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BACKGROUND: Intraperitoneal hyperthermic perfusion (IPHP) has achieved positive results in treating various abdominal cancers but infrequently reported in resectable pancreatic head cancer. This study was designed to explore the safety and efficacy of pancreaticoduodenectomy plus intraperitoneal hyperthermic perfusion (PD + IPHP) in patients with pancreatic cancer. METHODS: Data of pancreatic cancer patients undergoing pancreaticoduodenectomy were retrospectively analyzed, including PD + IPHP (n = 28) and PD group (n = 29). IPHP was performed during surgery, on postoperative day (POD) 2, and POD 4 with normal saline as the perfusion solution. Complications and overall survival of these patients were observed and recorded. RESULTS: There was no significant difference in the incidence of major postoperative complications between PD + IPHP group and PD group. The median overall survival (OS) time of the PD + IPHP group was 19.0 months, the 1-year survival rate was 82.35%, and the 2-year survival rate was 49.41%. The median OS time of the PD group was 13.0 months, the 1-year survival rate was 51.00%, and the 2-year survival rate was 27.33% (Log-rank, P = 0.030; Breslow, P = 0.039). Cox proportional risk model showed that IPHP was an independent factor to improve survival outcomes of these patients (hazard ratio = 0.363, 95% confidence interval: 0.14-0.94; P = 0.038). CONCLUSIONS: Intraperitoneal hyperthermic perfusion significantly improves the survival outcomes of pancreatic head cancer patients undergoing PD and does not bring extra risks of complications.
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Hipertermia Inducida , Neoplasias Pancreáticas , Neoplasias Gástricas , Estudios de Cohortes , Terapia Combinada , Humanos , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Perfusión , Estudios Retrospectivos , Neoplasias Gástricas/cirugíaRESUMEN
On the North China Plain, one of the most water-deficient regions in China, bare fallow has been implemented over a large-scale area to conserve water during the growth season of water-intensive winter wheat since 2015. However, the effects of this bare fallow on fungal community and the occurrence of crop diseases are poorly understood. Here we measured soil chemical properties, fungal community composition, and the occurrence of crop diseases after 15 years of long-term fallow (continuous maize or soybean) and non-fallow (maize-wheat rotation; soybean-wheat rotation) cropping systems. Bare fallow during the winter-wheat growth season significantly decreased soil organic matter, available nitrogen, and phosphorus. It also changed the composition of soil fungal communities, i.e., increased relative abundances of some potentially pathogenic species of Lectera, Fusarium, and Volutella but decreased beneficial Cladorrhium and Schizothecium. Meanwhile, the epidemic tendency of maize diseases changed correspondingly: the disease index of southern corn leaf blight and maize brown spot increased, but the incidence of stalk rot decreased compared with the non-fallow system. Soybean diseases were very mild regardless of the cropping system during the total experimental period. Network analysis demonstrated that the soil fungal diversity associated with maize diseases was affected by the decreased soil organic matter and available nitrogen and phosphorus. Our results suggest that bare fallow in the winter-wheat season affected the soil chemical properties, fungal community, and the occurrence of maize fungal diseases.
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Micobioma , Micosis , Fertilizantes/análisis , Estaciones del Año , Suelo , Triticum , Zea maysRESUMEN
BACKGROUND: Open surgery for hilar cholangiocarcinoma (HCCA) has already been widely reported and analyzed. However, the laparoscopic technique for treating HCCA remains controversial because of the lack of radicality and poor assessment of the resectability of hilar structures without direct palpation. The aim of this study was to provide detailed surgical procedures and photographs of this technically demanding operation, describe our experience in assessing resectability before and during surgery, and confirm the radicality of laparoscopic resection of Bismuth type III and IV HCCA. METHODS: From November 2016 to November 2018, nine patients received laparoscopic resection of Bismuth type III or IV HCCA in our department. RESULTS: Laparoscopic right hepatectomy was performed in four patients, and laparoscopic left hepatectomy was performed in five patients. Negative margins were achieved in all patients. Complications were found in two (22.22%) patients, with bile leakage and hepatic insufficiency each in one patient. The patient developing hepatic insufficiency had persistent and ongoing liver failure and finally expired. CONCLUSION: The radicality of laparoscopic resection for Bismuth type III and IV HCCA can be technically improved through extended lymphadenectomy, visual assessment of hilar structures, and frozen section techniques.
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Neoplasias de los Conductos Biliares/cirugía , Hepatectomía/métodos , Tumor de Klatskin/cirugía , Laparoscopía/métodos , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea , Transfusión de Eritrocitos , Femenino , Humanos , Tumor de Klatskin/patología , Masculino , Persona de Mediana Edad , Tempo Operativo , Selección de Paciente , Complicaciones PosoperatoriasRESUMEN
Fusarium pseudograminearum causes destructive crown disease in wheat. The velvet protein family is a crucial regulator in development, virulence, and secondary metabolism of fungi. We conducted a functional analysis of FpVelB using a gene replacement strategy. The deletion of FpVelB decreased radial growth and enhanced conidial production compared to that of wild type. Furthermore, FpVelB modulates the fungal responses to abiotic stress through diverse mechanisms. Significantly, virulence decreased after the deletion of FpVelB in both the stem base and head of wheat. Genome-wide gene expression profiling revealed that the regulation of genes by FpVelB is associated with several processes related to the aforementioned phenotype, including "immune", "membrane", and "antioxidant activity", particularly with regard to secondary metabolites. Most importantly, we demonstrated that FpVelB regulates pathogen virulence by influencing deoxynivalenol production and modulating the expression of the PKS11 gene. In conclusion, FpVelB is crucial for plant growth, asexual development, and abiotic stress response and is essential for full virulence via secondary metabolism in F. pseudograminearum.
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Proteínas Fúngicas , Fusarium , Regulación Fúngica de la Expresión Génica , Metabolismo Secundario , Fusarium/patogenicidad , Fusarium/genética , Fusarium/metabolismo , Metabolismo Secundario/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Virulencia/genética , Enfermedades de las Plantas/microbiología , Triticum/microbiología , Estrés Fisiológico , Tricotecenos/metabolismo , Esporas Fúngicas/metabolismoRESUMEN
Bipolaris maydis partitivirus 36 (BmPV36) is a mycovirus that can significantly reduce the virulence of the host Bipolaris maydis, but its hypovirulence mechanism is not clear. To investigate the response of B. maydis to BmPV36, the effects of BmPV36 on host cell structure and gene expression were studied via transmission electron microscopy and transcriptome sequencing using BmPV36-carrying and virus-free mycelium on the second and fifth culture. The results of transmission electron microscopy showed that the cell wall microfibrils of B. maydis were shortened, the cell membrane was broken, and membrane-bound vesicles and vacuoles appeared in the cells after carrying BmPV36. Transcriptome sequencing results showed that after carrying BmPV36, B. maydis membrane-related genes were significantly up-regulated, but membrane transport-related genes were significantly down-regulated. Genes related to carbohydrate macromolecule polysaccharide metabolic and catabolic processes were significantly down-regulated, as were genes related to the synthesis of toxins and cell wall degrading enzymes. Therefore, we speculated that BmPV36 reduces the virulence of B. maydis by destroying the host's cell structure, inhibiting the synthesis of toxins and cell wall degrading enzymes, and reducing cell metabolism. Gaining insights into the hypovirulence mechanism of mycoviruses will provide environmentally friendly strategies for the control of fungal diseases.
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The phase of secular evolution of continents is manifested as the degree of compositional differentiation, modification and maturation of continental crusts, which is vital in understanding the mechanism of continental evolution but is difficult to quantify. Here we use integrated passive- and active-source seismic profiling to conduct joint analysis and inversion and derive Vs and Vp/Vs section models across the North China Craton (NCC) to southeastern Altaids boundary zone that bears a tectonic transition from a reworked ancient craton margin to a Phanerozoic accretionary orogen. We systematically exploited the imaged multiple physical properties as precise and delicate proxies to constrain the compositional architecture in the crust across this important tectonic transition subject to various crustal evolutional phases. Our Vs and Vp/Vs imaging, together with the existing isotopic data, characterizes the Yin Shan-Yan Shan belt as the northern NCC margin with layered homogeneous compositions that point to an evolved crust. However, the lower-crustal low-Vs/high-Vp/Vs signature that overlaps the shallowly dipping to horizontal reflective fabrics suggests that the crust of the northern NCC margin has undergone considerable reworking through lower-crustal-stretching-assisted melt migration and mixing since the late Paleozoic to Mesozoic eras. The process probably involved crust-mantle interaction and thus resulted in a compositionally modified ancient crustal basement. On the contrary, the southeastern Altaids domain manifests crustal complexity in compositions and structures inferred to be indicative of a juvenile crust of the Phanerozoic accretionary orogen. Our results provide deep physical-property constraints that shed new light on the crustal evolution of a complex craton margin.
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Objective: To introduce laparoscopic neo-pancreaticogastrostomy (neo-PG) and investigate its application potential in total laparoscopic pancreaticoduodenectomy (TLPD). Materials and Methods: We performed a single-center prospective single-arm trial to evaluate the feasibility and safety of neo-PG for its initial application in TLPD. The first 50 patients who were operated by a single surgeon and who underwent TLPD with neo-PG at our institution were recruited. The pre/intra/postoperation data were collected and analyzed. Results: Twenty-nine male patients and 21 female patients from May 2022 to March 2023 were included. The mean operation time was 272.60 ± 47.30 minutes. The median PG time was 16 (15, 23) minutes. Six patients had delayed gastric emptying (DGE), and all underwent standard LPD. None of the patients had Grade B/C postoperative pancreatic fistula (POPF) or postoperative hemorrhage, or underwent reoperation. The median length of post-LPD hospital stay was 6 (6, 8) days. None of the patients died within 90 days after surgery. Nineteen cases were pathologically classified as pancreatic lesion, 6 cases as bile duct lesion, 18 cases as duodenal lesion, and 7 cases as ampullary lesion. Conclusion: The laparoscopic neo-PG is a simple, safe, and feasible pancreatic anastomosis that can be applied in TLPD. Pylorus-preserving LPD may decrease DGE rate. Further studies involving more surgeons are warranted to prove that our new technique may terminate POPF in TLPD.
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Laparoscopía , Neoplasias Pancreáticas , Femenino , Humanos , Masculino , Anastomosis Quirúrgica/métodos , Laparoscopía/métodos , Fístula Pancreática , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Pancreaticoduodenectomía/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Fusarium pseudograminearum is a soil-borne pathogen that is capable of causing a highly destructive crown disease in wheat. Secondary metabolites (SMs), especially deoxynivalenol (DON), are the primary virulence factors during infection. Here, we characterised the global regulator FpLaeB, an orthologue of LaeB protein function, to regulate the SM in Aspergillus nidulans. Through the utility of the gene targeting approach, we found that the vegetative growth of the FpLaeB deletion mutant was drastically reduced compared to that of the wild type. FpLaeB was also important for conidiation because the FpLaeB deletion mutant formed fewer conidia in induced medium. In addition, the sensitivity of the FpLaeB deletion mutant to the cell wall integrity inhibitor was decreased, while its growth was more severely inhibited by the cell membrane inhibitor sodium dodecyl sulfate (SDS) than that of the wild type. More importantly, the virulence was decreased when the FpLaeB deletion mutant was inoculated onto the wheat stem base or head. Through genome-wide gene expression profiling, FpLaeB was found to regulate several processes related to the above phenotypes such as the carbohydrate metabolic process, which is an integral and intrinsic component of membranes, especially SMs. Furthermore, the generation of DON was impaired in the FpLaeB deletion mutant via ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay. These results showed that FpLaeB plays an important role in the growth, development, and maintenance of the cell wall, and in membrane integrity. More importantly, FpLaeB is required for SMs and full virulence in F. pseudograminearum.
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Excessive fertilization is associated with nutrient loss, soil compaction, and weak plant resistance. Straw returning can increase soil fertility with a consequent reduction in fertilizer, but the effects of fertilizer reduction coupled with straw returning on crop endophytic microbes and crop disease are poorly understood. Therefore, using metagenomic sequencing methods we investigated the responses of soil fertility, diversity, the function of root endophytic bacteria, and the occurrence of wheat crown rot due to the application of fertilizer (no, moderate and excessive fertilizer) coupled with or without straw returning after 7 years of treatments. The results showed that, after excessive fertilization, the wheat crown rot became severe, registering a disease index of 23. Compared with excessive fertilization, moderate fertilization coupled with straw returning significantly reduced the incidence of wheat crown rot, the disease index was reduced by 38.50%, and the richness and diversity of endophytic bacteria were increased by 61.20 and 11.93%, respectively, but the soil fertility was not significantly affected. In addition, moderate fertilization coupled with straw returning changed the community structure of endophytic bacteria and increased the relative abundance of carbohydrate metabolism and nitrogen fixation-related genes by 4.72 and 9.32%, respectively. Our results indicated that fertilizer reduction coupled with straw returning reduced the occurrence of wheat crown rot, increased the diversity of endophytic bacteria, and changed the community structure and function of endophytic bacteria, which will provide a better understanding of the interaction of fertilization coupled with straw returning, endophytic bacteria and wheat crown rot.
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Background: Pancreatic leakage remains one of the most serious complications after laparoscopic pancreaticoduodenectomy (LPD). At present, most medical centers use local materials for the common pancreatic duct catheters required for pancreaticoenterostomy. However, there is a lack of a measurable and variable-diameter pancreatic duct catheter. Recently, a measurable variable-diameter pancreatic duct catheter was developed to remedy the limitation of the common pancreatic duct catheters. This study sought to evaluate its preventive effect on pancreatic leakage in LPD. Methods: A total of 202 patients who underwent LPD using the Hong's single-stitch method from January 2021 to April 2022 were included in the study. Patients were divided into the 2 groups: the variable-diameter group (n=111) and the normal group (n=91) according to the application of different pancreatic duct catheters. Patient characteristics and perioperative data, including operation time, pancreatic fistula rate, postoperative bleeding rate and postoperative length of stay in the two groups were collected and analyzed. The Chi-square test was used to compare the differences between the groups in relation to the categorical variables. Results: Among the 202 patients, there were 123 males and 79 females, with an average age of 58.79±7.89 years (range, 15-79 years), and an average body mass index (BMI) of 23.55±4.25 kg/m2. There were no statistically significant differences between the variable-diameter group and the normal group in terms of age, sex, BMI, operation time, intraoperative blood loss, preoperative bilirubin, and pancreatic texture (P>0.05). The pancreatic fistula rate (2.70% vs. 9.89%) and postoperative median length of stay (15 vs. 16 days) of the variable-diameter group was significantly lower than that of the normal group. Conclusions: The measurable variable-diameter pancreatic duct catheter could decrease the pancreatic fistula rate and postoperative median length of stay in the application of laparoscopic duodenectomy.
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Polypropylene (PP) fibers are employed commonly as the raw material of technical textiles (nonwovens), and the research focuses on fine-denier fibers and their functionalities. In this work, antibacterial PP masterbatches with different dosage (1-5 wt.%) of nano-ZnO particles as the antibacterial agent were prepared via a twin-screw extruder. The as-prepared PP masterbatches were electrospun on a home-made electrospinning device to afford ultra-fine PP fibers. The morphologies of as-spun ultrathin PP fibers with 16 µm of average diameter were observed by SEM. The structure and element distribution were characterized by means of energy-dispersive spectroscopy (EDS) and Fourier-transfer infrared spectroscopy (FTIR), respectively. There was some zinc obviously distributed on the surface when a dosage of ZnO more than 1 wt.% was used, which contributed to the antibacterial activity. The crystallinity of PP fibers was not affected strongly by the dosage of ZnO based on the differential scanning calorimetry (DSC) heating curves, while thermal decomposition improved with the increase in ZnO content, and the mechanical strength decreased predictably with the increase in inorganic ZnO content.
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A highly sensitive method has been developed for the determination of urinary 7-aminonitrazepam (7-ANZP), the major metabolite of nitrazepam, using high-performance electrospray liquid chromatography tandem mass spectrometry. The samples were prepared for analysis by adding 7-aminoclonazepam (7-ACZP, internal standard), hydrolysis with beta-glucuronidase and liquid-liquid extraction. Mass spectral acquisition was achieved by selectively monitoring the reaction between the two diagnostic transition reactions. Qualitative analysis was based on the retention time, and the quantitation was carried out by comparison with the internal standard. The recoveries of different concentrations of 7-ANZP from spiked blank samples was 89.0-95.2%, and the relative standard deviation was below 6.4%. The limit of determination in urine was 0.07 ng/mL, and the limit of quantitation was 0.5 ng/mL in the linear range of 1-50 ng/mL. This method possesses the merits of convenient operation, high sensitivity and good repeatability, making it a practical method for analysis of 7-ANZP in urine.
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Cromatografía Líquida de Alta Presión/métodos , Nitrazepam/análogos & derivados , Espectrometría de Masas en Tándem/métodos , Clonazepam/análogos & derivados , Clonazepam/análisis , Humanos , Modelos Lineales , Nitrazepam/metabolismo , Nitrazepam/orina , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
To clarify the changes in field populations of Fusarium head blight (FHB) pathogens over a decade, Fusarium species and trichothecene genotypes associated with FHB on wheat were monitored in Hebei province during the periods 2005-2006 and 2013-2016. Fusarium species determination was carried out by morphological identification, species-specific amplification and partial translation elongation factor (TEF-1α) gene sequencing. Trichothecene genotype prediction was carried out by primers 3CON/3NA/3D15A/3D3 or Tri13F/Tri13R, Tri303F/Tri303R and Tri315F/Tri315R. A total of 778 purified Fusarium isolates were recovered from 42 sampling sites in 17 counties during the period 2005-2006 and 1002 Fusarium isolates were recovered from 122 sampling sites in 65 counties during the period 2013-2016. F. graminearum was the predominant pathogen recovered during the periods 2005-2006 and 2013-2016. However, the pathogen composition differed slightly between the two periods. In 2005-2006, 752 out of 778 (96.7%) of the isolates belonged to F. graminearum. Two were identified as F. culmorum. Five other Fusarium species were also recovered, F. equiseti, F. verticillioides, F. proliferatum, F. subglutinans and F. chlamydosporum, with lower recoveries of 0.4%, 0.8%, 0.8%, 0.1% and 1.0%, respectively. Trichothecene genotype prediction showed that all the 752 F. graminearum isolates were of the 15-ADON genotype. Five Fusarium species were recovered from samples collected over the period 2013-2016. F. graminearum was again the predominant pathogen with an isolation frequency of 97.6%. F. pseudograminearum, F. asiaticum, F. culmorum and F. negundis were also isolated at a recovery of 1.4%, 0.7%, 0.2% and 0.1%, respectively. For the 2013-2016 isolates, 971 of the 978 F. graminearum strains were 15-ADON whereas seven isolates were of the 3-ADON type. All seven F. asiaticum isolates were of the NIV type and fourteen F. pseudograminearum isolates were classified as 3-ADON. F. pseudograminearum was first isolated from FHB in Hebei in 2013. Although the recovery of F. pseudograminearum is still low, it represents a small shift in the pathogen composition and trichothecene genotypes associated with FHB in Hebei province. As Fusarium crown rot of wheat caused by F. pseudograminearum is an increasing problem in Hebei province, it is appropriate to monitor the role of F. pseudograminearum in FHB in the future.
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Fusarium/genética , Enfermedades de las Plantas/microbiología , Tricotecenos , Triticum/microbiología , ADN de Hongos/genética , Fusarium/aislamiento & purificación , GenotipoRESUMEN
BACKGROUND: Programmed death 1 (PD-1) blockade has great effect in the prevention of oral precancerous lesions, but the drug resistance has also been observed. The determinants of immune resistance during the malignant transformation are poorly understood. METHODS: Anti-PD-1 antibody was administered in the 4NQO-induced carcinogenesis mouse models. The mice were then subdivided into PD-1 resistance(PD-1R) group and PD-1 sensitive(PD-1S) group according to the efficacy. The expression of PD-1 and PD-L1, and the abundance of CD3+ T cells in tumor microenvironment between the two groups was tested by immunohistochemistry. In addition, the activation and effector functions, as well as the accumulation of immunosuppressive cells and expression of immune checkpoints of T cells in the draining lymph nodes and spleen between PD-1R and PD-1S group were analyzed by flow cytometry. RESULTS: Our results showed that T cell infiltration in tumor microenvironment, effector T cell cytokine secretion and central memory T cell accumulation in peripheral lymphoid organs were all inhibited in the anti-PD-1 resistance group. Furthermore, we found that an increase of regulatory T cell (Treg) population contributed to the resistance of the anti-PD-1 therapy. Notably, TIM-3 was found to be the only immunosuppressive molecule that mediated the resistance to anti-PD-1 therapy in the oral malignant transformation model. CONCLUSIONS: Our findings identified a novel mechanism that T cell dysfunction contributes to the immune resistance during the malignant transformation of the oral mucosa. This study provides new targets for improving the efficacy of immunotherapy for early stage of tumorigenesis.
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Antineoplásicos Inmunológicos/farmacología , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/metabolismo , Resistencia a Antineoplásicos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Animales , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Receptor 2 Celular del Virus de la Hepatitis A/genética , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Humanos , Memoria Inmunológica , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Ratones , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/metabolismo , Mucosa Bucal/patología , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/etiología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Lesiones Precancerosas , Linfocitos T/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Elucidation of the mechanisms of T-cell-mediated antitumor responses will provide information for the rational design and development of cancer immunotherapies. Here, we found that calnexin, an endoplasmic reticulum (ER) chaperone protein, is significantly upregulated in oral squamous cell carcinoma (OSCC). Upregulation of its membranous expression on OSCC cells is associated with inhibited T-cell infiltration in tumor tissues and correlates with poor survival of patients with OSCC. We found that calnexin inhibits the proliferation of CD4+ and CD8+ T cells isolated from the whole blood of healthy donors and patients with OSCC and inhibits the secretion of IFNγ, TNFα, and IL2 from these cells. Furthermore, in a melanoma model, knockdown of calnexin enhanced the infiltration and effector functions of T cells in the tumor microenvironment and conferred better control of tumor growth, whereas treatment with a recombinant calnexin protein impaired the infiltration and effector functions of T cells and promoted tumor growth. We also found that calnexin enhanced the expression of PD-1 on CD4+ and CD8+ T cells by restraining the DNA methylation status of a CpG island in the PD-1 promoter. Thus, this work uncovers a mechanism by which T-cell antitumor responses are regulated by calnexin in tumor cells and suggests that calnexin might serve as a potential target for the improvement of antitumor immunotherapy.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Calnexina/inmunología , Carcinoma de Células Escamosas/inmunología , Neoplasias de la Boca/inmunología , Anciano , Animales , Calnexina/genética , Línea Celular Tumoral , Femenino , Humanos , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/inmunologíaRESUMEN
In this paper, a novel electrostatic-assisted melt blown process was reported to produce polypropylene (PP) microfibers with a diameter as fine as 600 nm. The morphology, web structure, pore size distribution, filtration efficiency, and the stress and strain behavior of the PP nonwoven fabric thus prepared were characterized. By introducing an electrostatic field into the conventional melt-blown apparatus, the average diameter of the melt-blown fibers was reduced from 1.69 to 0.96 µm with the experimental setup, and the distribution of fiber diameters was narrower, which resulted in a filter medium with smaller average pore size and improved filtration efficiency. The polymer microfibers prepared by this electrostatic-assisted melt blown method may be adapted in a continuous melt blown process for the production of filtration media used in air filters, dust masks, and so on.
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Curbing PD-1 immunosuppressive signaling represents an effective immune awakening or immune-reactivation approach for tumor eradication for many cancers. Yet, the potential involvement of this critical PD-1 immunosuppressive signaling in de novo malignant transformation of epithelial cells to pre-cancerous or cancerous lesions is largely unknown. In this study, we demonstrate that PD-1 signaling is critically involved in de novo malignant transformation of oral mucosa upon carcinogen exposure in vivo. Our findings revealed that 4NQO-treated mice had almost double the numbers of PD-1-positive CD4+ cells and PD-1-positive CD8+ cells in peripheral blood lymphocytes as well as elevated PD-1 expression in tumor infiltrating lymphocytes (when compared to that of control-treated mice), strongly supportive of a general immune-suppression induced by carcinogen challenges in vivo. Importantly, inhibition of PD-1 signaling during the carcinogenesis process (immediately after 4NQO challenge) significantly reduced and delayed de novo formation of both pre-cancerous and cancerous lesions in vivo, in conjunction with effective PD-1 down-modulation in the tumor infiltrating leukocyte and peripheral lymph organs. Lastly, reduction of carcinogen-induced lesions upon PD-1 mAb treatment in vivo was accompanied by reduction of potent immunosuppressive myeloid-derived suppressor cells (MDSCs), and increase in "activated" T cell accumulations in the lesion-microenvironment (127% increase) and peripheral lymph nodes (25% increase). These data support PD-1 blockade as a new approach to enhance the efficacy of T-cell immunotherapy and reduce canceration rate in premalignant lesions.
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Using a topography-dependent tomographic scheme, the seismic velocity structure of the Eastern Tibetan Plateau, including the uplifted Longmenshan (LMS) orogenic belt, is accurately imaged in spite of the extreme topographic relief in the LMS region and thick sedimentary covers in the neighbouring Sichuan Basin. The obtained image shows a high-resolution upper crustal structure on a 500 km-long profile that is perpendicular to the LMS. The image clearly shows that the crystalline basement was uplifted within the LMS orogenic belt, and that the neighbouring Songpan-Ganzi Terrane was covered by a thick flysch belt, with evidence of near-surface thrust faults caused by convergence between Eastern Tibet and the Sichuan Basin. The indication that the lower crust beneath the LMS was folded and pushed upwards and the upper crust was removed by exhumation, supports the concept of a lower crustal channel flow beneath Eastern Tibet. The image also reveals that the destructive Wenchuan earthquake of year 2008 occurred in the upper crust, directly at the structural discontinuity between Eastern Tibet Plateau and the Sichuan Basin.
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OBJECTIVE: To explore the potential biochemical mechanisms of neuromuscular junction transmission (NMJT) dysfunction induced by organophosphorus insecticides. METHODS: Ten rats were dosed with phoxim (1,144 mg/kg) and 5 of them developed myasthenia. The NMJT function was evaluated by the mean consecutive differences (MCD) measured by stimulation single fiber electromyography (SSFEMG) with the frequency of stimuli at 20 Hz. The activity of Ca(2+)-ATPase, Na(+), K(+)-ATPase, cAMP dependent protein kinase (PKA), Ca(2+)/phospholipid dependent protein kinase (PKC), and tyrosine protein kinase (TPK) were determined. RESULTS: In comparison with the control and non-myasthenic rats, the results in myasthenic rats showed that: (1) the MCDs increased; (2) the activities of Ca(2+)-ATPase, Na(+), K(+)-ATPase and PKA decreased and were negatively correlated with MCD; (3) the activities of PKC and TPK increased, and were positively correlated with MCD; (4) the phosphorylation of serine residuals in sarcolemma was weaker and the phosphorylation of tyrosine residuals was stronger. CONCLUSIONS: The NMJT dysfunction is likely associated with the decrease in Ca(2+)-ATPase and Na(+), K(+)-ATPase activity. The acceleration of desensitization and prolongation of resensitization of nicotinic acetylcholine receptors occur following the increase in tyrosine phosphorylation and the decrease in serine phosphorylation induced by OPs poisoning.