AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcino...AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.展开更多
BACKGROUND Syphilis is a common sexually transmitted disease caused by the Treponema pallidum (T.pallidum).Malignant syphilis is a rare presentation of secondary syphilis.Here,we present a case diagnosed with malignan...BACKGROUND Syphilis is a common sexually transmitted disease caused by the Treponema pallidum (T.pallidum).Malignant syphilis is a rare presentation of secondary syphilis.Here,we present a case diagnosed with malignant syphilis accompanied with neurosyphilis.CASE SUMMARY A 56-year-old man present with a 2-mo history of spreading ulcerous and necrotic papules and nodules covered with thick crusts over the face,trunk,extremities,and genitalia.The patient was diagnosed with malignant syphilis accompanied by neurosyphilis based on the characteristic morphology of the lesions,positive serological and cerebrospinal fluid tests for syphilis,brain magnetic resonance imaging,and histopathology,along with resolution of the lesions following the institution of penicillin therapy.The lesions and neurological condition successfully resolved after a course of treatment with penicillin.CONCLUSION We suggest that neurosyphilis should be considered whenever people have psychiatric symptoms without cutaneous lesions or human immunodeficiency virus.展开更多
De spite cisplatin has been widely used in the treatment of various cancers,the noteworthy nephrotoxicity greatly constrained its clinical value.For this reason,finding novel targeted therapies to attenuate the nephro...De spite cisplatin has been widely used in the treatment of various cancers,the noteworthy nephrotoxicity greatly constrained its clinical value.For this reason,finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant.Our previous study found that histone deacetylase sirtuin 6(SIRT6)could be an ideal target for the treatment of cisplatin-induced acute kidney injury.In this study,we explored the protective effects of ellagic acid,a natural polyphenol compound that activates SIRT6,on cisplatin-induced nephrotoxicity.Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells.Moreover,ellagic acid ameliorated renal dysfunction,apoptosis and fibrosis induced by cisplatin in mice.Furthermore,ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin(IL)-1βand IL-6 expression both in vitro and in vivo.Mechanistically,ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor(TNF)-αexpression.And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis,indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation.Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury,and support ellagic acid as a potential adjunctive therapy for future cancer treatment.展开更多
Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component ...Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component of staple foods that are consumed daily,and the effects,metabolic pathway,and molecular mechanism of starch in the context of NAFLD remain unclear.Our study showed that a high-starch carbohydrate diet(HCD)led to the occurrence and exacerbation of NAFLD in mice.Transcriptomics and metabonomic analyses showed that the increased fatty acid influx mediated by NADPH oxidase 2(NOX2)exacerbated NAFLD.Knocking down NOX2 specifically alleviated HCD-induced NAFLD in vivo and in vitro.Moreover,the large amounts of ROS produced by NOX2 further exacerbated insulin resistance and increased lipolysis in perirenal white adipose tissue(periWAT),thereby providing fatty acids for hepatic lipid synthesis.In addition,the interaction between AMPKα1 and p47phox was the pathway that mediated the high expression of NOX2 induced by a HCD.Our study systematically demonstrated the effect of a HCD on NAFLD.Elevated fatty acid influx is a unique molecular regulatory pathway that mediates HCD-induced NAFLD exacerbation,which is different from the effect of simple sugars.Additionally,NOX2 was suggested to be a specific and effective drug target for NAFLD.展开更多
Sensor networks tend to support different traffic patterns since more and more emerging applications have diverse needs. We present MGRP, a Multi-Gradient Routing Protocol for wireless sensor networks, which is fully ...Sensor networks tend to support different traffic patterns since more and more emerging applications have diverse needs. We present MGRP, a Multi-Gradient Routing Protocol for wireless sensor networks, which is fully distributed and efficiently supports endto-end, one-to-many and many-to-one traffic patterns by effectively construct and maintain a gradient vector for each node. We further combine neighbor link estimation with routing information to reduce packet exchange on network dynamics and node failures. We have implemented MGRP on Tiny OS and evaluated its performance on real-world testbeds. The result shows MGRP achieves lower end-to-end packet delay in different traffic patterns compared to the state of the art routing protocols while still remains high packet delivery ratio.展开更多
BACKGROUND Rhinocerebral mucormycosis(RCM)is a rare fatal fungal infection which is on the increase among immunocompromised hosts such as patients who have had hematological cancers,or have received immunosuppressive ...BACKGROUND Rhinocerebral mucormycosis(RCM)is a rare fatal fungal infection which is on the increase among immunocompromised hosts such as patients who have had hematological cancers,or have received immunosuppressive drugs,corticosteroids,or other T cell suppressing agents.CASE SUMMARY We report a case of RCM caused by Rhizopus oryzae,one of the most common opportunistic pathogens,in a patient suffering from a fourth relapse of acute myeloid leukemia.The patient developed RCM after he had received long-term antibiotic agents and corticosteroids.The pathogen was isolated three times from nasal secretions collected from the deep parts of the nasal cavity and was identified by morphology and internal transcribed spacer sequencing.Blood infection was excluded by droplet digital polymerase chain reaction and blood culture.The patient was empirically treated with caspofungin and voriconazole for several days while the lesions continued to progress.The patient was given amphotericin B in combination with caspofungin after RCM was suspected,and the lesions improved over the course of treatment,which lasted several days.However,the patient eventually died of the primary disease.CONCLUSION This case indicates that immunosuppressive drugs,including corticosteroids and antimetabolites in hematological tumor,do increase the risk of infections of this type.Early diagnosis,prompt and frequent surgical debridement,and treatment with amphotericin B without delay are all essential in combatting RCM.展开更多
This paper sets out to observe the governance effect of the heterogeneous debts on the overinvestment behavior by Chinese companies.On this basis,the authors examined the different relationships between heterogeneous ...This paper sets out to observe the governance effect of the heterogeneous debts on the overinvestment behavior by Chinese companies.On this basis,the authors examined the different relationships between heterogeneous debts and over-investment.The study results indicate that various types of debt have different governance effect on over-investment.Trade credit can curb over-investment effectively and bank loans may exacerbate over-investment.展开更多
Although primary vesical calculi is an ancient disease,the mechanism of calculi formation remains unclear.In this study,we established a novel primary vesical calculi model with D,L-choline tartrate in mice.Compared w...Although primary vesical calculi is an ancient disease,the mechanism of calculi formation remains unclear.In this study,we established a novel primary vesical calculi model with D,L-choline tartrate in mice.Compared with commonly used melamine and ethylene glycol models,our model was the only approach that induced vesical calculi without causing kidney injury.Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi,yet the effect of fat is overlooked.To assay the relationship of dietary fat with the formation of primary vesical calculi,D,L-choline tartrate-treated mice were fed a high-fat,low-fat,or normal-fat diet.Genetic changes in the mouse bladder were detected with transcriptome analysis.A high-fat diet remarkably reduced the morbidity of primary vesical calculi.Higher fatty acid levels in serum and urine were observed in the high-fat diet group,and more intact epithelia in bladder were observed in the same group compared with the normal-and low-fat diet groups,suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure.Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14(Cxcl14)was upregulated in the bladders of high-fat diet-fed mice compared with those of normal-or low-fat diet-fed mice,which was consistent with histological observations.The expression of CXCL14 significantly increased in the bladder in the high-fat diet group.CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages,which led to phagocytosis of budding crystals and prevented accumulation of calculi.In human bladder epithelia(HCV-29)cells,high fatty acid supplementation significantly increased the expression of CXCL14.Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi,which provides new ideas for the reduction of morbidity of primary vesical calculi.展开更多
Macrophages are highly plastic cells that differentially regulate multiple pathological conditions,including cancer and autoimmune diseases.In response to various stimuli,macrophages activate different intrinsic signa...Macrophages are highly plastic cells that differentially regulate multiple pathological conditions,including cancer and autoimmune diseases.In response to various stimuli,macrophages activate different intrinsic signaling pathways and polarize into distinct macrophage subsets.We aimed to identify key new effectors that could control macrophage polarization and impact the development of cancer or colitis.Following treatment with the supernatants of tumor cells,macrophages showed an upregulation in Fbxo38 expression.Subsequently,we further identified that FBXO38 promotes macrophage immunosuppressive function by upregulating the expression of M2-like genes via MAPK and IRF4 signaling without affecting M1-like macrophage polarization.Deletion of Fbxo38 in macrophages was found to block tumor development and protect against DSS-induced colitis.Considering the distinct regulation of tumor development by FBXO38 in T cells and macrophages,we suggest that a comprehensive understanding of FBXO38 function in different cell types is critical for its further translational usage.展开更多
Objective： In this study, we investigated the interrelationship between clinicopathologic findings and pre-B-cell leukemia transcription factor 2 （PBX2） expression in gingival squamous cell carcinoma （GSCC）. Meth...Objective： In this study, we investigated the interrelationship between clinicopathologic findings and pre-B-cell leukemia transcription factor 2 （PBX2） expression in gingival squamous cell carcinoma （GSCC）. Methods： Expression level of PBX2 was immunohistochemically examined in 66 GSCC subjects （30 men and 36 women） with ages ranging from 42 to 85 （median 64.5） years, in which staining intensity in tumor cells was categorized as either weaker （level 1 ） or equal to/stronger （level 2） than that in the endothelial cells. Results： PBX2 expression is correlated with valosin-containing protein （VCP） expression. Univariate and multivariate analyses revealed a high level of PBX2 expression to be a poor prognosticator for disease-free survival （DFS） and overall survival （OS）, and PBX2 expression was an independent prognostic factor for both DFS and OS in GSCC. Conclusions： PBX2 expression level in GSCC is proqnostic. PBX2 may be a useful marker to identify the potential for progression in GSCC.展开更多
A few-mode fiber （FMF） is designed to support three spatial modes （LP01, LP 11a, and LP 11 b） and fabricated through plasma chemical vapor deposition （PCVD）and rod-in-tube （RIT） method. Using PDM-DFTS-OFDM- 32...A few-mode fiber （FMF） is designed to support three spatial modes （LP01, LP 11a, and LP 11 b） and fabricated through plasma chemical vapor deposition （PCVD）and rod-in-tube （RIT） method. Using PDM-DFTS-OFDM- 32QAM modulation, wavelength division multiplexing, mode multiplexing, and coherent detection, we successfully demonstrated 200Tb/s （375× 3 × 178.125Gb/s） signal over 1 km FMF using C and L bands with 25 GHz channel spacing. After 1 km FMF transmission, all the tested bit error rates （BERs） are below 20% forward error correction （FEC） threshold （2.0 × 10-2）. Within each sub-channel, we achieved a spectral efficiency of 21.375 bits/Hz in the C and L bands.展开更多
Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without co...Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore,overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment.Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicininduced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice.These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.展开更多
基金Supported by Hong Kong Wang Kuan Cheng GrantInner Mongolia Stem Cell Grant, No. kjk10jhg
文摘AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.
基金Supported by the National Natural Science Foundation of China,No.81773337the Shandong Traditional Chinese Medicine Science and Technology Development Plans,China,No.2017-415+1 种基金the Medical and Health Science Technology Project of Shandong Province,China,No.2017WS345the Natural Science Foundation of Shandong Province,China,No.ZR2015HL127
文摘BACKGROUND Syphilis is a common sexually transmitted disease caused by the Treponema pallidum (T.pallidum).Malignant syphilis is a rare presentation of secondary syphilis.Here,we present a case diagnosed with malignant syphilis accompanied with neurosyphilis.CASE SUMMARY A 56-year-old man present with a 2-mo history of spreading ulcerous and necrotic papules and nodules covered with thick crusts over the face,trunk,extremities,and genitalia.The patient was diagnosed with malignant syphilis accompanied by neurosyphilis based on the characteristic morphology of the lesions,positive serological and cerebrospinal fluid tests for syphilis,brain magnetic resonance imaging,and histopathology,along with resolution of the lesions following the institution of penicillin therapy.The lesions and neurological condition successfully resolved after a course of treatment with penicillin.CONCLUSION We suggest that neurosyphilis should be considered whenever people have psychiatric symptoms without cutaneous lesions or human immunodeficiency virus.
基金financially supported by grants from the National Natural Science Foundation of China(82170873,81871095)the National Key R&D Program of China(2018YFC2000304)+1 种基金the Tsinghua Precision Medicine Foundation(10001020132)the Tsinghua University Spring Breeze Fund(20211080005)。
文摘De spite cisplatin has been widely used in the treatment of various cancers,the noteworthy nephrotoxicity greatly constrained its clinical value.For this reason,finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant.Our previous study found that histone deacetylase sirtuin 6(SIRT6)could be an ideal target for the treatment of cisplatin-induced acute kidney injury.In this study,we explored the protective effects of ellagic acid,a natural polyphenol compound that activates SIRT6,on cisplatin-induced nephrotoxicity.Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells.Moreover,ellagic acid ameliorated renal dysfunction,apoptosis and fibrosis induced by cisplatin in mice.Furthermore,ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin(IL)-1βand IL-6 expression both in vitro and in vivo.Mechanistically,ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor(TNF)-αexpression.And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis,indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation.Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury,and support ellagic acid as a potential adjunctive therapy for future cancer treatment.
基金financially supported by grants from the National Natural Science Foundation of China(8217087381871095)+1 种基金the National Key R&D Program of China(2018YFC2000304)the Tsinghua University Spring Breeze Fund(20211080005).
文摘Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component of staple foods that are consumed daily,and the effects,metabolic pathway,and molecular mechanism of starch in the context of NAFLD remain unclear.Our study showed that a high-starch carbohydrate diet(HCD)led to the occurrence and exacerbation of NAFLD in mice.Transcriptomics and metabonomic analyses showed that the increased fatty acid influx mediated by NADPH oxidase 2(NOX2)exacerbated NAFLD.Knocking down NOX2 specifically alleviated HCD-induced NAFLD in vivo and in vitro.Moreover,the large amounts of ROS produced by NOX2 further exacerbated insulin resistance and increased lipolysis in perirenal white adipose tissue(periWAT),thereby providing fatty acids for hepatic lipid synthesis.In addition,the interaction between AMPKα1 and p47phox was the pathway that mediated the high expression of NOX2 induced by a HCD.Our study systematically demonstrated the effect of a HCD on NAFLD.Elevated fatty acid influx is a unique molecular regulatory pathway that mediates HCD-induced NAFLD exacerbation,which is different from the effect of simple sugars.Additionally,NOX2 was suggested to be a specific and effective drug target for NAFLD.
基金supported by National Key Technologies Research and Development Program of China under Grant No.2014BAH14F01National Science and Technology Major Project of China under Grant No.2012ZX03005007+1 种基金National NSF of China Grant No.61402372Fundamental Research Funds for the Central Universities Grant No.3102014JSJ0003
文摘Sensor networks tend to support different traffic patterns since more and more emerging applications have diverse needs. We present MGRP, a Multi-Gradient Routing Protocol for wireless sensor networks, which is fully distributed and efficiently supports endto-end, one-to-many and many-to-one traffic patterns by effectively construct and maintain a gradient vector for each node. We further combine neighbor link estimation with routing information to reduce packet exchange on network dynamics and node failures. We have implemented MGRP on Tiny OS and evaluated its performance on real-world testbeds. The result shows MGRP achieves lower end-to-end packet delay in different traffic patterns compared to the state of the art routing protocols while still remains high packet delivery ratio.
基金National Natural Science Foundation of China,No.81773337Medical and Health Science Technology Project of Shandong Province,No.2017WS345and Traditional Chinese Medicine Science and Technology Development Plans of Shandong Province,No.2017-415.
文摘BACKGROUND Rhinocerebral mucormycosis(RCM)is a rare fatal fungal infection which is on the increase among immunocompromised hosts such as patients who have had hematological cancers,or have received immunosuppressive drugs,corticosteroids,or other T cell suppressing agents.CASE SUMMARY We report a case of RCM caused by Rhizopus oryzae,one of the most common opportunistic pathogens,in a patient suffering from a fourth relapse of acute myeloid leukemia.The patient developed RCM after he had received long-term antibiotic agents and corticosteroids.The pathogen was isolated three times from nasal secretions collected from the deep parts of the nasal cavity and was identified by morphology and internal transcribed spacer sequencing.Blood infection was excluded by droplet digital polymerase chain reaction and blood culture.The patient was empirically treated with caspofungin and voriconazole for several days while the lesions continued to progress.The patient was given amphotericin B in combination with caspofungin after RCM was suspected,and the lesions improved over the course of treatment,which lasted several days.However,the patient eventually died of the primary disease.CONCLUSION This case indicates that immunosuppressive drugs,including corticosteroids and antimetabolites in hematological tumor,do increase the risk of infections of this type.Early diagnosis,prompt and frequent surgical debridement,and treatment with amphotericin B without delay are all essential in combatting RCM.
文摘This paper sets out to observe the governance effect of the heterogeneous debts on the overinvestment behavior by Chinese companies.On this basis,the authors examined the different relationships between heterogeneous debts and over-investment.The study results indicate that various types of debt have different governance effect on over-investment.Trade credit can curb over-investment effectively and bank loans may exacerbate over-investment.
基金supported by grants from the National Natural Science Foundation of China(81974503 and 81871095)the National Key R&D Program of China(2018YFC2000304)+3 种基金the Key International S&T Cooperation Program of China(2016YFE0113700)the European Union’s Horizon 2020 Research and Innovation Program(633589)the Natural Science Foundation of Beijing,China(7202096)the Tsinghua University independent research program(7191007,China)。
文摘Although primary vesical calculi is an ancient disease,the mechanism of calculi formation remains unclear.In this study,we established a novel primary vesical calculi model with D,L-choline tartrate in mice.Compared with commonly used melamine and ethylene glycol models,our model was the only approach that induced vesical calculi without causing kidney injury.Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi,yet the effect of fat is overlooked.To assay the relationship of dietary fat with the formation of primary vesical calculi,D,L-choline tartrate-treated mice were fed a high-fat,low-fat,or normal-fat diet.Genetic changes in the mouse bladder were detected with transcriptome analysis.A high-fat diet remarkably reduced the morbidity of primary vesical calculi.Higher fatty acid levels in serum and urine were observed in the high-fat diet group,and more intact epithelia in bladder were observed in the same group compared with the normal-and low-fat diet groups,suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure.Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14(Cxcl14)was upregulated in the bladders of high-fat diet-fed mice compared with those of normal-or low-fat diet-fed mice,which was consistent with histological observations.The expression of CXCL14 significantly increased in the bladder in the high-fat diet group.CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages,which led to phagocytosis of budding crystals and prevented accumulation of calculi.In human bladder epithelia(HCV-29)cells,high fatty acid supplementation significantly increased the expression of CXCL14.Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi,which provides new ideas for the reduction of morbidity of primary vesical calculi.
基金We thank Hangzhou Institute for Advanced Study and Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,University of Chinese Academy of Sciences.This work was supported by grants from the National Natural Science Foundation of China(81825011,32221002,81930038 and 82303154)the Ministry of Science and Technology of China(2018YFA0800702)+1 种基金the Science and Technology Commission of Shanghai Municipality(22JC1403001,HS2021SHZX001)the China Postdoctoral Science Foundation(2022M723141).
文摘Macrophages are highly plastic cells that differentially regulate multiple pathological conditions,including cancer and autoimmune diseases.In response to various stimuli,macrophages activate different intrinsic signaling pathways and polarize into distinct macrophage subsets.We aimed to identify key new effectors that could control macrophage polarization and impact the development of cancer or colitis.Following treatment with the supernatants of tumor cells,macrophages showed an upregulation in Fbxo38 expression.Subsequently,we further identified that FBXO38 promotes macrophage immunosuppressive function by upregulating the expression of M2-like genes via MAPK and IRF4 signaling without affecting M1-like macrophage polarization.Deletion of Fbxo38 in macrophages was found to block tumor development and protect against DSS-induced colitis.Considering the distinct regulation of tumor development by FBXO38 in T cells and macrophages,we suggest that a comprehensive understanding of FBXO38 function in different cell types is critical for its further translational usage.
基金Project (No. 30801382) supported by the National Natural Science Foundation of China
文摘Objective： In this study, we investigated the interrelationship between clinicopathologic findings and pre-B-cell leukemia transcription factor 2 （PBX2） expression in gingival squamous cell carcinoma （GSCC）. Methods： Expression level of PBX2 was immunohistochemically examined in 66 GSCC subjects （30 men and 36 women） with ages ranging from 42 to 85 （median 64.5） years, in which staining intensity in tumor cells was categorized as either weaker （level 1 ） or equal to/stronger （level 2） than that in the endothelial cells. Results： PBX2 expression is correlated with valosin-containing protein （VCP） expression. Univariate and multivariate analyses revealed a high level of PBX2 expression to be a poor prognosticator for disease-free survival （DFS） and overall survival （OS）, and PBX2 expression was an independent prognostic factor for both DFS and OS in GSCC. Conclusions： PBX2 expression level in GSCC is proqnostic. PBX2 may be a useful marker to identify the potential for progression in GSCC.
基金Aeknowledgements This work was supported by the Major Scientific and Technological hmovation Projects of Hubci Province （No. 2014AAA001）, the National Basic Research Program of China （Nos. 2014CB340100, 2014CB340101, and 2014CB340105）. and the Natural Science Foundation of Hubei Prov incc （No. 2015CFA056）.
文摘A few-mode fiber （FMF） is designed to support three spatial modes （LP01, LP 11a, and LP 11 b） and fabricated through plasma chemical vapor deposition （PCVD）and rod-in-tube （RIT） method. Using PDM-DFTS-OFDM- 32QAM modulation, wavelength division multiplexing, mode multiplexing, and coherent detection, we successfully demonstrated 200Tb/s （375× 3 × 178.125Gb/s） signal over 1 km FMF using C and L bands with 25 GHz channel spacing. After 1 km FMF transmission, all the tested bit error rates （BERs） are below 20% forward error correction （FEC） threshold （2.0 × 10-2）. Within each sub-channel, we achieved a spectral efficiency of 21.375 bits/Hz in the C and L bands.
基金supported by the National Natural Science Foundation of China (81871095 and 82170873)the National Key R&D Program of China (2018YFC2000304)+1 种基金the Tsinghua Precision Medicine Foundation (10001020132, China)the Tsinghua University Spring Breeze Fund (20211080005, China)。
文摘Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore,overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment.Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicininduced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice.These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.
