In-situ stress is a common stress in the exploration and development of oil reservoirs. Therefore, it is of great significance to study the propagation characteristics of borehole acoustic waves in fluid-saturated por...In-situ stress is a common stress in the exploration and development of oil reservoirs. Therefore, it is of great significance to study the propagation characteristics of borehole acoustic waves in fluid-saturated porous media under stress.Based on the acoustoelastic theory of fluid-saturated porous media, the field equation of fluid-saturated porous media under the conditions of confining pressure and pore pressure and the acoustic field formula of multipole source excitation in open hole are given. The influences of pore pressure and confining pressure on guided waves of multipole borehole acoustic field in fluid-saturated porous media are investigated. The numerical results show that the phase velocity and excitation intensity of guided wave increase significantly under the confining pressure. For a given confining pressure, the phase velocity of the guided wave decreases with pore pressure increasing. The excitation intensity of guided wave increases at low frequency and then decreases at high frequency with pore pressure increasing, except for that of Stoneley wave which decreases in the whole frequency range. These results will help us get an insight into the influences of confining pressure and pore pressure on the acoustic field of multipole source in borehole around fluid-saturated porous media.展开更多
Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus.It is the most common gynecological disorder,affecting up to 80%of women of reproductive age.Uterine fibroids can cause various ...Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus.It is the most common gynecological disorder,affecting up to 80%of women of reproductive age.Uterine fibroids can cause various symptoms such as abnormal uterine bleeding,pelvic pain,infertility,and pregnancy complications.The treatment options for uterine fibroids include medical therapy,surgical intervention,and minimally invasive techniques.AIM To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization(UAE).METHODS This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE,and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments.The two groups were matched for age,body mass index,parity,and baseline characteristics of uterine fibroids.The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),and anti-Müllerian hormone(AMH),as well as ovarian reserve tests,such as antral follicle count(AFC)and ovarian volume(OV).The secondary outcome was fertility that was evaluated based on the menstrual cycle,ovulation,conception,pregnancy,and delivery.The participants were followed-up for 36 months and assessed at 1,3,6,12,24,and 36 months after treatment.RESULTS The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women,resolving within a week.No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones(FSH,LH,E2,AMH)and ovarian reserve indicators(AFC,OV)at any point up to 36 months post-treatment.Additionally,there were no significant differences in conception,pregnancy,or delivery rates,with the average time to conception and gestational age at delivery being similar between the two groups.Birth weights were also comparable.Finally,there was no significant correlation between ovarian function,fertility indicators,and the type or amount of embolic agent used or the change in fibroids posttreatment.CONCLUSION UAE resulted in significantly positive pregnancy outcomes,no adverse events post-treatment,and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.展开更多
As one of the common malignancies that threaten human life,bladder cancer occurs frequently with a high mortality rate in the world,due to its invasion,recurrence and drug resistance.Natural products from marine micro...As one of the common malignancies that threaten human life,bladder cancer occurs frequently with a high mortality rate in the world,due to its invasion,recurrence and drug resistance.Natural products from marine microorganisms are becoming the hotspots in discovery of new candidate drug entities,especially in the area of cancer.Brefeldin A(BFA)is a natural Arf-GEFs inhibitor,but due to the low aqueous solubility,strong toxicity,and poor bioavailability,it is urgent to conduct structural optimization research.Herein,a new BFA pyridine acrylate derivative CHNQD-01281 with improved solubility was prepared and found to exert moderate to strong antiproliferative activity on a variety of human cancer cell lines.It was noteworthy that CHNQD-01281 was most sensitive to two bladder cancer cell lines T24 and J82(IC50=0.079 and 0.081μmol/L)with high selectivity index(SI=14.68 and 14.32),suggesting a superior safety to BFA.In vivo studies revealed that CHNQD-01281 remarkably suppressed tumor growth in a T24 nude mice xenograft model(TGI=52.63%)and prolonged the survival time(ILS=68.16%)in an MB49 allogeneic mouse model via inducing infiltration of cytotoxic T cells.Further mechanism exploration indicated that CHNQD-01281 regulated both EGFR/PI3K/AKT and EGFR/ERK pathways and mediated the chemotactic effect of chemokines on immune effector cells.Overall,CHNQD-01281 may serve as a potential therapeutic agent for bladder cancer through multiple mechanisms.展开更多
Non-alcoholic steatohepatitis(NASH)is a primary cause of cirrhosis and hepatocellular carcinoma.Unfortunately,there is no approved drug treatment for NASH.AMP-activated kinase(AMPK)is an important metabolic sensor and...Non-alcoholic steatohepatitis(NASH)is a primary cause of cirrhosis and hepatocellular carcinoma.Unfortunately,there is no approved drug treatment for NASH.AMP-activated kinase(AMPK)is an important metabolic sensor and whole-body regulator.It has been proposed that AMPK activators could be used for treating metabolic diseases such as obesity,type 2 diabetes and NASH.In this study,we screened a marine natural compound library by monitoring AMPK activity and found a potent AMPK activator,candidusin A(CHNQD-0803).Further studies showed that CHNQD-0803 directly binds recombinant AMPK with a K_(D) value of 4.728×10^(-8) M and activates AMPK at both molecular and intracellular levels.We then investigated the roles and mechanisms of CHNQD-0803 in PA-induced fat deposition,LPS-stimulated infammation,TGF-β-induced fbrosis cell models and the MCD-induced mouse model of NASH.The results showed that CHNQD-0803 inhibited the expression of adipogenesis genes and reduced fat deposition,negatively regulated the NF-κB-TNFαinfammatory axis to suppress infammation,and ameliorated liver injury and fbrosis.These data indicate that CHNQD-0803 as an AMPK activator is a novel potential therapeutic candidate for NASH treatment.展开更多
基金Project supported by the National Natural Science Foundation of China (Grant No.42074139)the Natural Science Foundation of Jilin Province,China (Grant No.20210101140JC)。
文摘In-situ stress is a common stress in the exploration and development of oil reservoirs. Therefore, it is of great significance to study the propagation characteristics of borehole acoustic waves in fluid-saturated porous media under stress.Based on the acoustoelastic theory of fluid-saturated porous media, the field equation of fluid-saturated porous media under the conditions of confining pressure and pore pressure and the acoustic field formula of multipole source excitation in open hole are given. The influences of pore pressure and confining pressure on guided waves of multipole borehole acoustic field in fluid-saturated porous media are investigated. The numerical results show that the phase velocity and excitation intensity of guided wave increase significantly under the confining pressure. For a given confining pressure, the phase velocity of the guided wave decreases with pore pressure increasing. The excitation intensity of guided wave increases at low frequency and then decreases at high frequency with pore pressure increasing, except for that of Stoneley wave which decreases in the whole frequency range. These results will help us get an insight into the influences of confining pressure and pore pressure on the acoustic field of multipole source in borehole around fluid-saturated porous media.
基金Supported by Key Project of Medical Science Research in Hebei Province,China,No.20160005.
文摘Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus.It is the most common gynecological disorder,affecting up to 80%of women of reproductive age.Uterine fibroids can cause various symptoms such as abnormal uterine bleeding,pelvic pain,infertility,and pregnancy complications.The treatment options for uterine fibroids include medical therapy,surgical intervention,and minimally invasive techniques.AIM To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization(UAE).METHODS This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE,and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments.The two groups were matched for age,body mass index,parity,and baseline characteristics of uterine fibroids.The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),and anti-Müllerian hormone(AMH),as well as ovarian reserve tests,such as antral follicle count(AFC)and ovarian volume(OV).The secondary outcome was fertility that was evaluated based on the menstrual cycle,ovulation,conception,pregnancy,and delivery.The participants were followed-up for 36 months and assessed at 1,3,6,12,24,and 36 months after treatment.RESULTS The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women,resolving within a week.No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones(FSH,LH,E2,AMH)and ovarian reserve indicators(AFC,OV)at any point up to 36 months post-treatment.Additionally,there were no significant differences in conception,pregnancy,or delivery rates,with the average time to conception and gestational age at delivery being similar between the two groups.Birth weights were also comparable.Finally,there was no significant correlation between ovarian function,fertility indicators,and the type or amount of embolic agent used or the change in fibroids posttreatment.CONCLUSION UAE resulted in significantly positive pregnancy outcomes,no adverse events post-treatment,and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.
基金supported by the Special Funds of Shandong Province for Qingdao National Laboratory of Marine Sci-ence and Technology(No.2022QNLM030003)the open foundation of Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education(RDZH2024004)+4 种基金Natural Science Foundation of Shan-dong Province(No.ZR2020QH026)Shandong Province Special Fund“Frontier Technology and Free Exploration”from Laoshan Laboratory(No.8-01)the National Key Research and Development Program of China(No.2022YFC2601305)the Fundamental Research Funds for the Central Universities(No.202264001)the Innovation Center for Academicians of Hainan Province.
文摘As one of the common malignancies that threaten human life,bladder cancer occurs frequently with a high mortality rate in the world,due to its invasion,recurrence and drug resistance.Natural products from marine microorganisms are becoming the hotspots in discovery of new candidate drug entities,especially in the area of cancer.Brefeldin A(BFA)is a natural Arf-GEFs inhibitor,but due to the low aqueous solubility,strong toxicity,and poor bioavailability,it is urgent to conduct structural optimization research.Herein,a new BFA pyridine acrylate derivative CHNQD-01281 with improved solubility was prepared and found to exert moderate to strong antiproliferative activity on a variety of human cancer cell lines.It was noteworthy that CHNQD-01281 was most sensitive to two bladder cancer cell lines T24 and J82(IC50=0.079 and 0.081μmol/L)with high selectivity index(SI=14.68 and 14.32),suggesting a superior safety to BFA.In vivo studies revealed that CHNQD-01281 remarkably suppressed tumor growth in a T24 nude mice xenograft model(TGI=52.63%)and prolonged the survival time(ILS=68.16%)in an MB49 allogeneic mouse model via inducing infiltration of cytotoxic T cells.Further mechanism exploration indicated that CHNQD-01281 regulated both EGFR/PI3K/AKT and EGFR/ERK pathways and mediated the chemotactic effect of chemokines on immune effector cells.Overall,CHNQD-01281 may serve as a potential therapeutic agent for bladder cancer through multiple mechanisms.
基金This work was supported by the“Frontier Technology and Free Exploration”Special Project of Laoshan Laboratory(No.8-01)the Program of National Natural Science Foundation of China(Nos.82273846,U1706210,81871868,41776141,and 41322037)+3 种基金the Program of Natural Science Foundation of Shandong Province of China(No.JQ201510)the Fundamental Research Funds for the Central Universities(Nos.201841004 and 202042011)the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(Nos.2018SDKJ0403-2 and 2015ASKJ02)the Taishan Scholars Program,China(No.tsqn20161010).
文摘Non-alcoholic steatohepatitis(NASH)is a primary cause of cirrhosis and hepatocellular carcinoma.Unfortunately,there is no approved drug treatment for NASH.AMP-activated kinase(AMPK)is an important metabolic sensor and whole-body regulator.It has been proposed that AMPK activators could be used for treating metabolic diseases such as obesity,type 2 diabetes and NASH.In this study,we screened a marine natural compound library by monitoring AMPK activity and found a potent AMPK activator,candidusin A(CHNQD-0803).Further studies showed that CHNQD-0803 directly binds recombinant AMPK with a K_(D) value of 4.728×10^(-8) M and activates AMPK at both molecular and intracellular levels.We then investigated the roles and mechanisms of CHNQD-0803 in PA-induced fat deposition,LPS-stimulated infammation,TGF-β-induced fbrosis cell models and the MCD-induced mouse model of NASH.The results showed that CHNQD-0803 inhibited the expression of adipogenesis genes and reduced fat deposition,negatively regulated the NF-κB-TNFαinfammatory axis to suppress infammation,and ameliorated liver injury and fbrosis.These data indicate that CHNQD-0803 as an AMPK activator is a novel potential therapeutic candidate for NASH treatment.