Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathol...Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs.Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.展开更多
Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and...Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.展开更多
Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was ...Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.展开更多
Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness an...Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.展开更多
Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as&...Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").Despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.展开更多
Background: Chronic Kidney Disease (CKD), associated with a slow and progressive loss of kidney function over a period of several years, is an important clinical disaster with an increasing rate of morbidity and morta...Background: Chronic Kidney Disease (CKD), associated with a slow and progressive loss of kidney function over a period of several years, is an important clinical disaster with an increasing rate of morbidity and mortality especially in the least developed countries. Many hematological parameters are thought to alter dramatically during the course of the disease. These include white blood cells, red blood cells, and platelets. Methods: We tried, retrospectively, to evaluate the peripheral blood hematological alterations in a group of patients undergoing hemodialysis in an eastern Sudan dialysis center to add local medical information. Results: Anemia (Low hemoglobin and hematocrit) was detected in 94% of the patients’ group. Mean Erythrocyte count (3.32vs.4.76 (×109/L)), Hemoglobin concentration (9.4vs.13 (g/dl)), Hematocrit (28.7vs.38.7 (L/L)) and platelet count (296 vs. 238 (×109/L)) were significantly lower in the patients’ group than in the control group (P-values Conclusion: Five out of eight studied parameters (Red cell count, hemoglobin, hematocrit, mean cell hemoglobin concentration, and platelets count) have shown a significant alteration in CKD patients. As the complete blood count (CBC) test is the most utilized test in clinical laboratory practice, these alterations may be considered as early indicators for CKD. Furthermore, all patients with CKD must be routinely checked for these alterations.展开更多
Currently, gastric cancer(GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possi...Currently, gastric cancer(GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the procarcinogenic activity of important genes. These factors include genetic susceptibility expressed in a singlenucleotide polymorphism, various acquired mutations(chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances(e.g., helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma(EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesisare modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.展开更多
Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair(MMR). About 15% of sporadic colorectal cancers(CRCs) manifest hypermethylation of the DNA MMR gene MLH1, resulting ...Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair(MMR). About 15% of sporadic colorectal cancers(CRCs) manifest hypermethylation of the DNA MMR gene MLH1, resulting in mono-and di-nucleotide frameshifts to classify it as microsatellite instability-high(MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic nonMSI-H CRCs demonstrate frameshifts at di-and tetra-nucleotide microsatellites to classify it as MSIlow/elevated microsatellite alterations at selected tetranucleotide repeats(EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA MMR system.展开更多
Phloem plays a fundamental role in plants by transporting hormones,nutrients,proteins,RNAs,and carbohydrates essential for plant growth and development.However,the identity of the underlying phloem genes and pathways ...Phloem plays a fundamental role in plants by transporting hormones,nutrients,proteins,RNAs,and carbohydrates essential for plant growth and development.However,the identity of the underlying phloem genes and pathways remain enigmatic especially in agriculturally important perennial crops,in part,due to the technical difficulty of phloem sampling.Here,we used two phloem-specific promoters and a translating ribosome affinity purification(TRAP)strategy to characterize the phloem translatome during leaf development at 2,4,and 6 weeks post vernalization in plum(Prunus domestica L.).Results provide insight into the changing phloem processes that occur during leaf development.These processes included the early activation of DNA replication genes that are likely involved in phloem cell division during leaf expansion,as well as the upregulation of phloem genes associated with sink to source conversion,induction of defense processes,and signaling for reproduction.Combined these results reveal the dynamics of phloem gene expression during leaf development and establish the TRAP system as a powerful tool for studying phloem-specific functions and responses in trees.展开更多
Background Palpitation is a common complaint in generalised anxiety disorder(GAD).Brain imaging studies have Investigated the neural mechanism of heartbeat perception in healthy volunteers.This study explored the neur...Background Palpitation is a common complaint in generalised anxiety disorder(GAD).Brain imaging studies have Investigated the neural mechanism of heartbeat perception in healthy volunteers.This study explored the neuroanatomical differences of altered heartbeat perception in patients with GAD using structural MRI.Aims Based on the strong somatic-interoceptive symptoms in GAD,we explored the regional structural brain abnormalities involved in heartbeat perception in patients with GAD.Methods This study was applied to the a priori regions using neuroanatomical theories of heartbeat perception,including the insula,anterior cingulate cortex,supplementary motor area and prefrontal cortex.A total of 19 patients with GAD and 19 healthy control subjects were enrolled.We used the FMRIB Software Library voxel-based morphometry software for estimating the grey matter volume of these regions of interest and analysed the correlation between heartbeat perception sensitivity and the volume of abnormal grey matter.Results Patients with GAD showed a significantly decreased volume of grey matter in their left medial prefrontal cortex,right orbital frontal cortex and anterior cingulate cortex.The grey matter volume of the left medial prefrontal cortex negatively correlated with heartbeat perception sensitivity in patients with GAD.Conclusions It should be the first study that shows heartbeat perception is associated with brain structure in GAD.Our findings suggest that the frontal region may play an important role in aberrant heartbeat perception processing in patients with GAD,and this may be an underlying mechanism resulting in the abnormal cardiovascular complaints in GAD.This is hypothesised as a'top-down'deficiency,especially in the medial prefrontal cortex.This will provide the foundation for a more targeted region for neuromodulation intervention in the future.展开更多
The Kehdolan area is located at 20 kilometers to the?south-east of Dozdozan Town (Eastern Azarbaijan Province). According to structural geology, volconic rocks are situated in Alborz-Azarbyjan zone, and faults?are?obs...The Kehdolan area is located at 20 kilometers to the?south-east of Dozdozan Town (Eastern Azarbaijan Province). According to structural geology, volconic rocks are situated in Alborz-Azarbyjan zone, and faults?are?observed?in?the?same direction to this system with SE-NW trend. The results show that kaolinite alteration trend with Argilic and propylitic veins?is the?same direction with SW-NE faults in this area. Therefore, these faults with these trends can be considered as the mineralization control for determination of the alterations. Different image processing techniques,?such as false color composite?(FCC), band ratios, color ratio composite?(CRC), principal component?analysis?(PCA), Crosta technique, supervised spectral angle mapping?(SAM), are used for?identification of the alteration zones associated with copper mineralization. In this project ASTER?data are process and spectral analysis to fit for recognizing intensity and kind of argillic, propylitic,?philic, and ETM+ data?which?are process and to fit for iron oxide and relation to metal mineralization of the area. For recognizing different alterations of the study area, some chemical and mineralogical analysis data from the samples showed that ASTER data and ETM+ data were?capable of hydrothermal alteration mapping with copper mineralization.?Copper mineralization in the region is in agreement with argillic alteration. SW-NE trending faults controlled the mineralization process.展开更多
Present study deals with the straight impact of hypobaric hypoxia on the quantity and composition of some predominant fecal microflora and its functional aspects. For that, isolated fecal contents of rat were exposed ...Present study deals with the straight impact of hypobaric hypoxia on the quantity and composition of some predominant fecal microflora and its functional aspects. For that, isolated fecal contents of rat were exposed to two different simulated air pressures (70 kPa and 40 kPa) for different time durations (1, 3, and 5 h) and the bacterial community composition was compared with normobaric groups (101.3 kPa). It was found that the total anaerobes, Escherichio coli, Enterbocters spp., Bi^idobocterium spp., CIostridium spp. were increased whereas total aerobes were decreased at both hypobaric treatments. The increased number of amplicon was detected in the pressure-treated groups than the control that clearly mentioned the disruption of microbiota structure at different simulated hypobaric-hypoxia. The amylase, protease, tannase, 13-glucuronidase, and alkaline phosphatase activities were increased at these atmospheric pressures. Thus, the present investigation demonstrates that the hypobaric hypoxia is an important environmental factor which can strongly modulate the composition of intestinal flora as well as microfiora-derived functional aspects.展开更多
基金supported by the National Nature Science Foundation of China (China, grant numbers 81671006, 81300894)CAMS Innovation Fund for Medical Sciences (China, grant number 2019-I2M-5-038)National Clinical Key Discipline Construction Project (China, PKUSSNKP-202102)。
文摘Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs.Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.
基金supported by NIH funding(RF1NS110637,2RF1NS094527,R01NS110635)to JW.
文摘Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.
文摘Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.
基金supported by the Project on InterGovernmental International Scientific and Technological Innovation Cooperation in National Key Projects of Research and Development Plan (No. 2019YFE0106400)the National Natural Science Foundation of China (No. 81771875)。
文摘Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.
文摘Trypanosoma cruzi is the etiologic agent of Chagas disease.This flagellated protozoan is transmitted to humans as well as different species of domestic and wild animals via vectors from the Reduviidae family(known as"kissing bugs").Despite the fact that hundreds of species of wild mammals are part of the reservoir system,the morphologi-cal changes and clinical manifestations resulting from the pathogenesis of the infection have been largely neglected.The aim of this review is to systematically compile the available information regarding clinicopathological altera-tions in wild mammals due to natural infection by T.cruzi.Information was obtained from six online bibliographic data search platforms,resulting in the identification of 29 publications that met the inclusion criteria.Mortality was the most common clinical manifestation,cardiac damage was the main finding at necropsy,and lymphoplas-macytic inflammation was the most frequent microscopic injury.Thus,regardless of its role as a reservoir,T.cruzi has the potential to affect the health status of wild mammals,a situation that highlights the need for further research to analyze,measure,and compare its effects at both the individual and population levels.
文摘Background: Chronic Kidney Disease (CKD), associated with a slow and progressive loss of kidney function over a period of several years, is an important clinical disaster with an increasing rate of morbidity and mortality especially in the least developed countries. Many hematological parameters are thought to alter dramatically during the course of the disease. These include white blood cells, red blood cells, and platelets. Methods: We tried, retrospectively, to evaluate the peripheral blood hematological alterations in a group of patients undergoing hemodialysis in an eastern Sudan dialysis center to add local medical information. Results: Anemia (Low hemoglobin and hematocrit) was detected in 94% of the patients’ group. Mean Erythrocyte count (3.32vs.4.76 (×109/L)), Hemoglobin concentration (9.4vs.13 (g/dl)), Hematocrit (28.7vs.38.7 (L/L)) and platelet count (296 vs. 238 (×109/L)) were significantly lower in the patients’ group than in the control group (P-values Conclusion: Five out of eight studied parameters (Red cell count, hemoglobin, hematocrit, mean cell hemoglobin concentration, and platelets count) have shown a significant alteration in CKD patients. As the complete blood count (CBC) test is the most utilized test in clinical laboratory practice, these alterations may be considered as early indicators for CKD. Furthermore, all patients with CKD must be routinely checked for these alterations.
基金Supported by A grant from the Polish Ministry of Science and Higher EducationNo.N N402 423838
文摘Currently, gastric cancer(GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the procarcinogenic activity of important genes. These factors include genetic susceptibility expressed in a singlenucleotide polymorphism, various acquired mutations(chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances(e.g., helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma(EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesisare modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.
基金Supported by United States Public Health Service,Nos.DK067287,CA162147 and CA206010the A.Alfred Taubman Medical Research Institute of the University of Michigan
文摘Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair(MMR). About 15% of sporadic colorectal cancers(CRCs) manifest hypermethylation of the DNA MMR gene MLH1, resulting in mono-and di-nucleotide frameshifts to classify it as microsatellite instability-high(MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic nonMSI-H CRCs demonstrate frameshifts at di-and tetra-nucleotide microsatellites to classify it as MSIlow/elevated microsatellite alterations at selected tetranucleotide repeats(EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA MMR system.
基金supported by the USDA National Institute of Food and Agriculture,Plant-Associated Microbes and Plant-Microbe Interactions Program(2015–67013-23004)the NSF Division of Integrative Organismal Systems(ISO-1644713).
文摘Phloem plays a fundamental role in plants by transporting hormones,nutrients,proteins,RNAs,and carbohydrates essential for plant growth and development.However,the identity of the underlying phloem genes and pathways remain enigmatic especially in agriculturally important perennial crops,in part,due to the technical difficulty of phloem sampling.Here,we used two phloem-specific promoters and a translating ribosome affinity purification(TRAP)strategy to characterize the phloem translatome during leaf development at 2,4,and 6 weeks post vernalization in plum(Prunus domestica L.).Results provide insight into the changing phloem processes that occur during leaf development.These processes included the early activation of DNA replication genes that are likely involved in phloem cell division during leaf expansion,as well as the upregulation of phloem genes associated with sink to source conversion,induction of defense processes,and signaling for reproduction.Combined these results reveal the dynamics of phloem gene expression during leaf development and establish the TRAP system as a powerful tool for studying phloem-specific functions and responses in trees.
基金supported by Shanghai Science and Technology Commission(16411965000,18411952400)Shanghai Jiao Tong University Foundation(YG2016MS37)+2 种基金National Key R&D Program of China(2018YFC2001605,2019YFA0706200)Natural Science Foundation of Shanghai(18ZR1432600,81071098)Shanghai Municipal Commission of Health and Family Planning Foundation(20164Y0215).
文摘Background Palpitation is a common complaint in generalised anxiety disorder(GAD).Brain imaging studies have Investigated the neural mechanism of heartbeat perception in healthy volunteers.This study explored the neuroanatomical differences of altered heartbeat perception in patients with GAD using structural MRI.Aims Based on the strong somatic-interoceptive symptoms in GAD,we explored the regional structural brain abnormalities involved in heartbeat perception in patients with GAD.Methods This study was applied to the a priori regions using neuroanatomical theories of heartbeat perception,including the insula,anterior cingulate cortex,supplementary motor area and prefrontal cortex.A total of 19 patients with GAD and 19 healthy control subjects were enrolled.We used the FMRIB Software Library voxel-based morphometry software for estimating the grey matter volume of these regions of interest and analysed the correlation between heartbeat perception sensitivity and the volume of abnormal grey matter.Results Patients with GAD showed a significantly decreased volume of grey matter in their left medial prefrontal cortex,right orbital frontal cortex and anterior cingulate cortex.The grey matter volume of the left medial prefrontal cortex negatively correlated with heartbeat perception sensitivity in patients with GAD.Conclusions It should be the first study that shows heartbeat perception is associated with brain structure in GAD.Our findings suggest that the frontal region may play an important role in aberrant heartbeat perception processing in patients with GAD,and this may be an underlying mechanism resulting in the abnormal cardiovascular complaints in GAD.This is hypothesised as a'top-down'deficiency,especially in the medial prefrontal cortex.This will provide the foundation for a more targeted region for neuromodulation intervention in the future.
文摘The Kehdolan area is located at 20 kilometers to the?south-east of Dozdozan Town (Eastern Azarbaijan Province). According to structural geology, volconic rocks are situated in Alborz-Azarbyjan zone, and faults?are?observed?in?the?same direction to this system with SE-NW trend. The results show that kaolinite alteration trend with Argilic and propylitic veins?is the?same direction with SW-NE faults in this area. Therefore, these faults with these trends can be considered as the mineralization control for determination of the alterations. Different image processing techniques,?such as false color composite?(FCC), band ratios, color ratio composite?(CRC), principal component?analysis?(PCA), Crosta technique, supervised spectral angle mapping?(SAM), are used for?identification of the alteration zones associated with copper mineralization. In this project ASTER?data are process and spectral analysis to fit for recognizing intensity and kind of argillic, propylitic,?philic, and ETM+ data?which?are process and to fit for iron oxide and relation to metal mineralization of the area. For recognizing different alterations of the study area, some chemical and mineralogical analysis data from the samples showed that ASTER data and ETM+ data were?capable of hydrothermal alteration mapping with copper mineralization.?Copper mineralization in the region is in agreement with argillic alteration. SW-NE trending faults controlled the mineralization process.
基金Council for Scientific and Industrial Research (CSIR),New Delhi for providing the fellowshipthe Defence Institute of Physiology & Allied Sciences (DIPAS),the Defence Research & Development Organisation (DRDO),Government of India,for their consecutive financial support
文摘Present study deals with the straight impact of hypobaric hypoxia on the quantity and composition of some predominant fecal microflora and its functional aspects. For that, isolated fecal contents of rat were exposed to two different simulated air pressures (70 kPa and 40 kPa) for different time durations (1, 3, and 5 h) and the bacterial community composition was compared with normobaric groups (101.3 kPa). It was found that the total anaerobes, Escherichio coli, Enterbocters spp., Bi^idobocterium spp., CIostridium spp. were increased whereas total aerobes were decreased at both hypobaric treatments. The increased number of amplicon was detected in the pressure-treated groups than the control that clearly mentioned the disruption of microbiota structure at different simulated hypobaric-hypoxia. The amylase, protease, tannase, 13-glucuronidase, and alkaline phosphatase activities were increased at these atmospheric pressures. Thus, the present investigation demonstrates that the hypobaric hypoxia is an important environmental factor which can strongly modulate the composition of intestinal flora as well as microfiora-derived functional aspects.