BACKGROUND A solitary fibrous tumor(SFT)is often located in the pleura,while SFT of the pancreas is extremely rare.Here,we report a case of SFT of the pancreas and discuss imaging,histopathology,and immunohistochemist...BACKGROUND A solitary fibrous tumor(SFT)is often located in the pleura,while SFT of the pancreas is extremely rare.Here,we report a case of SFT of the pancreas and discuss imaging,histopathology,and immunohistochemistry for accurate diagnosis and treatment.CASE SUMMARY A 54-year-old man presented to our hospital with pancreatic occupancy for over a month.There were no previous complaints of discomfort.His blood pressure was normal.Blood glucose,tumor markers,and enhanced computed tomography(CT)suggested a malignant tumor.Because the CT appearance of pancreatic cancer varies,we could not confirm the diagnosis;therefore,we performed endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB).Pathology and immunohistochemistry were consistent with SFT of the pancreas.The posto-perative pathology and immunohistochemistry were consistent with the puncture results.The patient presented for a follow-up examination one month after discharge with no adverse effects.CONCLUSION Other diseases must be excluded in patients with a pancreatic mass that cannot be diagnosed.CT and pathological histology have diagnostic value for pancreatic tumors.Endoscopic puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed preoperatively.Surgery is an effective treatment for SFT of the pancreas;however,long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.展开更多
Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis.Various factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal microbiome.Conversely,enrichme...Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis.Various factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal microbiome.Conversely,enrichment and diversity of the esophageal microbiome can also impact its function.Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC development.Additionally,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment outcomes.In this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and prognosis.Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.展开更多
Parking in a small parking lot within limited space poses a difficult task. It often leads to deviations between the final parking posture and the target posture. These deviations can lead to partial occupancy of adja...Parking in a small parking lot within limited space poses a difficult task. It often leads to deviations between the final parking posture and the target posture. These deviations can lead to partial occupancy of adjacent parking lots, which poses a safety threat to vehicles parked in these parking lots. However, previous studies have not addressed this issue. In this paper, we aim to evaluate the impact of parking deviation of existing vehicles next to the target parking lot(PDEVNTPL) on the automatic ego vehicle(AEV) parking, in terms of safety, comfort, accuracy, and efficiency of parking. A segmented parking training framework(SPTF) based on soft actor-critic(SAC) is proposed to improve parking performance. In the proposed method, the SAC algorithm incorporates strategy entropy into the objective function, to enable the AEV to learn parking strategies based on a more comprehensive understanding of the environment. Additionally, the SPTF simplifies complex parking tasks to maintain the high performance of deep reinforcement learning(DRL). The experimental results reveal that the PDEVNTPL has a detrimental influence on the AEV parking in terms of safety, accuracy, and comfort, leading to reductions of more than 27%, 54%, and 26%respectively. However, the SAC-based SPTF effectively mitigates this impact, resulting in a considerable increase in the parking success rate from 71% to 93%. Furthermore, the heading angle deviation is significantly reduced from 2.25 degrees to 0.43degrees.展开更多
BACKGROUND Epithelioid trophoblastic tumor(ETT)is an extremely rare malignant gestational trophoblastic neoplasm commonly presenting with abnormal vaginal bleeding,abdominal pain,and increased human chorionic gonadotr...BACKGROUND Epithelioid trophoblastic tumor(ETT)is an extremely rare malignant gestational trophoblastic neoplasm commonly presenting with abnormal vaginal bleeding,abdominal pain,and increased human chorionic gonadotropin(hCG).This study reported a case of uterine ETT with the main manifestation being increased hCG.CASE SUMMARY A 39-year-old female was referred to the Ningbo Maternal and Child Hospital of China in December 2022,complaining of increased hCG levels for 1 month.Magnetic resonance imaging revealed gestational trophoblastic tumor,and hysteroscopic electrotomy and curettage of intrauterine hyperplasia were performed.The patient was diagnosed with uterine ETT through postoperative pathological examination and immunohistochemical results.Total laparoscopic hysterectomy and bilateral salpingectomy were performed,and hCG levels returned to normal.The patient was without recurrence during the postoperative 3-month follow-up.CONCLUSION This study reported a case of uterine ETT with the main manifestation being increased hCG,highlighting that ETT should be considered in the presence of abnormal hCG.A total laparoscopic hysterectomy is recommended.展开更多
The direct delivery of inhaled antibiotics to the respiratory tract has been a subject of enduring interest among medical practitioners and researchers due to the associated favorable pharmacokinetics.This interest ha...The direct delivery of inhaled antibiotics to the respiratory tract has been a subject of enduring interest among medical practitioners and researchers due to the associated favorable pharmacokinetics.This interest has been particularly pronounced in the context of critically illpatients,wherehealthcare-associatedpulmonary infections represent a significant challenge,driving continued exploration of inhaled antibiotics for intubated patients.Recent high-level evidence has shown a very promising application in the field of ventilator-associated pneumonia (VAP) prevention.^([1]).展开更多
The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer ...The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.展开更多
BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attract...BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.展开更多
Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three t...Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP.Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays.Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.展开更多
Helicobacter pylori(H.pylori)has been found in the oral cavity and stomach,and its infection is one of the most frequent worldwide.We reviewed the literature and conducted a Topic Highlight,which identified studies re...Helicobacter pylori(H.pylori)has been found in the oral cavity and stomach,and its infection is one of the most frequent worldwide.We reviewed the literature and conducted a Topic Highlight,which identified studies reporting an association between H.pylori-infection in the oral cavity and H.pylori-positive stomach bacterium.This work was designed to determine whether H.pylori is the etiologic agent in periodontal disease,recurrent aphthous stomatitis(RAS),squamous cell carcinoma,burning and halitosis.Record selection focused on the highest quality studies and meta-analyses.We selected 48 articles reporting on the association between saliva and plaque and H.pylori-infection.In order to assess periodontal disease data,we included 12 clinical trials and 1 meta-analysis.We evaluated 13 published articles that addressed the potential association with RAS,and 6 with squamous cell carcinoma.Fourteen publications focused on our questions on burning and halitosis.There is a close relation between H.pylori infection in the oral cavity and the stomach.The mouth is the first extra-gastric reservoir.Regarding the role of H.pylori in the etiology of squamous cell carcinoma,no evidence is still available.展开更多
BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate...BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate latent EBV,complicating the clinical course of IBD.Moreover,the clinical significance of EBV expression in B lymphocytes derived from IBD patients’intestinal tissues has not been explored in detail.AIM To explore the clinical significance of latent EBV infection in IBD patients.METHODS Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection.Based on the staining results,the patients were divided into two groups,according to their latent EBV infection states-negative(n=33)and positive(n=10).Illness severity of IBD were assigned according to Crohn’s disease activity index(ulcerative colitis)and Mayo staging system(Crohn’s disease).The clinicpathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups.RESULTS Systolic pressure(P=0.005),variety of disease(P=0.005),the severity of illness(P=0.002),and pre-op corticosteroids(P=0.025)were significantly different between the EBV-negative and EBV-positive groups.Systolic pressure(P=0.001),variety of disease(P=0.000),pre-op corticosteroids(P=0.011)and EBV infection(P=0.003)were significantly different between the mild-to-moderate and severe disease groups.CONCLUSION IBD patients with latent EBV infection may manifest more severe illnesses.It is suggested that the role of EBV in IBD development should be further investigated,latent EBV infection in patients with serious IBD should be closely monitored,and therapeutic course should be optimized.展开更多
Mueller matrix imaging is emerging for the quantitative characterization of pathological microstructures and is especially sensitive to fibrous structures.Liver fibrosis is a characteristic of many types of chronic li...Mueller matrix imaging is emerging for the quantitative characterization of pathological microstructures and is especially sensitive to fibrous structures.Liver fibrosis is a characteristic of many types of chronic liver diseases.The clinical diagnosis of liver fibrosis requires time-consuming multiple staining processes that specifically target on fibrous structures.The staining proficiency of technicians and the subjective visualization of pathologists may bring inconsistency to clinical diagnosis.Mueller matrix imaging can reduce the multiple staining processes and provide quantitative diagnostic indicators to characterize liver fibrosis tissues.In this study,a fibersensitive polarization feature parameter(PFP)was derived through the forward sequential feature selection(SFS)and linear discriminant analysis(LDA)to target on the identification of fibrous structures.Then,the Pearson correlation coeffcients and the statistical T-tests between the fiber-sensitive PFP image textures and the liver fibrosis tissues were calculated.The results show the gray level run length matrix(GLRLM)-based run entropy that measures the heterogeneity of the PFP image was most correlated to the changes of liver fibrosis tissues at four stages with a Pearson correlation of 0.6919.The results also indicate the highest Pearson correlation of 0.9996 was achieved through the linear regression predictions of the combination of the PFP image textures.This study demonstrates the potential of deriving a fiber-sensitive PFP to reduce the multiple staining process and provide textures-based quantitative diagnostic indicators for the staging of liver fibrosis.展开更多
Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This co...Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology.This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer.This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis,deciphering the intricate mechanisms governing AICD,elucidating its intricate involvement in cancer signaling pathways,and scrutinizing validated key genes.Moreover,the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.展开更多
Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV6307...Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV63072),which achieve“target-and-release”drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo.Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA(USA300LAC::lux).Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging(BLI)after debridement and implant exchange surgery on day 7,and mice were randomized into seven groups:1)Baseline(harvested at day7,no treatment);2)HPBP(bisphosphonate control for BCS)+vancomycin;3)HPHBP(hydroxybisphosphonate control for HBCS)+vancomycin;4)vancomycin;5)sitafloxacin;6)BCS+vancomycin;and 7)HBCS+vancomycin.BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS+vancomycin.Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS+vancomycin,which also displayed decreases in peri-implant bone loss,osteoclast numbers,and biofilm.To confirm this,we assessed the efficacy of vancomycin,sitafloxacin,and HBCS monotherapy in a transtibial implant model.The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control,and some had evidence of osseous integrated septic implants,suggestive of biofilm eradication.Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.展开更多
Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development. Despite current treatments, pregnant women with pregestational diabetes are at increased risk for congenital malfor...Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development. Despite current treatments, pregnant women with pregestational diabetes are at increased risk for congenital malformations, materno-fetal complications, placental abnormalities and intrauterine malprogramming. The complications during pregnancy concern the mother (gravidic hypertension and/or preeclampsia, cesarean section) and the fetus (macrosomia or intrauterine growth restriction, shoulder dystocia, hypoglycemia and respiratory distress). The fetoplacental impairment and intrauterine programming of diseases in the offspring's later life induced by gestational diabetes are similar to those induced by type 1 and type 2 diabetes mellitus. Despite the existence of several developmental and morphological differences in the placenta from rodents and women, there are similarities in the alterations induced by maternal diabetes in the placenta from diabetic patients and diabetic experimental models. From both human and rodent diabetic experimentalmodels, it has been suggested that the placenta is a compromised target that largely suffers the impact of maternal diabetes. Depending on the maternal metabolic and proin ammatory derangements, macrosomia is explained by an excessive availability of nutrients and an increase in fetal insulin release, a phenotype related to the programming of glucose intolerance. The degree of fetal damage and placental dysfunction and the availability and utilisation of fetal substrates can lead to the induction of macrosomia or intrauterine growth restriction. In maternal diabetes, both the maternal environment and the genetic background are important in the complex and multifactorial processes that induce damage to the embryo, the placenta, the fetus and the offspring. Nevertheless, further research is needed to better understand the mechanisms that govern the early embryo development, the induction of congenital anomalies and fetal overgrowth in maternal diabetes.展开更多
Objective To investigate the effects of quercetin and X-ray on collagen synthesis of cultured human keloid-derived fibroblast and the mechanism.Methods Collagen synthesis of cultured human keloid and normal fibroblast...Objective To investigate the effects of quercetin and X-ray on collagen synthesis of cultured human keloid-derived fibroblast and the mechanism.Methods Collagen synthesis of cultured human keloid and normal fibroblasts were detected by hydroxyproline colorimetric analysis. Immunocytochemical staining was used to investigate collagen I and III expression. mRNA expression of collagen I and III, and transforming growth factor (TGF)-β1 were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. Results Quercetin inhibited the collagen synthesis of both keloid and normal fibroblasts in a dose-dependent manner. Immunocytochemical staining indicated that collagen I and III were down-regulated by quercetin and X-ray (P<0.05), particularly collagen I (P<0.05). mRNA expression of both collagen I and III in quercetin groups significantly decreased compared with that in control group (P<0.05), especially in the group treated with both quercetin and X-ray (P<0.01). mRNA level of TGF-β1 gene was down-regulated by quercertin (P<0.05). Conclusions Quercetin will probably be one of the new medicines which could effectively treat keloid. Quercetin combined with X-ray could reduce the dose of radiation.展开更多
Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As anima...Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion.展开更多
Certain pseudogenes may regulate their protein-coding cousins by competing for miRNAs and play an active biological role in cancer. However, few studies have focused on the association of genetic variations in pseudog...Certain pseudogenes may regulate their protein-coding cousins by competing for miRNAs and play an active biological role in cancer. However, few studies have focused on the association of genetic variations in pseudogenes with cancer prognosis. We selected six potentially functional single nucleotide polymorphisms (SNPs) in cancerrelated pseudogenes, and performed a case-only study to assess the association between those SNPs and the prognosis of hepatocellular carcinoma (HCC) in 331 HBV-positive HCC patients without surgical treatment. Log-rank test and Cox proportional hazard models were used for survival analysis. We found that the A allele of rs9909601 in E2F3P1 was significantly associated with a better prognosis compared with the G allele [adjusted hazard ratio (HR) = 0.69, 95% confidence interval (CI) = 0.56-0.86, P = 0.001]. Additionally, this protective effect was more predominant for patients without chemotherapy and transcatheter hepatic arterial chemoembolization (TACE) treatment. Interestingly, we also detected a statistically significant multiplicative interaction between genotypes of rs9909601 and chemotherapy or TACE status on HCC survival (P for multiplicative interaction 〈 0.001). These findings indicate that rs9909601 in the pseudogene E2F3P1 may be a genetic marker for HCC prognosis in Chinese.展开更多
Objective To study the passive immunization with human monoclonal antibodies as for prophylaxis of human cytomegalovirus (HCMV) infection. Methods Fab monoclonal antibodies to HCMV were recovered by repertoire cloni...Objective To study the passive immunization with human monoclonal antibodies as for prophylaxis of human cytomegalovirus (HCMV) infection. Methods Fab monoclonal antibodies to HCMV were recovered by repertoire cloning of mRNA from a HCMV infected individual. Antigen binding specificity, CDR sequence of VH and VL and neutralizing activity on HCMV AD169 stain were analyzed in vitro. The light and heavy chain Fd fragment genes of Fab antibodies were further cloned into a recombinant baculovirus expression vector pAC-K-Fc to express intact IgG. Secreted products were purified with affinity chromatography using protein G. Results SDS-PAGE and Western blot confirmed the expression of the intact IgG. Immuno-blotting and -precipitation were used to identify HCMV proteins. One Fab monoclonal antibody recognized a conformational HCMV protein. Conclusion IgG antibodies can neutralize the HCMV AD169 strain efficiently at a titer of 2.5 μg/mL and may prove valuable for passive immunoprophylaxis against HCMV infection in humans.展开更多
The gut hormone apelin is a major therapeutic focus for several diseases involving inflammation and aberrant cell growth. We investigated whether apelin-36 contained alternative bioactive peptides associated with norm...The gut hormone apelin is a major therapeutic focus for several diseases involving inflammation and aberrant cell growth. We investigated whether apelin-36 contained alternative bioactive peptides associated with normal physiology or disease. Amino acid sequence analysis of apelin-36 identified an amidation motif consistent with the formation of a secondary bioactive peptide (SCNH2). SCNH2 is proven to be mitogenic and chemotactic in normal/malignant cells and augments angiogenesis via a PTX-resistant/CT-X-sensitive G protein-coupled receptor (GPCR). Notably, SCNH2 is substantially more potent and sensitive than apelin-13 and vascular endothelial growth factor-A. Endogenous SCNH2 is highly expressed in human tumors and placenta and in mouse embryonic tissues. Our findings demonstrate that SCNH2 is a new apelinergic member with critical pluripotent roles in angiogenesis related diseases and embryogenesis via a non-APJ GPCR.展开更多
文摘BACKGROUND A solitary fibrous tumor(SFT)is often located in the pleura,while SFT of the pancreas is extremely rare.Here,we report a case of SFT of the pancreas and discuss imaging,histopathology,and immunohistochemistry for accurate diagnosis and treatment.CASE SUMMARY A 54-year-old man presented to our hospital with pancreatic occupancy for over a month.There were no previous complaints of discomfort.His blood pressure was normal.Blood glucose,tumor markers,and enhanced computed tomography(CT)suggested a malignant tumor.Because the CT appearance of pancreatic cancer varies,we could not confirm the diagnosis;therefore,we performed endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB).Pathology and immunohistochemistry were consistent with SFT of the pancreas.The posto-perative pathology and immunohistochemistry were consistent with the puncture results.The patient presented for a follow-up examination one month after discharge with no adverse effects.CONCLUSION Other diseases must be excluded in patients with a pancreatic mass that cannot be diagnosed.CT and pathological histology have diagnostic value for pancreatic tumors.Endoscopic puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed preoperatively.Surgery is an effective treatment for SFT of the pancreas;however,long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.
基金supported by grants from the Health Commission of Henan Province(Grant No.SBGJ20211008)the Henan Provincial Department of Science and Technology(Grant No.222300420574)。
文摘Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis.Various factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal microbiome.Conversely,enrichment and diversity of the esophageal microbiome can also impact its function.Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC development.Additionally,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment outcomes.In this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and prognosis.Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.
基金supported by National Natural Science Foundation of China(52222215, 52272420, 52072051)。
文摘Parking in a small parking lot within limited space poses a difficult task. It often leads to deviations between the final parking posture and the target posture. These deviations can lead to partial occupancy of adjacent parking lots, which poses a safety threat to vehicles parked in these parking lots. However, previous studies have not addressed this issue. In this paper, we aim to evaluate the impact of parking deviation of existing vehicles next to the target parking lot(PDEVNTPL) on the automatic ego vehicle(AEV) parking, in terms of safety, comfort, accuracy, and efficiency of parking. A segmented parking training framework(SPTF) based on soft actor-critic(SAC) is proposed to improve parking performance. In the proposed method, the SAC algorithm incorporates strategy entropy into the objective function, to enable the AEV to learn parking strategies based on a more comprehensive understanding of the environment. Additionally, the SPTF simplifies complex parking tasks to maintain the high performance of deep reinforcement learning(DRL). The experimental results reveal that the PDEVNTPL has a detrimental influence on the AEV parking in terms of safety, accuracy, and comfort, leading to reductions of more than 27%, 54%, and 26%respectively. However, the SAC-based SPTF effectively mitigates this impact, resulting in a considerable increase in the parking success rate from 71% to 93%. Furthermore, the heading angle deviation is significantly reduced from 2.25 degrees to 0.43degrees.
文摘BACKGROUND Epithelioid trophoblastic tumor(ETT)is an extremely rare malignant gestational trophoblastic neoplasm commonly presenting with abnormal vaginal bleeding,abdominal pain,and increased human chorionic gonadotropin(hCG).This study reported a case of uterine ETT with the main manifestation being increased hCG.CASE SUMMARY A 39-year-old female was referred to the Ningbo Maternal and Child Hospital of China in December 2022,complaining of increased hCG levels for 1 month.Magnetic resonance imaging revealed gestational trophoblastic tumor,and hysteroscopic electrotomy and curettage of intrauterine hyperplasia were performed.The patient was diagnosed with uterine ETT through postoperative pathological examination and immunohistochemical results.Total laparoscopic hysterectomy and bilateral salpingectomy were performed,and hCG levels returned to normal.The patient was without recurrence during the postoperative 3-month follow-up.CONCLUSION This study reported a case of uterine ETT with the main manifestation being increased hCG,highlighting that ETT should be considered in the presence of abnormal hCG.A total laparoscopic hysterectomy is recommended.
文摘The direct delivery of inhaled antibiotics to the respiratory tract has been a subject of enduring interest among medical practitioners and researchers due to the associated favorable pharmacokinetics.This interest has been particularly pronounced in the context of critically illpatients,wherehealthcare-associatedpulmonary infections represent a significant challenge,driving continued exploration of inhaled antibiotics for intubated patients.Recent high-level evidence has shown a very promising application in the field of ventilator-associated pneumonia (VAP) prevention.^([1]).
基金the Chinese Scholarship Council(Grant No.202206240086)the National Natural Science Foundation of China(Grant No.82170432)programs from Science and Technology Department of Sichuan Province(Grant No.2020YFSY0024).
文摘The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.
基金Supported by National Natural Science Foundation of China,No.81960877University Innovation Fund of Gansu Province,No.2021A-076+5 种基金Gansu Province Science and Technology Plan(Innovation Base and Talent Plan),No.21JR7RA561Natural Science Foundation of Gansu Province,No.21JR1RA267 and No.22JR5RA582Education Technology Innovation Project of Gansu Province,No.2022A-067Innovation Fund of Higher Education of Gansu Province,No.2023A-088Gansu Province Science and Technology Plan International Cooperation Field Project,No.23YFWA0005and Open Project of Key Laboratory of Dunhuang Medicine and Transformation of Ministry of Education,No.DHYX21-07,No.DHYX22-05,and No.DHYX21-01.
文摘BACKGROUND Breast cancer is a multifaceted and formidable disease with profound public health implications.Cell demise mechanisms play a pivotal role in breast cancer pathogenesis,with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence.AIM To investigate the impact of ATP-induced cell death(AICD)on breast cancer,enhancing our understanding of its mechanism.METHODS The foundational genes orchestrating AICD mechanisms were extracted from the literature,underpinning the establishment of a prognostic model.Simultaneously,a microRNA(miRNA)prognostic model was constructed that mirrored the gene-based prognostic model.Distinctions between high-and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized,with the aim of delineating common influence mechanisms,substantiated through enrichment analysis and immune infiltration assessment.RESULTS The mRNA prognostic model in this study encompassed four specific mRNAs:P2X purinoceptor 4,pannexin 1,caspase 7,and cyclin 2.The miRNA prognostic model integrated four pivotal miRNAs:hsa-miR-615-3p,hsa-miR-519b-3p,hsa-miR-342-3p,and hsa-miR-324-3p.B cells,CD4+T cells,CD8+T cells,endothelial cells,and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes.Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways,while miRNA risk scores significantly enriched 29 signaling pathways,with 16 pathways being jointly enriched.CONCLUSION Of paramount significance,distinct mRNA and miRNA signature models were devised tailored to AICD,both potentially autonomous prognostic factors.This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools,offering an unparalleled window for innovative interventions.Essentially,this paper reveals the hitherto enigmatic link between AICD and breast cancer,potentially leading to revolutionary progress in personalized oncology.
基金funded by the National Key R&D Program of China[2021YFC2301102]National Natural Science Foundation of China[82202593]Key R&D Program of Hebei Province[223777100D].
文摘Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP.Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays.Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.
文摘Helicobacter pylori(H.pylori)has been found in the oral cavity and stomach,and its infection is one of the most frequent worldwide.We reviewed the literature and conducted a Topic Highlight,which identified studies reporting an association between H.pylori-infection in the oral cavity and H.pylori-positive stomach bacterium.This work was designed to determine whether H.pylori is the etiologic agent in periodontal disease,recurrent aphthous stomatitis(RAS),squamous cell carcinoma,burning and halitosis.Record selection focused on the highest quality studies and meta-analyses.We selected 48 articles reporting on the association between saliva and plaque and H.pylori-infection.In order to assess periodontal disease data,we included 12 clinical trials and 1 meta-analysis.We evaluated 13 published articles that addressed the potential association with RAS,and 6 with squamous cell carcinoma.Fourteen publications focused on our questions on burning and halitosis.There is a close relation between H.pylori infection in the oral cavity and the stomach.The mouth is the first extra-gastric reservoir.Regarding the role of H.pylori in the etiology of squamous cell carcinoma,no evidence is still available.
基金Supported by Clinical and Translational Medicine Research Foundation of Chinese Academy of Medical Sciences,No. 2020-I2M-C&T-B-038Capital Health Research and Development of Special Project,No. 2022-1-2181Group Medical Aid Project of the Tibet Autonomous Region Natural Science Foundation,No. XZ2020ZR-ZY28[Z]
文摘BACKGROUND Emerging studies indicate the critical involvement of microorganisms,such as Epstein-Barr virus(EBV),in the pathogenesis of inflammatory bowel disease(IBD).Immunosuppressive therapies for IBD can reactivate latent EBV,complicating the clinical course of IBD.Moreover,the clinical significance of EBV expression in B lymphocytes derived from IBD patients’intestinal tissues has not been explored in detail.AIM To explore the clinical significance of latent EBV infection in IBD patients.METHODS Latent EBV infection was determined by double staining for EBV encoded RNA and CD20 in colon specimens of 43 IBD patients who underwent bowel resection.Based on the staining results,the patients were divided into two groups,according to their latent EBV infection states-negative(n=33)and positive(n=10).Illness severity of IBD were assigned according to Crohn’s disease activity index(ulcerative colitis)and Mayo staging system(Crohn’s disease).The clinicpathological data were analyzed between the two different latent EBV groups and also between the mild-to-moderate and severe disease groups.RESULTS Systolic pressure(P=0.005),variety of disease(P=0.005),the severity of illness(P=0.002),and pre-op corticosteroids(P=0.025)were significantly different between the EBV-negative and EBV-positive groups.Systolic pressure(P=0.001),variety of disease(P=0.000),pre-op corticosteroids(P=0.011)and EBV infection(P=0.003)were significantly different between the mild-to-moderate and severe disease groups.CONCLUSION IBD patients with latent EBV infection may manifest more severe illnesses.It is suggested that the role of EBV in IBD development should be further investigated,latent EBV infection in patients with serious IBD should be closely monitored,and therapeutic course should be optimized.
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.11974206 and 61527826).
文摘Mueller matrix imaging is emerging for the quantitative characterization of pathological microstructures and is especially sensitive to fibrous structures.Liver fibrosis is a characteristic of many types of chronic liver diseases.The clinical diagnosis of liver fibrosis requires time-consuming multiple staining processes that specifically target on fibrous structures.The staining proficiency of technicians and the subjective visualization of pathologists may bring inconsistency to clinical diagnosis.Mueller matrix imaging can reduce the multiple staining processes and provide quantitative diagnostic indicators to characterize liver fibrosis tissues.In this study,a fibersensitive polarization feature parameter(PFP)was derived through the forward sequential feature selection(SFS)and linear discriminant analysis(LDA)to target on the identification of fibrous structures.Then,the Pearson correlation coeffcients and the statistical T-tests between the fiber-sensitive PFP image textures and the liver fibrosis tissues were calculated.The results show the gray level run length matrix(GLRLM)-based run entropy that measures the heterogeneity of the PFP image was most correlated to the changes of liver fibrosis tissues at four stages with a Pearson correlation of 0.6919.The results also indicate the highest Pearson correlation of 0.9996 was achieved through the linear regression predictions of the combination of the PFP image textures.This study demonstrates the potential of deriving a fiber-sensitive PFP to reduce the multiple staining process and provide textures-based quantitative diagnostic indicators for the staging of liver fibrosis.
基金Supported by National Natural Science Foundation of China,No.81960877University Innovation Fund of Gansu Province,No.2021A-076+4 种基金Gansu Province Science and Technology Plan(Innovation Base and Talent Plan),No.21JR7RA561Natural Science Foundation of Gansu Province,No.21JR1RA267 and No.22JR5RA582Education Technology Innovation Project of Gansu Province,No.2022A-067Innovation Fund of Higher Education of Gansu Province,No.2023A-088Gansu Province Science and Technology Plan International Cooperation Field Project,No.23YFWA0005.
文摘Adenosine triphosphate(ATP)induced cell death(AICD)is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions.This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology.This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer.This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis,deciphering the intricate mechanisms governing AICD,elucidating its intricate involvement in cancer signaling pathways,and scrutinizing validated key genes.Moreover,the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.
基金supported by grants from the National Institutes of Health(SBIR R44 AI125060,NIAMS P50 AR072000,and NIAMS P30 AR069655)。
文摘Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV63072),which achieve“target-and-release”drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo.Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA(USA300LAC::lux).Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging(BLI)after debridement and implant exchange surgery on day 7,and mice were randomized into seven groups:1)Baseline(harvested at day7,no treatment);2)HPBP(bisphosphonate control for BCS)+vancomycin;3)HPHBP(hydroxybisphosphonate control for HBCS)+vancomycin;4)vancomycin;5)sitafloxacin;6)BCS+vancomycin;and 7)HBCS+vancomycin.BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS+vancomycin.Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS+vancomycin,which also displayed decreases in peri-implant bone loss,osteoclast numbers,and biofilm.To confirm this,we assessed the efficacy of vancomycin,sitafloxacin,and HBCS monotherapy in a transtibial implant model.The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control,and some had evidence of osseous integrated septic implants,suggestive of biofilm eradication.Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.
文摘Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development. Despite current treatments, pregnant women with pregestational diabetes are at increased risk for congenital malformations, materno-fetal complications, placental abnormalities and intrauterine malprogramming. The complications during pregnancy concern the mother (gravidic hypertension and/or preeclampsia, cesarean section) and the fetus (macrosomia or intrauterine growth restriction, shoulder dystocia, hypoglycemia and respiratory distress). The fetoplacental impairment and intrauterine programming of diseases in the offspring's later life induced by gestational diabetes are similar to those induced by type 1 and type 2 diabetes mellitus. Despite the existence of several developmental and morphological differences in the placenta from rodents and women, there are similarities in the alterations induced by maternal diabetes in the placenta from diabetic patients and diabetic experimental models. From both human and rodent diabetic experimentalmodels, it has been suggested that the placenta is a compromised target that largely suffers the impact of maternal diabetes. Depending on the maternal metabolic and proin ammatory derangements, macrosomia is explained by an excessive availability of nutrients and an increase in fetal insulin release, a phenotype related to the programming of glucose intolerance. The degree of fetal damage and placental dysfunction and the availability and utilisation of fetal substrates can lead to the induction of macrosomia or intrauterine growth restriction. In maternal diabetes, both the maternal environment and the genetic background are important in the complex and multifactorial processes that induce damage to the embryo, the placenta, the fetus and the offspring. Nevertheless, further research is needed to better understand the mechanisms that govern the early embryo development, the induction of congenital anomalies and fetal overgrowth in maternal diabetes.
文摘Objective To investigate the effects of quercetin and X-ray on collagen synthesis of cultured human keloid-derived fibroblast and the mechanism.Methods Collagen synthesis of cultured human keloid and normal fibroblasts were detected by hydroxyproline colorimetric analysis. Immunocytochemical staining was used to investigate collagen I and III expression. mRNA expression of collagen I and III, and transforming growth factor (TGF)-β1 were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. Results Quercetin inhibited the collagen synthesis of both keloid and normal fibroblasts in a dose-dependent manner. Immunocytochemical staining indicated that collagen I and III were down-regulated by quercetin and X-ray (P<0.05), particularly collagen I (P<0.05). mRNA expression of both collagen I and III in quercetin groups significantly decreased compared with that in control group (P<0.05), especially in the group treated with both quercetin and X-ray (P<0.01). mRNA level of TGF-β1 gene was down-regulated by quercertin (P<0.05). Conclusions Quercetin will probably be one of the new medicines which could effectively treat keloid. Quercetin combined with X-ray could reduce the dose of radiation.
文摘Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion.
基金funded by the National Natural Science Foundation of China(81372606 and 81072344)supported by the National Key Basic Research Program Grant(2013CB911400)+6 种基金the project supportedby the National Science Foundation for Distinguished Young Scholarsof China(81225020)Foundation of Jiangsu Province for Distinguished Young Scholars(BK2012042)Foundation for the Program for NewCentury Excellent Talents in University(NCET-10-0178)the Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions(122031)Young Tip-top Talents Support Program by the Organization Department of the CPC Central Committee,the Author of National Excellent Doctoral Dissertation(201081)Jiangsu Province Clinical Science and Technology Projects(BL2012008)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and PreventiveMedicine)
文摘Certain pseudogenes may regulate their protein-coding cousins by competing for miRNAs and play an active biological role in cancer. However, few studies have focused on the association of genetic variations in pseudogenes with cancer prognosis. We selected six potentially functional single nucleotide polymorphisms (SNPs) in cancerrelated pseudogenes, and performed a case-only study to assess the association between those SNPs and the prognosis of hepatocellular carcinoma (HCC) in 331 HBV-positive HCC patients without surgical treatment. Log-rank test and Cox proportional hazard models were used for survival analysis. We found that the A allele of rs9909601 in E2F3P1 was significantly associated with a better prognosis compared with the G allele [adjusted hazard ratio (HR) = 0.69, 95% confidence interval (CI) = 0.56-0.86, P = 0.001]. Additionally, this protective effect was more predominant for patients without chemotherapy and transcatheter hepatic arterial chemoembolization (TACE) treatment. Interestingly, we also detected a statistically significant multiplicative interaction between genotypes of rs9909601 and chemotherapy or TACE status on HCC survival (P for multiplicative interaction 〈 0.001). These findings indicate that rs9909601 in the pseudogene E2F3P1 may be a genetic marker for HCC prognosis in Chinese.
文摘Objective To study the passive immunization with human monoclonal antibodies as for prophylaxis of human cytomegalovirus (HCMV) infection. Methods Fab monoclonal antibodies to HCMV were recovered by repertoire cloning of mRNA from a HCMV infected individual. Antigen binding specificity, CDR sequence of VH and VL and neutralizing activity on HCMV AD169 stain were analyzed in vitro. The light and heavy chain Fd fragment genes of Fab antibodies were further cloned into a recombinant baculovirus expression vector pAC-K-Fc to express intact IgG. Secreted products were purified with affinity chromatography using protein G. Results SDS-PAGE and Western blot confirmed the expression of the intact IgG. Immuno-blotting and -precipitation were used to identify HCMV proteins. One Fab monoclonal antibody recognized a conformational HCMV protein. Conclusion IgG antibodies can neutralize the HCMV AD169 strain efficiently at a titer of 2.5 μg/mL and may prove valuable for passive immunoprophylaxis against HCMV infection in humans.
文摘The gut hormone apelin is a major therapeutic focus for several diseases involving inflammation and aberrant cell growth. We investigated whether apelin-36 contained alternative bioactive peptides associated with normal physiology or disease. Amino acid sequence analysis of apelin-36 identified an amidation motif consistent with the formation of a secondary bioactive peptide (SCNH2). SCNH2 is proven to be mitogenic and chemotactic in normal/malignant cells and augments angiogenesis via a PTX-resistant/CT-X-sensitive G protein-coupled receptor (GPCR). Notably, SCNH2 is substantially more potent and sensitive than apelin-13 and vascular endothelial growth factor-A. Endogenous SCNH2 is highly expressed in human tumors and placenta and in mouse embryonic tissues. Our findings demonstrate that SCNH2 is a new apelinergic member with critical pluripotent roles in angiogenesis related diseases and embryogenesis via a non-APJ GPCR.