BACKGROUND Diabetic retinopathy(DR)is a major ocular complication of diabetes mellitus,leading to visual impairment.Retinal pigment epithelium(RPE)injury is a key component of the outer blood retinal barrier,and its d...BACKGROUND Diabetic retinopathy(DR)is a major ocular complication of diabetes mellitus,leading to visual impairment.Retinal pigment epithelium(RPE)injury is a key component of the outer blood retinal barrier,and its damage is an important indicator of DR.Receptor for activated C kinase 1(RACK1)activates protein kinase C-ε(PKC-ε)to promote the generation of reactive oxygen species(ROS)in RPE cells,leading to apoptosis.Therefore,we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS,thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR.AIM To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR.METHODS In this study,Sprague-Dawley rats and adult RPE cell line-19(ARPE-19)cells were used as in vivo and in vitro models,respectively,to explore the role of RACK1 in mediating PKC-εin early DR.Furthermore,the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model.RESULTS Streptozotocin-induced diabetic rats showed increased apoptosis and upregulated expression of RACK1 and PKC-εproteins in RPE cells following a prolonged modeling.Similarly,ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε,accompanied by an increases in ROS production,apoptosis rate,and monolayer permeability.However,silencing RACK1 significantly downregulated the expression of PKC-εand ROS,reduced cell apoptosis and permeability,and protected barrier function.CONCLUSION RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.展开更多
BACKGROUND Laparoscopic-assisted radical gastrectomy(LARG)is the standard treatment for early-stage gastric carcinoma(GC).However,the negative impact of this proce-dure on respiratory function requires the optimized i...BACKGROUND Laparoscopic-assisted radical gastrectomy(LARG)is the standard treatment for early-stage gastric carcinoma(GC).However,the negative impact of this proce-dure on respiratory function requires the optimized intraoperative management of patients in terms of ventilation.AIM To investigate the influence of pressure-controlled ventilation volume-guaranteed(PCV-VG)and volume-controlled ventilation(VCV)on blood gas analysis and pulmonary ventilation in patients undergoing LARG for GC based on the lung ultrasound score(LUS).METHODS The study included 103 patients with GC undergoing LARG from May 2020 to May 2023,with 52 cases undergoing PCV-VG(research group)and 51 cases undergoing VCV(control group).LUS were recorded at the time of entering the operating room(T0),20 minutes after anesthesia with endotracheal intubation(T1),30 minutes after artificial pneumoperitoneum(PP)establishment(T2),and 15 minutes after endotracheal tube removal(T5).For blood gas analysis,arterial partial pressure of oxygen(PaO_(2))and partial pressure of carbon dioxide(PaCO_(2))were observed.Peak airway pressure(P_(peak)),plateau pressure(Pplat),mean airway pressure(P_(mean)),and dynamic pulmonary compliance(C_(dyn))were recorded at T1 and T2,1 hour after PP establishment(T3),and at the end of the operation(T4).Postoperative pulmonary complications(PPCs)were recorded.Pre-and postoperative serum interleukin(IL)-1β,IL-6,and tumor necrosis factor-α(TNF-α)were measured by enzyme-linked immunosorbent assay.RESULTS Compared with those at T0,the whole,anterior,lateral,posterior,upper,lower,left,and right lung LUS of the research group were significantly reduced at T1,T2,and T5;in the control group,the LUS of the whole and partial lung regions(posterior,lower,and right lung)decreased significantly at T2,while at T5,the LUS of the whole and some regions(lateral,lower,and left lung)increased significantly.In comparison with the control group,the whole and regional LUS of the research group were reduced at T1,T2,and T5,with an increase in PaO_(2),decrease in PaCO_(2),reduction in P_(peak) at T1 to T4,increase in P_(mean) and C_(dyn),and decrease in Pplat at T4,all significant.The research group showed a significantly lower incidence of PPCs than the control group within 3 days postoperatively.Postoperative IL-1β,IL-6,and TNF-αsignificantly increased in both groups,with even higher levels in the control group.CONCLUSION LUS can indicate intraoperative non-uniformity and postural changes in pulmonary ventilation under PCV-VG and VCV.Under the lung protective ventilation strategy,the PCV-VG mode more significantly improved intraop-erative lung ventilation in patients undergoing LARG for GC and reduced lung injury-related cytokine production,thereby alleviating lung injury.展开更多
AIM: To investigate the biological effects of internal irradiation, and the therapeutic effectiveness was assessed of ^(131)I-labeled anti-epidermal growth factor receptor(EGFR) liposomes, derived from cetuximab, when...AIM: To investigate the biological effects of internal irradiation, and the therapeutic effectiveness was assessed of ^(131)I-labeled anti-epidermal growth factor receptor(EGFR) liposomes, derived from cetuximab, when used as a tumor-targeting carrier in a colorectal cancer mouse model.METHODS: We described the liposomes and characterized their EGFR-targeted binding and cellular uptake in EGFR-overexpressing LS180 colorectal cancer cells. After intra-tumor injections of 74 MBq(740 MBq/m L) ^(131)I-anti EGFR-BSA-PCL, we investigated the biological effects of internal irradiation and the therapeutic efficacy of ^(131)I-anti EGFR-BSA-PCL on colorectal cancer in a male BALB/c mouse model. Tumor size, body weight, histopathology, and SPECT imaging were monitored for 33 d post-therapy.RESULTS: The rapid radioiodine uptake of ^(131)I-antiEGFR-BSA-PCL and ^(131)I-BSA-PCL reached maximum levels at 4 h after incubation, and the ^(131)I uptake of ^(131)I-anti EGFR-BSA-PCL was higher than that of ^(131)I-BSAPCL in vitro. The ^(131)I tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor. Furthermore, a tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor and reached its maximal uptake value of 21.0 ± 1.01 %ID/g(%ID/g is the percentage injected dose per gram of tissue) at 72 h following therapy; the drug concentration in the tumor was higher than that in the liver, heart, colon, or spleen. Tumor size measurements showed that tumor development was significantly inhibited by treatments with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL. The volume of tumor increased, and treatment rate with ^(131)I-anti EGFR-BSA-PCL was 124% ± 7%, lower than that with ^(131)I-BSA-PCL(127% ± 9%), ^(131)I(143% ± 7%), and normal saline(146% ± 10%). The percentage losses in original body weights were 39% ± 3%, 41% ± 4%, 49% ± 5%, and 55% ± 13%, respectively. The best survival and cure rates were obtained in the group treated with ^(131)I-anti EGFR-BSA-PCL. The animals injected with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL showed more uniform focused liposome distribution within the tumor area.CONCLUSION: This study demonstrated the potential beneficial application of ^(131)I-anti EGFR-BSA-PCL for treating colorectal cancer. ^(131)I-anti EGFR-BSA-PCL suppressed the development of xenografted colorectal cancer in nude mice, thereby providing a novel candidate for receptor-mediated targeted radiotherapy.展开更多
BACKGROUND N-terminal pro-B-type natriuretic peptide(NT-proBNP)is often viewed as an indicator for heart failure.However,the prognostic association and the predictive utility of NT-proBNP for postoperative major adver...BACKGROUND N-terminal pro-B-type natriuretic peptide(NT-proBNP)is often viewed as an indicator for heart failure.However,the prognostic association and the predictive utility of NT-proBNP for postoperative major adverse cardiovascular events(MACEs)and myocardial injury after noncardiac surgery(MINS)among older patients are unclear.METHODS In this study,we included 5033 patients aged 65 years or older who underwent noncardiac surgery with preoperative NT-proBNP recorded.Logistic regression was adopted to model the associations between preoperative NT-proBNP and the risk of MACEs and MINS.The receiver operating characteristic curve was used to determine the predictive value of NT-proBNP.RESULTS A total of 5033 patients were enrolled,63 patients(1.25%)and 525 patients(10.43%)had incident postoperative MACEs and MINS,respectively.Analysis of the receiver operating characteristic curve indicated that the cutoff values of ln(NT-proBNP)for MACEs and MINS were 5.16(174 pg/mL)and 5.30(200 pg/mL),respectively.Adding preoperative ln(NT-proBNP)to the Revised Cardiac Risk Index score and the Cardiac and Stroke Risk Model boosted the area under the receiver operating characteristic curves from 0.682 to 0.726 and 0.787 to 0.804,respectively.The inclusion of preoperative NT-proBNP in the prediction models significantly increased the reclassification and discrimination.CONCLUSIONS Increased preoperative NT-proBNP was associated with a higher risk of postoperative MACEs and MINS.The inclusion of NT-proBNP enhances the predictive ability of the preexisting models.展开更多
Microglial apoptosis is associated with neuroinflammation and no effective strategies are currently available to protect microglia against inflammation-induced apoptosis. Mouse microglial BV-2 cells(5 × 10^6) wer...Microglial apoptosis is associated with neuroinflammation and no effective strategies are currently available to protect microglia against inflammation-induced apoptosis. Mouse microglial BV-2 cells(5 × 10^6) were incubated with 10 μg/mL lipopolysaccharides for 12 hours to mimic an inflammatory environment. Then the cells were co-cultured with mitochonic acid 5(MA-5) for another 12 hours. MA-5 improved the survival of lipopolysaccharide-exposed cells. MA-5 decreased the activity of caspase-3, which is associated with apoptosis. MA-5 reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells, and increased adenosine triphosphate levels in cells. MA-5 decreased the open state of the mitochondrial permeability transition pore and reduced calcium overload and diffusion of second mitochondria-derived activator of caspase(Smac). MA-5 decreased the expression of apoptosis-related proteins(mitochondrial Smac, cytoplasmic Smac, pro-caspase-3, cleaved-caspase-3, and caspase-9), and increased the levels of anti-apoptotic proteins(Bcl2 and X-linked inhibitor of apoptosis protein), mitochondria-related proteins(mitochondrial fusion protein 2, mitochondrial microtubule-associated proteins 1 A/1 B light chain 3 B II), and autophagy-related proteins(Beclin1, p62 and autophagy related 5). However, MA-5 did not promote mitochondrial homeostasis or decrease microglial apoptosis when Mitofusin 2 expression was silenced. This shows that MA-5 increased Mitofusin 2-related mitophagy, reversed cellular energy production and maintained energy metabolism in BV-2 cells in response to lipopolysaccharide-induced inflammation. These findings indicate that MA-5 may promote the survival of microglial cells via Mitofusin 2-related mitophagy in response to lipopolysaccharide-induced inflammation.展开更多
<div style="text-align:justify;"> A test method and system for AI industrial application capabilities of smart terminals. The method includes the following steps: According to the temperature change va...<div style="text-align:justify;"> A test method and system for AI industrial application capabilities of smart terminals. The method includes the following steps: According to the temperature change values of different AI industrial applications executed by standard smart terminal equipment under different equipment parameters, the equipment parameters and temperature changes of standard smart terminal equipment are constructed. Correlation model;obtain the device parameters of the smart terminal device to be tested, and obtain the predicted value of the temperature change of the smart terminal device to be tested based on the correlation model between the device parameters of the standard smart terminal device and the temperature change;Measure the actual value of the temperature change of the intelligent terminal device executing different AI industrial applications;obtain the test result of the intelligent terminal device to be tested according to the predicted value of the temperature change and the actual value of the temperature change. </div>展开更多
Heritability estimates may be severely biased when a large common environmental effect on a family arises from a longlasting separate rearing at early stages(SRES)in traditional selective breeding programs,especially ...Heritability estimates may be severely biased when a large common environmental effect on a family arises from a longlasting separate rearing at early stages(SRES)in traditional selective breeding programs,especially when bred populations have weak genetic ties.Communal rearing at early stages(CRES)may reduce common environmental effect since all families are reared in the same environment immediately after hatching.Here,we compared the effects of CRES and SRES strategies on genetic parameter estimation for harvest body weight in a selective breeding population of Litopenaeus vannamei with a small number of half-sib families.Genetic parameters of each strategy were estimated by using animal models excluding and including the common environmental effect(Model 1 and Model 2,respectively).Heritability estimates for body weight were 0.21±0.06(P<0.05)and 0.69±0.09(P<0.05)for CRES and SRES,respectively,in Model 1,and 0.21±0.06(P<0.05)and 0.52±0.27(P>0.05)in Model 2.The ratio of common environmental variance to phenotypic variance was 0.002±0.000 and 0.071±0.112 for CRES and SRES,respectively.Neither strategy precisely partitioned the common environmental variance according to likelihood ratio test.Lower heritability for body weight in CRES than in SRES implied that a large common environmental variance was confounded with additive genetic variance and was not effectively partitioned in SRES.Moreover,genetic correlation of body weight between the two strategies was 0.75±0.15,indicating that family rankings truly changed.The CRES should be followed in the selective breeding program of shrimp,especially in a population with a shallow pedigree and weak genetic ties between families.展开更多
<div style="text-align:justify;"> In distributed AI system, the models trained on data from potentially unreliable sources can be attacked by manipulating the training data distribution by inserting ca...<div style="text-align:justify;"> In distributed AI system, the models trained on data from potentially unreliable sources can be attacked by manipulating the training data distribution by inserting carefully crafted samples into the training set, which is known as Data Poisoning. Poisoning will to change the model behavior and reduce model performance. This paper proposes an algorithm that gives an improvement of both efficiency and security for data poisoning in a distributed AI system. The past methods of active defense often have a large number of invalid checks, which slows down the operation efficiency of the whole system. While passive defense also has problems of missing data and slow detection of error source. The proposed algorithm establishes the suspect hypothesis level to test and extend the verification of data packets and estimates the risk of terminal data. It can enhance the health degree of a distributed AI system by preventing the occurrence of poisoning attack and ensuring the efficiency and safety of the system operation. </div>展开更多
Without intervention,a considerable proportion of patients with metabolism‐associated fatty liver disease(MAFLD)will progress from simple steatosis to metabolism‐associated steatohepatitis(MASH),liver fibrosis,and e...Without intervention,a considerable proportion of patients with metabolism‐associated fatty liver disease(MAFLD)will progress from simple steatosis to metabolism‐associated steatohepatitis(MASH),liver fibrosis,and even hepatocellular carcinoma.However,the molecular mechanisms that control progressive MAFLD have yet to be fully determined.Here,we unraveled that the expression of the N6-methyladenosine(m6A)methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD,whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation,liver injury,and fibrosis.Conversely,hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet(HFD).Notably,in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner,which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1^(+)Ccr2^(+)monocyte-derived macrophages(Mo-macs).In detail,Cx3cr1^(+)Ccr2^(+)Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells(HSCs)to promote liver fibrosis.Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1^(+)Ccr2^(+)Mo-macs.Restoration of METTL14 or GLS2,or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis.Taken together,these findings indicate potential therapies for the treatment of MAFLD progression.展开更多
In this paper, we give a complete real-variable theory of local variable Hardy spaces.First, we present various real-variable characterization in terms of several local maximal functions.Next, the new atomic and the f...In this paper, we give a complete real-variable theory of local variable Hardy spaces.First, we present various real-variable characterization in terms of several local maximal functions.Next, the new atomic and the finite atomic decomposition for the local variable Hardy spaces are established. As an application, we also introduce the local variable Campanato space which is showed to be the dual space of the local variable Hardy spaces. Analogous to the homogeneous case, some equivalent definitions of the dual of local variable Hardy spaces are also considered. Finally, we show the boundedness of inhomogeneous Calderon–Zygmund singular integrals and local fractional integrals on local variable Hardy spaces and their duals.展开更多
Introduction Surgery remains the mainstay treatment for localized esophageal squamous cell carcinoma(ESCC).In recent years,three-incision McKeown esophagectomy has been widely applied for operable ESCC considering its...Introduction Surgery remains the mainstay treatment for localized esophageal squamous cell carcinoma(ESCC).In recent years,three-incision McKeown esophagectomy has been widely applied for operable ESCC considering its superiority in acquiring extensive lymphadenectomy and long-termsurvival[1].Cervical anastomotic fistula is one of the most dreaded complications in patients undergoing three-incision esophagectomy;it occurs in almost 10%–25%of patients and is responsible for almost 40%of post-operative deaths[2,3].Most surgeons prefer conservative approaches including perianastomotic drainage,total parenteral nutrition,nasogastric decompression,and the use of broad-spectrum antibiotics for cervical anastomotic fistula[4,5].However,the recovery period under this method is commonly long and unsatisfactory.Until now,the optimal treatment for cervical anastomotic fistula has not yet been established.In this study,we describe a flushingdrainage system under negative pressure conditions to treat cervical anastomotic fistula,named anastomotic vacuum-assisted closure(AVAC).展开更多
The vertical motion control of the roll was studied in order to improve the accuracy in simulation of variable gauge rolling. The discretization was carried out in the transition zone of TRB according to the principle...The vertical motion control of the roll was studied in order to improve the accuracy in simulation of variable gauge rolling. The discretization was carried out in the transition zone of TRB according to the principle of volume invariance. Based on this assumption, the formula for time step of vertical motion of rolls was proposed and the time-displacement curve of the verti- cal motion of rolls was established. In the preliminary simulation, the time-displacement curve was used as an initial method to control the vertical motion of rolls. Based on the simulation result, the formula for vertical velocity of roll in variable gauge rolling was derived from the common rolling principle. According to the formula, reasonable vertical velocity of rolls in the subsequent simulation was determined. It can accurately control the motion of rolls along the vertical direction. The desired thickness and out- line profile of transition zone were acquired and the formula proved effective by the simulation. Further analysis shows that the di fference of thickness in the thick zone and the thin zone of TRB, length of the transition zone of TRB, radius of work rolls and rota- tion speed of rolls have a significant effect on the vertical velocity of rolls.展开更多
We prove the boundedness for a class of multi-sublinear singular integral operators on the product of central Morrey spaces with variable exponents.Based on this result,we obtain the boundedness for the multilinear si...We prove the boundedness for a class of multi-sublinear singular integral operators on the product of central Morrey spaces with variable exponents.Based on this result,we obtain the boundedness for the multilinear singular integral operators and two kinds of multilinear singular integral commutators on the above spaces.展开更多
基金Supported by National Natural Science Foundation of China,No.82260211Key Research and Development Project in Jiangxi Province,No.20203BBG73058Chinese Medicine Science and Technology Project in Jiangxi Province,No.2020A0166.
文摘BACKGROUND Diabetic retinopathy(DR)is a major ocular complication of diabetes mellitus,leading to visual impairment.Retinal pigment epithelium(RPE)injury is a key component of the outer blood retinal barrier,and its damage is an important indicator of DR.Receptor for activated C kinase 1(RACK1)activates protein kinase C-ε(PKC-ε)to promote the generation of reactive oxygen species(ROS)in RPE cells,leading to apoptosis.Therefore,we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS,thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR.AIM To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR.METHODS In this study,Sprague-Dawley rats and adult RPE cell line-19(ARPE-19)cells were used as in vivo and in vitro models,respectively,to explore the role of RACK1 in mediating PKC-εin early DR.Furthermore,the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model.RESULTS Streptozotocin-induced diabetic rats showed increased apoptosis and upregulated expression of RACK1 and PKC-εproteins in RPE cells following a prolonged modeling.Similarly,ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε,accompanied by an increases in ROS production,apoptosis rate,and monolayer permeability.However,silencing RACK1 significantly downregulated the expression of PKC-εand ROS,reduced cell apoptosis and permeability,and protected barrier function.CONCLUSION RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.
文摘BACKGROUND Laparoscopic-assisted radical gastrectomy(LARG)is the standard treatment for early-stage gastric carcinoma(GC).However,the negative impact of this proce-dure on respiratory function requires the optimized intraoperative management of patients in terms of ventilation.AIM To investigate the influence of pressure-controlled ventilation volume-guaranteed(PCV-VG)and volume-controlled ventilation(VCV)on blood gas analysis and pulmonary ventilation in patients undergoing LARG for GC based on the lung ultrasound score(LUS).METHODS The study included 103 patients with GC undergoing LARG from May 2020 to May 2023,with 52 cases undergoing PCV-VG(research group)and 51 cases undergoing VCV(control group).LUS were recorded at the time of entering the operating room(T0),20 minutes after anesthesia with endotracheal intubation(T1),30 minutes after artificial pneumoperitoneum(PP)establishment(T2),and 15 minutes after endotracheal tube removal(T5).For blood gas analysis,arterial partial pressure of oxygen(PaO_(2))and partial pressure of carbon dioxide(PaCO_(2))were observed.Peak airway pressure(P_(peak)),plateau pressure(Pplat),mean airway pressure(P_(mean)),and dynamic pulmonary compliance(C_(dyn))were recorded at T1 and T2,1 hour after PP establishment(T3),and at the end of the operation(T4).Postoperative pulmonary complications(PPCs)were recorded.Pre-and postoperative serum interleukin(IL)-1β,IL-6,and tumor necrosis factor-α(TNF-α)were measured by enzyme-linked immunosorbent assay.RESULTS Compared with those at T0,the whole,anterior,lateral,posterior,upper,lower,left,and right lung LUS of the research group were significantly reduced at T1,T2,and T5;in the control group,the LUS of the whole and partial lung regions(posterior,lower,and right lung)decreased significantly at T2,while at T5,the LUS of the whole and some regions(lateral,lower,and left lung)increased significantly.In comparison with the control group,the whole and regional LUS of the research group were reduced at T1,T2,and T5,with an increase in PaO_(2),decrease in PaCO_(2),reduction in P_(peak) at T1 to T4,increase in P_(mean) and C_(dyn),and decrease in Pplat at T4,all significant.The research group showed a significantly lower incidence of PPCs than the control group within 3 days postoperatively.Postoperative IL-1β,IL-6,and TNF-αsignificantly increased in both groups,with even higher levels in the control group.CONCLUSION LUS can indicate intraoperative non-uniformity and postural changes in pulmonary ventilation under PCV-VG and VCV.Under the lung protective ventilation strategy,the PCV-VG mode more significantly improved intraop-erative lung ventilation in patients undergoing LARG for GC and reduced lung injury-related cytokine production,thereby alleviating lung injury.
基金Supported by the National Natural Science Foundation of China,No.81301244(to Li W)the National Key Clinical Specialty Project
文摘AIM: To investigate the biological effects of internal irradiation, and the therapeutic effectiveness was assessed of ^(131)I-labeled anti-epidermal growth factor receptor(EGFR) liposomes, derived from cetuximab, when used as a tumor-targeting carrier in a colorectal cancer mouse model.METHODS: We described the liposomes and characterized their EGFR-targeted binding and cellular uptake in EGFR-overexpressing LS180 colorectal cancer cells. After intra-tumor injections of 74 MBq(740 MBq/m L) ^(131)I-anti EGFR-BSA-PCL, we investigated the biological effects of internal irradiation and the therapeutic efficacy of ^(131)I-anti EGFR-BSA-PCL on colorectal cancer in a male BALB/c mouse model. Tumor size, body weight, histopathology, and SPECT imaging were monitored for 33 d post-therapy.RESULTS: The rapid radioiodine uptake of ^(131)I-antiEGFR-BSA-PCL and ^(131)I-BSA-PCL reached maximum levels at 4 h after incubation, and the ^(131)I uptake of ^(131)I-anti EGFR-BSA-PCL was higher than that of ^(131)I-BSAPCL in vitro. The ^(131)I tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor. Furthermore, a tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor and reached its maximal uptake value of 21.0 ± 1.01 %ID/g(%ID/g is the percentage injected dose per gram of tissue) at 72 h following therapy; the drug concentration in the tumor was higher than that in the liver, heart, colon, or spleen. Tumor size measurements showed that tumor development was significantly inhibited by treatments with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL. The volume of tumor increased, and treatment rate with ^(131)I-anti EGFR-BSA-PCL was 124% ± 7%, lower than that with ^(131)I-BSA-PCL(127% ± 9%), ^(131)I(143% ± 7%), and normal saline(146% ± 10%). The percentage losses in original body weights were 39% ± 3%, 41% ± 4%, 49% ± 5%, and 55% ± 13%, respectively. The best survival and cure rates were obtained in the group treated with ^(131)I-anti EGFR-BSA-PCL. The animals injected with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL showed more uniform focused liposome distribution within the tumor area.CONCLUSION: This study demonstrated the potential beneficial application of ^(131)I-anti EGFR-BSA-PCL for treating colorectal cancer. ^(131)I-anti EGFR-BSA-PCL suppressed the development of xenografted colorectal cancer in nude mice, thereby providing a novel candidate for receptor-mediated targeted radiotherapy.
基金supported by the National Key Research and Development Program of China(2018 YFC2001900)the Beijing Nova Program(Z211100002121171)。
文摘BACKGROUND N-terminal pro-B-type natriuretic peptide(NT-proBNP)is often viewed as an indicator for heart failure.However,the prognostic association and the predictive utility of NT-proBNP for postoperative major adverse cardiovascular events(MACEs)and myocardial injury after noncardiac surgery(MINS)among older patients are unclear.METHODS In this study,we included 5033 patients aged 65 years or older who underwent noncardiac surgery with preoperative NT-proBNP recorded.Logistic regression was adopted to model the associations between preoperative NT-proBNP and the risk of MACEs and MINS.The receiver operating characteristic curve was used to determine the predictive value of NT-proBNP.RESULTS A total of 5033 patients were enrolled,63 patients(1.25%)and 525 patients(10.43%)had incident postoperative MACEs and MINS,respectively.Analysis of the receiver operating characteristic curve indicated that the cutoff values of ln(NT-proBNP)for MACEs and MINS were 5.16(174 pg/mL)and 5.30(200 pg/mL),respectively.Adding preoperative ln(NT-proBNP)to the Revised Cardiac Risk Index score and the Cardiac and Stroke Risk Model boosted the area under the receiver operating characteristic curves from 0.682 to 0.726 and 0.787 to 0.804,respectively.The inclusion of preoperative NT-proBNP in the prediction models significantly increased the reclassification and discrimination.CONCLUSIONS Increased preoperative NT-proBNP was associated with a higher risk of postoperative MACEs and MINS.The inclusion of NT-proBNP enhances the predictive ability of the preexisting models.
基金supported by the Natural Science Foundation of Hunan Province of China,No.2017JJ3273(to ZJX)。
文摘Microglial apoptosis is associated with neuroinflammation and no effective strategies are currently available to protect microglia against inflammation-induced apoptosis. Mouse microglial BV-2 cells(5 × 10^6) were incubated with 10 μg/mL lipopolysaccharides for 12 hours to mimic an inflammatory environment. Then the cells were co-cultured with mitochonic acid 5(MA-5) for another 12 hours. MA-5 improved the survival of lipopolysaccharide-exposed cells. MA-5 decreased the activity of caspase-3, which is associated with apoptosis. MA-5 reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cells, and increased adenosine triphosphate levels in cells. MA-5 decreased the open state of the mitochondrial permeability transition pore and reduced calcium overload and diffusion of second mitochondria-derived activator of caspase(Smac). MA-5 decreased the expression of apoptosis-related proteins(mitochondrial Smac, cytoplasmic Smac, pro-caspase-3, cleaved-caspase-3, and caspase-9), and increased the levels of anti-apoptotic proteins(Bcl2 and X-linked inhibitor of apoptosis protein), mitochondria-related proteins(mitochondrial fusion protein 2, mitochondrial microtubule-associated proteins 1 A/1 B light chain 3 B II), and autophagy-related proteins(Beclin1, p62 and autophagy related 5). However, MA-5 did not promote mitochondrial homeostasis or decrease microglial apoptosis when Mitofusin 2 expression was silenced. This shows that MA-5 increased Mitofusin 2-related mitophagy, reversed cellular energy production and maintained energy metabolism in BV-2 cells in response to lipopolysaccharide-induced inflammation. These findings indicate that MA-5 may promote the survival of microglial cells via Mitofusin 2-related mitophagy in response to lipopolysaccharide-induced inflammation.
文摘<div style="text-align:justify;"> A test method and system for AI industrial application capabilities of smart terminals. The method includes the following steps: According to the temperature change values of different AI industrial applications executed by standard smart terminal equipment under different equipment parameters, the equipment parameters and temperature changes of standard smart terminal equipment are constructed. Correlation model;obtain the device parameters of the smart terminal device to be tested, and obtain the predicted value of the temperature change of the smart terminal device to be tested based on the correlation model between the device parameters of the standard smart terminal device and the temperature change;Measure the actual value of the temperature change of the intelligent terminal device executing different AI industrial applications;obtain the test result of the intelligent terminal device to be tested according to the predicted value of the temperature change and the actual value of the temperature change. </div>
基金the National Key R&D Program of China(No.2018YFD0901301),the Shandong Province’s Agricultural Seed Improvement Project(No.2017LZN011)the Central Public-interest Scientific Institution Basal Research Fund,CAFS(No.20603022020003)+3 种基金the China Agriculture Research System(CARS-48)the Projects of International Exchange and Cooperation in Agriculture of Ministry of Agriculture and Rural Affairs of China–Science,Technology and Innovation Cooperation Cooperation in Aquaculture with Tropical Countriesthe Introduction of International Advanced Agricultural Science and Technology Plan of China(No.2016-X39)the Major Applied Technology Innovation Project of Agriculture in Shandong Province(No.SD2019YY001).
文摘Heritability estimates may be severely biased when a large common environmental effect on a family arises from a longlasting separate rearing at early stages(SRES)in traditional selective breeding programs,especially when bred populations have weak genetic ties.Communal rearing at early stages(CRES)may reduce common environmental effect since all families are reared in the same environment immediately after hatching.Here,we compared the effects of CRES and SRES strategies on genetic parameter estimation for harvest body weight in a selective breeding population of Litopenaeus vannamei with a small number of half-sib families.Genetic parameters of each strategy were estimated by using animal models excluding and including the common environmental effect(Model 1 and Model 2,respectively).Heritability estimates for body weight were 0.21±0.06(P<0.05)and 0.69±0.09(P<0.05)for CRES and SRES,respectively,in Model 1,and 0.21±0.06(P<0.05)and 0.52±0.27(P>0.05)in Model 2.The ratio of common environmental variance to phenotypic variance was 0.002±0.000 and 0.071±0.112 for CRES and SRES,respectively.Neither strategy precisely partitioned the common environmental variance according to likelihood ratio test.Lower heritability for body weight in CRES than in SRES implied that a large common environmental variance was confounded with additive genetic variance and was not effectively partitioned in SRES.Moreover,genetic correlation of body weight between the two strategies was 0.75±0.15,indicating that family rankings truly changed.The CRES should be followed in the selective breeding program of shrimp,especially in a population with a shallow pedigree and weak genetic ties between families.
文摘<div style="text-align:justify;"> In distributed AI system, the models trained on data from potentially unreliable sources can be attacked by manipulating the training data distribution by inserting carefully crafted samples into the training set, which is known as Data Poisoning. Poisoning will to change the model behavior and reduce model performance. This paper proposes an algorithm that gives an improvement of both efficiency and security for data poisoning in a distributed AI system. The past methods of active defense often have a large number of invalid checks, which slows down the operation efficiency of the whole system. While passive defense also has problems of missing data and slow detection of error source. The proposed algorithm establishes the suspect hypothesis level to test and extend the verification of data packets and estimates the risk of terminal data. It can enhance the health degree of a distributed AI system by preventing the occurrence of poisoning attack and ensuring the efficiency and safety of the system operation. </div>
基金This research was supported by grants from the National Key Research and Development Program of China(2023YFC2505900,2016YFC1302303)the National Natural Science Foundation of China(nos.81972657 and 81830085).
文摘Without intervention,a considerable proportion of patients with metabolism‐associated fatty liver disease(MAFLD)will progress from simple steatosis to metabolism‐associated steatohepatitis(MASH),liver fibrosis,and even hepatocellular carcinoma.However,the molecular mechanisms that control progressive MAFLD have yet to be fully determined.Here,we unraveled that the expression of the N6-methyladenosine(m6A)methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD,whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation,liver injury,and fibrosis.Conversely,hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet(HFD).Notably,in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner,which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1^(+)Ccr2^(+)monocyte-derived macrophages(Mo-macs).In detail,Cx3cr1^(+)Ccr2^(+)Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells(HSCs)to promote liver fibrosis.Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1^(+)Ccr2^(+)Mo-macs.Restoration of METTL14 or GLS2,or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis.Taken together,these findings indicate potential therapies for the treatment of MAFLD progression.
基金Supported by National Natural Science Foundation of China (Grant No. 11901309)Natural Science Foundation of Jiangsu Province of China (Grant No. BK20180734)+1 种基金Natural Science Research of Jiangsu Higher Education Institutions of China (Grant No. 18KJB110022)Natural Science Foundation of Nanjing University of Posts and Telecommunications (Grant Nos. NY222168, NY219114)。
文摘In this paper, we give a complete real-variable theory of local variable Hardy spaces.First, we present various real-variable characterization in terms of several local maximal functions.Next, the new atomic and the finite atomic decomposition for the local variable Hardy spaces are established. As an application, we also introduce the local variable Campanato space which is showed to be the dual space of the local variable Hardy spaces. Analogous to the homogeneous case, some equivalent definitions of the dual of local variable Hardy spaces are also considered. Finally, we show the boundedness of inhomogeneous Calderon–Zygmund singular integrals and local fractional integrals on local variable Hardy spaces and their duals.
基金supported by the National Natural Science Foundation of China[grant number 82102955]the Guangzhou Basic Research Project[grant number 202201011326].
文摘Introduction Surgery remains the mainstay treatment for localized esophageal squamous cell carcinoma(ESCC).In recent years,three-incision McKeown esophagectomy has been widely applied for operable ESCC considering its superiority in acquiring extensive lymphadenectomy and long-termsurvival[1].Cervical anastomotic fistula is one of the most dreaded complications in patients undergoing three-incision esophagectomy;it occurs in almost 10%–25%of patients and is responsible for almost 40%of post-operative deaths[2,3].Most surgeons prefer conservative approaches including perianastomotic drainage,total parenteral nutrition,nasogastric decompression,and the use of broad-spectrum antibiotics for cervical anastomotic fistula[4,5].However,the recovery period under this method is commonly long and unsatisfactory.Until now,the optimal treatment for cervical anastomotic fistula has not yet been established.In this study,we describe a flushingdrainage system under negative pressure conditions to treat cervical anastomotic fistula,named anastomotic vacuum-assisted closure(AVAC).
基金Sponsored by Natural Science Foundation of CQ CSTC of China(cstc2012jj A70001)
文摘The vertical motion control of the roll was studied in order to improve the accuracy in simulation of variable gauge rolling. The discretization was carried out in the transition zone of TRB according to the principle of volume invariance. Based on this assumption, the formula for time step of vertical motion of rolls was proposed and the time-displacement curve of the verti- cal motion of rolls was established. In the preliminary simulation, the time-displacement curve was used as an initial method to control the vertical motion of rolls. Based on the simulation result, the formula for vertical velocity of roll in variable gauge rolling was derived from the common rolling principle. According to the formula, reasonable vertical velocity of rolls in the subsequent simulation was determined. It can accurately control the motion of rolls along the vertical direction. The desired thickness and out- line profile of transition zone were acquired and the formula proved effective by the simulation. Further analysis shows that the di fference of thickness in the thick zone and the thin zone of TRB, length of the transition zone of TRB, radius of work rolls and rota- tion speed of rolls have a significant effect on the vertical velocity of rolls.
基金supported in part by the National Natural Science Foundationof China(Grant Nos.11926343,11926342,11761026)the Natural Science Foundation of Guangxi Province(Grant No.2020GXNSFAA159085)the Open Project of Anhui University(Grant No.KF2019B02).
文摘We prove the boundedness for a class of multi-sublinear singular integral operators on the product of central Morrey spaces with variable exponents.Based on this result,we obtain the boundedness for the multilinear singular integral operators and two kinds of multilinear singular integral commutators on the above spaces.