out to evaluate the estimation performance.Compared with the support vector machine method,CNN method and long short-term memory method,the proposed algorithm has the best load estimation performance.

抵钉座经肛置入法腹部无切口手术与腹腔镜直肠前切除术的对比研究

目的:探讨抵钉座经肛置入法腹部无切口手术(natural orifice specimen extraction surgery,NOSES)与腹腔镜直肠前切除术(laparoscopic anterior rectectomy,LAR)的临床效果比较。方法:回顾性分析2019年1月至2020年1月在菏泽市立医院接受治疗的60例中低位直肠癌患者的临床资料,其中NOSES组(n=30)作为观察组行抵钉座经肛置入法肛门外翻切除标本腹部无切口手术,对照组(n=30)行LAR,对比分析两组术中和术后各临床相关指标。术后随访6~12个月,观察肿瘤复发情况。结果:两组患者手术均顺利完成,无中转开腹病例,两组术中出血量、术中淋巴结清扫数目、术后并发症发生率、肿瘤复发率等差异无统计学意义(P>0.05);NOSES组手术时间、术后疼痛评分、首次下床活动时间、肛门排气时间、首次进食时间、住院时间均优于对照组,差异有统计学意义(P<0.05)。结论:NOSES治疗中低位直肠癌安全可行、效果满意。相比传统腹腔镜手术具有手术时间短、术后疼痛轻、下床活动早、肛门排气早、进食时间早、住院时间短、腹部无切口疤痕、快速康复等优点,而术后并发症及肿瘤复发率无明显增加,值得临床上推广应用。

Designing Right-Turn Vehicle Box as a Supplemental Treatment to Eliminate Conflicts with Pedestrians and Bicycles

Field observations illustrated that, right-turn vehicles stopped at various positions when proceeding within the right-turn lanes, while some of them trespassed on the crosswalks with multiple stops. In this case, pedestrians and bikes (ped/bike) are encountered unsmooth and hazardous crossings when right-turn vehicles encroaching their lanes. Meanwhile, this also causes conflicts between right-turn and through vehicles at the crossing street. To better protect ped/bike at crossings with right-turn vehicles, this paper proposes a concept of “right-turn vehicle box” (RTVB) as a supplemental treatment within right-turn lanes. Sight distance, geometric conditions, and behaviors of vehicles and ped/bike are key factors to consider so as to set up the criteria and to design the suitable treatment. A case study was conducted at an intersection pair in Houston, USA to shape the idea of RTVB, together with driving simulator tests under relevant scenarios. The preliminary crosscheck examination shows that the right-turn vehicle box could possibly provide ped/ bike with smoother and safer crossings. In the interim, the safety and efficiency of right-turn operations were also improved. To further validate the effects, implementation studies should be conducted before the RTVB can make its debut in practice. Future works will focus on the complete warrants and design details of this treatment. Moreover, the concept of “vehicle box” could also be transplanted to other places where turning movement(s) needs assistance or improvements.

Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action

AIM： To study the effects of lysophosphatidic acid （LPA） on proliferation, adhesion, migration, and apoptosis in the human colon cancer cell line, SW480, and its mechanisms of action. METHODS： Methyl tetrazolium assay was used to assess cell proliferation. Flow cytometry was employed to detect cell apoptosis. Cell migration was measured by using a Boyden transweU migration chamber. Cell adhesion assay was performed in 96-well plates according to protocol. RESULTS： LPA significantly stimulated SW480 cell proliferation in a dose-dependent and timeependent manner compared with the control group （P 〈 0.05） while the mitogen-activated protein kinase （MAPK） inhibitor, PD98059, significantly blocked the LPA stimulation effect on proliferation. LPA also significantly stimulated adhesion and migration of SW480 cells in a dosedependent manner （P 〈 0.05）. Rho kinase inhibitor, Y-27632, significantly inhibited the upegulatory effect of LPA on adhesion and migration （P 〈 0.05）. LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs, cisplatin and 5-FU （P 〈 0.05）, but the phosphoinositide 3-kinase （PI3K） inhibitor, LY294002, significantly blocked the protective effect of LPA on apoptosis. CONCLUSION： LPA stimulated proliferation, adhesion,migration of 5W480 cells, and protected from apoptosis. The Ras/Raf-MAPK, G12/13-Rho-RhoA and PI3K- AKT/PKB signal pathways may be involved.

基于Hi-C技术哺乳动物三维基因组研究进展

基因组DNA在细胞核中并不是呈线性的一字排列,而是以三维结构高度折叠并浓缩成染色质的方式储存于核内,具有特定的高级空间结构和构象。高通量染色体构象捕获(high-througnput chromosome conformationcapture, Hi-C)技术于2009年首次被提出,目前已得到大规模运用,使得人们对于三维基因组学有了更深刻的认识。研究表明,哺乳动物基因组三维层级结构单元由大到小依次为染色体疆域(chromosome territory, CT)、染色质区室(chromatin compartment A/B)、拓扑关联结构域(topological associated domain, TAD)和染色质环(chromatin loop),这些层级结构单元在基因转录和表达调控过程中发挥着重要作用。本文基于Hi-C技术从染色质的三维层级结构划分、构象单元作用以及三维基因组在发育、疾病等方面的应用进行阐述,旨在为更深入地了解哺乳动物三维基因组学研究提供参考。

Martentoxin, a large-conductance Ca^(2+)-activated K^+ channel inhibitor, attenuated TNF-α-induced nitric oxide release by human umbilical vein endothelial cells

Martentoxin, a 4,046 Da polypeptide toxin purified from the venom of the scorpion Buthus martensii Karsch, has been demonstrated to block large-conductance Ca2＋-activated K＋ （BKca） channels; however, its biological roles are still largely unknown. In the present study, we investigated the pharmacological effects of martentoxin on regulating the production of nitric oxide induced by TNF-a in human umbilical vein endothelial cells （HU- VECs）. We found that, 1, 10 and 100 ~tmol/L martentoxin decreased nitric oxide production by HUVECs ex- posed to 10 ng/mL TNF for 6, 12 and 24 hours. We further demonstrated that martentoxin inhibited the activity of iNOS and retarded the down-regulation of eNOS mRNA induced by TNF-a. Therefore, martentoxin could be a potential therapeutic agent for vascular diseases.

miRNA sequencing analysis of healthy and atretic follicles of chickens revealed that miR-30a-5p inhibits granulosa cell death via targeting Beclin1

Background:The egg production performance of chickens is affected by many factors,including genetics,nutrition and environmental conditions.These factors all play a role in egg production by affecting the development of follicles.MicroRNAs(miRNAs)are important non-coding RNAs that regulate biological processes by targeting genes or other non-coding RNAs after transcription.In the animal reproduction process,miRNA is known to affect the development and atresia of follicles by regulating apoptosis and autophagy of granulosa cells(GCs).Results:In this study,we identified potential miRNAs in the atretic follicles of broody chickens and unatretic follicles of healthy chickens.We identified gga-miR-30a-5p in 50 differentially expressed miRNAs and found that gga-miR-30a-5p played a regulatory role in the development of chicken follicles.The function of miR-30a-5p was explored through the transfection test of miR-30a-5p inhibitor and miR-30a-5p mimics.In the study,we used qPCR,western blot and flow cytometry to detect granulosa cell apoptosis,autophagy and steroid hormone synthesis.Confocal microscopy and transmission electron microscopy are used for the observation of autophagolysosomes.The levels of estradiol(E2),progesterone(P4),malondialdehyde(MDA)and superoxide dismutase(SOD)were detected by ELISA.The results showed that miR-30a-5p showed a negative effect on autophagy and apoptosis of granulosa cells,and also contributed in steroid hormones and reactive oxygen species(ROS)production.In addition,the results obtained from the biosynthesis and dual luciferase experiments showed that Beclin1 was the target gene of miR-30a-5p.The rescue experiment conducted further confirmed that Beclin1 belongs to the miR-30a-5p regulatory pathway.Conclusions:In summary,after deep miRNA sequencing on healthy and atretic follicles,the results indicated that miR-30a-5p inhibits granulosa cell death by inhibiting Beclin1.

Successful treatment of lichen amyloidosis coexisting with atopic dermatitis by dupilumab:Four case reports

BACKGROUND Lichen amyloidosis(LA)is a chronic,severely pruritic skin disease,which is the most common form of primary cutaneous amyloidosis.The treatment of LA has been considered to be difficult.LA may be associated with atopic dermatitis(AD),and in this setting,the treatment options may be more limited.Herein,we report four cases of LA associated with AD successfully treated by dupilumab.CASE SUMMARY In this article,we describe four cases of patients who presented with recurrent skin rash accompanied by severe generalized intractable pruritus,diagnosed with refractory LA coexisting with chronic AD.Previous treatments had not produced any apparent improvement.Thus,we administered dupilumab injection subcutaneously at a dose of 600 mg for the first time and 300 mg every 2 wk thereafter.Their lesions all markedly improved.CONCLUSION Dupilumab may be a new useful treatment for LA coexisting with AD.

Effect of microRNA-208a on mitochondrial apoptosis of cardiomyocytes of neonatal rats

Objective: To explore the effect and mechanism of microRNA-208a(mi R-208a) in the mitochondrial apoptosis of cardiomyocytes of neonatal rats. Methods: The primary cultured cardiomyocytes of neonatal rats were added into the hypoxia incubator for the hypoxia induction. The overexpression system for mi R-208 a of cardiomyocytes of neonatal rats was built. The l ow cytometry assay was employed to detect the incidence of apoptosis in the overexpressed mi R-208 a. The mitochondrial staining technique was used to detect the change in the mitochondrial morphology of over-expressed mi R-208 a. The bioinformatic analysis was chosen to analyze and predict the target gene of mi R-208 a. Results: Firstly, the primary culture system of cardiomyocytes of neonatal rats was successfully built. The mi R-208 a was over-expressed in cardiomyocytes of neonatal rats by mi R-208 a Mimics. Results of flow cytometry assay showed that the over-expressed mi R-208 a could signii cantly reduce the incidence of apoptosis; while results of mitochondrial staining indicated the change in the mitochondrial morphology of over-expressed mi R-208 a and the mitochondrialfission process was inhibited. In conclusion, it was supposed that mi R-208 a could inhibit the activation of mitochondrialfission process to keep the cardiomyocytes from apoptosis. Conclusions: The over-expressed mi R-208 a can reduce the incidence of apoptosis in the cardiomyocytes of neonatal rats, signii cantly change the mitochondrial morphology and inhibit the mitochondrial fission process.

Systemic Vasculitis:An Important and Underestimated Cause of Malignant Hypertension

Objectives:Malignant hypertension(MHT)is defi ned as severe hypertension accompanied by ischemic failure of one or more organs.The aims of this study were to evaluate the current clinical and etiologic profi les of MHT.Methods:As a retrospective study,we selected all patients admitted to our center from January 2013 to December 2016.Seventy patients with MHT were included.Results:The average age of the patients was 40 years,and more than half of the patients were male(78.57%).There were 24 patients with essential hypertension,accounting for 34.29%of the patients,and 46 with secondary hypertension,accounting for 65.71%of the patients.For secondary MHT,systemic vasculitis(25.57%)was the most common cause,followed by severe obstructive sleep apnea syndrome(15.71%),primary renal parenchymal hypertension(11.43%),primary aldosteronism(7.14%),and Cushing syndrome(1.43%)and nutcracker phenomenon(1.43%).Twenty patients with systemic vasculitis were characterized by severe hypertension accompanied by damage to two or more target organs of differing severity.The levels of white blood cells,hypersensitive C-reactive protein,serum creatinine,and 24-hour urinary protein were above their normal range.Conclusion:Systemic vasculitis may be one of the main causes of MHT,and has been underestimated in the past.In future clinical work,clinicians need to pay more attention to patients with systemic vasculitis.

Robust adaptive control for uncertain systems with discrete and distributed delays

In this paper, a robust adaptive control scheme is proposed for the stabilization of uncertain linear systems with discrete and distributed delays and bounded perturbations. The uncertainty is assumed to be an unknown continuous function with norm-bounded restriction. The perturbation is sector-bounded. Combining with the liner matrix inequality method, neural networks and adaptive control, the control scheme ensures the exponential stability of the closed-loop system for any admissible uncertainty.

Fuzzy Adaptive Control of Delayed High Order Nonlinear Systems

This paper deals with the problem of tracking control for a class of high order nonlinear systems with input delay. The unknown continuous functions of the system are estimated by fuzzy logic systems （FLS）. A state conversion method is introduced to eliminate the delayed input item. By means of the backstepping algorithm, the property of semi-globally uniformly ultimately bounded （SGUUB） of the closed-loop system is achieved. The stability of the closed-loop system is proved according to Lyapunov second theorem on stability. The tracking error is proved to be bounded which ultimately converges to an adequately small compact set. Finally, a computer simulation example of high order nonlinear systems is presented, which illustrates the effectiveness of the control scheme.

Interface and border trapping effects in normally-off Al2O3/AlGaN/GaN MOS-HEMTs with different post-etch surface treatments

Trapping effect in normally-off Al2O3/AlGaN/GaN metal–oxide–semiconductor (MOS) high-electron-mobility transistors (MOS-HEMTs) with post-etch surface treatment was studied in this paper. Diffusion-controlled interface oxidation treatment and wet etch process were adopted to improve the interface quality of MOS-HEMTs. With capacitance–voltage (C–V) measurement, the density of interface and border traps were calculated to be 1.13 × 10^12 cm^−2 and 6.35 × 10^12 cm^−2, effectively reduced by 27% and 14% compared to controlled devices, respectively. Furthermore, the state density distribution of border traps with large activation energy was analyzed using photo-assisted C–V measurement. It is found that irradiation of monochromatic light results in negative shift of C–V curves, which indicates the electron emission process from border traps. The experimental results reveals that the major border traps have an activation energy about 3.29 eV and the change of post-etch surface treatment process has little effect on this major activation energy.

Nomogram for predicting early complications after distal gastrectomy

BACKGROUND Reducing or preventing postoperative morbidity in patients with gastric cancer(GC)is particularly important in perioperative treatment plans.AIM To identify risk factors for early postoperative complications of GC post-distal gastrectomy and to establish a nomogram prediction model.METHODS This retrospective study included 131 patients with GC who underwent distal gastrectomy at the Second Hospital of Shandong University between January 2019 and February 2023.The factors influencing the development of complications after distal gastrectomy in these patients were evaluated using univariate and multivariate logistic regression analysis.Based on the results obtained,a predictive nomogram was established.The nomogram was validated using internal and external(n=45)datasets.Its sensitivity and specificity were established by receiver operating characteristic curve analysis.Decision curve(DCA)analysis was used to determine its clinical benefit and ten-fold overfitting was used to establish its accuracy and stability.RESULTS Multivariate logistic regression analysis showed that hypertension,diabetes,history of abdominal surgery,and perioperative blood transfusion were independent predictors of postoperative complications of distal gastrectomy.The modeling and validation sets showed that the area under the curve was 0.843[95%confidence interval(CI):0.746-0.940]and 0.877(95%CI:0.719-1.000),the sensitivity was 0.762 and 0.778,respectively,and the specificity was 0.809 and 0.944,respectively,indicating that the model had good sensitivity and specificity.The C-indexes of the modeling and validation datasets were 0.843(95%CI:0.746-0.940)and 0.877(95%CI:0.719-1.000),respectively.The calibration curve(Hosmer Lemeshow test:χ^(2)=7.33)showed that the model had good consistency.The results of the DCA analysis indicated that this model offered good clinical benefits.The accuracy of 10-fold cross-validation was 0.878,indicating that the model had good accuracy and stability.CONCLUSION The nomogram prediction model based on independent risk factors related to postoperative complications of distal gastrectomy can facilitate perioperative intervention for high-risk populations and reduce the incidence of postoperative complications.

Method of evaluating interface traps in Al2O3/AlGaN/GaN high electron mobility transistors

In this paper, the interface states of the AlGaN/GaN metal–insulator–semiconductor(MIS) high electron mobility transistors(HEMTs) with an Al2 O3 gate dielectric are systematically evaluated. By frequency-dependent capacitance and conductance measurements, trap density and time constant at Al2 O3/AlGaN and AlGaN/GaN interface are determined.The experimental results reveal that the density of trap states and the activation energy at the Al2 O3/AlGaN interface are much higher than at the AlGaN/GaN interface. The photo-assisted capacitance-voltage measurements are performed to characterize the deep-level traps located near mid-gap at the Al2 O3/AlGaN interface, which indicates that a density of deep-level traps is lower than the density of the shallow-level states.

Negative bias-induced threshold voltage instability and zener/interface trapping mechanism in GaN-based MIS-HEMTs

We investigate the instability of threshold voltage in D-mode MIS-HEMT with in-situ SiN as gate dielectric under different negative gate stresses.The complex non-monotonic evolution of threshold voltage under the negative stress and during the recovery process is induced by the combination effect of two mechanisms.The effect of trapping behavior of interface state at SiN/AlGaN interface and the effect of zener traps in AlGaN barrier layer on the threshold voltage instability are opposite to each other.The threshold voltage shifts negatively under the negative stress due to the detrapping of the electrons at SiN/AlGaN interface,and shifts positively due to zener trapping in AlGaN barrier layer.As the stress is removed,the threshold voltage shifts positively for the retrapping of interface states and negatively for the thermal detrapping in AlGaN.However,it is the trapping behavior in the AlGaN rather than the interface state that results in the change of transconductance in the D-mode MIS-HEMT.

Improved RF power performance of InAlN/GaN HEMT by optimizing rapid thermal annealing process for high-performance low-voltage terminal applications

Improved radio-frequency(RF)power performance of InAlN/GaN high electron mobility transistor(HEMT)is achieved by optimizing the rapid thermal annealing(RTA)process for high-performance low-voltage terminal applications.By optimizing the RTA temperature and time,the optimal annealing condition is found to enable low parasitic resistance and thus a high-performance device.Besides,compared with the non-optimized RTA HEMT,the optimized one demonstrates smoother ohmic metal surface morphology and better heterojunction quality including the less degraded heterojunction sheet resistance and clearer heterojunction interfaces as well as negligible material out-diffusion from the barrier to the channel and buffer.Benefiting from the lowered parasitic resistance,improved maximum output current density of 2279 mA·mm^(-1)and higher peak extrinsic transconductance of 526 mS·mm^(-1)are obtained for the optimized RTA HEMT.In addition,due to the superior heterojunction quality,the optimized HEMT shows reduced off-state leakage current of 7×10^(-3)mA·mm^(-1)and suppressed current collapse of only 4%,compared with those of 1×10^(-1)mA·mm^(-1)and 15%for the non-optimized one.At 8 GHz and V_(DS)of 6 V,a significantly improved power-added efficiency of 62%and output power density of 0.71 W·mm^(-1)are achieved for the optimized HEMT,as the result of the improvement in output current,knee voltage,off-state leakage current,and current collapse,which reveals the tremendous advantage of the optimized RTA HEMT in high-performance low-voltage terminal applications.