Melatonin improves synapse development by PI3K/Akt signaling in a mouse model of autism spectrum disorder

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.

Recent progress in ternary mixed matrix membranes for CO_(2) separation

Mixed matrix membranes(MMMs)could combine the advantages of both polymeric membranes and porousfillers,making them an effective alternative to conventional polymer membranes.However,interfacial incompatibility issues,such as the presence of interfacial voids,hardening of polymer chains,and blockage of micropores by polymers between common MMMsfillers and the polymer matrix,currently limit the gas sep-aration performance of MMMs.Ternary phase MMMs(consisting of afiller,an additive,and a matrix)made by adding a third compound,usually functionalized additives,can overcome the structural problems of binary phase MMMs and positively impact membrane separation performance.This review introduces the structure and fabrication processes for ternary MMMs,categorizes various nanofillers and the third component,and summarizes and analyzes in detail the CO_(2) separation performance of newly developed ternary MMMs based on both rubbery and glassy polymers.Based on this separation data,the challenges of ternary MMMs are also discussed.Finally,future directions for ternary MMMs are proposed.

High-intensity spatial-mode steerable frequency up-converter toward on-chip integration

Integrated photonic devices are essential for on-chip optical communication,optical-electronic systems,and quantum information sciences.To develop a high-fidelity interface between photonics in various frequency domains without disturbing their quantum properties,nonlinear frequency conversion,typically steered with the quadratic(χ2)process,should be considered.Furthermore,another degree of freedom in steering the spatial modes during theχ2 process,with unprecedent mode intensity is proposed here by modulating the lithium niobate(LN)waveguide-based inter-mode quasi-phasematching conditions with both temperature and wavelength parameters.Under high incident light intensities(25 and 27.8 dBm for the pump and the signal lights,respectively),mode conversion at the sum-frequency wavelength with sufficient high output power(−7–8 dBm)among the TM01,TM10,and TM00 modes is realized automatically with characterized broad temperature(ΔT≥8°C)and wavelength windows(Δλ≥1 nm),avoiding the previous efforts in carefully preparing the signal or pump modes.The results prove that high-intensity spatial modes can be prepared at arbitrary transparent wavelength of theχ2 media toward on-chip integration,which facilitates the development of chip-based communication and quantum information systems because spatial correlations can be applied to generate hyperentangled states and provide additional robustness in quantum error correction with the extended Hilbert space.

Epidemiological characteristics of varicella in Chongqing,China,2014-2021

Background:To analyze the epidemiological characteristics of varicella epidemics in Chongqing Municipality from 2014 to 2021,and to provide a scientific basis for the formulation of varicella prevention and control measures.Methods:Data on the incidence of varicella outbreaks and vaccination data in Chongqing from 2014 to 2021 were collected through the China Disease Control and Prevention Information System and statistically analyzed using descriptive epidemiological methods.Results:From 2014 to 2021,213,715 cases of varicella were reported in Chongqing Municipality,with an average annual incidence rate of 86.26/100,000,with a statistically significant difference(χ^(2)=24,972.069,P<0.001);varicella incidence is seasonal,with peaks in May/June and October/December each year,presenting a“double-peak distribution”.The average annual incidence rate of varicella in municipal districts was 90.74/100,000,which was higher than that of counties 69.62/100,000 and autonomous counties 84.04/100,000;the average annual incidence rate of varicella in males was 89.37/100,000,and in females,82.22/100,000,with the difference not being statistically significant;the age of onset of the disease was mainly in the group of people under 15 years of age,with a total of 190,021 cases reported(88.9%),with 5-9 years old(35.7%)as the high incidence age group.The incidence occupation was dominated by students in 133,733 cases(62.6%).Conclusion:The overall varicella epidemic in Chongqing is on the rise,and has obvious seasonal,regional and population distribution characteristics.The prevention and control of varicella epidemic should be strengthened,the publicity of varicella vaccine should be increased,and it is recommended that varicella vaccine should be included in the national immunization program.

Evaluation of Attending Medical Teams and Their Impact on the DRG Components of Cholecystectomy

Objective:This study assessed the role of the attending medical team in the cost control of the cholecystectomy DRG components.Methods:The association between team structure,workflow,and treatment outcomes was analyzed using a mixed-methods approach combining quantitative data and qualitative interviews from 628 patients.Results:Inter-professional teamwork significantly affected length of stay,treatment costs,and recurrence rates,with experienced teams performing better in terms of emergency response and collaborative efficiency.Patient satisfaction was generally high,indicating that good teamwork enhances treatment outcomes.Significance:The study highlights the importance of optimizing team configuration to improve the quality,efficiency,and cost control of healthcare.

Research on the Application and Effectiveness of the DRG Model on Perioperative Medical Management of Cholecystectomy

Objective:This study aimed to explore the application and effectiveness of the DRG model in the perioperative management of cholecystectomy.By comparing the DRG model with traditional management methods,this study focused on evaluating the potential impact of the DRG model in improving surgical efficiency and reducing complication rates and medical costs.Methods:The random envelope method was used to divide patients scheduled for cholecystectomy from January 2021 to October 2023 into two groups:one group underwent surgery under the DRG model(experimental group),and the other group underwent the traditional management model(control group).Data including basic information,surgery-related data,length of stay,complication records,and medical expenses were collected.Data analysis was carried out using a t-test and chi-square(χ2)test.Results:Results showed that the DRG model shortened the average length of stay,decreased the incidence of complications,reduced medical expenses,and increased patient satisfaction.These results demonstrate the effectiveness of the DRG model in the perioperative management of cholecystectomy,especially in improving surgical efficiency,reducing medical costs,and improving patient satisfaction.Conclusion:The DRG model in the perioperative management of cholecystectomy can significantly improve medical service quality and efficiency and enhance patient satisfaction as compared to traditional treatment methods.

PhaseⅠstudy of chlorogenic acid injection for recurrent high-grade glioma with long-term follow-up

Objective:This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid(CGA)in patients with recurrent high-grade glioma after standard of care treatments,through a first-in-human,open-label,dose-escalation phase I trial.Methods:A total of 26 eligible patients were enrolled,received intramuscular CGA injections at 5 dose levels,and were followed up for 5 years.CGA was well tolerated,and the maximum tolerated dose was 5.5 mg/kg.Results:The most common treatment-related adverse events occurred at the sites of injection.No grade 3 or 4 adverse events(e.g.,drug allergy)were reported for these patients except for induration at the injection sites.A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma,with a t_(1/2)of 0.95–1.27 h on day 1 and 1.19–1.39 h on day 30,and no detectable CGA was observed on days 9,11,13,23,25,27,and 29 before CGA administration.After the first treatment cycle,52.2%of patients(12 of 23)achieved stable disease.Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients.Of the 18 patients with grade 3 glioma,the median overall survival was 9.5 months.Two patients remained alive at the cutoff day.Conclusions:This phase I study demonstrated that CGA has a favorable safety profile(with no severe toxicity),and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies,thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma.

Discussion on the Application Effect of Simplified Vacuum Sealing Drainage(VSD)in the Treatment of Chronic Refractory Wounds

Objective:To analyze the effect of simplified vacuum sealing drainage(VSD)in the treatment of chronic refractory wounds.Methods:A total of 90 patients with chronic refractory wounds treated from May 2022 to May 2023 were randomly divided into groups.The simplified VSD treatment was employed in group A,and conventional treatment was employed in group B,and the wound healing of both groups were compared.Results:Group A showed better wound healing compared to group B,P<0.05;the wound healing rate,wound healing duration,visual analog scale(VAS)score,wound dressing times and other indicators in group A were better than those in group B,P<0.05.The SF-36 score of group A was higher than that of group B,P<0.05;the complication rate of chronic refractory wounds in group A was no different from that in group B,P>0.05.Conclusion:Simplified VSD treatment is effective in treating patients with chronic refractory wounds,and it reduces the number of wound dressing changes and promote wound healing.

Integration of Theory and Practice in Medical Morphology Curriculum in Postgraduate Training:A Flipped Classroom and Case-based Learning Exercise

Objective:The integration of training in theory and practice across the medical education spectrum is being encouraged to increase student understanding and skills in the sciences.This study aimed to determine the deciding factors that drive students'perceived advantages in class to improve precision education and the teaching model.Methods:A mixed strategy of an existing flipped classroom(FC)and a case-based learning(CBL)model was conducted in a medical morphology curriculum for 575 postgraduate students.The subjective learning evaluation of the individuals(learning time,engagement,study interest and concentration,and professional integration)was collected and analyzed after FC-CBL model learning.Results:The results from the general evaluation showed promising results of the medical morphology in the FC-CBL model.Students felt more engaged by instructors in person and benefited in terms of time-saving,flexible arrangements,and professional improvement.Our study contributed to the FC-CBL model in Research Design in postgraduate training in 4 categories:1)advancing a guideline of precision teaching according to individual characteristics;2)revealing whether a learning background is needed for a Research Design course to guide setting up a preliminary course;3)understanding the perceived advantages and their interfaces;and 4)barriers and/or improvement to implement the FC-CBL model in the Research Design class,such as a richer description of e-learning and hands-on practice.Conclusion:Undertaking a FC-CBL combined model could be a useful addition to pedagogy for medical morphology learning in postgraduate training.

A Data Consistency Insurance Method for Smart Contract

As one of the major threats to the current DeFi(Decentralized Finance)ecosystem,reentrant attack induces data inconsistency of the victim smart contract,enabling attackers to steal on-chain assets from DeFi projects,which could terribly do harm to the confidence of the blockchain investors.However,protecting DeFi projects from the reentrant attack is very difficult,since generating a call loop within the highly automatic DeFi ecosystem could be very practicable.Existing researchers mainly focus on the detection of the reentrant vulnerabilities in the code testing,and no method could promise the non-existent of reentrant vulnerabilities.In this paper,we introduce the database lock mechanism to isolate the correlated smart contract states from other operations in the same contract,so that we can prevent the attackers from abusing the inconsistent smart contract state.Compared to the existing resolutions of front-running,code audit,andmodifier,our method guarantees protection resultswith better flexibility.And we further evaluate our method on a number of de facto reentrant attacks observed from Etherscan.The results prove that our method could efficiently prevent the reentrant attack with less running cost.

三阴性乳腺癌患者超声造影征象及其与抑癌蛋白P53、细胞角蛋白5/6的关系

目的探讨三阴性乳腺癌(TNBC)患者超声造影征象及其与抑癌蛋白P53、细胞角蛋白5/6(CK5/6)的关系。方法选取2014年7月-2020年6月于南京医科大学附属江宁医院和南京医科大学第一附属医院超声医学科行乳腺超声造影的98例TNBC患者(研究组)和103例其他分子分型乳腺癌患者(对照组)。患者均接受手术治疗,取TNBC患者术中切除的乳腺癌组织,采用免疫组织化学法检测P53和CK5/6的表达。分析TNBC患者二维超声以及造影征象与P53和CK5/6表达的关系。结果研究组肿块形态规则、后方回声增强、血流Ⅱ级和Ⅲ级比例患者多于对照组,边缘模糊、有微钙化患者少于对照组(P<0.05)。两组肿块直径、纵横比比较,差异无统计学意义(P>0.05)。研究组高增强、增强后结节范围扩大不明显、有充盈缺损患者多于对照组,有均匀增强患者少于对照组(P<0.05)。两组患者有无穿支血管比较,差异无统计学意义(P>0.05)。血流分级Ⅱ级、Ⅲ级患者P53阳性率高于血流分级0级、I级患者(P<0.05),边缘清晰患者CK5/6阳性率高于边缘模糊患者(P<0.05)。高增强患者P53阳性率低于等/低/无增强患者(P<0.05),增强后结节范围扩大不明显患者CK5/6阳性率高于增强后结节范围扩大明显患者(P<0.05)。结论TNBC超声造影征象与其他分子分型乳腺癌具有显著差异,P53、CK5/6表达与TNBC超声造影征象具有一定关系。

基于固体核磁共振方法的蛋白质组装体三维结构解析

蛋白质组装体广泛存在于生物体内,具有相关生物学功能或与人类的重要疾病密切相关。蛋白质组装体分子量大,通常难以溶解和结晶,限制了常用的结构研究手段如X射线晶体学和液体NMR等在其高分辨三维结构解析中的应用。固体核磁共振技术(ssNMR)在难溶、非结晶样品的三维结构解析中具有独特的优势,尤其随着固体NMR硬件包括高场磁体和高性能的探头、固体NMR多维脉冲实验技术和样品制备技术特别是同位素标记技术的快速发展,固体NMR已经成为了蛋白组装体三维结构解析的重要手段。在样品制备方法方面,强调了样品制备条件的优化对得到构象均一样品的重要性,以及丰富的同位素标记方法的使用对固体NMR谱图分辨率提高的重要作用。同时多种脉冲序列如质子驱动自旋扩散技术(PDSD),偶极辅助旋转共振技术(DARR),质子辅助重偶技术(PAR)或转移回波双共振技术(TEDOR)等的建立和发展为结构约束条件收集提供了基本的技术方法。此外,固体NMR与其它实验技术如扫描透射电镜(STEM),冷冻电镜(Cryo-EM)等和理论模拟方法的联用能显著地提高固体NMR的能力,从而能解析分子量更大、结构更复杂的蛋白质组装体的三维结构。本文以Aβ纤维和T3SS针状体的三维结构解析为例介绍固体NMR在蛋白质组装体结构研究的最新实验方法,重点介绍最新的距离约束条件获取的实验方法进展,以及固体NMR与其它实验和理论模拟研究手段的联用在蛋白质组装体结构解析上的最新进展,期望有助于读者对固体NMR技术在蛋白质组装体的三维结构解析方面的研究进展有所了解。

The R2R3-MYB transcription factor GhMYB1a regulates flavonol and anthocyanin accumulation in Gerbera hybrida

Anthocyanins and flavonols have vital roles in flower coloration,plant development,and defense.Because anthocyanins and flavonols share the same subcellular localization and common biosynthetic substrates,these pathways may compete for substrates.However,the mechanism regulating this potential competition remains unclear.Here,we identified GhMYB1a,an R2R3-MYB transcription factor involved in the regulation of anthocyanin and flavonol accumulation in gerbera(Gerbera hybrida).GhMYB1a shares high sequence similarity with that of other characterized regulators of flavonol biosynthesis.In addition,GhMYB1a is also phylogenetically grouped with these proteins.The overexpression of GhMYB1a in gerbera and tobacco(Nicotiana tabacum)resulted in decreased anthocyanin accumulation and increased accumulation of flavonols by upregulating the structural genes involved in flavonol biosynthesis.We further found that GhMYB1a functions as a homodimer instead of interacting with basic helix-loop-helix cofactors.These results suggest that GhMYB1a is involved in regulating the anthocyanin and flavonol metabolic pathways through precise regulation of gene expression.The functional characterization of GhMYB1a provides insight into the biosynthesis and regulation of flavonols and anthocyanins.

A Quantized Kernel Least Mean Square Scheme with Entropy-Guided Learning for Intelligent Data Analysis

Quantized kernel least mean square(QKLMS) algorithm is an effective nonlinear adaptive online learning algorithm with good performance in constraining the growth of network size through the use of quantization for input space. It can serve as a powerful tool to perform complex computing for network service and application. With the purpose of compressing the input to further improve learning performance, this article proposes a novel QKLMS with entropy-guided learning, called EQ-KLMS. Under the consecutive square entropy learning framework, the basic idea of entropy-guided learning technique is to measure the uncertainty of the input vectors used for QKLMS, and delete those data with larger uncertainty, which are insignificant or easy to cause learning errors. Then, the dataset is compressed. Consequently, by using square entropy, the learning performance of proposed EQ-KLMS is improved with high precision and low computational cost. The proposed EQ-KLMS is validated using a weather-related dataset, and the results demonstrate the desirable performance of our scheme.

Effect of Chaihu Shugan decoction on gastric smooth muscle cell apoptosis in rats with functional dyspepsia

Objective:To investigate the effect of Chaihu Shugan decoction(CSD)on gastric smooth muscle cells(GSMCs)apoptosis in rats with functional dyspepsia(FD).Methods:48Sprague-Dawley(SD)rats were randomly assigned into six groups:a normal control group,a model group,apositive control(domperidone)group and low-,middle-and high-dose CSD groups.A rat model of FD was established by constantly squeezing their tails.The rats were administered CSD(0.16g/mL,0.32g/mL,0.64g/mL)or domperidone(0.3 g/L)via intragastric gavage for four weeks.The gastric emptying rate was detected at 4 weeks post-administration.Apoptosis of GSMCs was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining and the mitochondrial morphology was observed by transmission electron microscopy.The expression of Bcl-2and Bax was measured by immunohistochemistry.Results:FD resulted in marked reduction of gastric emptying rate,severe gastric tissue damage and mitochondria injury,but were reversed by CSD treatment(P<0.05).The apoptosis-induced protein Bax was markedly down-regulated by CSD,whereas the expression of the anti-apoptotic Bcl-2 protein was notably increased(P<0.05).Furthermore,CSD could protect the FD rats against GSMCs apoptosis manifested by a decreased in TUNEL-positive cells(P<0.05).Conclusion:CSD could alleviate GSMCs apoptosis in FD rats,possibly by the modulation of Bcl-2 and Bax expression,and the suppression of mitochondria injury.

Changes in gas exchange,root growth,and biomass accumulation of Platycladus orientalis seedlings colonized by Serendipita indica

Serendipita indica(formerly known as Piriformospora indica),a root endophytic fungus,exhibits multiple functions in some agricultural,horticultural,and medicinal plant species.We studied colonization of the roots of Platycladus orientalis,a forest tree species,by S.indica to improve the quality of the seedlings in seedbeds and survival rates in sylviculture.At 20 days after inoculation,S.indica colonized the root cortex of P.orientalis seedlings.Root colonization by S.indica significantly increased net CO2 assimilation,light use efficiency,and biomass accumulation by both roots and shoots,whereas it did not affect the biomass allocation between roots and shoots.In addition,the symbiosis significantly increased root total length,surface area,and volume.In view of the two specific traits of S.indica,i.e.,axenic culture and wide colonization in plants,the fungus might be used for improving quality of P.orientalis seedlings and increasing their survival after transplanting.

Effect of MEK1 inhibitor PD98059 on the signal transduction of Tec in HepG2 hepatoma cells

Objective: To investigate the effect of MEK1 inhibitor PD98058 on Tec and ERK2 in HepG2 hepatoma cells. Methods: The expression of mRNA and protein of Tec and ERK2 in HepG2 cells was detected by immunocytochemistry as- say. After various concentration of PD98059 treatment, the expression of Tec and ERK2 mRNA in HepG2 cells was detected by RT-PCR and Western blotting. Results: Tec and ERK2 expressed highly in HepG2 cells. PD98059 obviously inhibited the expression of mRNA and protein of Tec and ERK2 in a dose-dependent manner, in which 40 μmol/L of PD98059 exhibited the strongest inhibiting effect. Conclusion: PD98058, as MEK1 inhibitor, can inhibit Tec, block the signal route of Ras/Raf/ERK and to impede the signal transduction in HepG2 cells. Tec may be the signal protein in the upper stream of Ras/Raf/ERK in hepatocarcinoma cells and is supposed to interact with the signal way of Ras/Raf/ERK.

Development of an injection-seeded single-frequency laser by using the phase modulated technique

An injection-seeded single-frequency Q-switched Nd：YAG laser is accomplished by using a phase modulated rampfire technique. A RbTiOPO4（RTP） electro-optic crystal is selected for effective optical path length modulation of the slave self-filtering unstable resonator. This single-frequency laser is capable of producing 50 m J pulse energy at 1 Hz repetition rate with a pulse width of 16 ns. The standard deviation of laser pulse intensity for consecutive 100 shots from the mean pulse intensity is less than 1.05%. A spectral linewidth of less than 0.5 pm with a frequency jitter of about 14 fm over30 min is obtained.

A Case Report of Monomorphic Epithelial Intestinal T-Cell Lymphoma and Literature Review

Background: Monomorphic epithelial intestinal T-cell lymphoma (MEITL), previously known as type II Enteropathy-associated T-cell lymphoma (EATL), is a rare intestinal tumor with strong invasiveness, poor prognosis, atypical clinical manifestations, and is difficult to diagnose. Aim: The clinical manifestations, imaging, histopathology, and immunohistochemical characteristics, treatment and prognosis of this case of MEITL were analyzed retrospectively, and combined with literatures learning to provide the experiences and lessons for diagnosis and treatment. Case Presentation: Here, we present a 68-year-old Asian woman with unexplained intestinal perforation and lung imaging changes as the first manifestation, and gradually appearing refractory diarrhea and pulmonary cavities. During the period, due to the unknown diagnosis, all treatments were mainly based on anti-infection and antidiarrhea, but her symptoms had no improvement after therapy, even died of poor basic physical conditions. Colonoscopy biopsy showed atypical lymphocyte infiltration-like growth and the formation of local superficial ulcers. Immunohistochemical tests showed that T-lymphocyte hyperplasia was predominant and led to a diagnosis of MEITL. Conclusion: MEITL is mainly manifested by gastrointestinal symptoms and lacks specific symptoms. The diagnosis of MEITL should be based on comprehensive judgment of clinical manifestations, pathological features and immunohistochemical detection results. Positive biopsy confirmed and timely chemotherapy may be conductive to a better prognosis.

Passively Q-switched Tm/Ho composite laser

We explored Q-switching mechanism for the newly proposed Tm/Ho composite laser via developing a hybrid resonator for separating the intra-cavity Tm laser modulated by the saturable absorber(SA).With a Cr:ZnSe SA,successful passively Q-switching process with the maximum average output power of 474 mW and the shortest pulse width of 145 ns were obtained at the pulse repetition frequency of 7.14 kHz,where dual wavelength oscillation in both 2090 nm and 2097 nm was observed.This work provides an effective way for a direct laser diode(LD)pumped Q-switched Ho laser,which is compact and accessible.Furthermore,the current SA could be replaced by the 2D materials with broadband saturable absorption such as topological insulators or transition-metal dichalcogenides for seeking novel PQS lasers.