Background: Increasing evidence indicates that Six2 contributes to tumorigenesis in various tumor in- cluding hepatocellular carcinoma (HCC). This study aimed to determine the role of Six2 in HCC and to elucidate the ...Background: Increasing evidence indicates that Six2 contributes to tumorigenesis in various tumor in- cluding hepatocellular carcinoma (HCC). This study aimed to determine the role of Six2 in HCC and to elucidate the association of Six2 with clinical pathological characteristics. Methods: The expressions of Six2 in HCC tumor, para-tumor tissue and portal vein tumor thrombus (PVTT) were detected by tissue microarray technique, immunohistochemistry, real-time RT-PCR and West- ern blotting. Chi-square and Kaplan-Meier analysis were used to analyze the correlation between Six2 expression and prognosis of HCC patients. Lentivirus mediated Six2 knockdown, spheroid formation as- say, proliferation assay and subcutaneous tumor implantation were performed to determine the function of Six2. Results: In 274 HCC samples, Six2 was strongly expressed. Kaplan-Meier analysis revealed that high ex- pression of Six2 was correlated with a shorter overall survival (OS) and disease-free survival (DFS). More- over, Six2 expression was associated with sex, alpha-fetoprotein, tumor size and portal vein invasion. Six2 was highly expressed in PVTT. Six2 knockdown inhibited HCC cell lines proliferation, migration, and self-renewal in vitro and in vivo. In addition, low-expression of Six2 weakened TGF-β induced Smad4 activation and epithelial-mesenchymal transition in HCC cell lines. Conclusions: Elevated Six2 expression in HCC tumor patients was associated with negative prognosis. Upregulated Six2 promoted tumor growth and facilitated HCC metastasis via TGF-β/Smad signal pathway.展开更多
The yield potential of japonica/indica hybrids(JIH)has been achieved over 13.5 t ha–1 in large-scale rice fields,and some physiological traits for yield advantage of JIH over japonica inbred rice(JI)and indica hybrid...The yield potential of japonica/indica hybrids(JIH)has been achieved over 13.5 t ha–1 in large-scale rice fields,and some physiological traits for yield advantage of JIH over japonica inbred rice(JI)and indica hybrid rice(IH)were also identified.To date,little attention has been paid to morphological traits for yield advantage of JIH over JI and IH.For this reason,three JIH,three JI,and three IH were field-grown at East China(Ningbo,Zhejiang Province)in 2015 and 2016.Compared with JI and IH,JIH had 14.3 and 20.8%higher grain yield,respectively,attributed to its more spikelets per panicle and relatively high percentage of filled grains.The advantage in spikelets per panicle of JIH over JI and IH was shown in number of grains on the upper,middle,and lower branches.Compared with JI and IH,JIH had higher leaf area through leaf width and lower leaf angle of upper three leaves,higher leaf area index and leaf area per tiller at heading and maturity stages,higher stem weight per tiller and K and Si concentrations of stem at maturity,higher dry matter weight in leaf,stem,and panicle at heading and maturity stages,and higher biomass accumulation after heading and lower biomass translocation from stem during ripening.Leaf width of upper three leaves were correlated positively,while leaf angle of upper three leaves were correlated negatively with biomass accumulation after heading,stem weight per tiller,and per unit length.Our results indicated that the grain yield advantage of JIH was ascribed mainly to the more spikelets per panicle and relatively high percentage of filled grains.Higher leaf area through leaf width and more erect leaves were associated with improved biomass accumulation and stem weighing during ripening,and were the primary morphological traits underlying higher grain yield of JIH.展开更多
Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)and its more advanced form,metabolic dysfunction-associated steatohepatitis,have emerged as the most prevalent liver diseases worldwid...Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)and its more advanced form,metabolic dysfunction-associated steatohepatitis,have emerged as the most prevalent liver diseases worldwide.Currently,lifestyle modification is the foremost guidelinerecommended management strategy for MASLD.However,it remains unclear which detrimental signals persist in MASLD even after disease remission.Thus,we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal.Methods:Male C57BL/6J mice were divided into three groups:Western diet(WD)feeding,chow diet(CD)feeding,or diet reversal from WD to CD.After 16 weeks of feeding,RNA sequencing was performed on the mice’s livers to identify persistent alterations characteristic of MASLD.Additionally,RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized.Results:WD-induced MASLD triggered persistent activation of the DNA damage response(DDR)and its primary transcription factor,P53,long after the resolution of the hepatic phenotype through dietary reversal.Elevated levels of P53 might promote apoptosis,thereby exacerbating metabolic dysfunction-associated steatohepatitis,as they strongly correlated with hepatocyte ballooning,an indicator of apoptosis activation.Moreover,P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver.Mechanistically,P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease(AEN).Consistently,P53,AEN,and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal.Conclusions:The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD.Our findings provide new insights into the mechanisms of MASLD relapse,highlighting DDR signaling as a promising target to prevent MASLD recurrence.展开更多
Kai-Xin-San consists of Ginseng Radix, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria at a ratio of 3:3:2:2. Kai-Xin-San has been widely used for the treatment of emotional disorders in China. However, no studi...Kai-Xin-San consists of Ginseng Radix, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria at a ratio of 3:3:2:2. Kai-Xin-San has been widely used for the treatment of emotional disorders in China. However, no studies have identified the key proteins implicated in response to Kai-Xin-San treatment. In this study, rat models of chronic mild stress were established using different stress methods over 28 days. After 14 days of stress stimulation, rats received daily intragastric administrations of 600 mg/kg Kai-Xin-San. The sucrose preference test was used to determine depression-like behavior in rats, while isobaric tags were used for relative and absolute quantitation-based proteomics to identify altered proteins following Kai-Xin-San treatment. Kai-Xin-San treatment for 2 weeks noticeably improved depression-like behaviors in rats with chronic mild stress. We identified 33 differentially expressed proteins: 7 were upregulated and 26 were downregulated. Functional analysis showed that these differentially expressed proteins participate in synaptic plasticity, neurodevelopment, and neurogenesis. Our results indicate that Kai-Xin-San has an important role in regulating the key node proteins in the synaptic signaling network, and are helpful to better understand the mechanism of the antidepressive effects of Kai-Xin-San and to provide objective theoretical support for its clinical application. The study was approved by the Ethics Committee for Animal Research from the Chinese PLA General Hospital(approval No. X5-2016-07) on March 5, 2016.展开更多
BACKGROUND Esophageal schwannomas originating from Schwann cells are extremely rare esophageal tumors.They commonly occur in the upper and middle esophagus but less frequently in the lower esophagus.Herein,we report a...BACKGROUND Esophageal schwannomas originating from Schwann cells are extremely rare esophageal tumors.They commonly occur in the upper and middle esophagus but less frequently in the lower esophagus.Herein,we report a rare case of a large lower esophageal schwannoma misdiagnosed as a leiomyoma.We also present a brief literature review on lower esophageal schwannomas.CASE SUMMARY A 62-year-old man presented with severe dysphagia lasting 6 mo.A barium esophagogram showed that the lower esophagus was compressed within approximately 5.5 cm.Endoscopy revealed the presence of a large submucosal protuberant lesion in the esophagus at a distance of 32-38 cm from the incisors.Endoscopic ultrasound findings demonstrated a 4.5 cm×5.0 cm hypoechoic lesion.Chest computed tomography revealed a mass of size approximately 53 mm×39 mm×50 mm.Initial tests revealed features indicative of leiomyoma.After multidisciplinary discussions,the patient underwent a video-assisted thoracoscopic partial esophagectomy.Further investigation involving immunohistochemical examination confirming palisading spindle cells as positive for S100 and Sox10 led to the final diagnosis of a lower esophageal schwannoma.There was no tumor recurrence or metastasis during follow-up.CONCLUSION The final diagnosis of esophageal schwannoma requires histopathological and immunohistochemical examination.The early appropriate surgery favors a remarkable prognosis.展开更多
基金supported by grants from the State Key Project for Liver Cancer(2017ZX10203206)the National Key Research and Development Program(2017YFC0906900)+2 种基金the National Natural Science Foundation of China(813700 6 6,81670516)the Funds for Creative Research Groups of China(81521091)the Precision Medicine Project of Second Military Medical University(2017JZ30)
文摘Background: Increasing evidence indicates that Six2 contributes to tumorigenesis in various tumor in- cluding hepatocellular carcinoma (HCC). This study aimed to determine the role of Six2 in HCC and to elucidate the association of Six2 with clinical pathological characteristics. Methods: The expressions of Six2 in HCC tumor, para-tumor tissue and portal vein tumor thrombus (PVTT) were detected by tissue microarray technique, immunohistochemistry, real-time RT-PCR and West- ern blotting. Chi-square and Kaplan-Meier analysis were used to analyze the correlation between Six2 expression and prognosis of HCC patients. Lentivirus mediated Six2 knockdown, spheroid formation as- say, proliferation assay and subcutaneous tumor implantation were performed to determine the function of Six2. Results: In 274 HCC samples, Six2 was strongly expressed. Kaplan-Meier analysis revealed that high ex- pression of Six2 was correlated with a shorter overall survival (OS) and disease-free survival (DFS). More- over, Six2 expression was associated with sex, alpha-fetoprotein, tumor size and portal vein invasion. Six2 was highly expressed in PVTT. Six2 knockdown inhibited HCC cell lines proliferation, migration, and self-renewal in vitro and in vivo. In addition, low-expression of Six2 weakened TGF-β induced Smad4 activation and epithelial-mesenchymal transition in HCC cell lines. Conclusions: Elevated Six2 expression in HCC tumor patients was associated with negative prognosis. Upregulated Six2 promoted tumor growth and facilitated HCC metastasis via TGF-β/Smad signal pathway.
基金financed by the National Key Research and Development Program of China (2018YFD0300802)the Key Research and Development Program of Jiangsu Province, China (BE2016351)the Priority Academic Program Development of Jiangsu Higher Education Institutions, China (PAPD)
文摘The yield potential of japonica/indica hybrids(JIH)has been achieved over 13.5 t ha–1 in large-scale rice fields,and some physiological traits for yield advantage of JIH over japonica inbred rice(JI)and indica hybrid rice(IH)were also identified.To date,little attention has been paid to morphological traits for yield advantage of JIH over JI and IH.For this reason,three JIH,three JI,and three IH were field-grown at East China(Ningbo,Zhejiang Province)in 2015 and 2016.Compared with JI and IH,JIH had 14.3 and 20.8%higher grain yield,respectively,attributed to its more spikelets per panicle and relatively high percentage of filled grains.The advantage in spikelets per panicle of JIH over JI and IH was shown in number of grains on the upper,middle,and lower branches.Compared with JI and IH,JIH had higher leaf area through leaf width and lower leaf angle of upper three leaves,higher leaf area index and leaf area per tiller at heading and maturity stages,higher stem weight per tiller and K and Si concentrations of stem at maturity,higher dry matter weight in leaf,stem,and panicle at heading and maturity stages,and higher biomass accumulation after heading and lower biomass translocation from stem during ripening.Leaf width of upper three leaves were correlated positively,while leaf angle of upper three leaves were correlated negatively with biomass accumulation after heading,stem weight per tiller,and per unit length.Our results indicated that the grain yield advantage of JIH was ascribed mainly to the more spikelets per panicle and relatively high percentage of filled grains.Higher leaf area through leaf width and more erect leaves were associated with improved biomass accumulation and stem weighing during ripening,and were the primary morphological traits underlying higher grain yield of JIH.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39020600)the National Natural Science Foundation of China(81900507,82100606,82170593,82222071,91957116)the Shanghai Municipal Science and Technology Major Project.
文摘Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)and its more advanced form,metabolic dysfunction-associated steatohepatitis,have emerged as the most prevalent liver diseases worldwide.Currently,lifestyle modification is the foremost guidelinerecommended management strategy for MASLD.However,it remains unclear which detrimental signals persist in MASLD even after disease remission.Thus,we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal.Methods:Male C57BL/6J mice were divided into three groups:Western diet(WD)feeding,chow diet(CD)feeding,or diet reversal from WD to CD.After 16 weeks of feeding,RNA sequencing was performed on the mice’s livers to identify persistent alterations characteristic of MASLD.Additionally,RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized.Results:WD-induced MASLD triggered persistent activation of the DNA damage response(DDR)and its primary transcription factor,P53,long after the resolution of the hepatic phenotype through dietary reversal.Elevated levels of P53 might promote apoptosis,thereby exacerbating metabolic dysfunction-associated steatohepatitis,as they strongly correlated with hepatocyte ballooning,an indicator of apoptosis activation.Moreover,P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver.Mechanistically,P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease(AEN).Consistently,P53,AEN,and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal.Conclusions:The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD.Our findings provide new insights into the mechanisms of MASLD relapse,highlighting DDR signaling as a promising target to prevent MASLD recurrence.
基金supported by the National Natural Science Foundation of China,No.81573876(to YH)
文摘Kai-Xin-San consists of Ginseng Radix, Polygalae Radix, Acori Tatarinowii Rhizoma, and Poria at a ratio of 3:3:2:2. Kai-Xin-San has been widely used for the treatment of emotional disorders in China. However, no studies have identified the key proteins implicated in response to Kai-Xin-San treatment. In this study, rat models of chronic mild stress were established using different stress methods over 28 days. After 14 days of stress stimulation, rats received daily intragastric administrations of 600 mg/kg Kai-Xin-San. The sucrose preference test was used to determine depression-like behavior in rats, while isobaric tags were used for relative and absolute quantitation-based proteomics to identify altered proteins following Kai-Xin-San treatment. Kai-Xin-San treatment for 2 weeks noticeably improved depression-like behaviors in rats with chronic mild stress. We identified 33 differentially expressed proteins: 7 were upregulated and 26 were downregulated. Functional analysis showed that these differentially expressed proteins participate in synaptic plasticity, neurodevelopment, and neurogenesis. Our results indicate that Kai-Xin-San has an important role in regulating the key node proteins in the synaptic signaling network, and are helpful to better understand the mechanism of the antidepressive effects of Kai-Xin-San and to provide objective theoretical support for its clinical application. The study was approved by the Ethics Committee for Animal Research from the Chinese PLA General Hospital(approval No. X5-2016-07) on March 5, 2016.
基金Supported by National Natural Science Foundation of China,No.81770525.
文摘BACKGROUND Esophageal schwannomas originating from Schwann cells are extremely rare esophageal tumors.They commonly occur in the upper and middle esophagus but less frequently in the lower esophagus.Herein,we report a rare case of a large lower esophageal schwannoma misdiagnosed as a leiomyoma.We also present a brief literature review on lower esophageal schwannomas.CASE SUMMARY A 62-year-old man presented with severe dysphagia lasting 6 mo.A barium esophagogram showed that the lower esophagus was compressed within approximately 5.5 cm.Endoscopy revealed the presence of a large submucosal protuberant lesion in the esophagus at a distance of 32-38 cm from the incisors.Endoscopic ultrasound findings demonstrated a 4.5 cm×5.0 cm hypoechoic lesion.Chest computed tomography revealed a mass of size approximately 53 mm×39 mm×50 mm.Initial tests revealed features indicative of leiomyoma.After multidisciplinary discussions,the patient underwent a video-assisted thoracoscopic partial esophagectomy.Further investigation involving immunohistochemical examination confirming palisading spindle cells as positive for S100 and Sox10 led to the final diagnosis of a lower esophageal schwannoma.There was no tumor recurrence or metastasis during follow-up.CONCLUSION The final diagnosis of esophageal schwannoma requires histopathological and immunohistochemical examination.The early appropriate surgery favors a remarkable prognosis.
