The paper proposes a three-scale binary medium-based constitutive model on the basis of the meso structures and micro components to describe the elasto-plastic mechanical behavior of mudstone samples.Based on the brea...The paper proposes a three-scale binary medium-based constitutive model on the basis of the meso structures and micro components to describe the elasto-plastic mechanical behavior of mudstone samples.Based on the breakage mechanism of geomaterials,mudstone samples are considered as two different materials(bonded and frictional elements)at mesoscales.From micro to meso scales,given the similar but different mineralogy composition and porosity of the bonded and frictional elements at microscale,as well as their separate mechanical characteristics,different homogenization methods are adopted to obtain their respective meso mechanical properties.At the mesoscale,in view of the unique meso structures and the continuous material transformation,the extended self-consistent scheme(SCS)is improved to be adaptable to elasto-plastic composites with varying meso components.With the consideration of the evolution form of the breakage ratio under the external loading being given based on the assumed strength distribution of the meso bonded elements,the mechanical relations between meso and macro scales are established.Finally,on the basis of the mean-field method and combined with the critical mechanical connections between different scales,the micro-meso-macro constitutive model for mudstone samples are proposed.The model validation shows that,with a few model parameters,the proposed model can well reflect the stress and deformation features of mudstone samples with complex micro-components.展开更多
AIM: To investigate the health related quality of life (HRQoL) and psychological outcome of donors after living donor liver transplantation. METHODS: Participants were 92 consecutive liver transplant donors who underw...AIM: To investigate the health related quality of life (HRQoL) and psychological outcome of donors after living donor liver transplantation. METHODS: Participants were 92 consecutive liver transplant donors who underwent hepatectomy with- out middle hepatic vein at West China Hospital of Sichuan University between January 2007 and Sep- tember 2010. HRQoL was measured using the Chinese version of the Medical Outcomes Study Short Form-36 (SF-36), and psychological symptoms were measured using the Symptom Checklist-90-Revised (SCL-90-R). Data collected from donors were compared to previ- ously published data from the general population. Clin- ical and demographic data were collected from medical records and questionnaires.RESULTS: The general health score of the SF-36 was significantly lower in females (59.78 ± 12.25) than in males (75.83 ± 22.09). Donors more than 40 years old scored higher in social functioning (85.71 ± 14.59) and mental health (82.61 ± 20.00) than those younger than 40 (75.00 ± 12.13, 68.89 ± 12.98; social func- tioning and mental health, respectively). Donors who had surgery more than two years prior to the study scored highest in physical functioning (P = 0.001) and bodily pain (P = 0.042) while those less than one year from surgery scored lowest. The health of the liver recipient significantly influenced the general health (P = 0.042), social functioning (P = 0.010), and role- emotional (P = 0.028) of donors. Donors with full-time employment scored highest in role-physical (P = 0.005), vitality (P = 0.001), social functioning (P = 0.016), mental health (P < 0.001), the physical component summary scale (P < 0.001), and the mental compo- nent summary scale (MCS) (P < 0.001). Psychological measures indicated that donors were healthier than the general population in obsessive-compulsive behav- ior, interpersonal sensitivity, phobic anxiety, and para- noid ideation. The MCS of the SF-36 was significantly correlated with most symptom scores of the SCL-90-R. CONCLUSION: HRQoL and psychological outcome were favorable in living liver transplant donors after donation. Specifically, gender, age, time since opera- tion, recipient health condition, and employment after donation, influenced postoperative quality of life.展开更多
Tropical cyclones(TCs)in the South China Sea(SCS)cause serious disasters and loss every year to the coastal and inland areas of southern China.The types of TCs are usually difficult to forecast,and studies on the unde...Tropical cyclones(TCs)in the South China Sea(SCS)cause serious disasters and loss every year to the coastal and inland areas of southern China.The types of TCs are usually difficult to forecast,and studies on the understanding of the TCs affecting the SCS are lacking.In this study,the authors use the TC data during 1965–2017 from two best-track datasets to analyse the climatic characteristics in terms of the frequency,the track activity,and the influencing indexes of the TCs affecting the SCS and investigate the possible causes.The results show that,during 1965–2017,there were 535 TCs affecting the SCS,mainly occurring from June to November of each year,with the annual average frequency exhibiting a significant downward trend.Meanwhile,the frequency of the track activity in most areas of the SCS also demonstrate a remarkable decreasing trend but an increase in the Gulf of Tonkin and the Taiwan Strait.The large-scale environmental anomalous westerlies and the decrease of humidity in the mid-and low-level over the northern part of the SCS are likely the main causes for the decrease in frequency and the track activity.In addition,the analysis using the cyclone activity index shows that the influence of the before mentioned TCs in southern China gradually decreases,while the influence of TCs in the SCS show a decreasing trend during past decades.展开更多
We present a new digital phase lock technology to achieve the frequency control and transformation through high precision multi-cycle group synchronization between signals without the frequency transformation circuit....We present a new digital phase lock technology to achieve the frequency control and transformation through high precision multi-cycle group synchronization between signals without the frequency transformation circuit. In the case of digital sampling, the passing zero point of the phase of the controlled signal has the phase step characteristic, the phase step of the passing zero point is monotonic continuous with high resolution in the phase lock process, and using the border effect of digital fuzzy area, the gate can synchronize with the two signals, the quantization error is reduced. This technique is quite different from the existing methods of frequency transformation and frequency synthesis, the phase change characteristic between the periodic signals with different nominal is used. The phase change has the periodic phenomenon, and it has the high resolution step value. With the application of the physical law, the noise is reduced because of simplifying frequency transformation circuits, and the phase is locked with high precision. The regular phase change between frequency signals is only used for frequency measurement, and the change has evident randomness, but this randomness is greatly reduced in frequency control, and the certainty of the process result is clear. The experiment shows that the short term frequency stability can reach 10-12/s orders of magnitude.展开更多
Natural killer(NK)cells act as a first line of defense in innate immune system against new malignant transformed cells without prior exposure to tumor antigens.The activity of NK cells is tightly controlled by a balan...Natural killer(NK)cells act as a first line of defense in innate immune system against new malignant transformed cells without prior exposure to tumor antigens.The activity of NK cells is tightly controlled by a balance between inhibitory receptors and activating receptors,and when activation signals outweigh inhibitory signals,NK cells can mediate a response to eliminate the targeted cells.As a bridge between the innate and adaptive immune responses to enhance destruction of tumors,NK cells kill their tumor targets through a variety of mechanisms,including receptor-mediated cytotoxicity,antibody-dependent cell-mediated cytotoxicity(ADCC),death receptor Fas/FasL signaling pathway-mediated cancer apoptosis.However,the efficacy of using NK cells for tumor immunotherapy has been limited by a lack of antigen specificity.To overcome this limitation,Vallera and colleagues developed a bispecific killer cell engager(BiKE),which is comprised of a first ScFv that recognizes a tumor antigen and a second ScFv against CD16(expressed on NK cells)to trigger ADCC.To overcome the poor expansion of NK cells in vivo,a novel trispecific killer cell engager(TriKE)was evolved from the BiKE by the same team.In this molecule,IL-15 was integrated to promote NK cell expansion,thereby eliciting superior NK cytotoxicity and NK cell persistence in vivo compared to BiKE.In order to simultaneously target drug-refractory cancer stem cells(CSC)and cancer cells,a novel tetraspecific killer engager(TetraKE)comprising anti-CD133,EpCAM,CD16 ScFvs and a sustaining IL-15 signal cross-linker was recently developed.Compared to BiKE or TriKE,TetraKE1615EpCAM133 was highly specific against EpCAM-and CD133-bearing cells,leading to enhanced NK cell proliferation,prolonged survival and a limited cytokine response.This TetraKE represents a promising new modality for immunotherapy.展开更多
Objective:To explore the emotional impact of psychological nursing intervention on patients with malignant tumor radiotherapy,and further verify the specific application value of this nursing model in the oncology dep...Objective:To explore the emotional impact of psychological nursing intervention on patients with malignant tumor radiotherapy,and further verify the specific application value of this nursing model in the oncology department.Methods:A total of 129 patients with tumor radiotherapy admitted to our hospital from June 2018 to June 2021 were selected as subjects,and they were divided into control group and observation group by random number method.Among them,64 cases in the control group received routine clinical nursing.65 cases in the observation group received psychological nursing intervention.Then,the clinical nursing effect,self-rating anxiety scale(SAS)score,self-rating depression scale(SDS)score,immune function level change condition and clinical nursing satisfaction were compared under the two nursing modes,in order to fully verify the clinical application value of psychological nursing intervention mode for patients with cancer radiotherapy.Results:Comparing the clinical indexes of the two groups,SDS and SAS scores of the observation group were significantly lower than those of the control group.In terms of nursing satisfaction,the observation group is 96.92%and the control group is 90.62%,the difference was significant,and had clinical statistical significance(P<0.05);After the comprehensive evaluation of the immune function of the two groups,it was found that the observation group was significantly better than the control group,and the difference between the two groups was statistically significant(P<0.05).Conclusion:In the mode of psychological nursing,medical staff can carry out precise psychological nursing intervention and nutritional nursing for patients according to the specific conditions and treatment process of patients,which can greatly promote the psychological stability of patients,significantly reduce patients5 negative emotions.In addition,the scientific implementation of psychological nursing intervention in the treatment of tumor radiotherapy patients can effectively strengthen the improvement of the immune function of patients,which has a very important application value to improve the physical function of patients,promotes the patienfs body rehabilitation,and is worth in the field of widespread application.展开更多
Background:Bladder cancer is a highly prevalent and lethal malignant tumor characterized by frequent mutations/deletions of lysine-specific demethylase 6A(KDM6A),which is suggested to be a key event in cancer progress...Background:Bladder cancer is a highly prevalent and lethal malignant tumor characterized by frequent mutations/deletions of lysine-specific demethylase 6A(KDM6A),which is suggested to be a key event in cancer progression and metastasis.Beta-elemene has been shown to inhibit metastasis and growth of various tumors,but its effect on KDM6A-null bladder cancer cells remains unknown.Objective:This study aimed to investigate the potential and molecular mechanism ofβ-elemene in inhibiting the growth of KDM6A-null bladder cancer.Methods:This study examined the migration ability and viability of RT-4(KDM6A wild-type)and KU19-19(KDM6A-null)cell lines using wound healing assay and CCK-8,respectively.The inhibitory effect ofβ-elemene on KU19-19 cell migration was evaluated using transwell and immunofluorescence assays,and the expression of transfer-related proteins and genes was analyzed through western blot and qRT-PCR,respectively.Molecular docking was performed to predict the targeting ofβ-elemene,and the effects were confirmed in KDM6Aknockdown RT-4 cells.Finally,the therapeutic effect ofβ-elemene on bladder cancer was tested in animal models.Results:The study observed that loss of KDM6A increased bladder cancer cell migration,with KU19-19 exhibiting significantly stronger migration than RT-4.Further investigation revealed thatβ-elemene effectively inhibited KU19-19 cell migration,likely through targeting EZH2 as determined by molecular docking.Overexpression of KDM6A inhibited KU19-19 metastasis,while knockdown of KDM6A in RT-4 cells enhanced cell migration,which was reversed byβ-elemene treatment.Notably,in vivo testing revealed a significant suppression of KU19-19 cell growth withβ-elemene administered at a dosage of 100 mg/kg.Conclusion:β-elemene has the potential to suppress the growth of KDM6A-null bladder cancer by inhibiting epithelial-mesenchymal transition(EMT),which could make it a promising therapeutic option for patients with KDM6A-null bladder cancer.展开更多
Hirschsprung's disease(HsCR)is the most common type of developmental gastrointestinal malformation causing intestinal obstruction in children,with an incidence of 1/5000 in live births.1 it is characterized by the...Hirschsprung's disease(HsCR)is the most common type of developmental gastrointestinal malformation causing intestinal obstruction in children,with an incidence of 1/5000 in live births.1 it is characterized by the absence of intrinsic ganglion cells in the myenteric and submucosal plexuses of the distal gastrointestinal tract,leading to the dysregulation of smooth muscle contraction/relaxation and resulting in intestinal obstruction.Depending on the length of the aganglionic intestine,HSCR can be categorized into short-segmental HSCR(S-HSCR),which affects up to the sigmoid colon from the anus,and long-segmental HSCR(LHSCR),which affects beyond the sigmoid colon.1 In some rare conditions,aganglionic lesions can affect the full length of the colon or even the whole intestine.展开更多
Mounting evidence has revealed that the therapeutic efficacy of immunotherapies is restricted to a small portion of cancer patients.A deeper understanding of how metabolic reprogramming in the tumor microenvironment(T...Mounting evidence has revealed that the therapeutic efficacy of immunotherapies is restricted to a small portion of cancer patients.A deeper understanding of how metabolic reprogramming in the tumor microenvironment(TME)regulates immunity remains a major challenge to tumor eradication.It has been suggested that metabolic reprogramming in the TME may affect metabolism in immune cells and subsequently suppress immune function.Tumor cells compete with infiltrating immune cells for nutrients and metabolites.Notably,the immunosuppressive TME is characterized by catabolic and anabolic processes that are critical for immune cell function,and elevated inhibitory signals may favor cancer immune evasion.The major energy sources that supply different immune cell subtypes also undergo reprogramming.We herein summarize the metabolic remodeling in tumor cells and different immune cell subtypes and the latest advances underlying the use of metabolic checkpoints in antitumor immunotherapies.In this context,targeting both tumor and immune cell metabolic reprogramming may enhance therapeutic efficacy.展开更多
The structure of side chains ofπ-conjugated segments is a critical factor determining living crystallization-driven self-assembly(CDSA),a versatile platform to generate fiber-like nanostructures with precise length a...The structure of side chains ofπ-conjugated segments is a critical factor determining living crystallization-driven self-assembly(CDSA),a versatile platform to generate fiber-like nanostructures with precise length and composition.Herein,we design and synthesize three block copolymers(BCPs)containing same corona-forming poly(N-isopropyl acrylamide)(PNIPAM)segment,but different core-formingπ-conjugated oligo(p-phenylene vinylene)(OPV)with linear pentyl(l-OPV),racemic 2-methyl butyl(r-OPV)and stereo-regular chiral(S)-2-methyl butyl(c-OPV)side chains,respectively.By using these BCPs of l-OPV-b-PNIPAM_(47),r-OPV-b-PNIPAM_(47)and c-OPV-b-PNIPAM_(47)as model,we aim to get a deep insight into how steric and stereo-regular effect induced by branched alkyl side chains of OPV segment affects the living CDSA.The results showed that l-OPV-b-PNIPAM_(47)exhibits typical characteristics of self-seeding and seeded growth of living CDSA to give uniform fiber-like micelles of controlled length.On the contrary,r-OPV-b-PNIPAM_(47)and c-OPV-b-PNIPAM_(47)with branched racemic and stereo-regular chiral alkyl side chains are more prone to self-nucleation during the micellar elongation to give short and polydisperse fiber-like micelles.The obvious selfnucleation during the micellar elongation of r-OPV-b-PNIPAM_(47)and c-OPV-b-PNIPAM_(47)is due to the increase of steric repulsion with OPV units induced by branched alkyl side chains,not the stereo-irregular effect of racemic alkyl side chains.展开更多
Introduction:Hepatoblastoma(HB)is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected patients.The precise molecular mechanisms responsi...Introduction:Hepatoblastoma(HB)is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected patients.The precise molecular mechanisms responsible for HB metastasis remain incom-pletely understood.However,there is evidence suggesting a connection between the dysregulation of microRNAs(miRNAs)and the progression of tumor metastasis in HB.Methods:The study utilized weighted gene co-expression network analysis(WGCNA)to analyze a miRNA microarray dataset of HB.The expression of miR-181b-5p in HB tissues and cells was detected using quantitative real-time PCR.The impact of miR-181b-5p on the metastatic capacity of HB was evaluated through scratch and Transwell assays.The effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated in vivo.Furthermore,a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in HB.Results:We found that miR-181b-5p was highly expressed in HB tissues and HB cell lines.Overexpression of miR-181b enhanced scratch healing,cell migration,and invasion abilities in vitro,as well as enhancing HB lung metastasis potential in vivo.Dual-luciferase reporter assays showed that Suppressor Of Cytokine Signaling 2(SOCS2)was a direct target of miR-181b.The overexpression of miR-181b resulted in the suppression of SOCS2 expression,subsequently activating the epithelial-mesenchymal transition and JAK2/STAT5 signaling pathways.The rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB cells.Conclusion:Our study showed that miR-181b promotes HB metastasis by targeting SOCS2 and may be a potential therapeutic target for HB.展开更多
The current study was designed to explore how disruption of specific molecular circuits in the cerebral cortex may cause sensorimotor cortico-striatal community structure deficits in both a mouse model and patients wi...The current study was designed to explore how disruption of specific molecular circuits in the cerebral cortex may cause sensorimotor cortico-striatal community structure deficits in both a mouse model and patients with schizophrenia.We used prepulse inhibition(PPI)and brain structural and diffusion MRI scans in 23 mice with conditional ErbB4 knockout in parvalbumin interneurons and 27 matched controls.Quantitative real-time PCR was used to assess the differential levels of GABA-related transcripts in brain regions.Concurrently,we measured structural and diffusion MRI and the cumulative contribution of risk alleles in the GABA pathway genes in firstepisode treatment-naı¨ve schizophrenic patients(n=117)and in age-and sex-matched healthy controls(n=86).We present the first evidence of gray and white matter impairment of right sensorimotor cortico-striatal networks and reproduced the sensorimotor gating deficit in a mouse model of schizophrenia.Significant correlations between gray matter volumes(GMVs)in the somatosensory cortex and PPI as well as glutamate decarboxylase 1 mRNA expression were found in controls but not in knockout mice.Furthermore,these findings were confirmed in a human sample in which we found significantly decreased gray and white matter in sensorimotor cortico-striatal networks in schizophrenic patients.The psychiatric risk alleles of the GABA pathway also displayed a significant negative correlation with the GMVs of the somatosensory cortex in patients.Our study identified that ErbB4 ablation in parvalbumin interneurons induced GABAergic dysregulation,providing valuable mechanistic insights into the sensorimotor cortico-striatal community structure deficits associated with schizophrenia.展开更多
The National Central Cancer Registry of China (NCCRC) up- dated their nationwide statistics of cancer incidence and mor- tality in China according to 2013 population-based cancer registration data (due to the time ...The National Central Cancer Registry of China (NCCRC) up- dated their nationwide statistics of cancer incidence and mor- tality in China according to 2013 population-based cancer registration data (due to the time required for data collection, quality control and analysis, the latest cancer statistics avail- able in China have a 3-year lag behind the current year).展开更多
基金the funding of Highway Planning,Survey and Design Research Institute,Sichuan Provincial Transport Department(No.2020-WX-15)the National Natural Science Foundation of China(NSFC)(No.U22A20596).
文摘The paper proposes a three-scale binary medium-based constitutive model on the basis of the meso structures and micro components to describe the elasto-plastic mechanical behavior of mudstone samples.Based on the breakage mechanism of geomaterials,mudstone samples are considered as two different materials(bonded and frictional elements)at mesoscales.From micro to meso scales,given the similar but different mineralogy composition and porosity of the bonded and frictional elements at microscale,as well as their separate mechanical characteristics,different homogenization methods are adopted to obtain their respective meso mechanical properties.At the mesoscale,in view of the unique meso structures and the continuous material transformation,the extended self-consistent scheme(SCS)is improved to be adaptable to elasto-plastic composites with varying meso components.With the consideration of the evolution form of the breakage ratio under the external loading being given based on the assumed strength distribution of the meso bonded elements,the mechanical relations between meso and macro scales are established.Finally,on the basis of the mean-field method and combined with the critical mechanical connections between different scales,the micro-meso-macro constitutive model for mudstone samples are proposed.The model validation shows that,with a few model parameters,the proposed model can well reflect the stress and deformation features of mudstone samples with complex micro-components.
基金Supported by National Science and Technology Key Projects,No.2008ZX10002-026
文摘AIM: To investigate the health related quality of life (HRQoL) and psychological outcome of donors after living donor liver transplantation. METHODS: Participants were 92 consecutive liver transplant donors who underwent hepatectomy with- out middle hepatic vein at West China Hospital of Sichuan University between January 2007 and Sep- tember 2010. HRQoL was measured using the Chinese version of the Medical Outcomes Study Short Form-36 (SF-36), and psychological symptoms were measured using the Symptom Checklist-90-Revised (SCL-90-R). Data collected from donors were compared to previ- ously published data from the general population. Clin- ical and demographic data were collected from medical records and questionnaires.RESULTS: The general health score of the SF-36 was significantly lower in females (59.78 ± 12.25) than in males (75.83 ± 22.09). Donors more than 40 years old scored higher in social functioning (85.71 ± 14.59) and mental health (82.61 ± 20.00) than those younger than 40 (75.00 ± 12.13, 68.89 ± 12.98; social func- tioning and mental health, respectively). Donors who had surgery more than two years prior to the study scored highest in physical functioning (P = 0.001) and bodily pain (P = 0.042) while those less than one year from surgery scored lowest. The health of the liver recipient significantly influenced the general health (P = 0.042), social functioning (P = 0.010), and role- emotional (P = 0.028) of donors. Donors with full-time employment scored highest in role-physical (P = 0.005), vitality (P = 0.001), social functioning (P = 0.016), mental health (P < 0.001), the physical component summary scale (P < 0.001), and the mental compo- nent summary scale (MCS) (P < 0.001). Psychological measures indicated that donors were healthier than the general population in obsessive-compulsive behav- ior, interpersonal sensitivity, phobic anxiety, and para- noid ideation. The MCS of the SF-36 was significantly correlated with most symptom scores of the SCL-90-R. CONCLUSION: HRQoL and psychological outcome were favorable in living liver transplant donors after donation. Specifically, gender, age, time since opera- tion, recipient health condition, and employment after donation, influenced postoperative quality of life.
基金This work was jointly supported by General Project of Technological Innovation and Application Demonstration of Chongqing Municipality[cstc2018jscx-msybX0165]Special Project for Development of Key Technology for Meteorological Forecast Service of China Meteorological Administration[YBGJXM(2018)04-08]+1 种基金National Natural Science Foundation of China[41875111]Innovation Team Project of Intelligent Meteorological Technology of Chongqing Meteorological Bureau[ZHCXTD-201804].
文摘Tropical cyclones(TCs)in the South China Sea(SCS)cause serious disasters and loss every year to the coastal and inland areas of southern China.The types of TCs are usually difficult to forecast,and studies on the understanding of the TCs affecting the SCS are lacking.In this study,the authors use the TC data during 1965–2017 from two best-track datasets to analyse the climatic characteristics in terms of the frequency,the track activity,and the influencing indexes of the TCs affecting the SCS and investigate the possible causes.The results show that,during 1965–2017,there were 535 TCs affecting the SCS,mainly occurring from June to November of each year,with the annual average frequency exhibiting a significant downward trend.Meanwhile,the frequency of the track activity in most areas of the SCS also demonstrate a remarkable decreasing trend but an increase in the Gulf of Tonkin and the Taiwan Strait.The large-scale environmental anomalous westerlies and the decrease of humidity in the mid-and low-level over the northern part of the SCS are likely the main causes for the decrease in frequency and the track activity.In addition,the analysis using the cyclone activity index shows that the influence of the before mentioned TCs in southern China gradually decreases,while the influence of TCs in the SCS show a decreasing trend during past decades.
基金Supported by the National Natural Science Foundation of China under Grant No 11173026the International GNSS Monitoring and Assessment System(iGMAS)of National Time Service Centre
文摘We present a new digital phase lock technology to achieve the frequency control and transformation through high precision multi-cycle group synchronization between signals without the frequency transformation circuit. In the case of digital sampling, the passing zero point of the phase of the controlled signal has the phase step characteristic, the phase step of the passing zero point is monotonic continuous with high resolution in the phase lock process, and using the border effect of digital fuzzy area, the gate can synchronize with the two signals, the quantization error is reduced. This technique is quite different from the existing methods of frequency transformation and frequency synthesis, the phase change characteristic between the periodic signals with different nominal is used. The phase change has the periodic phenomenon, and it has the high resolution step value. With the application of the physical law, the noise is reduced because of simplifying frequency transformation circuits, and the phase is locked with high precision. The regular phase change between frequency signals is only used for frequency measurement, and the change has evident randomness, but this randomness is greatly reduced in frequency control, and the certainty of the process result is clear. The experiment shows that the short term frequency stability can reach 10-12/s orders of magnitude.
文摘Natural killer(NK)cells act as a first line of defense in innate immune system against new malignant transformed cells without prior exposure to tumor antigens.The activity of NK cells is tightly controlled by a balance between inhibitory receptors and activating receptors,and when activation signals outweigh inhibitory signals,NK cells can mediate a response to eliminate the targeted cells.As a bridge between the innate and adaptive immune responses to enhance destruction of tumors,NK cells kill their tumor targets through a variety of mechanisms,including receptor-mediated cytotoxicity,antibody-dependent cell-mediated cytotoxicity(ADCC),death receptor Fas/FasL signaling pathway-mediated cancer apoptosis.However,the efficacy of using NK cells for tumor immunotherapy has been limited by a lack of antigen specificity.To overcome this limitation,Vallera and colleagues developed a bispecific killer cell engager(BiKE),which is comprised of a first ScFv that recognizes a tumor antigen and a second ScFv against CD16(expressed on NK cells)to trigger ADCC.To overcome the poor expansion of NK cells in vivo,a novel trispecific killer cell engager(TriKE)was evolved from the BiKE by the same team.In this molecule,IL-15 was integrated to promote NK cell expansion,thereby eliciting superior NK cytotoxicity and NK cell persistence in vivo compared to BiKE.In order to simultaneously target drug-refractory cancer stem cells(CSC)and cancer cells,a novel tetraspecific killer engager(TetraKE)comprising anti-CD133,EpCAM,CD16 ScFvs and a sustaining IL-15 signal cross-linker was recently developed.Compared to BiKE or TriKE,TetraKE1615EpCAM133 was highly specific against EpCAM-and CD133-bearing cells,leading to enhanced NK cell proliferation,prolonged survival and a limited cytokine response.This TetraKE represents a promising new modality for immunotherapy.
文摘Objective:To explore the emotional impact of psychological nursing intervention on patients with malignant tumor radiotherapy,and further verify the specific application value of this nursing model in the oncology department.Methods:A total of 129 patients with tumor radiotherapy admitted to our hospital from June 2018 to June 2021 were selected as subjects,and they were divided into control group and observation group by random number method.Among them,64 cases in the control group received routine clinical nursing.65 cases in the observation group received psychological nursing intervention.Then,the clinical nursing effect,self-rating anxiety scale(SAS)score,self-rating depression scale(SDS)score,immune function level change condition and clinical nursing satisfaction were compared under the two nursing modes,in order to fully verify the clinical application value of psychological nursing intervention mode for patients with cancer radiotherapy.Results:Comparing the clinical indexes of the two groups,SDS and SAS scores of the observation group were significantly lower than those of the control group.In terms of nursing satisfaction,the observation group is 96.92%and the control group is 90.62%,the difference was significant,and had clinical statistical significance(P<0.05);After the comprehensive evaluation of the immune function of the two groups,it was found that the observation group was significantly better than the control group,and the difference between the two groups was statistically significant(P<0.05).Conclusion:In the mode of psychological nursing,medical staff can carry out precise psychological nursing intervention and nutritional nursing for patients according to the specific conditions and treatment process of patients,which can greatly promote the psychological stability of patients,significantly reduce patients5 negative emotions.In addition,the scientific implementation of psychological nursing intervention in the treatment of tumor radiotherapy patients can effectively strengthen the improvement of the immune function of patients,which has a very important application value to improve the physical function of patients,promotes the patienfs body rehabilitation,and is worth in the field of widespread application.
基金various sources,including Zhejiang Provincial Natural Science Foundation of China(grant No.LQ20H160013,LQ21H160038,and LY23H160026)the Science and Technology Development Fund,Macao SAR(File No.:0098/2021/A2).
文摘Background:Bladder cancer is a highly prevalent and lethal malignant tumor characterized by frequent mutations/deletions of lysine-specific demethylase 6A(KDM6A),which is suggested to be a key event in cancer progression and metastasis.Beta-elemene has been shown to inhibit metastasis and growth of various tumors,but its effect on KDM6A-null bladder cancer cells remains unknown.Objective:This study aimed to investigate the potential and molecular mechanism ofβ-elemene in inhibiting the growth of KDM6A-null bladder cancer.Methods:This study examined the migration ability and viability of RT-4(KDM6A wild-type)and KU19-19(KDM6A-null)cell lines using wound healing assay and CCK-8,respectively.The inhibitory effect ofβ-elemene on KU19-19 cell migration was evaluated using transwell and immunofluorescence assays,and the expression of transfer-related proteins and genes was analyzed through western blot and qRT-PCR,respectively.Molecular docking was performed to predict the targeting ofβ-elemene,and the effects were confirmed in KDM6Aknockdown RT-4 cells.Finally,the therapeutic effect ofβ-elemene on bladder cancer was tested in animal models.Results:The study observed that loss of KDM6A increased bladder cancer cell migration,with KU19-19 exhibiting significantly stronger migration than RT-4.Further investigation revealed thatβ-elemene effectively inhibited KU19-19 cell migration,likely through targeting EZH2 as determined by molecular docking.Overexpression of KDM6A inhibited KU19-19 metastasis,while knockdown of KDM6A in RT-4 cells enhanced cell migration,which was reversed byβ-elemene treatment.Notably,in vivo testing revealed a significant suppression of KU19-19 cell growth withβ-elemene administered at a dosage of 100 mg/kg.Conclusion:β-elemene has the potential to suppress the growth of KDM6A-null bladder cancer by inhibiting epithelial-mesenchymal transition(EMT),which could make it a promising therapeutic option for patients with KDM6A-null bladder cancer.
基金supported by the Scientific Research Starting Foundation for Introduced Talents,West China Hospital,Sichuan University,China(to Jing Chen)Natural Science Foundation of Sichuan Province,China(No.2022NSFSC1436 to Qi Wang and No.2022NSFSC1301 to Jing Chen)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,China(No.ZYJC18003 to Yi Liu and No.2021HXFH020 to Bo Xiang).
文摘Hirschsprung's disease(HsCR)is the most common type of developmental gastrointestinal malformation causing intestinal obstruction in children,with an incidence of 1/5000 in live births.1 it is characterized by the absence of intrinsic ganglion cells in the myenteric and submucosal plexuses of the distal gastrointestinal tract,leading to the dysregulation of smooth muscle contraction/relaxation and resulting in intestinal obstruction.Depending on the length of the aganglionic intestine,HSCR can be categorized into short-segmental HSCR(S-HSCR),which affects up to the sigmoid colon from the anus,and long-segmental HSCR(LHSCR),which affects beyond the sigmoid colon.1 In some rare conditions,aganglionic lesions can affect the full length of the colon or even the whole intestine.
基金supported by the National Natural Science Foundation of China(81903138,81972776,81803025,81772928,81702907,81772901,81672993,81672683)the Natural Science Foundation of Hunan Province(2019JJ50778,2018SK21210,2018SK21211,2018JJ3704,2018JJ3815)。
文摘Mounting evidence has revealed that the therapeutic efficacy of immunotherapies is restricted to a small portion of cancer patients.A deeper understanding of how metabolic reprogramming in the tumor microenvironment(TME)regulates immunity remains a major challenge to tumor eradication.It has been suggested that metabolic reprogramming in the TME may affect metabolism in immune cells and subsequently suppress immune function.Tumor cells compete with infiltrating immune cells for nutrients and metabolites.Notably,the immunosuppressive TME is characterized by catabolic and anabolic processes that are critical for immune cell function,and elevated inhibitory signals may favor cancer immune evasion.The major energy sources that supply different immune cell subtypes also undergo reprogramming.We herein summarize the metabolic remodeling in tumor cells and different immune cell subtypes and the latest advances underlying the use of metabolic checkpoints in antitumor immunotherapies.In this context,targeting both tumor and immune cell metabolic reprogramming may enhance therapeutic efficacy.
基金National Science Foundation for Distinguished Young Scholars(No.51825304)the National Natural Science Foundation of China(Nos.52122314,U22A20131,51873229 and 51961145103)+3 种基金the Youth Innovation Promotion Association of CAS(No.Y2020062)Shanghai Scientific and Technological Innovation Project(Nos.20JC1415400,21520780100,22JC1401000 and 22ZR1475400)Innovation Program of Shanghai Municipal Education Commission(No.2019-01-07-00-05-E00012)East China University of Science and Technology(No.SLD13223004).
文摘The structure of side chains ofπ-conjugated segments is a critical factor determining living crystallization-driven self-assembly(CDSA),a versatile platform to generate fiber-like nanostructures with precise length and composition.Herein,we design and synthesize three block copolymers(BCPs)containing same corona-forming poly(N-isopropyl acrylamide)(PNIPAM)segment,but different core-formingπ-conjugated oligo(p-phenylene vinylene)(OPV)with linear pentyl(l-OPV),racemic 2-methyl butyl(r-OPV)and stereo-regular chiral(S)-2-methyl butyl(c-OPV)side chains,respectively.By using these BCPs of l-OPV-b-PNIPAM_(47),r-OPV-b-PNIPAM_(47)and c-OPV-b-PNIPAM_(47)as model,we aim to get a deep insight into how steric and stereo-regular effect induced by branched alkyl side chains of OPV segment affects the living CDSA.The results showed that l-OPV-b-PNIPAM_(47)exhibits typical characteristics of self-seeding and seeded growth of living CDSA to give uniform fiber-like micelles of controlled length.On the contrary,r-OPV-b-PNIPAM_(47)and c-OPV-b-PNIPAM_(47)with branched racemic and stereo-regular chiral alkyl side chains are more prone to self-nucleation during the micellar elongation to give short and polydisperse fiber-like micelles.The obvious selfnucleation during the micellar elongation of r-OPV-b-PNIPAM_(47)and c-OPV-b-PNIPAM_(47)is due to the increase of steric repulsion with OPV units induced by branched alkyl side chains,not the stereo-irregular effect of racemic alkyl side chains.
基金supported by Scientific Research Starting Foundation for Introduced Talents(to Jing Chen)Sichuan Science and Technology Department(Grants No.2022NSFSC1301&2020YFS0108)+1 种基金1·3·5 project for disciplines of excellence,West China Hospital,Sichuan University(Grants No.ZYJC18003,2021HXFH020)Shandong Provincial Natural Science Foundation(Grant No.ZR2022MH229).
文摘Introduction:Hepatoblastoma(HB)is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected patients.The precise molecular mechanisms responsible for HB metastasis remain incom-pletely understood.However,there is evidence suggesting a connection between the dysregulation of microRNAs(miRNAs)and the progression of tumor metastasis in HB.Methods:The study utilized weighted gene co-expression network analysis(WGCNA)to analyze a miRNA microarray dataset of HB.The expression of miR-181b-5p in HB tissues and cells was detected using quantitative real-time PCR.The impact of miR-181b-5p on the metastatic capacity of HB was evaluated through scratch and Transwell assays.The effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated in vivo.Furthermore,a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in HB.Results:We found that miR-181b-5p was highly expressed in HB tissues and HB cell lines.Overexpression of miR-181b enhanced scratch healing,cell migration,and invasion abilities in vitro,as well as enhancing HB lung metastasis potential in vivo.Dual-luciferase reporter assays showed that Suppressor Of Cytokine Signaling 2(SOCS2)was a direct target of miR-181b.The overexpression of miR-181b resulted in the suppression of SOCS2 expression,subsequently activating the epithelial-mesenchymal transition and JAK2/STAT5 signaling pathways.The rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB cells.Conclusion:Our study showed that miR-181b promotes HB metastasis by targeting SOCS2 and may be a potential therapeutic target for HB.
基金supported by the National Natural Science Foundation of China(81630030,81130024,and 81528008)the National Natural Science Foundation of China/Research Grants Council of Hong Kong Joint Research Scheme(81461168029)+2 种基金the National Basic Research Development Program of China(2016YFC0904300)the Science and Technology Project of the Health Planning Committee of Sichuan(19PJ090)the National Natural Science Foundation of China for Distinguished Young Scholars(81501159).
文摘The current study was designed to explore how disruption of specific molecular circuits in the cerebral cortex may cause sensorimotor cortico-striatal community structure deficits in both a mouse model and patients with schizophrenia.We used prepulse inhibition(PPI)and brain structural and diffusion MRI scans in 23 mice with conditional ErbB4 knockout in parvalbumin interneurons and 27 matched controls.Quantitative real-time PCR was used to assess the differential levels of GABA-related transcripts in brain regions.Concurrently,we measured structural and diffusion MRI and the cumulative contribution of risk alleles in the GABA pathway genes in firstepisode treatment-naı¨ve schizophrenic patients(n=117)and in age-and sex-matched healthy controls(n=86).We present the first evidence of gray and white matter impairment of right sensorimotor cortico-striatal networks and reproduced the sensorimotor gating deficit in a mouse model of schizophrenia.Significant correlations between gray matter volumes(GMVs)in the somatosensory cortex and PPI as well as glutamate decarboxylase 1 mRNA expression were found in controls but not in knockout mice.Furthermore,these findings were confirmed in a human sample in which we found significantly decreased gray and white matter in sensorimotor cortico-striatal networks in schizophrenic patients.The psychiatric risk alleles of the GABA pathway also displayed a significant negative correlation with the GMVs of the somatosensory cortex in patients.Our study identified that ErbB4 ablation in parvalbumin interneurons induced GABAergic dysregulation,providing valuable mechanistic insights into the sensorimotor cortico-striatal community structure deficits associated with schizophrenia.
基金supported by the National Natural Science Foundation of China (813 72907, 81472531, 81472595, 81672683, 81672688, 81772928)the Natural Science Foundation ofHunan Province (2015JJ1022, 2016JC2035)the Fundamental Research Funds of the Central South University (2014zzts066)
文摘The National Central Cancer Registry of China (NCCRC) up- dated their nationwide statistics of cancer incidence and mor- tality in China according to 2013 population-based cancer registration data (due to the time required for data collection, quality control and analysis, the latest cancer statistics avail- able in China have a 3-year lag behind the current year).