Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic enviro...Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.展开更多
The synchronous monitoring of cerebral blood flow and blood oxygen levels plays a pivotal role in the prevention,diagnosis,and treatment of cerebrovascular diseases.This study introduces a novel noninvasive device uti...The synchronous monitoring of cerebral blood flow and blood oxygen levels plays a pivotal role in the prevention,diagnosis,and treatment of cerebrovascular diseases.This study introduces a novel noninvasive device utilizing inductive sensing and near-infrared spectroscopy technology to facilitate simultaneous monitoring of cerebral blood flow and blood oxygen levels.The device consists of modules for cerebral blood flow monitoring,cerebral blood oxygen monitoring,control,communication,and a host machine.Through experiments conducted on healthy subjects,it was confirmed that the device can effectively achieve synchronous monitoring and recording of cerebral blood flow and blood oxygen signals.The results demonstrate the device’s capability to accurately measure these signals simultaneously.This technology enables dynamic monitoring of cerebral blood flow and blood oxygen signals with potential clinical applications in preventing,diagnosing,treating cerebrovascular diseases while reducing their associated harm.展开更多
To mitigate the wastage of seed resources and reduce the usage of pesticides and fertilizers, seed coating agentshave gained popularity. This study employs single-factor and multi-index orthogonal experimental design ...To mitigate the wastage of seed resources and reduce the usage of pesticides and fertilizers, seed coating agentshave gained popularity. This study employs single-factor and multi-index orthogonal experimental design methodsto investigate the seed coating formula and physical properties of Tartary buckwheat. The specific effects ofeach component on Tartary buckwheat seed germination are analyzed. The findings reveal that the seed coatingagent formulated with 1.5% polyvinyl alcohol, 0.15% sodium alginate, 0.2% op-10, 0.1% polyacrylamide, 8% colorant,3% ammonium sulfate, 1% potassium dihydrogen phosphate, and 0.15% carbendazim exhibits the mosteffective coating. It demonstrates optimal physical properties and promotes seed germination efficiently. The suspensionrate of this seed coating agent reaches 91.12%, with a mere 2.13% coating shedding rate and 2.5% coatingseed rot rate. Furthermore, it achieves a germination percentage of 99.17%, which is 20.84% higher than the lowestgroup. The germination potential and index are also significantly higher than the lowest group, with anincrease of 20.84% and 26.56%, respectively. Additionally, the vitality index is 553.08, a 15.75% increase comparedto the lowest group. The application of seed coating agents helps reduce seed resource loss, increase plant numbers,and ultimately enhance agricultural yields. This finding holds practical significance in agriculturalproduction.展开更多
AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal...AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups(n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine(156 mg/kg per day)(berberine group) or metformin(184 mg/kg per day)(metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside(AICAR)(0.5 mg/kg per day)(AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested.The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator(TORC)2 was observed by immunohistochemical staining. RESULTS: Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance(HOMA-IR). Berberine upregulated protein expression of liver kinase(LK)B1, AMP-activated protein kinase(AMPK) and phosphorylated AMPK(p-AMPK). The level of phophorylated TORC2(p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes(phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.展开更多
This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR) rats with chronic partial sleep deprivation ...This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD). OR rats with PSD were orally given JTW and Estazolam for 4 weeks. The amount of food intake and metabolic parameters such as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured. The expression levels of circadian proteins cryptochrome 1 (Cryl) and cryptochrome 2 (Cry2) in hypothalamus, adipose and liver tissues were also determined. Meanwhile, the mRNA expression of inflammatory markers, activity of nuclear factor kappa B (NF-κB) p65 protein, as well as the expression levels of insulin signaling pathway proteins in hypothalamus, adipose and liver tissues were measured. Additionally, cyclic adenosine 3', 5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP) in hypothalamus tissue were measured. JTW significantly decreased the body weight increase rate and food intake, ameliorated systemic inflammation and insulin resistance. JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus, adipose and liver. Interestingly, all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression. We also found that in hypothalamus tissue of PSD rats, down-regulation of Cryl and Cry2 activated cAMP/PKA signaling and then led to inflammation, while JTW inhibited this signaling. These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.展开更多
The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal g...The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal group and fed on a standard diet.The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin(STZ)for 2 weeks to induce the diabetic models.The diabetic rat models were confirmed by oral glucose tolerance test(OGTT)and randomly divided into 4 groups(n=8 each),which were all fed on a high-fat diet.Berberine(3 g/kg per day)or metformin(183 mg/kg per day)was intragastrically administered to the diabetic rats for 12 weeks,serving as berberine group and metformin group respectively.5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside[AICAR,an agonist of AMP-activated protein kinase(AMPK),0.5 mg/kg per day]was subcutaneously injected to the diabetic rats for 12 weeks,serving as AICAR group.The remaining 8 diabetic rats served as the model group,which was given a 0.5%carboxyl methylcellulose solution by oral gavage.Fasting serum insulin(FINS),OGTT as well as lipid parameters were tested by commercial kit.The protein levels of liver kinase B1(LKB1),AMPK,phosphorylated AMP-activated protein kinase(p-AMPK),transducer of regulated CREB activity 2(TORC2),phosphorylated transducer of regulated CREB activity 2(p-TORC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase)in skeletal muscles and adipose tissues were examined by Western blotting.The results showed that berberine significantly decreased the body weight,plasma glucose,insulin levels,and homeostatic model assessment for insulin resistance(HOMA-IR)of diabetic rats compared with those in the model group.Meanwhile,the serum total triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were markedly decreased and high-density lipoprotein cholesterol(HDL-C)level was significantly increased after the treatment with berberine.In addition,we found that berberine significantly increased the expression of p-AMPK and LKB1,while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues.Moreover,the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group.It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.展开更多
AIM: To investigate the effect of fenugreek lactone(FL) on palmitate(PA)-induced apoptosis and dysfunction in insulin secretion in pancreatic NIT-1 β-cells. METHODS: Cells were cultured in the presence or absence of ...AIM: To investigate the effect of fenugreek lactone(FL) on palmitate(PA)-induced apoptosis and dysfunction in insulin secretion in pancreatic NIT-1 β-cells. METHODS: Cells were cultured in the presence or absence of FL and PA(0.25 mmol/L) for 48 h. Then, lipid droplets in NIT-1 cells were observed by oil red O staining, and the intracellular triglyceride content was measured by colorimetric assay. The insulin content in the supernatant was determined using an insulin radioimmunoassay. Oxidative stress-associated parameters, including total superoxide dismutase, glutathione peroxidase and catalase activity and malondialdehyde levels in the suspensions were also examined. The expression of upstream regulators of oxidative stress, such as protein kinase C-α(PKC-α), phospho-PKC-α and P47 phox, were determined by Western blot analysis and real-time PCR. In addition, apoptosis was evaluated in NIT-1 cells by flow cytometry assays and caspase-3 viability assays.RESULTS: Our results indicated that compared to the control group, PA induced an increase in lipid accumulation and apoptosis and a decrease in insulin secretion in NIT-1 cells. Oxidative stress in NIT-1 cells was activated after 48 h of exposure to PA. However, FL reversed the above changes. These effects were accompanied by the inhibition of PKC-α, phosphoPKC-α and P47 phox expression and the activation of caspase-3. CONCLUSION: FL attenuates PA-induced apoptosis and insulin secretion dysfunction in NIT-1 pancreatic β-cells. The mechanism for this action may be associated with improvements in levels of oxidative stress.展开更多
BACKGROUND Gastric cancer is the third deadliest cancer in the world and ranks second in incidence and mortality of cancers in China.Despite advances in prevention,diagnosis,and therapy,the absolute number of cases is...BACKGROUND Gastric cancer is the third deadliest cancer in the world and ranks second in incidence and mortality of cancers in China.Despite advances in prevention,diagnosis,and therapy,the absolute number of cases is increasing every year due to aging and the growth of high-risk populations,and gastric cancer is still a leading cause of cancer-related death.Gastric cancer is a consequence of the complex interaction of microbial agents,with environmental and host factors,resulting in the dysregulation of multiple oncogenic and tumor-suppressing signaling pathways.Global efforts have been made to investigate in detail the genomic and epigenomic heterogeneity of this disease,resulting in the identification of new specific and sensitive predictive and prognostic biomarkers.Trastuzumab,a monoclonal antibody against the HER2 receptor,is approved in the first-line treatment of patients with HER2+tumors,which accounts for 13%-23%of the gastric cancer population.Ramucirumab,a monoclonal antibody against VEGFR2,is currently recommended in patients progressing after first-line treatment.Several clinical trials have also tested novel agents for advanced gastric cancer but mostly with dis-appointing results,such as anti-EGFR and anti-MET monoclonal antibodies.Therefore,it is still of great significance to screen specific molecular targets for gastric cancer and drugs directed against the molecular targets.AIM To investigate the effect and mechanism of berberine against tumor growth in gastric cancer xenograft models and to explore the role of hepatocyte nuclear factor 4α(HNF4α)-WNT5a/β-catenin pathways played in the antitumor effects of berberine.METHODS MGC803 and SGC7901 subcutaneous xenograft models were established.The control group was intragastrically administrated with normal saline,and the berberine group was administrated intragastrically with 100 mg/kg/d berberine.The body weight of nude mice during the experiment was measured to assess whether berberine has any adverse reaction.The volume of subcutaneous tumors during this experiment was recorded to evaluate the inhibitory effect of berberine on the growth of MGC803 and SGC7901 subcutaneous transplantation tumors.Polymerase chain reaction assays were conducted to evaluate the alteration of transcriptional expression of HNF4α,WNT5a andβ-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models.Western blotting and IHC were performed to assess the protein expression of HNF4α,WNT5a andβ-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models.RESULTS In the both MGC803 and SGC7901 xenograft tumor models,berberine significantly reduced tumor volume and weight and thus retarded the growth rate of tumors.In the SGC7901 and MGC803 subcutaneously transplanted tumor models,berberine down-regulated the expression of HNF4α,WNT5a andβ-catenin in tumor tissues from both transcription and protein levels.Besides,berberine also suppressed the protein expression of HNF4α,WNT5a andβ-catenin in liver tissues.CONCLUSION Berberine retarded the growth of MGC803 and SGC7901 xenograft model tumors,and the mechanism behind these anti-growth effects might be the downregulation of the expression of HNF4α-WNT5a/β-catenin signaling pathways both in tumor tissues and liver tissues of the xenograft models.展开更多
Since 2003, there has been a strong RMB appreciation expectation in the market. RMB exchange rate becomes the world focus again. This paper insists that the depreciation pressure of US dollar is the main reason that c...Since 2003, there has been a strong RMB appreciation expectation in the market. RMB exchange rate becomes the world focus again. This paper insists that the depreciation pressure of US dollar is the main reason that causes RMB appreciation expectation; the "double price action" of the Chinese tradable goods and non-tradable goods is the special reason that leads to RMB appreciation expectation; furthermore, the asymmetric foreign exchange rate management system in China strengthens RMB appreciation expectation.展开更多
Abnormal grain growth(AGG)has been widely observed in many friction stir welded(FSWed)joints during post-weld heat treatment(PWHT).The coarse grain structure not only reduces the strength of the joint but also limits ...Abnormal grain growth(AGG)has been widely observed in many friction stir welded(FSWed)joints during post-weld heat treatment(PWHT).The coarse grain structure not only reduces the strength of the joint but also limits its usage in superplastic forming.Several methods have been reported in previous studies to inhibit AGG,but all of them can only mitigate AGG.Complete inhibition of AGG was not achieved.In the current research,AGG was widely observed during the PWHT of friction stir welded AA6061.Multi-pass FSW enhanced the thermal stability of the as-welded grain structure but did not eliminate the occurrence of AGG.A new welding method was developed with the ball-milled Al–Ti powder mixture introduced into the stir zone and proved effective in inhibiting AGG in FSWed AA6061 during PWHT.The adoption of 5-pass FSW with an alternate rotation mode succeeded in producing an AGG-free sample.Microscopic characterizations conducted in the stir zone showed an evolution of Al–Ti powder mixture into different particle formations and Al3Ti new phase.Quantitative analysis of the second phase particles(SPPs)in the stir zone confirmed the increases in both particle number and average size.The quantitative results fit well with Humphreys’grain growth model,which theoretically explains the mechanism for AGG inhibition,i.e.,the significantly enhanced particle pinning effect.展开更多
It has been known that,the novel coronavirus,2019-nCoV,which is considered similar to SARS-CoV,invades human cells via the receptor angiotensin converting enzyme II(ACE2).Moreover,lung cells that have ACE2 expression ...It has been known that,the novel coronavirus,2019-nCoV,which is considered similar to SARS-CoV,invades human cells via the receptor angiotensin converting enzyme II(ACE2).Moreover,lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection.However,some patients also exhibit non-respiratory symptoms,such as kidney failure,implying that 2019-nCoV could also invade other organs.To construct a risk map of different human organs,we analyzed the single-cell RNA sequencing(scRNA-seq)datasets derived from major human physiological systems,including the respiratory,cardiovascular,digestive,and urinary systems.Through scRNA-seq data analyses,we identified the organs at risk,such as lung,heart,esophagus,kidney,bladder,and ileum,and located specific cell types(i.e.,type II alveolar cells(AT2),myocardial cells,proximal tubule cells of the kidney,ileum and esophagus epithelial cells,and bladder urothelial cells),which are vulnerable to 2019-nCoV infection.Based on the findings,we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection.This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection.展开更多
In this paper,the dynamic coupling between the wind turbine rotor speed recovery(WTRSR)and inertial response of the conventional virtual synchronous generator(VSG)controlled wind farms(WFs)is analyzed.Three distinguis...In this paper,the dynamic coupling between the wind turbine rotor speed recovery(WTRSR)and inertial response of the conventional virtual synchronous generator(VSG)controlled wind farms(WFs)is analyzed.Three distinguishing features are revealed.Firstly,the inertial response characteristics of VSG controlled WFs(VSG-WFs)are impaired by the dynamic coupling.Secondly,when the influence of WTRSR is dominant,the inertial response characteristics of VSG-WFs are even worse than the condition under which WFs do not participate in the response of grid frequency.Thirdly,this phenomenon cannot be eliminated by only enlarging the inertia parameter of VSG-WFs,because the influence of WTRSR would also increase with the enhancement of inertial response.A decoupling scheme to eliminate the negative influence is then proposed in this paper.By starting the WTRSR process after inertial response period,the dynamic coupling is eliminated and the inertial response characteristics of WFs are improved.Finally,the effectiveness of the analysis and the proposed scheme are verified by simulation results.展开更多
The Tianwen-1 Mars entry vehicle successfully landed on the surface of Mars in southern Utopia Planitia on May 15,2021,at 7:18(UTC+8).To acquire valuable Martian flight data,a scientific instrumentation package consis...The Tianwen-1 Mars entry vehicle successfully landed on the surface of Mars in southern Utopia Planitia on May 15,2021,at 7:18(UTC+8).To acquire valuable Martian flight data,a scientific instrumentation package consisting of a flush air data system and a multilayer temperature-sensing system was installed aboard the entry vehicle.A combined approach was applied in the entry,descent,and landing trajectory reconstruction using all available data obtained by the inertial measurement unit and the flush air data system.An aerodynamic database covering the entire flight regime was generated using computational fluid dynamics methods to assist in the reconstruction process.A preliminary analysis of the trajectory reconstruction result,along with the atmosphere reconstruction and aerodynamic performance,was conducted.The results show that the trajectory agrees closely with the nominal trajectory and the wind-relative attitude.Suspected wind occurred at the end of the trajectory.展开更多
Haemorheological abnormalities have been described in diabetes mellitus,as well as in non-alcoholic fatty liver disease(NAFLD).However,the relationship between the changes in liver fat content and haemorheology is unk...Haemorheological abnormalities have been described in diabetes mellitus,as well as in non-alcoholic fatty liver disease(NAFLD).However,the relationship between the changes in liver fat content and haemorheology is unknown.The current study aims to show the correlation between haemorheological parameters and intrahepatic lipid content(IHLC)in patients with type 2 diabetes.The serum biochemical markers,such as fasting plasma glucose(FPG),haemoglobin A1c(HbA1c),liver enzymes,lipid profiles,and haemorheological properties,were examined.IHLC was quantified using proton magnetic resonance spectroscopy(1 H-MRS)scanning of the liver.A significant correlation was observed between IHLC and whole blood viscosity at high,middle,and low shear rates.IHLC also positively correlated with haematocrit,the reduced whole blood viscosity at low and middle shear rates,and the erythrocyte aggregation index.Diabetic patients with NAFLD exhibited significant haemorheological abnormalities compared with patients without NAFLD.In summary,haemorheological disorders are linked to non-alcoholic fatty liver in type 2 diabetes.展开更多
Objective:Laboratory diagnosis of neurosyphilis(NS)remains a great challenge.This study was the aimed to identify miRNA candidates as biomarkers to distinguish between NS,non-neurosyphilis,and healthy controls(HCs).Me...Objective:Laboratory diagnosis of neurosyphilis(NS)remains a great challenge.This study was the aimed to identify miRNA candidates as biomarkers to distinguish between NS,non-neurosyphilis,and healthy controls(HCs).Methods:We analyzed miRNA expression profiles in peripheral blood mononuclear cells(PBMCs)from six patients with NS,eight patients with secondary syphilis(SS),and five HCs using microarray technology.The differentially expressed miRNAs were validated in 33 NS samples,31 SS samples,and 30 HC samples using TaqMan miRNA real-time qPCR(qRT-PCR).Results:Thirty-nine miRNAs were differentially expressed in SS and NS patients compared with HCs.Thirteen miRNAs were randomly selected to validate their expression levels in the same samples used in microarray assay by qRT-PCR.All miRNAs were upregulated in SS and NS samples compared with HC.qRT-PCR analysis of the expression of the 13 miRNAs in a second cohort(76 samples)showed that the average expression levels of nine miRNAs were higher in SS than in NS(SS:0.185,NS:0.136,P=3.8E-10),while the expressions of the other four miRNAs were lower in SS than in NS(SS:0.000757,NS:0.000873,P=0.022).ROC curve analysis of the 13 miRNAs showed the area under the curve value to be 1.00 for distinguishing SS patients from HCs,1.00 for distinguishing NS patients from HCs,1.00 for distinguishing SS and NS patients from HCs,and 0.968 for distinguishing NS from SS patients.Conclusion:The present study is the first one that identified differentially expressed miRNAs in PBMCs from patients with NS.Our results suggest that the 13 candidate miRNAs in PBMCs may be novel noninvasive biomarkers for NS diagnosis.展开更多
基金supported by the Natural Science Foundation of China (82002851)funding of postdoctoral of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine+2 种基金fundamental research program funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYZZ180)funding of academician workstation in HainanShanghai Anticancer Association EYAS PROJECT (SACA-CY21A01)。
文摘Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
基金National Natural Science Foundation of China(No.51977214)Science and Technology Research Project of Chongqing Education Commission(No.KJQN202212805)Special funding project of Army Medical University(No.2021XJS08)。
文摘The synchronous monitoring of cerebral blood flow and blood oxygen levels plays a pivotal role in the prevention,diagnosis,and treatment of cerebrovascular diseases.This study introduces a novel noninvasive device utilizing inductive sensing and near-infrared spectroscopy technology to facilitate simultaneous monitoring of cerebral blood flow and blood oxygen levels.The device consists of modules for cerebral blood flow monitoring,cerebral blood oxygen monitoring,control,communication,and a host machine.Through experiments conducted on healthy subjects,it was confirmed that the device can effectively achieve synchronous monitoring and recording of cerebral blood flow and blood oxygen signals.The results demonstrate the device’s capability to accurately measure these signals simultaneously.This technology enables dynamic monitoring of cerebral blood flow and blood oxygen signals with potential clinical applications in preventing,diagnosing,treating cerebrovascular diseases while reducing their associated harm.
基金the Sichuan Science and Technology Program(2023NSFSC0214)China Agriculture Research System(CARS-07-B-1)+1 种基金National Natural Sciences Foundation of China(Nos.3230185031771716).
文摘To mitigate the wastage of seed resources and reduce the usage of pesticides and fertilizers, seed coating agentshave gained popularity. This study employs single-factor and multi-index orthogonal experimental design methodsto investigate the seed coating formula and physical properties of Tartary buckwheat. The specific effects ofeach component on Tartary buckwheat seed germination are analyzed. The findings reveal that the seed coatingagent formulated with 1.5% polyvinyl alcohol, 0.15% sodium alginate, 0.2% op-10, 0.1% polyacrylamide, 8% colorant,3% ammonium sulfate, 1% potassium dihydrogen phosphate, and 0.15% carbendazim exhibits the mosteffective coating. It demonstrates optimal physical properties and promotes seed germination efficiently. The suspensionrate of this seed coating agent reaches 91.12%, with a mere 2.13% coating shedding rate and 2.5% coatingseed rot rate. Furthermore, it achieves a germination percentage of 99.17%, which is 20.84% higher than the lowestgroup. The germination potential and index are also significantly higher than the lowest group, with anincrease of 20.84% and 26.56%, respectively. Additionally, the vitality index is 553.08, a 15.75% increase comparedto the lowest group. The application of seed coating agents helps reduce seed resource loss, increase plant numbers,and ultimately enhance agricultural yields. This finding holds practical significance in agriculturalproduction.
基金Supported by National Natural Science Foundation of China,No.30973836
文摘AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups(n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine(156 mg/kg per day)(berberine group) or metformin(184 mg/kg per day)(metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside(AICAR)(0.5 mg/kg per day)(AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested.The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator(TORC)2 was observed by immunohistochemical staining. RESULTS: Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance(HOMA-IR). Berberine upregulated protein expression of liver kinase(LK)B1, AMP-activated protein kinase(AMPK) and phosphorylated AMPK(p-AMPK). The level of phophorylated TORC2(p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes(phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.
基金This study was supported by National Natural Science Foundation of China (No. 81373871 and No. 81473637).
文摘This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD). OR rats with PSD were orally given JTW and Estazolam for 4 weeks. The amount of food intake and metabolic parameters such as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured. The expression levels of circadian proteins cryptochrome 1 (Cryl) and cryptochrome 2 (Cry2) in hypothalamus, adipose and liver tissues were also determined. Meanwhile, the mRNA expression of inflammatory markers, activity of nuclear factor kappa B (NF-κB) p65 protein, as well as the expression levels of insulin signaling pathway proteins in hypothalamus, adipose and liver tissues were measured. Additionally, cyclic adenosine 3', 5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP) in hypothalamus tissue were measured. JTW significantly decreased the body weight increase rate and food intake, ameliorated systemic inflammation and insulin resistance. JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus, adipose and liver. Interestingly, all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression. We also found that in hypothalamus tissue of PSD rats, down-regulation of Cryl and Cry2 activated cAMP/PKA signaling and then led to inflammation, while JTW inhibited this signaling. These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.
基金This project was supported by the National Natural Science Foundation of China(No.81673757 and No.81603652).
文摘The effect and potential molecular mechanisms of berberine on gluconeogenesis in skeletal muscles and adipose tissues were investigated.After adaptive feeding for one week,8 rats were randomly selected as the normal group and fed on a standard diet.The remaining 32 rats were fed on a high-fat diet and given an intravenous injection of streptozotocin(STZ)for 2 weeks to induce the diabetic models.The diabetic rat models were confirmed by oral glucose tolerance test(OGTT)and randomly divided into 4 groups(n=8 each),which were all fed on a high-fat diet.Berberine(3 g/kg per day)or metformin(183 mg/kg per day)was intragastrically administered to the diabetic rats for 12 weeks,serving as berberine group and metformin group respectively.5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside[AICAR,an agonist of AMP-activated protein kinase(AMPK),0.5 mg/kg per day]was subcutaneously injected to the diabetic rats for 12 weeks,serving as AICAR group.The remaining 8 diabetic rats served as the model group,which was given a 0.5%carboxyl methylcellulose solution by oral gavage.Fasting serum insulin(FINS),OGTT as well as lipid parameters were tested by commercial kit.The protein levels of liver kinase B1(LKB1),AMPK,phosphorylated AMP-activated protein kinase(p-AMPK),transducer of regulated CREB activity 2(TORC2),phosphorylated transducer of regulated CREB activity 2(p-TORC2),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase)in skeletal muscles and adipose tissues were examined by Western blotting.The results showed that berberine significantly decreased the body weight,plasma glucose,insulin levels,and homeostatic model assessment for insulin resistance(HOMA-IR)of diabetic rats compared with those in the model group.Meanwhile,the serum total triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)levels were markedly decreased and high-density lipoprotein cholesterol(HDL-C)level was significantly increased after the treatment with berberine.In addition,we found that berberine significantly increased the expression of p-AMPK and LKB1,while decreasing the p-TORC2 levels in skeletal muscles and adipose tissues.Moreover,the expression of PEPCK and G6Pase was significantly down-regulated after the treatment with berberine compared to the model group.It was suggested that the mechanism by which berberine inhibited peripheral tissue gluconeogenesis may be attributed to the activation of the LKB1-AMPK-TORC2 signaling pathway.
基金Supported by The National Natural Science Foundation of ChinaNo.81273683 and No.81473637
文摘AIM: To investigate the effect of fenugreek lactone(FL) on palmitate(PA)-induced apoptosis and dysfunction in insulin secretion in pancreatic NIT-1 β-cells. METHODS: Cells were cultured in the presence or absence of FL and PA(0.25 mmol/L) for 48 h. Then, lipid droplets in NIT-1 cells were observed by oil red O staining, and the intracellular triglyceride content was measured by colorimetric assay. The insulin content in the supernatant was determined using an insulin radioimmunoassay. Oxidative stress-associated parameters, including total superoxide dismutase, glutathione peroxidase and catalase activity and malondialdehyde levels in the suspensions were also examined. The expression of upstream regulators of oxidative stress, such as protein kinase C-α(PKC-α), phospho-PKC-α and P47 phox, were determined by Western blot analysis and real-time PCR. In addition, apoptosis was evaluated in NIT-1 cells by flow cytometry assays and caspase-3 viability assays.RESULTS: Our results indicated that compared to the control group, PA induced an increase in lipid accumulation and apoptosis and a decrease in insulin secretion in NIT-1 cells. Oxidative stress in NIT-1 cells was activated after 48 h of exposure to PA. However, FL reversed the above changes. These effects were accompanied by the inhibition of PKC-α, phosphoPKC-α and P47 phox expression and the activation of caspase-3. CONCLUSION: FL attenuates PA-induced apoptosis and insulin secretion dysfunction in NIT-1 pancreatic β-cells. The mechanism for this action may be associated with improvements in levels of oxidative stress.
基金Supported by the National Natural Science Foundation of China,No. 81673757 and No. 81573787
文摘BACKGROUND Gastric cancer is the third deadliest cancer in the world and ranks second in incidence and mortality of cancers in China.Despite advances in prevention,diagnosis,and therapy,the absolute number of cases is increasing every year due to aging and the growth of high-risk populations,and gastric cancer is still a leading cause of cancer-related death.Gastric cancer is a consequence of the complex interaction of microbial agents,with environmental and host factors,resulting in the dysregulation of multiple oncogenic and tumor-suppressing signaling pathways.Global efforts have been made to investigate in detail the genomic and epigenomic heterogeneity of this disease,resulting in the identification of new specific and sensitive predictive and prognostic biomarkers.Trastuzumab,a monoclonal antibody against the HER2 receptor,is approved in the first-line treatment of patients with HER2+tumors,which accounts for 13%-23%of the gastric cancer population.Ramucirumab,a monoclonal antibody against VEGFR2,is currently recommended in patients progressing after first-line treatment.Several clinical trials have also tested novel agents for advanced gastric cancer but mostly with dis-appointing results,such as anti-EGFR and anti-MET monoclonal antibodies.Therefore,it is still of great significance to screen specific molecular targets for gastric cancer and drugs directed against the molecular targets.AIM To investigate the effect and mechanism of berberine against tumor growth in gastric cancer xenograft models and to explore the role of hepatocyte nuclear factor 4α(HNF4α)-WNT5a/β-catenin pathways played in the antitumor effects of berberine.METHODS MGC803 and SGC7901 subcutaneous xenograft models were established.The control group was intragastrically administrated with normal saline,and the berberine group was administrated intragastrically with 100 mg/kg/d berberine.The body weight of nude mice during the experiment was measured to assess whether berberine has any adverse reaction.The volume of subcutaneous tumors during this experiment was recorded to evaluate the inhibitory effect of berberine on the growth of MGC803 and SGC7901 subcutaneous transplantation tumors.Polymerase chain reaction assays were conducted to evaluate the alteration of transcriptional expression of HNF4α,WNT5a andβ-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models.Western blotting and IHC were performed to assess the protein expression of HNF4α,WNT5a andβ-catenin in tumor tissues and liver tissues from the MGC803 and SGC7901 xenograft models.RESULTS In the both MGC803 and SGC7901 xenograft tumor models,berberine significantly reduced tumor volume and weight and thus retarded the growth rate of tumors.In the SGC7901 and MGC803 subcutaneously transplanted tumor models,berberine down-regulated the expression of HNF4α,WNT5a andβ-catenin in tumor tissues from both transcription and protein levels.Besides,berberine also suppressed the protein expression of HNF4α,WNT5a andβ-catenin in liver tissues.CONCLUSION Berberine retarded the growth of MGC803 and SGC7901 xenograft model tumors,and the mechanism behind these anti-growth effects might be the downregulation of the expression of HNF4α-WNT5a/β-catenin signaling pathways both in tumor tissues and liver tissues of the xenograft models.
文摘Since 2003, there has been a strong RMB appreciation expectation in the market. RMB exchange rate becomes the world focus again. This paper insists that the depreciation pressure of US dollar is the main reason that causes RMB appreciation expectation; the "double price action" of the Chinese tradable goods and non-tradable goods is the special reason that leads to RMB appreciation expectation; furthermore, the asymmetric foreign exchange rate management system in China strengthens RMB appreciation expectation.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.51204108 and 51675337)the National Research Foundation for Doctoral Program of Higher Education of China(Grant No.20120073120120)the Shanghai Committee of Science and Technology(Grant No.11ZR1418100).
文摘Abnormal grain growth(AGG)has been widely observed in many friction stir welded(FSWed)joints during post-weld heat treatment(PWHT).The coarse grain structure not only reduces the strength of the joint but also limits its usage in superplastic forming.Several methods have been reported in previous studies to inhibit AGG,but all of them can only mitigate AGG.Complete inhibition of AGG was not achieved.In the current research,AGG was widely observed during the PWHT of friction stir welded AA6061.Multi-pass FSW enhanced the thermal stability of the as-welded grain structure but did not eliminate the occurrence of AGG.A new welding method was developed with the ball-milled Al–Ti powder mixture introduced into the stir zone and proved effective in inhibiting AGG in FSWed AA6061 during PWHT.The adoption of 5-pass FSW with an alternate rotation mode succeeded in producing an AGG-free sample.Microscopic characterizations conducted in the stir zone showed an evolution of Al–Ti powder mixture into different particle formations and Al3Ti new phase.Quantitative analysis of the second phase particles(SPPs)in the stir zone confirmed the increases in both particle number and average size.The quantitative results fit well with Humphreys’grain growth model,which theoretically explains the mechanism for AGG inhibition,i.e.,the significantly enhanced particle pinning effect.
基金This work was supported in part by the China National Science and Technology Major Project for Prevention and Treatment of Infectious Diseases(No.2017ZX10203207 to Z.-G.H.)National Natural Science Foundation of China(No.81672772 to Z.-G.H.,No.31601070 to J.H.,No.31800253 to K.C.)+1 种基金Interdisciplinary Program of Shanghai Jiao Tong University(Nos.2019TPA09 and ZH2018ZDA33 to Z.-G.H.,J.H.,and X.Z.)Shanghai Sailing Program(No.17YF1410400 to K.C.)and Innovative Research Team of High-Level Local Universities in Shanghai.
文摘It has been known that,the novel coronavirus,2019-nCoV,which is considered similar to SARS-CoV,invades human cells via the receptor angiotensin converting enzyme II(ACE2).Moreover,lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection.However,some patients also exhibit non-respiratory symptoms,such as kidney failure,implying that 2019-nCoV could also invade other organs.To construct a risk map of different human organs,we analyzed the single-cell RNA sequencing(scRNA-seq)datasets derived from major human physiological systems,including the respiratory,cardiovascular,digestive,and urinary systems.Through scRNA-seq data analyses,we identified the organs at risk,such as lung,heart,esophagus,kidney,bladder,and ileum,and located specific cell types(i.e.,type II alveolar cells(AT2),myocardial cells,proximal tubule cells of the kidney,ileum and esophagus epithelial cells,and bladder urothelial cells),which are vulnerable to 2019-nCoV infection.Based on the findings,we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection.This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection.
基金supported by Science and Technology Project of State Grid Corporation of China(No.5102-201956300A-0-0-00)。
文摘In this paper,the dynamic coupling between the wind turbine rotor speed recovery(WTRSR)and inertial response of the conventional virtual synchronous generator(VSG)controlled wind farms(WFs)is analyzed.Three distinguishing features are revealed.Firstly,the inertial response characteristics of VSG controlled WFs(VSG-WFs)are impaired by the dynamic coupling.Secondly,when the influence of WTRSR is dominant,the inertial response characteristics of VSG-WFs are even worse than the condition under which WFs do not participate in the response of grid frequency.Thirdly,this phenomenon cannot be eliminated by only enlarging the inertia parameter of VSG-WFs,because the influence of WTRSR would also increase with the enhancement of inertial response.A decoupling scheme to eliminate the negative influence is then proposed in this paper.By starting the WTRSR process after inertial response period,the dynamic coupling is eliminated and the inertial response characteristics of WFs are improved.Finally,the effectiveness of the analysis and the proposed scheme are verified by simulation results.
基金The authors are grateful to Ying Li for extraction of the raw pressure and temperature data,Fajun Yi for calibration of pressure sensors,Minwen Guo for providing inertial data,and Francois Forget and Millour Ehouarn for collaboration in the Martian atmospheric model.
文摘The Tianwen-1 Mars entry vehicle successfully landed on the surface of Mars in southern Utopia Planitia on May 15,2021,at 7:18(UTC+8).To acquire valuable Martian flight data,a scientific instrumentation package consisting of a flush air data system and a multilayer temperature-sensing system was installed aboard the entry vehicle.A combined approach was applied in the entry,descent,and landing trajectory reconstruction using all available data obtained by the inertial measurement unit and the flush air data system.An aerodynamic database covering the entire flight regime was generated using computational fluid dynamics methods to assist in the reconstruction process.A preliminary analysis of the trajectory reconstruction result,along with the atmosphere reconstruction and aerodynamic performance,was conducted.The results show that the trajectory agrees closely with the nominal trajectory and the wind-relative attitude.Suspected wind occurred at the end of the trajectory.
基金supported by the National Natural Science Foundation of China(Grant No.30801492).
文摘Haemorheological abnormalities have been described in diabetes mellitus,as well as in non-alcoholic fatty liver disease(NAFLD).However,the relationship between the changes in liver fat content and haemorheology is unknown.The current study aims to show the correlation between haemorheological parameters and intrahepatic lipid content(IHLC)in patients with type 2 diabetes.The serum biochemical markers,such as fasting plasma glucose(FPG),haemoglobin A1c(HbA1c),liver enzymes,lipid profiles,and haemorheological properties,were examined.IHLC was quantified using proton magnetic resonance spectroscopy(1 H-MRS)scanning of the liver.A significant correlation was observed between IHLC and whole blood viscosity at high,middle,and low shear rates.IHLC also positively correlated with haematocrit,the reduced whole blood viscosity at low and middle shear rates,and the erythrocyte aggregation index.Diabetic patients with NAFLD exhibited significant haemorheological abnormalities compared with patients without NAFLD.In summary,haemorheological disorders are linked to non-alcoholic fatty liver in type 2 diabetes.
基金supported by grants from the National Natural Science Foundation of China(No.81572039)Shanghai Science and Technology Commission(Nos.17DZ2293300,YDZX20193100002868)+2 种基金Clinical Research Plan of SHDC(No.16CR1029B)National mega project on key infectious diseases(No.2017ZX10202102-001-007)Shanghai Municipal Commission of Health and Family Planning(No.20164Y0260).
文摘Objective:Laboratory diagnosis of neurosyphilis(NS)remains a great challenge.This study was the aimed to identify miRNA candidates as biomarkers to distinguish between NS,non-neurosyphilis,and healthy controls(HCs).Methods:We analyzed miRNA expression profiles in peripheral blood mononuclear cells(PBMCs)from six patients with NS,eight patients with secondary syphilis(SS),and five HCs using microarray technology.The differentially expressed miRNAs were validated in 33 NS samples,31 SS samples,and 30 HC samples using TaqMan miRNA real-time qPCR(qRT-PCR).Results:Thirty-nine miRNAs were differentially expressed in SS and NS patients compared with HCs.Thirteen miRNAs were randomly selected to validate their expression levels in the same samples used in microarray assay by qRT-PCR.All miRNAs were upregulated in SS and NS samples compared with HC.qRT-PCR analysis of the expression of the 13 miRNAs in a second cohort(76 samples)showed that the average expression levels of nine miRNAs were higher in SS than in NS(SS:0.185,NS:0.136,P=3.8E-10),while the expressions of the other four miRNAs were lower in SS than in NS(SS:0.000757,NS:0.000873,P=0.022).ROC curve analysis of the 13 miRNAs showed the area under the curve value to be 1.00 for distinguishing SS patients from HCs,1.00 for distinguishing NS patients from HCs,1.00 for distinguishing SS and NS patients from HCs,and 0.968 for distinguishing NS from SS patients.Conclusion:The present study is the first one that identified differentially expressed miRNAs in PBMCs from patients with NS.Our results suggest that the 13 candidate miRNAs in PBMCs may be novel noninvasive biomarkers for NS diagnosis.