Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive ...Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.展开更多
To simulate the rumor propagation process on online social network during emergency, a new rumor propagation model was built based on active immune mechanism. The rumor propagation mechanisms were analyzed and corresp...To simulate the rumor propagation process on online social network during emergency, a new rumor propagation model was built based on active immune mechanism. The rumor propagation mechanisms were analyzed and corresponding parameters were defined. BA scale free network and NW small world network that can be used for representing the online social network structure were constructed and their characteristics were compared. Agent-based simulations were conducted on both networks and results show that BA scale free network is more conductive to spreading rumors and it can facilitate the rumor refutation process at the same time. Rumors paid attention to by more people is likely to spread quicker and broader but for which the rumor refutation process will be more effective. The model provides a useful tool for understanding and predicting the rumor propagation process on online social network during emergency, providing useful instructions for rumor propagation intervention.展开更多
Oncological hyperthermia is one of the most versatile forms of oncotherapy. It can complement every conventional treatment method and be applied to any tumorous cancer, irrespective of its stages and localization. Num...Oncological hyperthermia is one of the most versatile forms of oncotherapy. It can complement every conventional treatment method and be applied to any tumorous cancer, irrespective of its stages and localization. Numerous technical realizations are conventionally compared by their thermal effect, measured by temperature. However, nonthermal (mainly electric) excitation effects are more recognized nowadays. The technical variants alter the synergy between thermal and nonthermal energy components. Nonthermal energy absorption-induced molecular mechanisms include essential behaviors like selectivity and immunogenicity. The nonthermal electromagnetic effects excite molecular changes, intracellular signals, gene expressions, and many other chemical reactions. Their synergy with thermal conditions is based on the Arrhenius law, which describes the rapid growth of chemical reactions with temperature. A unique technical realization of hyperthermia, modulated electrohyperthermia (mEHT) tries to optimize the thermal and nonthermal effects. The results look very perspective, containing the high accuracy of targeting the tumor cells, the immunogenic cell death, and the activation of tumor-specific immune reactions restoring the healthy immune surveillance to destroy the cancer.展开更多
Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted...Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors.Several genes have been implicated in the pathogenesis of ASD,most of them are involved in neuronal synaptogenesis.A number of environmental factors and associated conditions such as gastrointestinal(GI)abnormalities and immune imbalance have been linked to the pathophysiology of ASD.According to the March 2012 report released by United States Centers for Disease Control and Prevention,the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms.Although there is a strong genetic base for the disease,several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem.Many children suffering from ASD have GI problems such as abdominal pain,chronic diarrhea,constipation,vomiting,gastroesophageal reflux,and intestinal infections.A number of studies focusing on the intestinal mucosa,its permeability,abnormal gut development,leaky gut,and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas.GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children.Maternal infection or autoimmune diseases have been suspected.Activation of the immune system during early development may have deleterious effect on various organs including the nervous system.In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.展开更多
A marine bacterium, Pseudoalteromonas sp. BC228 was supplemented to feed in a feeding experiment aiming to determine its ability of enhancing the digestive enzyme activity and immune response of juvenile Apostichopus ...A marine bacterium, Pseudoalteromonas sp. BC228 was supplemented to feed in a feeding experiment aiming to determine its ability of enhancing the digestive enzyme activity and immune response of juvenile Apostichopus japonicus. Sea cucumber individuals were fed with the diets containing 0(control), 105, 107 and 109 CFU g-1 diet of BC228 for 45 days. Results showed that intestinal trypsin and lipase activities were significantly enhanced by 107 and 109 CFU g-1 diet of BC228 in comparison with control(P < 0.01). The phagocytic activity in the coelomocytes of sea cucumber fed the diet supplemented with 107 CFU g-1 diet of BC228 was significantly higher than that of those fed control diet(P < 0.05). In addition, 105 and 107 CFU g-1 diet of BC228 significantly enhanced lysozyme and phenoloxidase activities in the coelomic fluid of sea cucumber, respectively, in comparison with other diets(P < 0.01). Sea cucumbers, 10 each diet, were challenged with Vibrio splendidus NB13 after 45 days of feeding. It was found that the cumulative incidence and mortality of sea cucumber fed with BC228 containing diets were lower than those of animals fed control diet. Our findings evidenced that BC228 supplemented in diets improved the digestive enzyme activity of juvenile sea cucumber, stimulated its immune response and enhanced its resistance to the infection of V. splendidus.展开更多
The killing effects of lymphocytes on Hela cells expressing interleukin-12 (IL-12) in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression...The killing effects of lymphocytes on Hela cells expressing interleukin-12 (IL-12) in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression of IL-12 in Hela cells was detected quantitatively by ELISA; Changes in killing effects of lymphocytes on Hela cells expressing IL-12 were observed by MTT. It was found that Hela cells could express IL- 12 between 24 h and 72 h after transfection. Killing activity of lymphocytes on Hela cells expressing IL-12 was significantly enhanced. It was concluded by cell transfection technique, Hela cells could express 1L-12 and were more easily killed by lymphocytes.展开更多
Survival, growth and immune response of the scallop, Chlamys farreri, cultured in lantern nets at five different depths (2, 5, 10, 15, and 20 m below the sea surface) were studied in Haizhou Bay during the hot season ...Survival, growth and immune response of the scallop, Chlamys farreri, cultured in lantern nets at five different depths (2, 5, 10, 15, and 20 m below the sea surface) were studied in Haizhou Bay during the hot season (summer and autumn) of 2007. Survival and growth rates were quantified bimonthly. Immune activities in hemolymph (superoxide dismutase (SOD) and acid phosphatase (ACP)) were measured to evaluate the health of scallops at the end of the study. Environmental parameters at the five depths were also monitored during the experiment. Mortalities mainly occurred during summer. Survival of scallops suspended at 15 m (78.0%) and 20 m (86.7%) was significantly higher than at 2 m (62.9%), 5 m (60.8%) or 10 m (66.8%) at the end of the study. Mean shell height grew significantly faster at 10 m (205.0 μm/d) and 20 m (236.9 μm/d) than at 2, 5 or 15 m in summer (July 9 to September 1); however, shell growth rate at 20 m was significantly lower than at the other four depths in autumn (September 2 to November 6). In contrast to summer, scallops at 5 m grew faster (262.9 μm/d) during autumn. The growth of soft tissue at different depths showed a similar trend to the shell. Growth rates of shell height and soft tissue were faster in autumn than in summer, with the exception of shell height at 20 m. SOD activity of scallops increased with depth, and ACP activity was significantly higher at 15 and 20 m than at other depths, which suggests that scallops were healthier near the bottom. Factors explaining the depth-related mortality and growth of scallops are also discussed. We conclude that the mass mortality of scallop, C. farreri, during summer can be prevented by moving the culture area to deeper water and yield can be maximized by suspending the scallops in deep water during summer and then transferring them to shallow water in autumn.展开更多
Two hundred and seventy multiparous Chinese Yellow cattle (beef) were selected at 1 to 3 months postpartum and divided into three groups (90 cows for each). Animals were given both a primary and booster immunizations ...Two hundred and seventy multiparous Chinese Yellow cattle (beef) were selected at 1 to 3 months postpartum and divided into three groups (90 cows for each). Animals were given both a primary and booster immunizations with a total dose of 3 mg (Group Th) or 1.5 mg (Group Tl) of seminal preparation containing inhibin activity, emulsified with Freund's complete adjuvant and incomplete adjuvant (for booster) , at 3 or 4-week intervals. Other cows were treated with the same volume of seminal preparation without inhibin activity as procedures mentioned above to serve as a control (Group C). Artificial inseminations were given twice at 8 - 12 h intervals when the cow was in heat. Jugular venous blood samples were collected from each cow and used to assay the presence of antibody against seminal preparation by double-diffusion in agar precipitation test and to detect the titer of inhibin antibody by an ELISA method. Data from 247 cows showed that 83.9% (73/87) of cows were in estrus and ovulated 89 ova altogether, of which 19 cows ovulated twin ova and 15 cows produced twins in Group Th (n = 87). However, only 61.1% (44/72) of cows in Group TI (n = 72) and 62.5% (55/88) of cows in Group C were in estrus and ovulated 46 and 52 ova altogether respectively. The ovulation rate (1.27 ± 0.03), calving rate (126.3%) and twinning rate (26.3%) in Group Th were greater than those in Groups Tl or C (P<0.01). Furthermore, the ovulation rate was associated with antibody titer in sera of immunized animals (r = 0.7507, P<0.01). These results indicate that active immunization of postpartum cows against inhibin purified from porcine seminal plasma may increase the ovulation rate and induce twinning, suggesting the potential to develop a method to improve fertility in cows.展开更多
The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the im...The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the immune system. The infected host undergoes an asymptomatic period lasting several years with low viral load and ostensibly healthy status, which is presumably due to virus-specific adaptive immune responses. In the absence of therapy, an overwhelming majority of cases develop to AIDS within 8-10 years of latent infection. In this review, we discuss the roles in AIDS pathogenesis played by massive CD4+ T lymphocytes depletion in gut-associated lymphoid tissue (GALT) during acute infection and abnormal immune activation emerging in the later part of chronic phase.展开更多
We have modified the previously described one-pot peptide synthesis method. The modified method has been successfully applied to the synthesis of TP3. Furthermore, the immune regulatory activity of TP3 has been charac...We have modified the previously described one-pot peptide synthesis method. The modified method has been successfully applied to the synthesis of TP3. Furthermore, the immune regulatory activity of TP3 has been characterized. The results show that the modified one-pot method can be used to synthesize the biological active peptide with the advantages of low cost and high productivity. Moreover, TP3 has a higher immune regulatory activity than TP5.展开更多
Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environmen...Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environment where the fetus becomes exposed and adapted to the maternal milieu.Maternal exposure to high-energy dense diets can affect motivated behavior in the offs p ring leading to addiction and impaired sociability.A high-energy dense exposure also increases the pro-inflammatory cytokines profile in plasma and brain and favors microglia activation in the offspring.While still under investigation,prenatal exposure to high-energy dense diets promotes structural abnormalities in selective brain regions regulating motivation and social behavior in the offspring.The current review addresses the role of energy-dense foods programming central and peripheral inflammatory profiles during embryonic development and its effect on motivated behavior in the offspring.We provide preclinical and clinical evidence that supports the contribution of prenatal programming in shaping immune profiles that favor structural and brain circuit disruption leading to aberrant motivated behaviors after birth.We hope this minireview encourages future research on novel insights into the mechanisms underlying maternal programming of motivated behavior by central immune networks.展开更多
Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME...Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.展开更多
Due to its multiple features,including the ability to orchestrate remote communication between different tissues,the exosomes are the extracellular vesicles arousing the highest interest in the scientific community.Th...Due to its multiple features,including the ability to orchestrate remote communication between different tissues,the exosomes are the extracellular vesicles arousing the highest interest in the scientific community.Their size,established as an average of 30-150 nm,allows them to be easily uptaken by most cells.According to the type of cells-derived exosomes,they may carry specific biomolecular cargoes used to reprogram the cells they are interacting with.In certain circumstances,exosomes stimulate the immune response by facilitating or amplifying the release of foreign antigens-killing cells,inflammatory factors,or antibodies(immune activation).Meanwhile,in other cases,they are efficiently used by malignant elements such as cancer cells to mislead the immune recognition mechanism,carrying and transferring their cancerous cargoes to distant healthy cells,thus contributing to antigenic invasion(immune suppression).Exosome dichotomic patterns upon immune system regulation present broad advantages in immunotherapy.Its perfect comprehension,from its early biogenesis to its specific interaction with recipient cells,will promote a significant enhancement of immunotherapy employing molecular biology,nanomedicine,and nanotechnology.展开更多
Nanocatalytic therapy shows great potential for therapeutic interventions.However,therapeutic efficiency is often limited by unsatisfactory enzyme activity and lack of the coordination of immune system.Therefore,engin...Nanocatalytic therapy shows great potential for therapeutic interventions.However,therapeutic efficiency is often limited by unsatisfactory enzyme activity and lack of the coordination of immune system.Therefore,engineering nanozymes activity enhancement while activating immune system will be an effective strategy to achieve efficient tumor therapy.Herein,we synthesize a DSPE-PEG-FA modified manganese dioxide-based dual-atom nanozyme(MDF),on which iridium and platinum atoms are anchored.The obtained MDF can simultaneously mimic four enzyme activities of catalase,oxidase,peroxidase,and glutathione oxidase,set off a reactive oxygen species(ROS)storm,cause tumor cell death.The enzyme activity of MDF can be enhanced by its own photothermal effect.Meanwhile,MDF can consume intracellular glutathione and release Mn^(2+),which can prevent generated ROS from consumption and further activate cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes(cGAS-STING)pathway and promote the secretion of type I interferon,which will help promote dendritic cells maturation,present antigens to T lymphocytes to help kill tumor cells.Ultimately,MDF shows excellent tumor suppressive effects.This work provides a new paradigm for the field of nanozymes and offers a new reference for involvement of cGAS-STING pathway activation in tumor catalytic therapy.展开更多
Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently.Based on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed b...Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently.Based on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QDAU5,which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and antigen pre-conditioning and maturation of dendritic cells and CD8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic drugs.Additionally,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic effects.Overall,our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.展开更多
Hyaluronic acid (HA) preparations have emerged as pivotal components in contemporary dentistry, gaining widespread recognition for their multifaceted roles in various biological functions. Extensive literature undersc...Hyaluronic acid (HA) preparations have emerged as pivotal components in contemporary dentistry, gaining widespread recognition for their multifaceted roles in various biological functions. Extensive literature underscores the significance of HA in maintaining tissue water balance, fostering cell proliferation, promoting rapid cell migration, influencing cell differentiation during organism development, and facilitating tissue regeneration. Notably, HA’s interactions with cell surface receptors contribute to the viscosity of synovial fluid, activate the immune system, and enhance cartilage elasticity. Beyond these established functions, HA has also been investigated for its potential involvement in determining and studying the hormetic effects of radon water, adding a novel dimension to its applications in dental research. A thorough exploration of existing studies reveals a nuanced understanding of how HA interventions impact the outcomes of dental procedures. The comprehensive scope of these investigations allows for a more accurate assessment of the potential effectiveness of specific interventions and provides valuable insights into post-procedural prognoses for individual patients. This synthesis of literature serves as the foundation for elucidating the intricate interplay between HA, radon exposure, and their relevance in modern dental practices.展开更多
The efficacy of cell therapy is compromised by the suboptimal survival and function of transplanted cells,which can be partly attributed to uncontrolled immunomodulation.To address this issue,the dual role of biomater...The efficacy of cell therapy is compromised by the suboptimal survival and function of transplanted cells,which can be partly attributed to uncontrolled immunomodulation.To address this issue,the dual role of biomaterials in assisting immune activation and evasion can be used to fine-tune immune responses and improve the efficacy and safety of cell therapy.Herein,we summarize different methods used to engineer therapeutic cells with biomaterials across multiple spatial scales and review how biomaterials assist in immune activation or evasion in cell therapy based on a discussion of the effects of biomaterials on endogenous immune cells.We also discuss the appealing features of biomaterials that polarize immune responses toward type 1 or type 2 immunity.In future studies,the biophysical and biochemical properties of biomaterials could be better leveraged for immunomodulatory purposes to fuel prominent improvements in cell therapy,and the relevant regulatory mechanisms should be investigated in a more systematic and in-depth manner.展开更多
Psychological stress is an important factor for the development of irritable bowel syndrome(IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brai...Psychological stress is an important factor for the development of irritable bowel syndrome(IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stresssensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.展开更多
According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence abou...According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate into gut dysfunctions.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837)the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100)。
文摘Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.
基金This work was supported by the National Natural Science Foundation of China the Fund of Chinese National Educational Commissionhad been accepted by the International Symposium on New Drug Research and Development.October,1991.Beijing.
基金Supported by the National Natural Science Foundation of China(51374242,51504286)China Postdoctoral Science Foundation(2015M572270)the Fundamental Research Funds for the Central Universities of Central South University(2015zzts079)
文摘To simulate the rumor propagation process on online social network during emergency, a new rumor propagation model was built based on active immune mechanism. The rumor propagation mechanisms were analyzed and corresponding parameters were defined. BA scale free network and NW small world network that can be used for representing the online social network structure were constructed and their characteristics were compared. Agent-based simulations were conducted on both networks and results show that BA scale free network is more conductive to spreading rumors and it can facilitate the rumor refutation process at the same time. Rumors paid attention to by more people is likely to spread quicker and broader but for which the rumor refutation process will be more effective. The model provides a useful tool for understanding and predicting the rumor propagation process on online social network during emergency, providing useful instructions for rumor propagation intervention.
文摘Oncological hyperthermia is one of the most versatile forms of oncotherapy. It can complement every conventional treatment method and be applied to any tumorous cancer, irrespective of its stages and localization. Numerous technical realizations are conventionally compared by their thermal effect, measured by temperature. However, nonthermal (mainly electric) excitation effects are more recognized nowadays. The technical variants alter the synergy between thermal and nonthermal energy components. Nonthermal energy absorption-induced molecular mechanisms include essential behaviors like selectivity and immunogenicity. The nonthermal electromagnetic effects excite molecular changes, intracellular signals, gene expressions, and many other chemical reactions. Their synergy with thermal conditions is based on the Arrhenius law, which describes the rapid growth of chemical reactions with temperature. A unique technical realization of hyperthermia, modulated electrohyperthermia (mEHT) tries to optimize the thermal and nonthermal effects. The results look very perspective, containing the high accuracy of targeting the tumor cells, the immunogenic cell death, and the activation of tumor-specific immune reactions restoring the healthy immune surveillance to destroy the cancer.
文摘Autism spectrum disorders(ASD)comprise a group of neurodevelopmental abnormalities that begin in early childhood and are characterized by impairment of social communication and behavioral problems including restricted interests and repetitive behaviors.Several genes have been implicated in the pathogenesis of ASD,most of them are involved in neuronal synaptogenesis.A number of environmental factors and associated conditions such as gastrointestinal(GI)abnormalities and immune imbalance have been linked to the pathophysiology of ASD.According to the March 2012 report released by United States Centers for Disease Control and Prevention,the prevalence of ASD has sharply increased during the recent years and one out of 88 children suffers now from ASD symptoms.Although there is a strong genetic base for the disease,several associated factors could have a direct link to the pathogenesis of ASD or act as modifiers of the genes thus aggravating the initial problem.Many children suffering from ASD have GI problems such as abdominal pain,chronic diarrhea,constipation,vomiting,gastroesophageal reflux,and intestinal infections.A number of studies focusing on the intestinal mucosa,its permeability,abnormal gut development,leaky gut,and other GI problem raised many questions but studies were somehow inconclusive and an expert panel of American Academy of Pediatrics has strongly recommended further investigation in these areas.GI tract has a direct connection with the immune system and an imbalanced immune response is usually seen in ASD children.Maternal infection or autoimmune diseases have been suspected.Activation of the immune system during early development may have deleterious effect on various organs including the nervous system.In this review we revisited briefly the GI and immune system abnormalities and neuropeptide imbalance and their role in the pathophysiology of ASD and discussed some future research directions.
基金financially supported by the National High Technology Research and Development Program of China (863 Project) of China (2012AA10A412)
文摘A marine bacterium, Pseudoalteromonas sp. BC228 was supplemented to feed in a feeding experiment aiming to determine its ability of enhancing the digestive enzyme activity and immune response of juvenile Apostichopus japonicus. Sea cucumber individuals were fed with the diets containing 0(control), 105, 107 and 109 CFU g-1 diet of BC228 for 45 days. Results showed that intestinal trypsin and lipase activities were significantly enhanced by 107 and 109 CFU g-1 diet of BC228 in comparison with control(P < 0.01). The phagocytic activity in the coelomocytes of sea cucumber fed the diet supplemented with 107 CFU g-1 diet of BC228 was significantly higher than that of those fed control diet(P < 0.05). In addition, 105 and 107 CFU g-1 diet of BC228 significantly enhanced lysozyme and phenoloxidase activities in the coelomic fluid of sea cucumber, respectively, in comparison with other diets(P < 0.01). Sea cucumbers, 10 each diet, were challenged with Vibrio splendidus NB13 after 45 days of feeding. It was found that the cumulative incidence and mortality of sea cucumber fed with BC228 containing diets were lower than those of animals fed control diet. Our findings evidenced that BC228 supplemented in diets improved the digestive enzyme activity of juvenile sea cucumber, stimulated its immune response and enhanced its resistance to the infection of V. splendidus.
文摘The killing effects of lymphocytes on Hela cells expressing interleukin-12 (IL-12) in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression of IL-12 in Hela cells was detected quantitatively by ELISA; Changes in killing effects of lymphocytes on Hela cells expressing IL-12 were observed by MTT. It was found that Hela cells could express IL- 12 between 24 h and 72 h after transfection. Killing activity of lymphocytes on Hela cells expressing IL-12 was significantly enhanced. It was concluded by cell transfection technique, Hela cells could express 1L-12 and were more easily killed by lymphocytes.
基金Supported by the National Key Technology R&D Program (No. 2006BAD09A02)the High Technology Research and Development Program of China (863 Program) (Nos. 2006AA100304, 2006AA100307)the Knowledge Innovation Program of Chinese Academy of Sciences (No. KZCX2-YW-Q07-03)
文摘Survival, growth and immune response of the scallop, Chlamys farreri, cultured in lantern nets at five different depths (2, 5, 10, 15, and 20 m below the sea surface) were studied in Haizhou Bay during the hot season (summer and autumn) of 2007. Survival and growth rates were quantified bimonthly. Immune activities in hemolymph (superoxide dismutase (SOD) and acid phosphatase (ACP)) were measured to evaluate the health of scallops at the end of the study. Environmental parameters at the five depths were also monitored during the experiment. Mortalities mainly occurred during summer. Survival of scallops suspended at 15 m (78.0%) and 20 m (86.7%) was significantly higher than at 2 m (62.9%), 5 m (60.8%) or 10 m (66.8%) at the end of the study. Mean shell height grew significantly faster at 10 m (205.0 μm/d) and 20 m (236.9 μm/d) than at 2, 5 or 15 m in summer (July 9 to September 1); however, shell growth rate at 20 m was significantly lower than at the other four depths in autumn (September 2 to November 6). In contrast to summer, scallops at 5 m grew faster (262.9 μm/d) during autumn. The growth of soft tissue at different depths showed a similar trend to the shell. Growth rates of shell height and soft tissue were faster in autumn than in summer, with the exception of shell height at 20 m. SOD activity of scallops increased with depth, and ACP activity was significantly higher at 15 and 20 m than at other depths, which suggests that scallops were healthier near the bottom. Factors explaining the depth-related mortality and growth of scallops are also discussed. We conclude that the mass mortality of scallop, C. farreri, during summer can be prevented by moving the culture area to deeper water and yield can be maximized by suspending the scallops in deep water during summer and then transferring them to shallow water in autumn.
基金supported by the National Natural Science Foundation of China(No.39370512)the Foundation of Doctor Degree Unit Authorized by China Education Ministry(No.960204)the National Key Research Progress(No.96030311)of Chinese Ministry of Science and Technology,respectively.
文摘Two hundred and seventy multiparous Chinese Yellow cattle (beef) were selected at 1 to 3 months postpartum and divided into three groups (90 cows for each). Animals were given both a primary and booster immunizations with a total dose of 3 mg (Group Th) or 1.5 mg (Group Tl) of seminal preparation containing inhibin activity, emulsified with Freund's complete adjuvant and incomplete adjuvant (for booster) , at 3 or 4-week intervals. Other cows were treated with the same volume of seminal preparation without inhibin activity as procedures mentioned above to serve as a control (Group C). Artificial inseminations were given twice at 8 - 12 h intervals when the cow was in heat. Jugular venous blood samples were collected from each cow and used to assay the presence of antibody against seminal preparation by double-diffusion in agar precipitation test and to detect the titer of inhibin antibody by an ELISA method. Data from 247 cows showed that 83.9% (73/87) of cows were in estrus and ovulated 89 ova altogether, of which 19 cows ovulated twin ova and 15 cows produced twins in Group Th (n = 87). However, only 61.1% (44/72) of cows in Group TI (n = 72) and 62.5% (55/88) of cows in Group C were in estrus and ovulated 46 and 52 ova altogether respectively. The ovulation rate (1.27 ± 0.03), calving rate (126.3%) and twinning rate (26.3%) in Group Th were greater than those in Groups Tl or C (P<0.01). Furthermore, the ovulation rate was associated with antibody titer in sera of immunized animals (r = 0.7507, P<0.01). These results indicate that active immunization of postpartum cows against inhibin purified from porcine seminal plasma may increase the ovulation rate and induce twinning, suggesting the potential to develop a method to improve fertility in cows.
文摘The occurrence of massive CD4+ T cell depletion is one of the most prominent characteristics of human immunodeficiency virus type 1 (HIV-1) infection during acute phase, resulting in unrestorable destruction to the immune system. The infected host undergoes an asymptomatic period lasting several years with low viral load and ostensibly healthy status, which is presumably due to virus-specific adaptive immune responses. In the absence of therapy, an overwhelming majority of cases develop to AIDS within 8-10 years of latent infection. In this review, we discuss the roles in AIDS pathogenesis played by massive CD4+ T lymphocytes depletion in gut-associated lymphoid tissue (GALT) during acute infection and abnormal immune activation emerging in the later part of chronic phase.
文摘We have modified the previously described one-pot peptide synthesis method. The modified method has been successfully applied to the synthesis of TP3. Furthermore, the immune regulatory activity of TP3 has been characterized. The results show that the modified one-pot method can be used to synthesize the biological active peptide with the advantages of low cost and high productivity. Moreover, TP3 has a higher immune regulatory activity than TP5.
基金supported by the National Council of Science and Technology in Mexico(CONACYT)708452 CONACYT to LMM855559 CONACYT to GCC+1 种基金573686 CONACYT to RMRPAICYT 2021 to ACM。
文摘Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environment where the fetus becomes exposed and adapted to the maternal milieu.Maternal exposure to high-energy dense diets can affect motivated behavior in the offs p ring leading to addiction and impaired sociability.A high-energy dense exposure also increases the pro-inflammatory cytokines profile in plasma and brain and favors microglia activation in the offspring.While still under investigation,prenatal exposure to high-energy dense diets promotes structural abnormalities in selective brain regions regulating motivation and social behavior in the offspring.The current review addresses the role of energy-dense foods programming central and peripheral inflammatory profiles during embryonic development and its effect on motivated behavior in the offspring.We provide preclinical and clinical evidence that supports the contribution of prenatal programming in shaping immune profiles that favor structural and brain circuit disruption leading to aberrant motivated behaviors after birth.We hope this minireview encourages future research on novel insights into the mechanisms underlying maternal programming of motivated behavior by central immune networks.
基金supported by grants from the China Postdoctoral Science Foundation(Grant No.2022M712880)the Program of the Major Research Plan of the National Natural Science Foundation of China(Grant No.91942314)the National Natural Science Foundation of China(Grant No.82001659).
文摘Plasmacytoid dendritic cells(pDCs)are a pioneer cell type that produces type I interferon(IFN-I)and promotes antiviral immune responses.However,they are tolerogenic and,when recruited to the tumor microenvironment(TME),play complex roles that have long been a research focus.The interactions between p DCs and other components of the TME,whether direct or indirect,can either promote or hinder tumor development;consequently,p DCs are an intriguing target for therapeutic intervention.This review provides a comprehensive overview of p DC crosstalk in the TME,including crosstalk with various cell types,biochemical factors,and microorganisms.An in-depth understanding of p DC crosstalk in TME should facilitate the development of novel p DC-based therapeutic methods.
基金supported by the National Key Research&Development Program of China(2021YFA1201000,2021YFC2302400,2021YFE0106900)the National Natural Science Foundation of China(32171394)+3 种基金the Fundamental Research Funds for the Central Universities(2022CX01013)Beijing Nova Program(Interdisciplinary Cooperation Project)from Beijing Municipal Science&Technology Commission(20220484207)the project from China Bio-Medicine Park(Daxing Biomedical Industrial Base of Zhongguancun Science and Technology Park)the project from Suzhou Biomedical Industrial Park(BioBAY).
文摘Due to its multiple features,including the ability to orchestrate remote communication between different tissues,the exosomes are the extracellular vesicles arousing the highest interest in the scientific community.Their size,established as an average of 30-150 nm,allows them to be easily uptaken by most cells.According to the type of cells-derived exosomes,they may carry specific biomolecular cargoes used to reprogram the cells they are interacting with.In certain circumstances,exosomes stimulate the immune response by facilitating or amplifying the release of foreign antigens-killing cells,inflammatory factors,or antibodies(immune activation).Meanwhile,in other cases,they are efficiently used by malignant elements such as cancer cells to mislead the immune recognition mechanism,carrying and transferring their cancerous cargoes to distant healthy cells,thus contributing to antigenic invasion(immune suppression).Exosome dichotomic patterns upon immune system regulation present broad advantages in immunotherapy.Its perfect comprehension,from its early biogenesis to its specific interaction with recipient cells,will promote a significant enhancement of immunotherapy employing molecular biology,nanomedicine,and nanotechnology.
基金supported by the National Natural Science Foundation of China(52371254,22020102003)the Jilin Province Youth Science and Technology Talent Support Project(QT202229)+1 种基金the Program of Science and Technology Development Plan of Jilin Province of China(YDZJ202302CXJD065)the Natural Science Foundation of Chongqing of China(cstc2021jcyj-msxmX0936)。
文摘Nanocatalytic therapy shows great potential for therapeutic interventions.However,therapeutic efficiency is often limited by unsatisfactory enzyme activity and lack of the coordination of immune system.Therefore,engineering nanozymes activity enhancement while activating immune system will be an effective strategy to achieve efficient tumor therapy.Herein,we synthesize a DSPE-PEG-FA modified manganese dioxide-based dual-atom nanozyme(MDF),on which iridium and platinum atoms are anchored.The obtained MDF can simultaneously mimic four enzyme activities of catalase,oxidase,peroxidase,and glutathione oxidase,set off a reactive oxygen species(ROS)storm,cause tumor cell death.The enzyme activity of MDF can be enhanced by its own photothermal effect.Meanwhile,MDF can consume intracellular glutathione and release Mn^(2+),which can prevent generated ROS from consumption and further activate cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes(cGAS-STING)pathway and promote the secretion of type I interferon,which will help promote dendritic cells maturation,present antigens to T lymphocytes to help kill tumor cells.Ultimately,MDF shows excellent tumor suppressive effects.This work provides a new paradigm for the field of nanozymes and offers a new reference for involvement of cGAS-STING pathway activation in tumor catalytic therapy.
基金supported by the National Natural Science Foundation of China(NSFC,Nos.82373793,82173742)the Science Fund for Distinguished Young Scholars of Shaanxi Province(No.2022JC-54)the Key Research and Development Program of Shaanxi Province(No.2023-YBSF-131).
文摘Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently.Based on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QDAU5,which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and antigen pre-conditioning and maturation of dendritic cells and CD8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic drugs.Additionally,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic effects.Overall,our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.
文摘Hyaluronic acid (HA) preparations have emerged as pivotal components in contemporary dentistry, gaining widespread recognition for their multifaceted roles in various biological functions. Extensive literature underscores the significance of HA in maintaining tissue water balance, fostering cell proliferation, promoting rapid cell migration, influencing cell differentiation during organism development, and facilitating tissue regeneration. Notably, HA’s interactions with cell surface receptors contribute to the viscosity of synovial fluid, activate the immune system, and enhance cartilage elasticity. Beyond these established functions, HA has also been investigated for its potential involvement in determining and studying the hormetic effects of radon water, adding a novel dimension to its applications in dental research. A thorough exploration of existing studies reveals a nuanced understanding of how HA interventions impact the outcomes of dental procedures. The comprehensive scope of these investigations allows for a more accurate assessment of the potential effectiveness of specific interventions and provides valuable insights into post-procedural prognoses for individual patients. This synthesis of literature serves as the foundation for elucidating the intricate interplay between HA, radon exposure, and their relevance in modern dental practices.
基金financially supported by the National Natural Science Foundation of China(82061148010,92068204)Beijing Municipal Science&Technology Commission(Z181100001818005).
文摘The efficacy of cell therapy is compromised by the suboptimal survival and function of transplanted cells,which can be partly attributed to uncontrolled immunomodulation.To address this issue,the dual role of biomaterials in assisting immune activation and evasion can be used to fine-tune immune responses and improve the efficacy and safety of cell therapy.Herein,we summarize different methods used to engineer therapeutic cells with biomaterials across multiple spatial scales and review how biomaterials assist in immune activation or evasion in cell therapy based on a discussion of the effects of biomaterials on endogenous immune cells.We also discuss the appealing features of biomaterials that polarize immune responses toward type 1 or type 2 immunity.In future studies,the biophysical and biochemical properties of biomaterials could be better leveraged for immunomodulatory purposes to fuel prominent improvements in cell therapy,and the relevant regulatory mechanisms should be investigated in a more systematic and in-depth manner.
文摘Psychological stress is an important factor for the development of irritable bowel syndrome(IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stresssensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.
文摘According to epidemiological studies,twice as many women as men are affected by irritable bowel syndrome(IBS)in western countries,suggesting a role for sex hormones in IBS pathophysiology.Despite growing evidence about the implications of sex hormones in IBS symptom modulation,data on mechanisms by which they influence disease development are sparse.This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS.The scientific bibliography was searched using the following keywords:irritable bowel syndrome,sex,gender,ovarian hormone,estradiol,progesterone,testosterone,symptoms,pain,sensitivity,motility,permeability,stress,immune system,brain activity,spinal,supraspinal,imaging.Ovarian hormones variations along themenstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations.They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception.These hormones can also modulate the susceptibility to stress,which is a pivotal factor in IBS occurrence and symptom severity.For instance,estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function.In conclusion,whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS,they arguably modulate IBS onset and symptomatology.However,our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender.Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS.Finally,investigation of brain-gut interactions is critical to decipher how stress,ovarian hormones,and female brain processing of pain can translate into gut dysfunctions.