Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.

Altered fear engram encoding underlying conditioned versus unconditioned stimulus-initiated memory updating.

It is known that post-retrieval extinction but not extinction alone could erase fear memory. However, whether the coding pattern of original fear engrams is remodeled or inhibited remains largely unclear. We found increased reactivation of engram cells in the prelimbic cortex and basolateral amygdala during memory updating. Moreover, conditioned stimulus- and unconditioned stimulus-initiated memory updating depends on the engram cell reactivation in the prelimbic cortex and basolateral amygdala, respectively. Last, we found that memory updating causes increased overlapping between fear and extinction cells, and the original fear engram encoding was altered during memory updating. Our data provide the first evidence to show the overlapping ensembles between fear and extinction cells and the functional reorganization of original engrams underlying conditioned stimulus- and unconditioned stimulus-initiated memory updating.

Aerobic granulation and microbial community succession in sequencing batch reactors treating the low strength wastewater: The dual effects of weak magnetic field and exogenous signal molecule.

The application of magneto-biological effects in wastewater treatment has been brought under the spotlight recently. This work explored the dual effects of magnetic field (MF) and exogenous N-hexanoyl-l-homoserine lactone (C6-HSL) on activated sludge granulation. Results showed that exposure to MF and C6-HSL obviously accelerated the aerobic granulation process and promoted the secretion of extracellular polymeric substances, especially polysaccharides, humic acid-like substances, aromatic proteins, and tryptophan-like substrates. Illumina MiSeq sequencing results indicated that the introduction of MF and C6-HSL can increase the diversity and richness of microbial community without antagonism, and the biological basis for rapid granulation process in this study was the enrichment of slow-growing bacteria Candidatus_Competibacter. Besides, the overgrowth of filamentous bacteria Thiothrix could be suppressed due to the presence of MF, improving the stabilities of aerobic granular sludge. This study provides a new understanding of the MF and C6-HSL effects on rapid aerobic granulation when treating the low-strength wastewater.

Carboxypeptidase E Regulates Activity-Dependent TrkB Neuronal Surface Insertion and Hippocampal Memory.

Activity-dependent insertion of the tropomyosin-related kinase B (TrkB) receptor into the plasma membrane can explain, in part, the preferential effect of brain-derived neurotrophic factor (BDNF) on active neurons and synapses; however, the underlying molecular mechanisms remain obscure. Here, we report a novel function for carboxypeptidase E (CPE) in controlling chemical long-term potentiation stimuli-induced TrkB surface delivery in hippocampal neurons. Total internal reflection fluorescence assays and line plot assays showed that CPE facilitates TrkB transport from dendritic shafts to the plasma membrane. The Box2 domain in the juxtamembrane region of TrkB and the C terminus of CPE are critical for the activity-dependent plasma membrane insertion of TrkB. Moreover, the transactivator of transcription TAT-CPE452-466, which could block the association between CPE and TrkB, significantly inhibited neuronal activity-enhanced BDNF signaling and dendritic spine morphologic plasticity in cultured hippocampal neurons. Microinfusion of TAT-CPE452-466 into the dorsal hippocampus of male C57BL/6 mice inhibited the endogenous interaction between TrkB and CPE and diminished fear-conditioning-induced TrkB phosphorylation, which might lead to an impairment in hippocampal memory acquisition and consolidation but not retrieval. These results suggest that CPE modulates activity-induced TrkB surface insertion and hippocampal-dependent memory and sheds light on our understanding of the role of CPE in TrkB-dependent synaptic plasticity and memory modulation.SIGNIFICANCE STATEMENT It is well known that BDNF acts preferentially on active neurons; however, the underlying molecular mechanism is not fully understood. In this study, we found that the cytoplasmic tail of CPE could interact with TrkB and facilitate the neuronal activity-dependent movement of TrkB vesicles to the plasma membrane. Blocking the association between CPE and TrkB decreased fear-conditioning-induced TrkB phosphorylation and led to hippocampal memory deficits. These findings provide novel insights into the role of CPE in TrkB intracellular trafficking as well as in mediating BDNF/TrkB function in synaptic plasticity and hippocampal memory.

Identification and investigation of Calodium hepaticum in rodents and insectivores from Wuhan section of the Yangtze River in China

Objective: To investigate the prevalence of Calodium hepaticum (C. hepaticum) in rodents and insectivores from Wuhan section of the Yangtze River in China, and to provide evidence for the prevention and treatment of hepatic Calodium infection.Methods: Rodents and insectivores were captured from three selected Yangtze River beaches using mousetraps. The three survey sites were divided into six areas according to natural conditions, with 60 mousetraps placed in each area. The liver lesions in the captured rodents were observed by the naked eye and the eggs in the liver tissue were observed by microscopic examination. Results: A total of 1080 mousetraps were placed, and 1075 mousetraps were retrieved, with the retrieve rate as 99.5％. A total of 101 Apodemus agrarius, 12 Rattus norvegicus, and 9 Crocidura attenuata were caught. The average density of rodents and insectivores was 10.5％ and 0.8％, respectively. DNA of egg nodules from infected rodents showed 98％ similarity with that of C. hepaticum 18S rRNA (LC425008.1). One Rattus norvegicus was infected with C. hepaticum, with an infection rate of 3.23％ in the Erqi river beach; the other two beaches did not show the incidence of C. hepaticum. Conclusions: The monitoring of C. hepaticum in the Yangtze River beaches should be strengthened to reduce the risk of human C. hepaticum infection.

Identification and investigation of Calodium hepaticum in rodents and insectivores from Wuhan section of the yangtze river in China

Objective: To investigate the prevalence of Calodium hepaticum (C. hepaticum) in rodents and insectivores from Wuhan section of the Yangtze River in China, and to provide evidence for the prevention and treatment of hepatic Calodium infection. Methods: Rodents and insectivores were captured from three selected Yangtze River beaches using mousetraps. The three survey sites were divided into six areas according to natural conditions, with 60 mousetraps placed in each area. The liver lesions in the captured rodents were observed by the naked eye and the eggs in the liver tissue were observed by microscopic examination. Results: A total of 1 080 mousetraps were placed, and 1 075 mousetraps were retrieved, with the retrieve rate as 99.5%. A total of 101 Apodemus agrarius, 12 Rattus norvegicus, and 9 Crocidura attenuata were caught. The average density of rodents and insectivores was 10.5% and 0.8%, respectively. DNA of egg nodules from infected rodents showed 98% similarity with that of C. hepaticum 18S rRNA (LC425008.1). One Rattus norvegicus was infected with C. hepaticum, with an infection rate of 3.23% in the Erqi river beach; the other two beaches did not show the incidence of C. hepaticum. Conclusions: The monitoring of C. hepaticum in the Yangtze River beaches should be strengthened to reduce the risk of human C. hepaticum infection. Zhou Shui-Mao 1 Wuhan Centers for Disease Prevention and Control, Wuhan 430015 Jin Xian-Ling 2 Wuhan Xinzhou Schistosomiasis Control Institute, Wuhan 430015 Wang Hao 3 Wuhan Centers for Disease Prevention and Control, Wuhan 430015 Luo Hua-Tang 4 Wuhan Centers for Disease Prevention and Control, Wuhan 430015 Jia Xi-Shuai 5 Wuhan Centers for Disease Prevention and Control, Wuhan 430015 Wang ZQ, Lin XM, Wang Y, Cui J. The emerging but neglected hepatic capillariasis in China. Asian Pac J Trop Biomed 2013; 3(2): 146-147. Shen LJ, Luo ZY, Li W, Li ZH, Gao C, Yang WB, et al. Investigation on rats infected with Capillaria hepatica in Da li. Chin J Parasit Dis Con 2003; 16(5): 296-298. Fischer K, Gankpala A, Gankpala L, Bolay FK, Curtis KC, Weil GJ, et al. Capillaria ova and diagnosis of Trichuris trichiura infection in humans by Kato-Katz smear, Liberia. Emerg Infect Dis 2018; 24(8): 1551-1554. Fuehrer HP. An overview of the host spectrum and distribution of Calodium hepaticum (syn. Capillaria hepatica): Part 1-Muroidea. Parasitol Res 2014; 113(2): 619-640. Lin XM, Xu BL, ZHao XD, Li H, Huang Q, Deng Y, et al. Epidemiological investigation on Capillaria hepatica infection among little animal in Henan Province. J Pathogen Bio 2007; 2(1): 44-46. Ling HB, Pan CW, Yi WP, Huang HC, Liu QZ, Zheng XY, et al. Epidemiological and biological studies of Capillaria hepatica of rodents in Wenzhou district. J Wenzhou Med Col 2000; 30(1): 13-15. Fuehrer HP, Igel P, Auer H. Capillaria hepatica in man-an overview of hepatic capillariosis and spurious infections. Parasitol Res 2011; 109(4): 969-979. Simoes RO, Luque JL, Faro MJ, Motta E, Maldonado JR. Prevalence of Calodium hepaticum (syn. Capillaria hepatica) in Rattus norvegicus in the urban area of Rio de Janeiro, Brazil. Rev Inst Med Trop Sao Paulo 2014; 56(5): 455-457. Wang ZQ, Cui J, Wang Y. Persistent febrile hepatomegaly with eosinophilia due to hepatic capillariasis in Central China. Ann Trop Med Parasitol 2011; 105(6): 469-472. Klenzak J, Mattia A, Valenti A, Goldberg J. Hepatic capillariasis in Maine presenting as a hepatic mass. Am J Trop Med Hyg 2005; 72(5): 651-653.

Author Correction: Investigation of Dietary Factors and Esophageal Cancer Knowledge: Comparison of Rural Residents in High- and Low-incidence Areas.

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Investigation of Dietary Factors and Esophageal Cancer Knowledge: Comparison of Rural Residents in High- and Low-incidence Areas.

To compare the differences in dietary status and knowledge of esophageal cancer (EC) between residents of high- and low-incidence areas. We investigated dietary conditions and EC knowledge among residents in high- and low-EC incidence areas (Yanting and Qingzhen counties). Residents in Yanting consumed more pickled vegetables, salted meat and barbecued food (P < 0.05). Analysis of the past ten-year trend in Yanting consumed fresh vegetables/fruits, beans, sauerkraut, hot food, and barbecued food had gradually increased, and the trend was less than that in Qingzhen County. However, the gradual increasing trend in consumption of pickled vegetables, pickled meat, and spicy food over the past 10 years was greater (P < 0.05). Drinking water in Yanting County was healthier than that in Qingzhen County (P < 0.05). In terms of EC knowledge, the proportions of residents in Yanting who had a clear understanding, knowledge or had heard of EC or knew the common causes, primary symptoms, therapeutic measures, preventive measures, and government interventions for EC were all higher than in Qingzhen (P < 0.05). Residents in Yanting had greater EC knowledge but more harmful dietary habits than those in Qingzhen.

Clinical efficacy of surgical treatment for stage Ⅳ gastric cancer after conversion therapy / 中华消化外科杂志

Objective To investigate the clinical efficacy of surgical treatment for stage Ⅳ gastric cancer after conversion therapy.Methods The retrospective cohort study was conducted.The clinicopathological data of 50 stage Ⅳ gastric cancer patients who were admitted to the First Affiliated Hospital of Dalian Medical University between January 2012 and June 2016 were collected.All the 50 patients who were diagnosed with single distal metastasis underwent chemotherapy.After chemotherapy,21 patients with operation indication receiving gastrectomy (R0 or R1 resection) were allocated into the conversion surgery group and 29 without operation indication continuing to chemotherapy were allocated into the chenotherapy group.Patients received S-1 + oxaliplatin or S-1 + docetaxel regimen.Patients underwent open distal or total gastrectomy.Observation indicators:(1) response assessment of chemotherapy (complete remission,partial remission,stable disease and progressive disease),grading of of adverse reactions;(2) intra-and post-operative situations of conversion surgery group:operation procedures,intraoperative situations (operation time,volume of blood loss,number of lymph node dissected and surgical margin) and postoperative situations (complications and duration of hospital stay);(3)comparison of follow-up and survival between the 2 groups;(4) prognostic factors analysis affecting stage Ⅳ gastric cancer patients.Follow-up using outpatient examination,correspondence and telephone interview was performed to detect postoperative survival of patients up to September 2016.Survival time was from operation to the last follow-up or death.Measurement data with normal distribution were represented as x±s.Comparison of count data and univariate analysis were done using the chi-square test.Ordinal data were analyzed by the nonparametric test.The survival rate was calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.Multivariate analysis was done using the COX regression model.Results (1) Response assessment of chemotherapy:of 50 patients,24 received S-1 + oxaliplatin regimen and 26 received S-1 + docetaxel regimen.Twenty-one patients in the conversion surgery group underwent chemotherapy,with negative peritoneal metastasis,N2 and below of lymph node metastasis (No.16 lymph node disappeared or reduced),invasive depth ＜T4b and narrowing or disappeared hepatic metastasis.A median preoperative chemotherapy cycle was 4.2 cycles (range,2.0-9.0 cycles).Chemotherapy reaction of 21 patients:15 had partial remission and 6 had stable disease.Twenty-nine patients without operation indication in the chemotherapy group didn't receive surgery.The median cycle of first-line chemotherapy was 5.5 cycles (range,2.0-10.0 cycles).Chemotherapy reaction of 29 patients:13 had partial remission,11 had stable disease and 5 patient had progressive disease.Chemotherapy adverse reactions of 50 patients:26 had reduced white blood cells (WBCs),including 6 with grade Ⅲ-Ⅳ of adverse reactions;29 had reduced neutrophils,including 12 with grade Ⅲ-Ⅳ of adverse reactions;18 had anemia,including 6 with grade Ⅲ-Ⅳ of adverse reactions;12 had reduced platelets,including 2 with grade Ⅲ-Ⅳ of adverse reactions;27 had apositia,including 5 with grade Ⅲ-Ⅳ of adverse reactions;7 had stomatitis;9 had diarrhea;3 had elevated serum creatinin;4 had hand-foot syndrome;3 had abnormal sensory nerve.There was no chemotherapy-related death.(2) Intra-and post-operative situations of conversion surgery group:of 21 patients in the conversion surgery group,8 underwent radical total gastrectomy + D3 lymph node dissection,6 underwent radical distal gastrectomy + D3 lymph node dissection and 7 underwent radical distal gastrectomy + D2 lymph node dissection (including 4 combined with resection of hepatic metastatic tumors and 1 combined with radiofrequency ablation of hepatic metastatic tumor).Operation time,volume of blood loss,number of lymph node dissected and recovery time of gastrointestinal function of 21 patients were (216±31)minutes,(128±52)mL,31±8 and (3.0± 0.7)days,respectively.There were 17 patients receiving R0 resection and 4 receiving R1 resection (3 with positive gastric margin and 1 with positive hepatic margin).There was no death.Seven of 21 patients with complications were cured by conservative treatment,including 2 with pancreatic fistula,1 with intra-abdominal hemorrhage,1 with intestinal obstruction,1 with pneumonia,1 with intra-abdominal infection and 1 with wound infection.Duration of hospital stay of 21 patients was (13.0±3.0) days.(3) Comparison of follow-up and survival between the 2 groups:50 patients were followed up for 6-46 months,with a median time of 24 months.The 3-year cumulative survival rates in the conversion surgery and chemotherapy groups were respectively 33.3％ and 6.9％,with a statistically significant difference between the 2 groups (x2 =7.678,P＜0.05).Results of further analysis showed that R0 resection of 17 patients and R1 resection of 4 patients in the conversion surgery group were respecgtively (25.3±2.8)months and (8.3±0.9)months,with a statistically significant difference between the 2 groups (X2=16.242,P＜0.05).(4) Prognostic factors analysis affecting stage Ⅳ gastric cancer patients:results of univariate analysis showed that T stage,N stage,response assessment of chemotherapy,surgery after chemotherapy and degree of tumor radical resection were related factors affecting prognosis of stage Ⅳ gastric cancer patients (X2 =5.288,12.645,25.581,8.372,12.001,P＜0.05).Results of multivariate analysis showed that R1 resection after conversion therapy was an independent risk factor affecting prognosis of stage Ⅳ gastric cancer patients (HR=14.021,95％ confidence interval:1.928-10.938,P＜0.05).Conclusion Radical resection after conversion therapy can increase survival rate of stage Ⅳ gastric cancer patients,and R1 resection after conversion therapy is an independent risk factor affecting poor prognosis of stage Ⅳ gastric cancer patients.