The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain functio...The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.展开更多
BACKGROUND Chronic enteropathy associated with solute carrier organic anion transporter family member 2A1(SLCO2A1)(CEAS)is a rare autosomal recessive hereditary disease characterized by anemia,hypoproteinemia,abdomina...BACKGROUND Chronic enteropathy associated with solute carrier organic anion transporter family member 2A1(SLCO2A1)(CEAS)is a rare autosomal recessive hereditary disease characterized by anemia,hypoproteinemia,abdominal pain,diarrhea,and multiple shallow ulcers in the small intestine.Genetic analysis for SLCO2A1 mutations has identified more than 10 variant types,including the mostly reported c.940+1G>A splice site mutation.CASE SUMMARY Herein,we described a 33-year-old female patient who was admitted for anemia,edema,and a positive fecal occult blood test,unaccompanied by abdominal pain and diarrhea.She was diagnosed with CEAS due to compound heterozygous variants,c.940+1G>cA(splice-5)and c.1658T>A(p.Ile553Asn)in SLCO2A1,which had not been previously reported.Importantly,we reviewed 132 reported CEAS patients,which showed that anemia(87.3%)and hypoproteinemia(81%)were the most common symptoms.Nearly 25.8%of patients only had a positive result of fecal occult blood,without any symptoms of gastrointestinal bleeding.CONCLUSION In conclusion,fecal tests should be repeated in patients with anemia and edema to find clues for chronic enteropathy,including the rare cause-CEAS.展开更多
BACKGROUND Pancreatic cancer,characterized by aggressive proliferation and metastasis,is a lethal malignancy.The nightly hormone melatonin serves as a rhythm-regulating hormone,and is used to treat different cancers i...BACKGROUND Pancreatic cancer,characterized by aggressive proliferation and metastasis,is a lethal malignancy.The nightly hormone melatonin serves as a rhythm-regulating hormone,and is used to treat different cancers including pancreatic cancer.AIM To investigate how melatonin acts against human pancreatic cancer cell lines and analyze the biological processes that cause the observed effects.METHODS Panc-1 and AsPC-1 cells were treated with melatonin.Cell viability was measured using the cell counting kit-8 assay.Western blotting and immunofluorescence were used to analyze protein expression levels.Ferroptosis was measured by analyzing lipid reactive oxygen species and malondialdehyde levels;apoptosis was assessed using flow cytometry.RESULTS Melatonin significantly inhibited the viability,colony formation,migration,and invasion of Panc-1 and AsPC-1 cells.Additionally,melatonin activated the endoplasmic reticulum(ER)stress pathway(protein kinase R-like ER kinase eukaryotic initiation factor 2α-activating transcription factor 4),inhibited glutamine metabolism(alanine-serinecysteine transporter 2-glutaminase 1-glutathione peroxidase 4,alanine-serine-cysteine transporter 2-glutathione peroxidase 4),and promoted ferroptosis in pancreatic cancer cells.Co-treatment with a high melatonin concentration and protein kinase R-like ER kinase agonist(CCT020312)enhanced melatonin-induced ferroptosis in pancreatic cancer cells.Melatonin demonstrated a variety of anticancer effects by inhibiting autophagy.This was achieved through the increased expression of sequestosome-1 and decreased expression of light chain 3.Additionally,melatonin facilitated the promotion of apoptosis.CONCLUSION Melatonin induces ferroptosis in pancreatic cancer cells by activating transcription factor 4-dependent ER stress and inhibiting glutamine metabolism,promotes apoptosis in pancreatic cancer cells,and inhibits autophagy,leading to synergistic anticancer effects.展开更多
This study presents novel findings on the potential of phloretin,an apple polyphenol,to enhance the effectiveness of anti-human epidermal growth factor receptor-2(HER2)antibody therapy in HER2-positive breast cancer p...This study presents novel findings on the potential of phloretin,an apple polyphenol,to enhance the effectiveness of anti-human epidermal growth factor receptor-2(HER2)antibody therapy in HER2-positive breast cancer patients.Our research reveals that phloretin inhibits typeⅡglucose transporter(GLUT2)activity,significantly reducing cancer cell glucose uptake.We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues,with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients.Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins,attenuate glycolysis,and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells.Furthermore,the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft tumor animal model,particularly in suppressing the growth of trastuzumab-resistant HER2-positive(HER2+)breast cancer.These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer,offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.展开更多
Monocarboxylic acid transporter 2 （MCT2） transports pyruvate and lactate outside and inside of sperms, mainly as energy sources and plays roles in the regulation of spermatogenesis. We investigated the association a...Monocarboxylic acid transporter 2 （MCT2） transports pyruvate and lactate outside and inside of sperms, mainly as energy sources and plays roles in the regulation of spermatogenesis. We investigated the association among genetic variations in the MCT2 gene, male infertility and MCT2 expression levels in sperm. The functional and genetic significance of the intron 2 （＋28201A 〉 G, rs10506398） and 3＇ untranslated region （UTR） single nucleotide polymorphism （SNP） （＋2626G 〉 A, rs10506399） of MCT2 variants were investigated. Two MCT2 polymorphisms were associated with male infertility （n = 471, P 〈 0.05）. In particular, the MCT2-3＇ UTR SNP （＋2626 G 〉 A） had a strong association with the oligoasthenoteratozoospermia （OAT） group. The ＋2626GG type had an almost 2.4-fold higher sperm count than that of the ＋2626AA type （＋2626GG; 66 x 106 vs ＋2626AA; 27 x 106, P 〈 0.0001）. The MCT2-3＇ UTR SNP may be important for expression, as it is located at the MCT2 3＇ UTR. The average MCT2 protein amount in sperm of the ＋2626GG type was about two times higher than that of the ＋2626AA type. The results suggest that genetic variation in MCT2 has functional and clinical relevance with male infertility.展开更多
AIM： TO investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 （GLUT2） in obese rat intestinal mucosa. METHODS： We divided ...AIM： TO investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 （GLUT2） in obese rat intestinal mucosa. METHODS： We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls. The obese rats were separated into an octreotide treated group 9f 16 rats and an obese group of 15. The intervention （：jroup was injected with octreotide at 40 ±g/kg body weight every 12 h for 8 d. Rat body weight was measured weekly to calculate Lee＇s index. After euthanization, maltase and sucrase activities in the small intestine were measured by activity assays, and the fasting plasma glucose level was measured. The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction and Western blotting assays. RESULTS： Body weight, Lee＇s index, fasting plasma glucose level, maltase activity in small intestinal mucosa, mucosa and apical GLUT2, GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group （605.61 ± 141.00 vs 378.54 ±111.75, 337.61 ± 10.82 vs 318.73 ± 20.10, 8.60± 1.38 vs 7.33 ± 0.70, 156.01 ± 58.81 vs 50.43 ± 30.49, 390 744.2± 62 469.21 vs 170 546.50 ± 50 646.14, 26 740.18 ±3809.60 vs 354.98± 57.19, 0.26± 0.11 vs 0.07± 0.02, and 2.08 ± 0.59 vs 1.27 ± 0.38, respectively, all P 〈 0.01）. Sucrase activity did not differ between the two groups. Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats （508.27 ± 94.39 vs 605.61 ± 141.00, 7.58 ± 1.51 vs 8.60±1.38, respectively, all P 〈 0.05）. The intestinal mucosa and apical GLUT2, expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group （269 975.2 ± 53 730.94 vs 390 744.2 ± 62 469.21, 3758.06 ± 364.51 vs 26 740.18 ± 3809.60, 0.08 ± 0.02 vs 0.26 ±0.11, and 1.31 ± 0.27 vs 2.08 ±0.59, respectively, all P 〈 0.01）. CONCLUSION： High fat dietinduced obesity is associated with elevated intestinal maltase activity, GLUT2 expression, and permanent apical GLUT2 in the small intestinal mucosa of rats. Octreotide can inhibit these effects.展开更多
BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions...BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.展开更多
Plasma membrane intrinsic proteins(PIPs)are conserved plant aquaporins that transport small molecules across the plasma membrane to trigger instant stress responses and maintain cellular homeostasis under biotic and a...Plasma membrane intrinsic proteins(PIPs)are conserved plant aquaporins that transport small molecules across the plasma membrane to trigger instant stress responses and maintain cellular homeostasis under biotic and abiotic stress.To elucidate their roles in plant immunity to pathogen attack,we characterized the expression patterns,subcellular localizations,and H_(2)O_(2)-transport ability of 11 OsPIPs in rice(Oryza sativa),and identified OsPIP2;6 as necessary for rice disease resistance.OsPIP2;6 resides on the plasma membrane and facilitates cytoplasmic import of the immune signaling molecule H_(2)O_(2).Knockout of OsPIP2;6 increases rice susceptibility to Magnaporthe oryzae,indicating a positive function in plant immunity.OsPIP2;6 interacts with OsPIP2;2,which has been reported to increase rice resistance to pathogens via H_(2)O_(2)transport.Our findings suggest that OsPIP2;6 cooperates with OsPIP2;2 as a defense signal transporter complex during plant–pathogen interaction.展开更多
As the global demographic shifts toward an aging population,understanding the efficiency of protein uti-lization in older adults becomes crucial.Our study explores the intricate relationship between protein intake and...As the global demographic shifts toward an aging population,understanding the efficiency of protein uti-lization in older adults becomes crucial.Our study explores the intricate relationship between protein intake and aging,with a focus on precision nutrition for older people.Through a meta-analysis,we con-firm a decline in protein-utilization capacity in older individuals and examine the different contributions of plant and animal protein.In experiments involving mice of different ages,older mice exhibited decreases in the biological utilization of four proteins(casein,beef protein,soy protein,and gluten),par-ticularly casein.In subsequent research,casein was studied as a key protein.A decline in gastric digestion function was observed through peptidomics and the examination of pepsin levels using casein.Nevertheless,this decline did not significantly affect the overall protein digestion during the aging pro-cess.The combined application of targeted amino acid metabolomics identified abnormal absorption of amino acids as the underlying cause of decreased protein utilization during aging,particularly emphasiz-ing a reduction in branched-chain amino acids(BCAAs)in older mice.Delving deeper into the proteomics of the intestinal protein digestion and absorption pathway,a reduction of over 60%in large neutral amino acid transporter 2(LAT2)protein expression was observed in both older humans and aged mice.The reduction in LAT2 protein was found to be a key factor influencing the diminished BCAA availability.Overall,our study establishes the significance of amino acid absorption through LAT2 in protein utiliza-tion during aging and offers a new theoretical foundation for improving protein utilization in the older adults.展开更多
In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epice...In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.展开更多
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general populat...Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general population and is also more severe histologically in this group. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, the newest class of antidiabetic agents, appear to represent a promising option for the management of NAFLD in patients with T2DM. In a number of studies, treatment with SGLT2 inhibitors resulted in a reduction in hepatic steatosis and in transaminase levels. However, existing studies are small, their follow-up period was short and none evaluated the effects of SGLT2 inhibitors on liver histology. Accordingly, larger studies are needed to verify these preliminary results and define the role of SGLT2 inhibitors in the treatment of NAFLD in patients with T2DM.展开更多
A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier(BBB)and overexpression of ATP-binding cassette(ABC)transporters,which dec...A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier(BBB)and overexpression of ATP-binding cassette(ABC)transporters,which decrease drug penetration into the central nervous system and ultimately into tumors.It is noteworthy that the ABC transporters,ABCB1[known as P-glycoprotein(P-gp)]and ABCG2[known as breast cancer resistance protein(BCRP)],are overexpressed in brain tumors,including common gliomas.The co-presence of these transporters may negate the inhibition of either transporter,particularly if both transport the same anticancer drug.The cellular export of drugs by ABC transporters has been implicated in mediating resistance to anticancer drugs.However,the clinical relevance as a therapeutic target in human tumors remains a matter of contention.Although effective and clinically approved ABC transporter inhibitors could potentially overcome drug resistance,none are currently approved.Furthermore,the ABC transporter inhibitors in clinical trials produced low or no clinical efficacy,significant toxicities,and unsuitable pharmacokinetic profiles.Therefore,innovative approaches are needed to efficaciously and simultaneously inhibit these transporters to surmount anticancer drug resistance.This review emphasizes the clinical significance of ABC transporters in diminishing the efficacy of brain tumor treatments.The molecular alterations in BBB following brain tumor development,which are linked to various cancer therapies,are discussed.The overexpression of ABCB1 and ABCG2 at the BBB is discussed,potential strategies to decrease the export of chemotherapeutics by these transporters and the associated challenges and failures are discussed,and the implementation of novel approaches is considered.展开更多
BACKGROUND： Developmental seizures are pathologically characterized by regenerative sprouting of hippocampal mossy fibers rich in Zn^2＋. Zn^2＋ metabolism in the mossy fiber pathway, and Zn^2＋ accumulation in presy...BACKGROUND： Developmental seizures are pathologically characterized by regenerative sprouting of hippocampal mossy fibers rich in Zn^2＋. Zn^2＋ metabolism in the mossy fiber pathway, and Zn^2＋ accumulation in presynaptic membrane vesicles, are dependent on zinc transporter 1 （ZnT1） and glutamate receptor subunit 2 （GluR2）. OBJECTIVE： To investigate the effects of long-term recurrent neonatal seizure, in the presence and absence of physical exercise, on the developmental expression of hippocampal zinc transporter 1 （ZnT1） and GluR2, and on cognitive function in rats. DESIGN, TIME AND SETTING： Based on behavioral examination and molecular biological research, a randomized, controlled animal experiment was performed at the Department of Neurobiology, Medical College of Soochow University, between January 2007 and April 2008. MATERIALS： Twenty-one 6-day-old Sprague Dawley rats of either gender were employed in this study. ZnT1 mRNA in situ hybridization kit was provided by Tianjin Haoyang Biological Manufacture Co.,Ltd., China. Rabbit anti-GluR2 was purchased from Santa Cruz Biotech, Inc, USA. METHODS： Rats were randomly divided into a recurrent seizure group （n = 11） and a control group （n = 10）. In the recurrent seizure group, 30-minute seizure was induced by flurothyl gas inhalation for a total of 6 consecutive days. Rats from the control group underwent experimental procedures similar to the recurrent seizure group, with the exception of flurothyl gas inhalation. Thirty minutes of treadmill exercise was performed daily by all rats at postnatal days 51–56. MAIN OUTCOME MEASURES： At postnatal day 82, rat hippocampal tissue was harvested for analysis of hippocampal ZnT1 and GluR2 expression by in situ hybridization and immunohistochemistry, respectively. Rat learning and memory capabilities were examined using the Y-maze test. RESULTS： In the recurrent seizure group, the gray scale value of ZnT1 in situ hybridization positive neurons in the hippocampal CA3 region was significantly greater （P 〈 0.05）, while the gray scale value of GluR2 immunoreactive neurons in the hippocampal hilus and dentate gyrus was significantly lower （P 〈 0.05）, than in the control group. At postnatal days 29–35, numbers of trials to criteria for successful learning were greater in the recurrent seizure group than in the control group （P 〈 0.05）; at postnatal days 61–67, the numbers of trials to criteria for successful learning were similar between the two groups （P 〉 0.05）. At postnatal days 29–35 and 61–67, there was no significant difference in memory capability between the recurrent seizure and control groups （P 〉 0.05）. CONCLUSION： Physical exercise likely improves the learning deficits caused by recurrent neonatal seizure in rats during brain development by modulating ZnT1 and GluR2 expression.展开更多
The structural design of n-i-p in antimony selenide(Sb_(2)Se_(3))thin film solar cells can effectively improve the low carrier collection efficiency caused by the lower doping concentration of Sb_(2)Se_(3).However,the...The structural design of n-i-p in antimony selenide(Sb_(2)Se_(3))thin film solar cells can effectively improve the low carrier collection efficiency caused by the lower doping concentration of Sb_(2)Se_(3).However,the unideal carrier transport ability of the intrinsic light-absorbing layer remains a major limitation for its power conversion efficiency improvement.Herein,it is discovered that the carrier transport in Sb_(2)Se_(3)thin films strongly depends on the film thickness of the absorber layer in n-i-p structure.By exploring the carrier transport mechanism under different thicknesses of light-absorbing layers,a suitable absorber layer with thickness of 550 nm is demonstrated can effectively separate,transport,and extract photogenerated carriers in Sb_(2)Se_(3)solar cells.Finally,the vapor transport deposition processed Sb_(2)Se_(3)solar cells achieve the highest PCE of 7.62%with a short-circuit current density of 30.71 mA·cm^(-2).This finding provides a constructive guidance for the future researches on Sb_(2)Se_(3)thin film solar cells with n-i-p structure.展开更多
In this study,the effects of hyperosmolality on the expression of urea transporter A2 (UTA2) and aquaporin 2 (AQP2) were investigated in transfected immortalized mouse medullary collecting duct (mIMCD3) cell line.AQP2...In this study,the effects of hyperosmolality on the expression of urea transporter A2 (UTA2) and aquaporin 2 (AQP2) were investigated in transfected immortalized mouse medullary collecting duct (mIMCD3) cell line.AQP2-GFP-pCMV6 and UTA2-GFP-pCMV6 plasmids were stably transfected into mIMCD3 cells respectively.Transfected mIMCD3 and control cells were cultured in different hy-pertonic media,which were made by NaCl alone,urea alone,or an equiosmolar mixture of NaCl and urea.The mRNA and protein expression of AQP2 was elevated by the stimulation of NaCl alone,urea alone and NaCl plus urea in AQP2-mIMCD3 cells;whereas NaCl alone and NaCl plus urea rather than urea alone increased the mRNA and protein expression of UTA2 in UTA2-mIMCD3 cells,and all the expression presented an osmolality-dependent manner.Moreover,the mRNA and protein expression of UTA2 rather than AQP2 was found to be synergistically up-regulated by a combination of NaCl and urea in mIMCD3 cells.It is concluded that NaCl and urea synergistically induce the expression of UTA2 rather than AQP2 in mIMCD3 cells,and hyperosmolality probably mediates the expression of AQP2 and UTA2 through different mechanisms.展开更多
Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chlorid...Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.展开更多
Mg_(2)V_(2)O_(7)is the most promising candidate for low-temperature co-fired ceramic(LTCC)multilayer devices.Selecting the appropriate precursors strongly requires reliable thermodynamic properties to be defined accur...Mg_(2)V_(2)O_(7)is the most promising candidate for low-temperature co-fired ceramic(LTCC)multilayer devices.Selecting the appropriate precursors strongly requires reliable thermodynamic properties to be defined accurately.In this study,the structural parameters of the Mg_(2)V_(2)O_(7)at ambient temperature indicate that it is crystallized in space group of P2_(1)/c.Notably,Mg_(2)V_(2)O_(7)has low lattice thermal conductivity(k_(L))of 4.77,5.12,and 4.52 W/m K,along the a,b,and c axes,respectively,which originates from the large phonon scattering rate and low phonon group velocity.The α-Mg_(2)V_(2)O_(7)←→β-Mg_(2)V_(2)O_(7) and β-Mg_(2)V_(2)O_(7)←→γ-Mg_(2)V_(2)O_(7)polymorphic transitions occur at 743℃and 908℃with enthalpy change of 1.82±0.04 kJ/mol and 1.51±0.04 kJ/mol,respectively.The endothermic effect at 1083℃ with an enthalpy change of 26.54±0.26 kJ/mol is related to the congruent melting of γ-Mg_(2)V_(2)O_(7).In addition,the molar heat capacity of Mg_(2)V_(2)O_(7) was measured utilizing drop calorimetry at high temperatures.The measured thermodynamic properties were then applied to select precursors for preparing Mg_(2)V_(2)O_(7)via a solid-state reaction,indicating that the V_(2)O_5 and Mg(OH)_(2) precursors are strongly recommended due to their thermodynamic superiority.展开更多
Sb_(2)S_(3)films are susceptible to the formation of nanogap defects during the crystallization process,leading to their experimental power conversion efficiency(PCE)falling significantly short of the theoretical limi...Sb_(2)S_(3)films are susceptible to the formation of nanogap defects during the crystallization process,leading to their experimental power conversion efficiency(PCE)falling significantly short of the theoretical limit.This investigation presents,a groundbreaking Sb_(2)S_(3)photovoltaic device model that integrates perovskite within these nanogaps,and systematically examines the mechanisms for enhancing the PCE.Our findings reveal that incorporating perovskite within the nanogaps yields a 10%enhancement in optical absorption performance.Furthermore,perovskite nanogaps function as effective electron transport channels,significantly reducing the recombination of photogenerated carriers within the highly defective Sb_(2)S_(3).The dimensions and arrangement of the nanochannels play a pivotal role in determining device performance,with optimal measurements of 5 nm in width and 15 nm in spacing.Additionally,this study examines the universality of the nanochannel structure.The projected PCE of this innovative structure is an impressive 25.40%.These findings provide valuable theoretical guidance for designing high-efficiency Sb_(2)S_(3)solar cells.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32371070 (to JT),31761163005 (to JT),32100824 (to QX)the Shenzhen Science and Technology Program,Nos.RCBS20210609104606024 (to QX),JCY20210324101813035 (to DL)+4 种基金the Guangdong Provincial Key S&T Program,No.2018B030336001 (to JT)the Key Basic Research Program of Shenzhen Science and Technology Innovation Commission,Nos.JCYJ20200109115405930 (to JT),JCYJ20220818101615033 (to DL),JCYJ20210324115811031 (to QX),JCYJ20200109150717745 (to QX)Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,No.ZDSYS20220304163558001 (to JT)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,No.2023B1212060055 (to JT)the China Postdoctoral Science Foundation,No.2021M693298 (to QX)。
文摘The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.
基金Supported by the National Natural Science Foundation of China(General Program),No.82000493Peking University People’s Hospital Scientific Research Development Funds,No.RDJP2023-09.
文摘BACKGROUND Chronic enteropathy associated with solute carrier organic anion transporter family member 2A1(SLCO2A1)(CEAS)is a rare autosomal recessive hereditary disease characterized by anemia,hypoproteinemia,abdominal pain,diarrhea,and multiple shallow ulcers in the small intestine.Genetic analysis for SLCO2A1 mutations has identified more than 10 variant types,including the mostly reported c.940+1G>A splice site mutation.CASE SUMMARY Herein,we described a 33-year-old female patient who was admitted for anemia,edema,and a positive fecal occult blood test,unaccompanied by abdominal pain and diarrhea.She was diagnosed with CEAS due to compound heterozygous variants,c.940+1G>cA(splice-5)and c.1658T>A(p.Ile553Asn)in SLCO2A1,which had not been previously reported.Importantly,we reviewed 132 reported CEAS patients,which showed that anemia(87.3%)and hypoproteinemia(81%)were the most common symptoms.Nearly 25.8%of patients only had a positive result of fecal occult blood,without any symptoms of gastrointestinal bleeding.CONCLUSION In conclusion,fecal tests should be repeated in patients with anemia and edema to find clues for chronic enteropathy,including the rare cause-CEAS.
基金Supported by Jinhua Municipal Science and Technology Bureau,No.2022-4-254.
文摘BACKGROUND Pancreatic cancer,characterized by aggressive proliferation and metastasis,is a lethal malignancy.The nightly hormone melatonin serves as a rhythm-regulating hormone,and is used to treat different cancers including pancreatic cancer.AIM To investigate how melatonin acts against human pancreatic cancer cell lines and analyze the biological processes that cause the observed effects.METHODS Panc-1 and AsPC-1 cells were treated with melatonin.Cell viability was measured using the cell counting kit-8 assay.Western blotting and immunofluorescence were used to analyze protein expression levels.Ferroptosis was measured by analyzing lipid reactive oxygen species and malondialdehyde levels;apoptosis was assessed using flow cytometry.RESULTS Melatonin significantly inhibited the viability,colony formation,migration,and invasion of Panc-1 and AsPC-1 cells.Additionally,melatonin activated the endoplasmic reticulum(ER)stress pathway(protein kinase R-like ER kinase eukaryotic initiation factor 2α-activating transcription factor 4),inhibited glutamine metabolism(alanine-serinecysteine transporter 2-glutaminase 1-glutathione peroxidase 4,alanine-serine-cysteine transporter 2-glutathione peroxidase 4),and promoted ferroptosis in pancreatic cancer cells.Co-treatment with a high melatonin concentration and protein kinase R-like ER kinase agonist(CCT020312)enhanced melatonin-induced ferroptosis in pancreatic cancer cells.Melatonin demonstrated a variety of anticancer effects by inhibiting autophagy.This was achieved through the increased expression of sequestosome-1 and decreased expression of light chain 3.Additionally,melatonin facilitated the promotion of apoptosis.CONCLUSION Melatonin induces ferroptosis in pancreatic cancer cells by activating transcription factor 4-dependent ER stress and inhibiting glutamine metabolism,promotes apoptosis in pancreatic cancer cells,and inhibits autophagy,leading to synergistic anticancer effects.
基金supported by the Science and Technology Council,Taiwan,China(NSTC 112-2320-B-039-057 and MOST 111-2320-B-039-067-MY3)the China Medical University,Taiwan,China(CMU112-S-18),awarded to Yuan-Soon Ho+1 种基金the China Medical University,Taiwan,China(CMU112-N-02),awarded to Li-Ching Chenthe Science and Technology Council,Taiwan,China(MOST 110-2320B-039-079)。
文摘This study presents novel findings on the potential of phloretin,an apple polyphenol,to enhance the effectiveness of anti-human epidermal growth factor receptor-2(HER2)antibody therapy in HER2-positive breast cancer patients.Our research reveals that phloretin inhibits typeⅡglucose transporter(GLUT2)activity,significantly reducing cancer cell glucose uptake.We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues,with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients.Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins,attenuate glycolysis,and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells.Furthermore,the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft tumor animal model,particularly in suppressing the growth of trastuzumab-resistant HER2-positive(HER2+)breast cancer.These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer,offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.
文摘Monocarboxylic acid transporter 2 （MCT2） transports pyruvate and lactate outside and inside of sperms, mainly as energy sources and plays roles in the regulation of spermatogenesis. We investigated the association among genetic variations in the MCT2 gene, male infertility and MCT2 expression levels in sperm. The functional and genetic significance of the intron 2 （＋28201A 〉 G, rs10506398） and 3＇ untranslated region （UTR） single nucleotide polymorphism （SNP） （＋2626G 〉 A, rs10506399） of MCT2 variants were investigated. Two MCT2 polymorphisms were associated with male infertility （n = 471, P 〈 0.05）. In particular, the MCT2-3＇ UTR SNP （＋2626 G 〉 A） had a strong association with the oligoasthenoteratozoospermia （OAT） group. The ＋2626GG type had an almost 2.4-fold higher sperm count than that of the ＋2626AA type （＋2626GG; 66 x 106 vs ＋2626AA; 27 x 106, P 〈 0.0001）. The MCT2-3＇ UTR SNP may be important for expression, as it is located at the MCT2 3＇ UTR. The average MCT2 protein amount in sperm of the ＋2626GG type was about two times higher than that of the ＋2626AA type. The results suggest that genetic variation in MCT2 has functional and clinical relevance with male infertility.
基金Supported by Grants from the National Natural Sciences Foundation of China,No.30870919Sichuan Provincial Department of Science and Technology,No.2010SZ0176
文摘AIM： TO investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 （GLUT2） in obese rat intestinal mucosa. METHODS： We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls. The obese rats were separated into an octreotide treated group 9f 16 rats and an obese group of 15. The intervention （：jroup was injected with octreotide at 40 ±g/kg body weight every 12 h for 8 d. Rat body weight was measured weekly to calculate Lee＇s index. After euthanization, maltase and sucrase activities in the small intestine were measured by activity assays, and the fasting plasma glucose level was measured. The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction and Western blotting assays. RESULTS： Body weight, Lee＇s index, fasting plasma glucose level, maltase activity in small intestinal mucosa, mucosa and apical GLUT2, GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group （605.61 ± 141.00 vs 378.54 ±111.75, 337.61 ± 10.82 vs 318.73 ± 20.10, 8.60± 1.38 vs 7.33 ± 0.70, 156.01 ± 58.81 vs 50.43 ± 30.49, 390 744.2± 62 469.21 vs 170 546.50 ± 50 646.14, 26 740.18 ±3809.60 vs 354.98± 57.19, 0.26± 0.11 vs 0.07± 0.02, and 2.08 ± 0.59 vs 1.27 ± 0.38, respectively, all P 〈 0.01）. Sucrase activity did not differ between the two groups. Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats （508.27 ± 94.39 vs 605.61 ± 141.00, 7.58 ± 1.51 vs 8.60±1.38, respectively, all P 〈 0.05）. The intestinal mucosa and apical GLUT2, expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group （269 975.2 ± 53 730.94 vs 390 744.2 ± 62 469.21, 3758.06 ± 364.51 vs 26 740.18 ± 3809.60, 0.08 ± 0.02 vs 0.26 ±0.11, and 1.31 ± 0.27 vs 2.08 ±0.59, respectively, all P 〈 0.01）. CONCLUSION： High fat dietinduced obesity is associated with elevated intestinal maltase activity, GLUT2 expression, and permanent apical GLUT2 in the small intestinal mucosa of rats. Octreotide can inhibit these effects.
文摘BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2020A1515111101,2022A1515110431).
文摘Plasma membrane intrinsic proteins(PIPs)are conserved plant aquaporins that transport small molecules across the plasma membrane to trigger instant stress responses and maintain cellular homeostasis under biotic and abiotic stress.To elucidate their roles in plant immunity to pathogen attack,we characterized the expression patterns,subcellular localizations,and H_(2)O_(2)-transport ability of 11 OsPIPs in rice(Oryza sativa),and identified OsPIP2;6 as necessary for rice disease resistance.OsPIP2;6 resides on the plasma membrane and facilitates cytoplasmic import of the immune signaling molecule H_(2)O_(2).Knockout of OsPIP2;6 increases rice susceptibility to Magnaporthe oryzae,indicating a positive function in plant immunity.OsPIP2;6 interacts with OsPIP2;2,which has been reported to increase rice resistance to pathogens via H_(2)O_(2)transport.Our findings suggest that OsPIP2;6 cooperates with OsPIP2;2 as a defense signal transporter complex during plant–pathogen interaction.
基金funded by the National Key Research and Development Program of China(2023YFF1104502)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(2022QNRC001).
文摘As the global demographic shifts toward an aging population,understanding the efficiency of protein uti-lization in older adults becomes crucial.Our study explores the intricate relationship between protein intake and aging,with a focus on precision nutrition for older people.Through a meta-analysis,we con-firm a decline in protein-utilization capacity in older individuals and examine the different contributions of plant and animal protein.In experiments involving mice of different ages,older mice exhibited decreases in the biological utilization of four proteins(casein,beef protein,soy protein,and gluten),par-ticularly casein.In subsequent research,casein was studied as a key protein.A decline in gastric digestion function was observed through peptidomics and the examination of pepsin levels using casein.Nevertheless,this decline did not significantly affect the overall protein digestion during the aging pro-cess.The combined application of targeted amino acid metabolomics identified abnormal absorption of amino acids as the underlying cause of decreased protein utilization during aging,particularly emphasiz-ing a reduction in branched-chain amino acids(BCAAs)in older mice.Delving deeper into the proteomics of the intestinal protein digestion and absorption pathway,a reduction of over 60%in large neutral amino acid transporter 2(LAT2)protein expression was observed in both older humans and aged mice.The reduction in LAT2 protein was found to be a key factor influencing the diminished BCAA availability.Overall,our study establishes the significance of amino acid absorption through LAT2 in protein utiliza-tion during aging and offers a new theoretical foundation for improving protein utilization in the older adults.
基金supported by COBRE(P30GM149367)the Puerto Rico Science&Technology Trust(2022-00125)+1 种基金MBRS-RISE Program(R25 GM061838)SC1GM144032 program(all to JDM)。
文摘In addition to the loss of motor function,~60% of patients develop pain after spinal cord injury.The cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic pain.Sprouting can lead to the formation of new connections triggering abnormal sensory transmission.The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity.Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen.In this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury.We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting.Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical allodynia.Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent effect.The expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes.Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents.Analyses of peptidergic(calcitonin gene-related peptide-α)and non-peptidergic(isolectin B4)fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/isolectin B4 ratio in comparison with sham,suggesting increased receptive fields in the dorsal horn.Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats,this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury.Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord.The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain,an area with a critical need for treatment.
文摘Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. NAFLD is considerably more frequent in patients with type 2 diabetes mellitus (T2DM) than in the general population and is also more severe histologically in this group. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, the newest class of antidiabetic agents, appear to represent a promising option for the management of NAFLD in patients with T2DM. In a number of studies, treatment with SGLT2 inhibitors resulted in a reduction in hepatic steatosis and in transaminase levels. However, existing studies are small, their follow-up period was short and none evaluated the effects of SGLT2 inhibitors on liver histology. Accordingly, larger studies are needed to verify these preliminary results and define the role of SGLT2 inhibitors in the treatment of NAFLD in patients with T2DM.
基金supported by Arkansas Bioscience Institute funds (ABI-GR020025) from University of Arkansas for Medical Sciences
文摘A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier(BBB)and overexpression of ATP-binding cassette(ABC)transporters,which decrease drug penetration into the central nervous system and ultimately into tumors.It is noteworthy that the ABC transporters,ABCB1[known as P-glycoprotein(P-gp)]and ABCG2[known as breast cancer resistance protein(BCRP)],are overexpressed in brain tumors,including common gliomas.The co-presence of these transporters may negate the inhibition of either transporter,particularly if both transport the same anticancer drug.The cellular export of drugs by ABC transporters has been implicated in mediating resistance to anticancer drugs.However,the clinical relevance as a therapeutic target in human tumors remains a matter of contention.Although effective and clinically approved ABC transporter inhibitors could potentially overcome drug resistance,none are currently approved.Furthermore,the ABC transporter inhibitors in clinical trials produced low or no clinical efficacy,significant toxicities,and unsuitable pharmacokinetic profiles.Therefore,innovative approaches are needed to efficaciously and simultaneously inhibit these transporters to surmount anticancer drug resistance.This review emphasizes the clinical significance of ABC transporters in diminishing the efficacy of brain tumor treatments.The molecular alterations in BBB following brain tumor development,which are linked to various cancer therapies,are discussed.The overexpression of ABCB1 and ABCG2 at the BBB is discussed,potential strategies to decrease the export of chemotherapeutics by these transporters and the associated challenges and failures are discussed,and the implementation of novel approaches is considered.
基金the National Natural Science Foundation of China, No. 30470555, 30571909, 30870808the Natural Science Foundation of Jiangsu Province, No. BK2007509Natural Science Foundation for Colleges and Universities in Jiangsu Province, No. 07KJB320103
文摘BACKGROUND： Developmental seizures are pathologically characterized by regenerative sprouting of hippocampal mossy fibers rich in Zn^2＋. Zn^2＋ metabolism in the mossy fiber pathway, and Zn^2＋ accumulation in presynaptic membrane vesicles, are dependent on zinc transporter 1 （ZnT1） and glutamate receptor subunit 2 （GluR2）. OBJECTIVE： To investigate the effects of long-term recurrent neonatal seizure, in the presence and absence of physical exercise, on the developmental expression of hippocampal zinc transporter 1 （ZnT1） and GluR2, and on cognitive function in rats. DESIGN, TIME AND SETTING： Based on behavioral examination and molecular biological research, a randomized, controlled animal experiment was performed at the Department of Neurobiology, Medical College of Soochow University, between January 2007 and April 2008. MATERIALS： Twenty-one 6-day-old Sprague Dawley rats of either gender were employed in this study. ZnT1 mRNA in situ hybridization kit was provided by Tianjin Haoyang Biological Manufacture Co.,Ltd., China. Rabbit anti-GluR2 was purchased from Santa Cruz Biotech, Inc, USA. METHODS： Rats were randomly divided into a recurrent seizure group （n = 11） and a control group （n = 10）. In the recurrent seizure group, 30-minute seizure was induced by flurothyl gas inhalation for a total of 6 consecutive days. Rats from the control group underwent experimental procedures similar to the recurrent seizure group, with the exception of flurothyl gas inhalation. Thirty minutes of treadmill exercise was performed daily by all rats at postnatal days 51–56. MAIN OUTCOME MEASURES： At postnatal day 82, rat hippocampal tissue was harvested for analysis of hippocampal ZnT1 and GluR2 expression by in situ hybridization and immunohistochemistry, respectively. Rat learning and memory capabilities were examined using the Y-maze test. RESULTS： In the recurrent seizure group, the gray scale value of ZnT1 in situ hybridization positive neurons in the hippocampal CA3 region was significantly greater （P 〈 0.05）, while the gray scale value of GluR2 immunoreactive neurons in the hippocampal hilus and dentate gyrus was significantly lower （P 〈 0.05）, than in the control group. At postnatal days 29–35, numbers of trials to criteria for successful learning were greater in the recurrent seizure group than in the control group （P 〈 0.05）; at postnatal days 61–67, the numbers of trials to criteria for successful learning were similar between the two groups （P 〉 0.05）. At postnatal days 29–35 and 61–67, there was no significant difference in memory capability between the recurrent seizure and control groups （P 〉 0.05）. CONCLUSION： Physical exercise likely improves the learning deficits caused by recurrent neonatal seizure in rats during brain development by modulating ZnT1 and GluR2 expression.
基金supported by the National Natural Science Foundation of China(No.62305064)the Beijing Nova Program from Beijing Municipal Science&Technology Commission(No.Z211100002121072).
文摘The structural design of n-i-p in antimony selenide(Sb_(2)Se_(3))thin film solar cells can effectively improve the low carrier collection efficiency caused by the lower doping concentration of Sb_(2)Se_(3).However,the unideal carrier transport ability of the intrinsic light-absorbing layer remains a major limitation for its power conversion efficiency improvement.Herein,it is discovered that the carrier transport in Sb_(2)Se_(3)thin films strongly depends on the film thickness of the absorber layer in n-i-p structure.By exploring the carrier transport mechanism under different thicknesses of light-absorbing layers,a suitable absorber layer with thickness of 550 nm is demonstrated can effectively separate,transport,and extract photogenerated carriers in Sb_(2)Se_(3)solar cells.Finally,the vapor transport deposition processed Sb_(2)Se_(3)solar cells achieve the highest PCE of 7.62%with a short-circuit current density of 30.71 mA·cm^(-2).This finding provides a constructive guidance for the future researches on Sb_(2)Se_(3)thin film solar cells with n-i-p structure.
基金supported by a grant from National Natural Science foundation of China (No. 30871173)
文摘In this study,the effects of hyperosmolality on the expression of urea transporter A2 (UTA2) and aquaporin 2 (AQP2) were investigated in transfected immortalized mouse medullary collecting duct (mIMCD3) cell line.AQP2-GFP-pCMV6 and UTA2-GFP-pCMV6 plasmids were stably transfected into mIMCD3 cells respectively.Transfected mIMCD3 and control cells were cultured in different hy-pertonic media,which were made by NaCl alone,urea alone,or an equiosmolar mixture of NaCl and urea.The mRNA and protein expression of AQP2 was elevated by the stimulation of NaCl alone,urea alone and NaCl plus urea in AQP2-mIMCD3 cells;whereas NaCl alone and NaCl plus urea rather than urea alone increased the mRNA and protein expression of UTA2 in UTA2-mIMCD3 cells,and all the expression presented an osmolality-dependent manner.Moreover,the mRNA and protein expression of UTA2 rather than AQP2 was found to be synergistically up-regulated by a combination of NaCl and urea in mIMCD3 cells.It is concluded that NaCl and urea synergistically induce the expression of UTA2 rather than AQP2 in mIMCD3 cells,and hyperosmolality probably mediates the expression of AQP2 and UTA2 through different mechanisms.
基金supported by a grant from Guangzhou Medical University,No.2008C24
文摘Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.
基金supported by the National Key Research and Development Program of China(No.2022YFC3901001-1)the National Natural Science Foundation of China(Grant No.U1902217)financial support from the Chinese Scholarship Council(CSC No.202106050084)。
文摘Mg_(2)V_(2)O_(7)is the most promising candidate for low-temperature co-fired ceramic(LTCC)multilayer devices.Selecting the appropriate precursors strongly requires reliable thermodynamic properties to be defined accurately.In this study,the structural parameters of the Mg_(2)V_(2)O_(7)at ambient temperature indicate that it is crystallized in space group of P2_(1)/c.Notably,Mg_(2)V_(2)O_(7)has low lattice thermal conductivity(k_(L))of 4.77,5.12,and 4.52 W/m K,along the a,b,and c axes,respectively,which originates from the large phonon scattering rate and low phonon group velocity.The α-Mg_(2)V_(2)O_(7)←→β-Mg_(2)V_(2)O_(7) and β-Mg_(2)V_(2)O_(7)←→γ-Mg_(2)V_(2)O_(7)polymorphic transitions occur at 743℃and 908℃with enthalpy change of 1.82±0.04 kJ/mol and 1.51±0.04 kJ/mol,respectively.The endothermic effect at 1083℃ with an enthalpy change of 26.54±0.26 kJ/mol is related to the congruent melting of γ-Mg_(2)V_(2)O_(7).In addition,the molar heat capacity of Mg_(2)V_(2)O_(7) was measured utilizing drop calorimetry at high temperatures.The measured thermodynamic properties were then applied to select precursors for preparing Mg_(2)V_(2)O_(7)via a solid-state reaction,indicating that the V_(2)O_5 and Mg(OH)_(2) precursors are strongly recommended due to their thermodynamic superiority.
基金Project(52203250)supported by the National Natural Science Foundation of ChinaProject(BS2024074)supported by the Ordos City New Energy Strategic Leading Technology Special Project,China+3 种基金Project(2025YFHH0119)supported by the Key Research and Development and Achievement Transformation Program of Inner Mongolia Autonomous Region,ChinaProject(2022ZY0187)supported by the Central Guiding Local Science and Technology Development Fund of Inner Mongolia Autonomous Region,ChinaProject(JY20220211)supported by the Basic Study Fund of Universities of Inner Mongolia Autonomous Region,ChinaProjects(JBGS-2023-005,JY20230026)supported by the Major“Unveiling”Project of Ordos City,China。
文摘Sb_(2)S_(3)films are susceptible to the formation of nanogap defects during the crystallization process,leading to their experimental power conversion efficiency(PCE)falling significantly short of the theoretical limit.This investigation presents,a groundbreaking Sb_(2)S_(3)photovoltaic device model that integrates perovskite within these nanogaps,and systematically examines the mechanisms for enhancing the PCE.Our findings reveal that incorporating perovskite within the nanogaps yields a 10%enhancement in optical absorption performance.Furthermore,perovskite nanogaps function as effective electron transport channels,significantly reducing the recombination of photogenerated carriers within the highly defective Sb_(2)S_(3).The dimensions and arrangement of the nanochannels play a pivotal role in determining device performance,with optimal measurements of 5 nm in width and 15 nm in spacing.Additionally,this study examines the universality of the nanochannel structure.The projected PCE of this innovative structure is an impressive 25.40%.These findings provide valuable theoretical guidance for designing high-efficiency Sb_(2)S_(3)solar cells.
