In the present study, eight strains were isolated from 20 cow vagina samples and identified using phenotype, biochemical analysis, sugar fermentation tests, and 16S rRNA sequence analysis. Among eight strains, only SQ...In the present study, eight strains were isolated from 20 cow vagina samples and identified using phenotype, biochemical analysis, sugar fermentation tests, and 16S rRNA sequence analysis. Among eight strains, only SQ0048 was identified as Lactobacillus johnsonii based on a series of biochemical testing (including the adhesion test, catalase test, bacteriocin production test, antibacterial test, and pH value), suggesting that its biological activity was superior to the other seven strains. Furthermore, SQ0048 had the lowest pH value (4.32) and the shortest fermentation time (8 h) compared with the other strains. The adhesion rate of SQ0048 was significantly higher than that of Lactobacillus delbrueckii, with an average adhesion number of 304 ± 2.67. The hydrogen peroxide production testing in SQ0048 was positive;in addition, bacteriocin gene of SQ0048, encoding an approximately 10-kDa product, was successfully cloned, expressed, and detected using the SDS-PAGE method. Meanwhile, SQ0048 had a weak inhibitory effect on Staphylococcus aureus and Escherichia coli. However, the expression products of the bacteriocin gene of SQ0048 had a very strong inhibitory effect on S. aureus and E. coli, with inhibition zone sizes of 18 ± 0.45 mm and 15 ± 0.60 mm, respectively. These data showed that SQ0048 has excellent antibacterial properties compared with other isolated strains and is a potential probiotic candidate to improve the health of the vaginas of cows by inhibiting pathogenic microorganisms.展开更多
[Objectives]To investigate the mechanism of miR-23a in the proliferation of human tongue squamous cell carcinoma cells.[Methods]Clinical tissue samples of tongue squamous cell carcinoma were collected and Tca8113 and ...[Objectives]To investigate the mechanism of miR-23a in the proliferation of human tongue squamous cell carcinoma cells.[Methods]Clinical tissue samples of tongue squamous cell carcinoma were collected and Tca8113 and CAL27 were cultured.Real-time quantitative PCR was performed to detect the expressions of miR-23a and PPP2R5E in clinical tissue samples of tongue squamous cell carcinoma.MTT assay,colony formation assay and growth curve assay were used to detect the effect of miR-23a and PPP2R5E on the proliferation of human tongue squamous carcinoma cell.Luciferase reporter assay verified the regulatory relationship between miR-23a and PPP2R5E.[Results]The expression of miR-23a in tongue squamous cell carcinoma was significantly up-regulated(P<0.01).miR-23a promoted the proliferation of tongue squamous cell carcinoma cells.Bioinformatics prediction and luciferin reporting experiments showed that PPP2R5E was a direct target gene of miR-23a.The expression of PPP2R5E was decreased in tongue squamous cell carcinoma.PPP2R5E inhibited the proliferation of tongue squamous cell carcinoma cells.Overexpression of PPP2R5E can reverse the proliferation promoting effect of miR-23a on tongue squamous cell carcinoma cells.[Conclusions]miR-23a can promote the proliferation of tongue squamous cell carcinoma cells through PPP2R5E and miR-23a plays an oncogene role in the occurrence and development of tongue squamous cell carcinoma.展开更多
Lipids have been found to modulate tumor biology,including proliferation,survival,and metastasis.With the new understanding of tumor immune escape that has developed in recent years,the influence of lipids on the can...Lipids have been found to modulate tumor biology,including proliferation,survival,and metastasis.With the new understanding of tumor immune escape that has developed in recent years,the influence of lipids on the cancer—immunity cycle has also been gradually discovered.First,regarding antigen presentation,cholesterol prevents tumor antigens from being identified by antigen presenting cells.Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells,impairing antigen presentation to T cells.Prostaglandin E2(PGE2)reduce the accumulation of tumor-infiltrating dendritic cells.Regarding T-cell priming and activation,cholesterol destroys the structure of the T-cell receptor and reduces immunodetection.In contrast,cholesterol also promotes T-cell receptor clustering and relative signal transduction.PGE2 represses T-cell proliferation.Finally,regarding T-cell killing of cancer cells,PGE2 and cholesterol weaken granule-dependent cytotoxicity.Moreover,fatty acids,cholesterol,and PGE2 can improve the activity of immunosuppressive cells,increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines.Given the regulatory role of lipids in the cancer—immunity cycle,drugs that modulate fatty acids,cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy.These strategies have been studied in both preclinical and clinical studies.展开更多
Mevalonate metabolism plays an important role in regulating tumor growth and progression;however,its role in immune evasion and immune checkpoint modulation remains unclear.Here,we found that non-small cell lung cance...Mevalonate metabolism plays an important role in regulating tumor growth and progression;however,its role in immune evasion and immune checkpoint modulation remains unclear.Here,we found that non-small cell lung cancer(NSCLC)patients with higher plasma mevalonate response better to antiPD-(L)1 therapy,as indicated by prolonged progression-free survival and overall survival.Plasma mevalonate levels were positively correlated with programmed death ligand-1(PD-L1)expression in tumor tissues.In NSCLC cell lines and patient-derived cells,supplementation of mevalonate significantly upregulated the expression of PD-L1,whereas deprivation of mevalonate reduced PD-L1 expression.Mevalonate increased CD274 mRNA level but did not affect CD274 transcription.Further,we confirmed that mevalonate improved CD274 mRNA stability.Mevalonate promoted the affinity of the AU-rich elementbinding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA.By in vivo study,we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1,increased the infiltration of CD8^(+)T cells,and improved cytotoxic function of T cells.Collectively,our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody,and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.展开更多
The authors regret that one author was missed in the author list when preparing the manuscript,while the foundation to him was mentioned in the section of Acknowledgments.Dr.Qinjie Weng should be added to the author l...The authors regret that one author was missed in the author list when preparing the manuscript,while the foundation to him was mentioned in the section of Acknowledgments.Dr.Qinjie Weng should be added to the author list because of his contribution in animal study and his foundation help us to complete this study.The authors sincerely apologize for any inconvenience caused to the journal and readers.展开更多
Immunotherapy strategies targeting the programmed cell death ligand 1(PD-L1)/programmed cell death 1(PD-1)pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer.However,ow...Immunotherapy strategies targeting the programmed cell death ligand 1(PD-L1)/programmed cell death 1(PD-1)pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer.However,owing to the heterogeneity of tumors and individual immune systems,PD-L1/PD-1 blockade still shows slow response rates in controlling malignancies in many patients.Accumulating evidence has shown that an effective response to anti-PD-Ll/anti-PD-1 therapy requires establishing an integrated immune cycle.Damage in any step of the immune cycle is one of the most important causes of immunotherapy failure.Impairments in the immune cycle can be restored by epigenetic modification,including reprogramming the environment of tumor-associated immunity,eliciting an immune response by increasing the presentation of tumor antigens,and by regulating T cell trafficking and reactivation.Thus,a rational combination of PD-L1/PD-1 blockade and epigenetic agents may offer great potential to retrain the immune system and to improve clinical outcomes of checkpoint blockade therapy.展开更多
Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with...Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems.Nowadays,however,accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression,inducing tumor invasion and metastasis.However,the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive.Therefore,in this review,we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance(MDR),metastasis,apoptosis,proliferation,immune surveillance evasion,and the alterations of relevant tumor micro-environment.Moreover,we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’efficacy.The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented.Furthermore,it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.展开更多
Integrated optical gyroscopes(IOGs)have been an efficient tool for numerous applications in various fields,including inertial navigation,flight control,and earthquake monitoring.Here,we review the progress of integrat...Integrated optical gyroscopes(IOGs)have been an efficient tool for numerous applications in various fields,including inertial navigation,flight control,and earthquake monitoring.Here,we review the progress of integrated optical gyroscopes based on two categories of integrated interferometric optical gyroscopes(IIOGs)and integrated resonant optical gyroscopes(IROGs).展开更多
文摘In the present study, eight strains were isolated from 20 cow vagina samples and identified using phenotype, biochemical analysis, sugar fermentation tests, and 16S rRNA sequence analysis. Among eight strains, only SQ0048 was identified as Lactobacillus johnsonii based on a series of biochemical testing (including the adhesion test, catalase test, bacteriocin production test, antibacterial test, and pH value), suggesting that its biological activity was superior to the other seven strains. Furthermore, SQ0048 had the lowest pH value (4.32) and the shortest fermentation time (8 h) compared with the other strains. The adhesion rate of SQ0048 was significantly higher than that of Lactobacillus delbrueckii, with an average adhesion number of 304 ± 2.67. The hydrogen peroxide production testing in SQ0048 was positive;in addition, bacteriocin gene of SQ0048, encoding an approximately 10-kDa product, was successfully cloned, expressed, and detected using the SDS-PAGE method. Meanwhile, SQ0048 had a weak inhibitory effect on Staphylococcus aureus and Escherichia coli. However, the expression products of the bacteriocin gene of SQ0048 had a very strong inhibitory effect on S. aureus and E. coli, with inhibition zone sizes of 18 ± 0.45 mm and 15 ± 0.60 mm, respectively. These data showed that SQ0048 has excellent antibacterial properties compared with other isolated strains and is a potential probiotic candidate to improve the health of the vaginas of cows by inhibiting pathogenic microorganisms.
基金Chengde Medical University Natural Science Foundation Projects"The Mechanism of miR-23a in the Development of Tongue Squamous Cell Carcinoma"(201722)Natural Science Foundation of Hebei Provincial Department of Education-Youth Foundatijon"The Mechanism of has-circ-0001862-miR-23a Axis in the Development of Tongue Squamous Cell Carcinoma"(QN2019079).
文摘[Objectives]To investigate the mechanism of miR-23a in the proliferation of human tongue squamous cell carcinoma cells.[Methods]Clinical tissue samples of tongue squamous cell carcinoma were collected and Tca8113 and CAL27 were cultured.Real-time quantitative PCR was performed to detect the expressions of miR-23a and PPP2R5E in clinical tissue samples of tongue squamous cell carcinoma.MTT assay,colony formation assay and growth curve assay were used to detect the effect of miR-23a and PPP2R5E on the proliferation of human tongue squamous carcinoma cell.Luciferase reporter assay verified the regulatory relationship between miR-23a and PPP2R5E.[Results]The expression of miR-23a in tongue squamous cell carcinoma was significantly up-regulated(P<0.01).miR-23a promoted the proliferation of tongue squamous cell carcinoma cells.Bioinformatics prediction and luciferin reporting experiments showed that PPP2R5E was a direct target gene of miR-23a.The expression of PPP2R5E was decreased in tongue squamous cell carcinoma.PPP2R5E inhibited the proliferation of tongue squamous cell carcinoma cells.Overexpression of PPP2R5E can reverse the proliferation promoting effect of miR-23a on tongue squamous cell carcinoma cells.[Conclusions]miR-23a can promote the proliferation of tongue squamous cell carcinoma cells through PPP2R5E and miR-23a plays an oncogene role in the occurrence and development of tongue squamous cell carcinoma.
基金supported by the National Natural Science Foundation of China(No.81930102 to Bo Yang),the National Natural Science Foundation of China(No.82273949 to Ling Ding),the National Natural Science Foundation of China(No.82104196 to Xi Chen)。
文摘Lipids have been found to modulate tumor biology,including proliferation,survival,and metastasis.With the new understanding of tumor immune escape that has developed in recent years,the influence of lipids on the cancer—immunity cycle has also been gradually discovered.First,regarding antigen presentation,cholesterol prevents tumor antigens from being identified by antigen presenting cells.Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells,impairing antigen presentation to T cells.Prostaglandin E2(PGE2)reduce the accumulation of tumor-infiltrating dendritic cells.Regarding T-cell priming and activation,cholesterol destroys the structure of the T-cell receptor and reduces immunodetection.In contrast,cholesterol also promotes T-cell receptor clustering and relative signal transduction.PGE2 represses T-cell proliferation.Finally,regarding T-cell killing of cancer cells,PGE2 and cholesterol weaken granule-dependent cytotoxicity.Moreover,fatty acids,cholesterol,and PGE2 can improve the activity of immunosuppressive cells,increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines.Given the regulatory role of lipids in the cancer—immunity cycle,drugs that modulate fatty acids,cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy.These strategies have been studied in both preclinical and clinical studies.
基金supported by National Natural Science Foundation of China(No.81930102 to Bo Yang,No.82104196 to Xi Chen,No.82273949 to Ling Ding)Key R&D Program of Zhejiang(No.2022C03143 to Qinjie Weng,China)。
文摘Mevalonate metabolism plays an important role in regulating tumor growth and progression;however,its role in immune evasion and immune checkpoint modulation remains unclear.Here,we found that non-small cell lung cancer(NSCLC)patients with higher plasma mevalonate response better to antiPD-(L)1 therapy,as indicated by prolonged progression-free survival and overall survival.Plasma mevalonate levels were positively correlated with programmed death ligand-1(PD-L1)expression in tumor tissues.In NSCLC cell lines and patient-derived cells,supplementation of mevalonate significantly upregulated the expression of PD-L1,whereas deprivation of mevalonate reduced PD-L1 expression.Mevalonate increased CD274 mRNA level but did not affect CD274 transcription.Further,we confirmed that mevalonate improved CD274 mRNA stability.Mevalonate promoted the affinity of the AU-rich elementbinding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA.By in vivo study,we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1,increased the infiltration of CD8^(+)T cells,and improved cytotoxic function of T cells.Collectively,our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody,and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.
文摘The authors regret that one author was missed in the author list when preparing the manuscript,while the foundation to him was mentioned in the section of Acknowledgments.Dr.Qinjie Weng should be added to the author list because of his contribution in animal study and his foundation help us to complete this study.The authors sincerely apologize for any inconvenience caused to the journal and readers.
基金supported by the National Natural Science Foundation of China for Distinguished Young Scholar(No.81625024 to Bo Yang)the National Natural Science Foundation of China(No.81773754 to Ling Ding)
文摘Immunotherapy strategies targeting the programmed cell death ligand 1(PD-L1)/programmed cell death 1(PD-1)pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer.However,owing to the heterogeneity of tumors and individual immune systems,PD-L1/PD-1 blockade still shows slow response rates in controlling malignancies in many patients.Accumulating evidence has shown that an effective response to anti-PD-Ll/anti-PD-1 therapy requires establishing an integrated immune cycle.Damage in any step of the immune cycle is one of the most important causes of immunotherapy failure.Impairments in the immune cycle can be restored by epigenetic modification,including reprogramming the environment of tumor-associated immunity,eliciting an immune response by increasing the presentation of tumor antigens,and by regulating T cell trafficking and reactivation.Thus,a rational combination of PD-L1/PD-1 blockade and epigenetic agents may offer great potential to retrain the immune system and to improve clinical outcomes of checkpoint blockade therapy.
基金This work was supported by the National Natural Science Foundation of China(No.81930102 to Bo Yang)the National Natural Science Foundation of China(No.81773754 to Ling Ding).
文摘Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems.Nowadays,however,accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression,inducing tumor invasion and metastasis.However,the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive.Therefore,in this review,we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance(MDR),metastasis,apoptosis,proliferation,immune surveillance evasion,and the alterations of relevant tumor micro-environment.Moreover,we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’efficacy.The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented.Furthermore,it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.
文摘Integrated optical gyroscopes(IOGs)have been an efficient tool for numerous applications in various fields,including inertial navigation,flight control,and earthquake monitoring.Here,we review the progress of integrated optical gyroscopes based on two categories of integrated interferometric optical gyroscopes(IIOGs)and integrated resonant optical gyroscopes(IROGs).
