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

Neural Regeneration Research 2024年第7期19卷 1618-1624页

作者： Luyi Wang Man Xu Yan Wang Feifei Wang Jing Deng Xiaoya Wang Yu Zhao Ailing Liao Feng Yang Shali Wang Yingbo Li Institute of Neuroscience Department of PhysiologySchool of Basic Medical ScienceChongqing Medical UniversityChongqingChina department of Pediatric Chongqing University Fuling HospitalChongqingChina department of Neurosurgery Xinqiao HospitalArmy Medical UniversityChongqingChina department of pathology Affiliated Hospital of North Sichuan Medical CollegeNanchongSichuan ProvinceChina NHC Key Laboratory of Birth Defects and Reproductive Health Chongqing Population and Family Planning Science and Technology Research InstituteChongqingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Advanced Innovation Center for human Brain Protection Capital Medical UniversityBeijingChina

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate ***2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic *** 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 *** 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 *** findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout ***,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this *** 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 *** 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.

关键词： autism Ctnnd2 deletion GABAergic neurons melatonin PI3K/Akt signal pathway prefrontal cortex social behavior spine density synaptic-associated proteins

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Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

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Chinese Journal of Cancer Research 2024年第2期36卷 124-137页

作者： Jialin Zhang Gengshen Yin Chunmiao Ye Man Feng Changhua Ji Wenzhong Zhou Fei Wang Lixiang Yu Shuya Huang Zhigang Yu department of Breast Surgery the Second Hospital of Shandong UniversityJinan 250033China Institute of Translational Medicine of Breast Disease Prevention and Treatment Shandong UniversityJinan 250033China Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast Disease Jinan 250033China department of pathology the Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China department of pathology the Second Hospital of Shandong UniversityJinan 250033China

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is ***: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to ***: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft ***: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance

关键词： Breast cancer HER2 pyrotinib trastuzumab primary resistance pertuzumab

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Small molecule conjugates with selective estrogen receptor β agonism promote anti-aging benefits in metabolism and skin recovery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2137-2152页

作者： Tarik Zahr Vijay K.Boda Jian Ge Lexiang Yu Zhongzhi Wu Jianwen Que Wei Li Li Qiang Naomi Berrie Diabetes Center Columbia UniversityNew YorkNY 10032USA department of Molecular Pharmacology and Therapeutics Columbia UniversityNew YorkNY 10032USA department of Pharmaceutical Sciences College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Drug Discovery Center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Division of Digestive and Liver Diseases Columbia UniversityNew YorkNY 10032USA Center for human Development Columbia UniversityNew YorkNY 10027USA department of pathology and Cell Biology Columbia UniversityNew YorkNY 10032USA department of Medicine Columbia UniversityNew YorkNY 10032USA

Estrogen is imperative to mammalian reproductivity,metabolism,and ***,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain *** contrast,ERβis more broadly expressed in metabolic tissues and the ***,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERα***,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or *** of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in *** further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound ***,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.

关键词： Estrogen receptorβ Aging Metabolism Skin injury Muscle metabolism Small molecule conjugates Regeneration Adiposity

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Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 687-698页

作者： Juan Lin Zhu-Feng Chen Guo-Dong Guo Xin Chen Shengli Clinical Medical College Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina department of pathology Fujian Provincial HospitalFuzhou 350001Fujian ProvinceChina department of Internal Medicine Fujian Provincial HospitalFuzhou 350001Fujian ProvinceChina

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,***,the clinical importance of the special combined AB and PAS stain is *** To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient *** Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed ***-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed *** cancer-specific survival(CSS)rate was estimated via Kaplan-Meier *** proportional hazards models were used for univariate and multivariate survival *** Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the *** multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor *** A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric *** expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

关键词： Alcian blue Periodic acid-Schiff Prognosis Gastric Signet ring cell carcinoma

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First report of the histopathological effect of electrocautery using on the urethral taste rosea during glans penis injury by incision in rabbits

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Asian Journal of Urology 2024年第1期11卷 115-120页

作者： Ozgur Caglar Ayhan Kanat Mehmet Dumlu Aydin Nezih Akca Sevilay Ozmen Ataturk University Medical FacultyDepartment of Pediatric SurgeryErzurumTurkey Recep Tayyip Erdogan University Medical FacultyDepartment of NeurosurgeryRizeTurkey Ataturk University Medical FacultyDepartment of NeurosurgeryErzurumTurkey Recep Tayyip Erdogan University Medical FacultyDepartment of UrologyRizeTurkey Ataturk University Medical FacultyDepartment of PathologyErzurumTurkey

Objective:Currently,electrocautery devices have frequently been used in penile surgical *** hypothesized that electrocautery using during penile surgical procedures may harm the taste rosea and the dorsal nerve of the penis or ***:Eighteen young age male New Zealand rabbits were studied:five in the control(Group I,n=5),five in the penile surgery without using electrocautery(sham group,Group II,n=5),eight in the monopolar cautery(study group,Group III,n=8)groups under general *** animals were followed for 3 weeks and *** tissue—pudendal nerve root complexes and dorsal root ganglion of sacral 3 level were examined using stereological *** results were compared ***:The live and degenerated taste bud-like structures and degenerated neuron densities of pudendal ganglia(mean±standard deviation,n/mm^(3))were estimated as 198±24/mm^(3),4±1/mm^(3),and 5±1/mm^(3) in Group I;8±3/mm^(3),174±21/mm^(3),and 24±7/mm^(3) in Group II;and 21±5/mm^(3),137±14/mm^(3),and 95±12/mm^(3) in Group III,*** of taste buds and pudendal ganglia was significantly different between ***:Intact spinal cord and normal parasympathetic and thoracolumbar sympathetic networks are crucial for human sexual *** present study indicates that the glans penis injury by using electrocautery may lead to pudendal ganglia *** damage to taste rosea and retrograde degeneration of the pudendal nerve may be the cause of sexual dysfunction responsible mechanism.

关键词： Urethral taste rosea Tastebuds Pudendalnerve Degeneration Penile surgery

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Mitochondrial carrier homolog 2 increases malignant phenotype of human gastric epithelial cells and promotes proliferation,invasion,and migration of gastric cancer cells

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 991-1005页

作者： Jing-Wen Zhang Ling-Yan Huang Ya-Ning Li Ying Tian Jia Yu Xiao-Fei Wang School of Basic Medical Science NHC Key Laboratory of Metabolic Cardiovascular Diseases ResearchNingxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina department of pathology General Hospital of Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina School of Clinical Medicine Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina department of pathology North China University of Science and Technology Affiliated HospitalTangshan 063000Hebei ProvinceChin

BACKGROUND The precise role of mitochondrial carrier homolog 2(MTCH2)in promoting malignancy in gastric mucosal cells and its involvement in gastric cancer cell metastasis have not been fully *** To determine the role of MTCH2 in gastric *** We collected 65 samples of poorly differentiated gastric cancer tissue and adjacent tissues,constructed MTCH2-overexpressing and MTCH2-knockdown cell models,and evaluated the proliferation,migration,and invasion of human gastric epithelial cells(GES-1)and human gastric cancer cells(AGS)*** mito-chondrial membrane potential(MMP),mitochondrial permeability transformation pore(mPTP)and ATP fluorescence probe were used to detect mitochondrial *** function and ATP synthase protein levels were detected via Western *** The expression of MTCH2 and ATP2A2 in gastric cancer tissues was significantly greater than that in adjacent *** of MTCH2 promoted colony formation,invasion,migration,MMP expression and ATP production in GES-1 and AGS cells while upregulating ATP2A2 expression and inhibiting cell apoptosis;knockdown of MTCH2 had the opposite effect,promoting overactivation of the mPTP and promoting *** MTCH2 can increase the malignant phenotype of GES-1 cells and promote the proliferation,invasion,and migration of gastric cancer cells by regulating mitochondrial function,providing a basis for targeted therapy for gastric cancer cells.

关键词： Gastric cancer Mitochondrial carrier homolog 2 ATP synthase ATP2A2 Mitochondrial permeability transformation pore

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Aldo-keto reductases:Role in cancer development and theranostics

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Oncology Research 2024年第8期32卷 1287-1308页

作者： SIDDAVARAM NAGINI PRATHAP REDDY KALLAMADI KRANTHI KIRAN KISHORE TANAGALA GEEREDDY BHANUPRAKASH REDDY World Neem Organization Mumbai400101India department of Biochemistry ICMR-National Institute of NutritionHyderabad500007India department of pathology and Cell Biology Columbia University Irving Medical CenterNew York10032USA

Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various *** are aberrantly expressed in a wide range of malignant *** expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to *** have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and *** of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for *** classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical *** AKR inhibitors from natural sources also exhibit anticancer *** molecule inhibitors targeting speciﬁc AKR isoforms have shown promise in preclinical *** inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to *** this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug ***,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized.

关键词： Aldo-keto reductases(AKRs) Aldo-keto reductase(AKR)inhibitors Cancer Drug-resistance Xenobiotics

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Comprehensive overview of genotype distribution and prevalence of human papillomavirus in cervical lesions

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Gynecology and Obstetrics Clinical Medicine 2024年第1期4卷 37-47页

作者： Yuhong Ye Terrel Jones Tiannan Wang Xianxu Zeng Yang Liu Chengquan Zhao department of pathology the First Affiliated HospitalFujian Medical UniversityFuzhouFujianChina department of pathology Magee-Womens HospitalUniversity of Pittsburgh Medical CenterPittsburghPennsylvaniaUSA department of pathology University of Southern CaliforniaLos AngelesCaliforniaUSA department of pathology The Third Affliated Hospital of Zhengzhou UniversityZhengzhouHenanChina departments of Medicine and Bioengineering University of PittsburghPittsburghPennsylvaniaUSA department of Bioengineering University of Illinois Urbana-ChampaignUrbanaIllinoisUSA

Acrosscervical squamousandgl and ular lesions,a spectrum of human papillomavirus(HPV)genotypes has been *** review aims to provide a comprehensive summary detailing the distribution and profile of HPV genotypes detected in cervical lesions,leveraging insights from histological and cytological ***-risk HPV(HR-HPV)genotypes exhibit varying degrees of oncogenic potential,with HPV16 and HPV18 identified as the most prevalent and oncogenic *** of HR-HPVgenotypes varies among different degrees of the cervical lesions and varies between squamous andglandular ***16 is predominantly associated with severe lesions(precancers and carcinomas),while HPV18 demonstrates a significantly higher prevalence in endocervical as compared with squamous *** distribution of HR-HPV in severe squamous lesions is complex,involving many HR-HPV genotypes in addition to HPV16,while the distribution of HR-HPV genotypes in endocervical glandular lesions is mainly limited in HPV18 and *** datasets from China have identified the three mostcommon HR-HPVgenotypes in this population as stratified by diagnostic category:HPV52,HPV16,HPV58 in histologically negative cases and cervical intraepithelial neoplasia 1(CIN1);HPV16,HPV52,HPV58 in CIN2/3;HPV16,HPV58,HPV52 or HPV18 in squamous cell carcinoma(SCC);HPV16,HPV18 and HPV52 in endocervical adenocarcinoma in situ(AIS),invasiveadenocarcinoma,as well asmixedsquamous and glandular ***33 is the fourth most common HPVtype in CIN2/3and SCC,whileHPV45occursmore commonly in AIS and adenocarcinoma,compared with squamous *** prevalence and distribution of multiple HR-HPV coinfections vary across different cervical *** clinical significance and pathogenesis of these multiple HR-HPV infections remain uncertain,although recent two large studies demonstrate that multiple HR-HPV infections are not associated with cumulatively higher risk of high-grade cervical squamous lesiondeve

关键词： cervical lesions prevalence

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Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma(PRP)

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Animal Models and Experimental Medicine 2024年第2期7卷 106-113页

作者： Qian Zhang Yanan Wang Cheng Ran Yingmei Zhou Zigang Zhao Tianhua Xu Hongwei Hou Yuan Lu Beijing Life Science Academy BeijingChina department of pathology Affiliated Hospital of Hebei UniversityBaodingChina department of Otolaryngology Affiliated Hospital of Hebei UniversityBaodingChina department of Dermatology Huazhong University of Science and Technology Union Shenzhen HospitalShenzhenChina department of Dermatology Hainan Hospital of PLA General HospitalSanyaChina department of Chemical Engineering Tsinghua UniversityBeijingChina

Background:Androgenic alopecia(AGA)is the most common type of hair loss in men,and there are many studies on the treatment of hair loss by platelet-rich plasma(PRP).The human scalp contains a huge microbiome,but its role in the process of hair loss remains unclear,and the relationship between PRP and the microbiome needs further ***,the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota ***:We performed PRP treatment on 14 patients with AGA,observed their clinical efficacy,and collected scalp swab samples before and after *** scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial ***:The results showed that PRP was effective in the treatment of AGA patients,and the hair growth increased *** results of relative abundance analysis of microbiota showed that after treatment,g_Cutibacterium increased and g_Staphylococcus decreased,which played a stable role in scalp *** addition,g_Lawsonella decreased,indicating that the scalp oil production decreased after ***:The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.

关键词： androgenic alopecia microbiome platelet-rich plasma scalp

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Primary gastroduodenal tuberculosis presenting as gastric outlet obstruction:A case report and review of literature

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World Journal of Clinical Cases 2024年第8期12卷 1536-1543页

作者： Abdihamid Mohamed Ali Yahye Garad Mohamed Abdirahman Ahmed Mohamud Abdulkadir Nor Mohamed Mohamed Rage Ahmed Ismail Mohamud Abdullahi Tuba Saydam department of General Surgery Mogadishu Somali Turkey Recep Tayyip Erdogan Training and Research HospitalMogadishu 2526Somalia department of Radiology Mogadishu Somali TurkeyTraining and Research HospitalMogadishu 2526Somalia department of pathology Mogadishu Somali Turkey Recep Tayyip Erdogan Training and Research HospitalMogadishu 2526Somalia

BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous *** disease is prevalent in low-income countries,posing a significant global health *** TB is one of the three *** disease can mimic other intra-abdominal conditions,leading to delayed diagnosis owing to the absence of specific *** gastric outlet obs-truction(GOO)remains a frequent complication,its incidence has declined with the advent of proton pump inhibitors and Helicobacter pylori eradication *** TB can cause upper gastrointestinal hemorrhage,obstruction,and malignancy-like *** SUMMARY A 23-year-old male presented with recurrent epigastric pain,distension,nausea,vomiting,and weight loss,prompting a referral to a gastroenterologist *** examination revealed distorted gastric mucosa and signs of chronic ***,treatment was interrupted,possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or *** surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal *** revealed gastric wall effacement with *** Primary gastric TB is rare,frequently leading to *** its rarity,suspicions should be promptly raised when encountering relevant symptoms,often requiring surgical intervention for diagnosis and treatment.

关键词： Tuberculosis Gastrointestinal tuberculosis Gastric outlet obstruction Gastroduodenal tuberculosis Case report

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