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1.
J Colloid Interface Sci ; 582(Pt B): 591-597, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32911407

RESUMO

Electrocatalytic hydrogen evolution reaction (HER) is a green approach to produce high-quality hydrogen fuel. Developing efficient electrocatalyst is the key to realize cost-effective HER. Pt is the state-of-the-art HER catalyst so far. However, the use of Pt for HER is limited by its high cost. Thus, it is essential to lower down the usage of Pt in the electrocatalyst by improving the intrinsic activity of Pt. In this work, we propose to achieve this goal by introducing synergistic interaction between Pt and substrate material (NiS2). The favorable synergy interaction can modify the d band structure of Pt (111) facet and modulate the hydrogen adsorption on Pt (111), which enhances the intrinsic electrocatalytic activity of Pt. The effectiveness of this strategy is demonstrated with both experimental and theoretical investigations.

2.
Methods Mol Biol ; 2158: 155-170, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32857372

RESUMO

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a potential treatment for cardiovascular disease, many of which are associated with tremendous loss of functional cardiomyocytes and simultaneous formation of scar tissue. Burgeoning studies have shown that the introduction of three minimal transcriptional factors, Gata4, Mef2c, and Tbx5 (G/M/T), could convert murine fibroblasts into iCMs that closely resemble endogenous CMs both in vitro and in vivo. Recent studies on iCM cell fate determination have demonstrated that the removal of genetic and epigenetic barriers could facilitate iCM reprogramming. However, varied reprogramming efficiency among research groups hinders its further study and potential applicability. Here, we provide a newly updated and detailed protocol for in vitro generation and evaluation of functional iCMs from mouse embryonic fibroblasts and neonatal cardiac fibroblasts using retroviral polycistronic construct encoding optimal expression of G/M/T factors. We hope that this optimized protocol will lay the foundation for future mechanistic studies of murine iCMs and further improvement of iCM generation.

3.
Carbohydr Polym ; 251: 117094, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33142632

RESUMO

Nanocellulose has gained increasing attention due to its excellent properties and wide application prospect. However, fast and low-waste preparation of nanocellulose is still challenging. Here, a time-saving and low-cost chemi-mechanical method was proposed to prepare cellulose nanocrystals (D-CNCs) and cellulose nanofibers (D-CNFs) by dilute sulfuric acid hydrolysis and the homogenization of the un-hydrolyzed cellulose residues, respectively. After hydrolyzed by 0.3 wt% sulfuric acid at 160 °C for 2 h, the diameter and length distribution of the obtained D-CNCs were 16 ∼ 45 nm and 150 ∼ 600 nm, respectively. The yield of D-CNCs and D-CNFs reached to 15.78 % and 69.11 %. The thermostability of D-CNCs was more superior to CNCs manufactured by 64 wt% sulfuric acid. In conclusion, this approach offers a promising strategy for high yield of nanocellulose due to its easy operation and low pollution.

4.
Carbohydr Polym ; 251: 117117, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33142652

RESUMO

The development of biopolymer films is crucial for the replacement of conventional plastics. Tremendous effort is made to improve their performances by introducing biopolymers through the film manufacturing process. Herein, a sandwich-architectured film was proposed to efficiently improve the adhesion between the PS and PLA layers by using octenyl succinic anhydride-modified pea starch (OMPS) layer as the interlayer, leading to a highly mechanically enhanced interpenetrating network. Accordingly, the properties of the films were enhanced due to the synergism effect of sandwich architecture. In particular, the WVP value of the sandwich-architectured films (0.25 ∼ 0.89×10-10g·m-1·s-1·Pa-1) decreased more than 7-fold compared with the OMPS20 film, and the OP value of the sandwich-architectured films (0.256 ∼ 1.229×10-12cm3·m·m-2·s-1·Pa-1) decreased more than 10-fold in comparison to the PLA film. Benefitting from the characteristics investigated above, the films exhibited a favorable effect on strawberry storage. Overall, the fabricated eco-friendly sandwich-architectured films have shown great potential for biodegradable packaging applications.

5.
Bioorg Med Chem Lett ; : 127681, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33189775

RESUMO

In this study, a series of trans-4-(2-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)ethyl)cyclohexan-1-amine derivatives as potential antipsychotics were synthesized and biologically evaluated to discover potential antipsychotics with good drug target selectivity. The preliminary structure-activity relationship was discussed, and optimal compound 12a showed both nanomolar affinity for D2/D3/5-HT1A/5-HT2A receptors and weak α1 and H1 receptor binding affinity. In addition, 12a was metabolically stable in vitro, displayed micromolar affinity for the hERG channel, and exhibited antipsychotic efficacy in the animal model of locomotor-stimulating effects of phencyclidine.

7.
Chin Med J (Engl) ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33156008

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM. METHODS: We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, < 25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance. RESULTS: Overall, 4496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1094 NSYM, and 2837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100 person-year (PY), 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100 PY, and TDR prevalences were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age <21 years, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (adjusted [aOR]: 2.5; 95% CI: 1.0-5.8). CONCLUSIONS: College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.

8.
Int Immunopharmacol ; : 107152, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33187908

RESUMO

RNA virus infection activates the RIG-I-like Receptor (RLR) signaling pathway to produce type I interferons (IFNs), the key components of the antiviral immune response. Forkhead box O1 (FoxO1) is a host transcription factor that participates in multiple biological processes. In this study, FoxO1 was identified as a critical negative regulator of RIG-I-triggered signaling. FoxO1 promoted Sendai virus (SeV) replication and downregulated type I IFN production. Upon SeV infection, FoxO1 suppressed K63-linked ubiquitination of TRAF3 and the interaction between TRAF3 and TBK1, after which the production of type I IFNs via the interferon regulatory transcription factor 3 (IRF3) pathways was reduced. In addition, FoxO1 destabilized IRF3 by facilitating E3 ligase TRIM22- or TRIM21-mediated K48-linked ubiquitination of IRF3. Moreover, the inhibitory effect of FoxO1 was found to depend on its DNA binding domain (DBD). Thus, our findings highlight novel important roles of FoxO1 in controlling RLR-mediated antiviral innate immunity.

9.
AIDS Care ; : 1-9, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33190511

RESUMO

We aimed to assess the effect of childhood parental rearing on post-traumatic stress disorder (PTSD) among young HIV-positive men who have sex with men (MSM), as well as the mediation effect of social support on this association. A convenient sampling method and questionnaire-based survey were used to recruit eligible participants from the Wuhan Medical Treatment Center from 20 December 2018 to 28 February 2019. Bivariate analyses were used to investigate the correlations between PTSD and childhood parental rearing, the number of sexual partners and social support. Mediation analyses were used to investigate the mediation of social support. Totally, 142 eligible MSM participated in our study, with prevalence of PTSD being 33.10%. It was found that maternal warmth (M1) and maternal favoring (M5) were positively correlated with social support. Paternal rejection (F5) was positively correlated with PTSD. The effects of M1 and M5 on PTSD were completely mediated by social support. The effects of paternal favoring (F4) and M5 on PTSD were completely mediated by subjective social support, and the effects of F5 and M1 were completely mediated by social support utility. Social support was an important mediator between parental rearing and PTSD.

10.
Biol Psychiatry ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-33190845

RESUMO

BACKGROUND: Deficiency in neuronal structural plasticity is involved in the development of major depressive disorder. TWIST1, a helix-loop-helix transcription factor that is essential for morphogenesis and organogenesis, is normally expressed at low levels in mature neurons. However, it is poorly understood what role TWIST1 plays in the brain and whether it is involved in the pathophysiology of depression. METHODS: Depressive-like behaviors in C57BL/6J mice were developed by chronic social defeat stress. Genetic and pharmacological approaches were used to investigate the role of the TWIST1-miR-214-PPAR-δ signaling pathway in depressive-like behaviors. Molecular biological and morphological studies were performed to define the molecular mechanisms downstream of TWIST1. RESULTS: The expression of TWIST1 was positively correlated with depressive behaviors in humans and mice. Chronic stress elevated TWIST1 expression in the medial prefrontal cortex of mice, which was reversed by fluoxetine treatment. While the overexpression of TWIST1 increased susceptibility to stress, the knockdown of TWIST1 prevented the defective morphogenesis of dendrites of pyramidal neurons in layer II/III of the medial prefrontal cortex and alleviated depressive-like behaviors. Mechanistically, this prodepressant property of TWIST1 was mediated, at least in part, through the repression of miR-214-PPAR-δ signaling and mitochondrial function, which was also mimicked by genetic and pharmacological inhibition of PPAR-δ. CONCLUSIONS: These results suggest that TWIST1 in the medial prefrontal cortex mediates chronic stress-induced dendritic remodeling and facilitates the occurrence of depressive-like behavior, providing new information for developing drug targets for depression therapy.

11.
Emerg Microbes Infect ; : 1-28, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33161824

RESUMO

Excretion of SARS-CoV-2 through faecal specimens Coronavirus disease 2019 (COVID-19) has become a pandemic with increasing numbers of cases worldwide. SARS-CoV-2, the causative virus of COVID-19, is mainly transmitted through respiratory droplets or through direct and indirect contact with an infected person. The possibility of potential faecal-oral transmission was investigated in this study. We collected 258 faecal specimens from nine provinces in China and detected the nucleic acid of SARS-CoV-2 using real-time RT-PCR. Vero cells were used to isolate the virus from SARS-CoV-2 nucleic acid positive samples, after which sequencing of Spike gene in eight samples was performed. In all, 93 of 258 (36%) stool samples were positive for SARS-CoV-2 RNA. The positive rates of critical, severe, moderate, and mild patients were 54.4%, 56.1%, 30.8%, and 33.3%, respectively. The content of nucleic acid increased within 2 weeks after the onset of the disease. From the perspective of clinical typing, the nucleic acid can be detected in the faeces of critical patients within two weeks and until four to five weeks in the faeces of severe and mild patients. SARS-CoV-2 was isolated from stool specimens of two severe patients. Four non-synonymous mutations in Spike gene were newly detected in three stool samples. A small number of patients had strong faecal detoxification ability. The live virus in faeces could be an important source of contamination, which may lead to infection and further spread in areas with poor sanitary conditions. The findings of this study have public health significance and they should be considered when formulating disease control strategies.

12.
Environ Sci Technol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225681

RESUMO

Sulfate radical (SO4•-) is widely recognized as the predominant species generated from the cobalt(II)-activated peroxymonosulfate (PMS) process. However, in this study, it was surprisingly found that methyl phenyl sulfoxide (PMSO) was readily oxidized to the corresponding sulfone (PMSO2) with a transformation ratio of ∼100% under acidic conditions, which strongly implied the generation of high-valent cobalt-oxo species [Co(IV)] instead of SO4•- in the Co(II)/PMS process. Scavenging experiments using methanol (MeOH), tert-butyl alcohol, and dimethyl sulfoxide further suggested the negligible role of SO4•- and hydroxyl radical (•OH) but favored the generation of Co(IV). By employing 18O isotope-labeling technique, the formation of Co(IV) was conclusively verified and the oxygen atom exchange reaction between Co(IV) and H2O was revealed. Density functional theory calculation determined that the formation of Co(IV) was thermodynamically favorable than that of SO4•- and •OH in the Co(II)/PMS process. The generated Co(IV) species was indicated to be highly reactive due to the existence of oxo-wall and capable of oxidizing the organic pollutant that is rather recalcitrant to SO4•- attack, for example, nitrobenzene. Additionally, the degradation intermediates of sulfamethoxazole (SMX) in the Co(II)/PMS process under acidic conditions were identified to further understand the interaction between Co(IV) and the representative contaminant. The developed kinetic model successfully simulated PMSO loss, PMSO2 production, SMX degradation, and/or PMS decomposition under varying conditions, which further supported the proposed mechanism. This study might shed new light on the Co(II)/PMS process.

13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1257-1260, 2020 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-33179234

RESUMO

OBJECTIVE: To carried out prenatal diagnosis and genetic analysis for a case with Nail-patella syndrome. METHODS: Based on the clinical phenotype and prenatal imaging, genetic testing and prenatal diagnosis were carried out through whole exome sequencing (WES) and Sanger sequencing. RESULTS: Analysis of amniotic fluid showed that the fetus has carried a heterozygous c.139+1G>T splicing site variant [Chr9(GRCh37): g.129376868G>T] of the LMX1B gene, which was verified by Sanger sequencing. The same heterozygous variant was found in the pregnant woman, her daughter and her mother but not in her husband. Searching of HGMD database showed that the c.139+1G>T was previously unreported. CONCLUSION: Nail-patella syndrome is an autosomal dominant genetic disorder with various clinical manifestations. WES is helpful for its genetic and prenatal diagnosis.


Assuntos
Síndrome da Unha-Patela , Diagnóstico Pré-Natal , Feminino , Heterozigoto , Humanos , Mutação , Síndrome da Unha-Patela/diagnóstico , Síndrome da Unha-Patela/genética , Linhagem , Gravidez , Sequenciamento Completo do Exoma
14.
Appl Microbiol Biotechnol ; 104(24): 10585-10599, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33156446

RESUMO

Acetic acid accumulation is a universal limiting factor to the vinegar manufacture because of the toxic effect of acetic acid on the acid producing strain, such as Acetobacter pasteurianus. In this study, we aimed to investigate the genome-wide transcriptional response of A. pasteurianus Ab3 to high acid stress during vinegar production. By comparing the transcriptional landscape of cells harvested from a long-term cultivation with high acidity (70 ± 3 g/L) to that of low acidity (10 ± 2 g/L), we demonstrated that 1005 genes were differentially expressed. By functional enrichment analysis, we found that the expression of genes related to the two-component systems (TCS) and toxin-antitoxin systems (TAS) was significantly regulated under high acid stress. Cells increased the genome stability to withstand the intracellular toxicity caused by the acetic acid accumulation by repressing the expression of transposases and integrases. Moreover, high acid stress induced the expression of genes involved in the pathways of peptidoglycan, ceramide, and phosphatidylcholine biosynthesis as well as the Tol-Pal and TonB-ExbB systems. In addition, we observed that cells increased and diversified the ATP production to resist high acid stress. Transcriptional upregulation in the pathways of pyrroloquinoline quinone (PQQ) synthesis and thiamine metabolism suggested that cells may increase the production of prosthetic groups to ensure the enzyme activity upon high acid stress. Collectively, the results of this study increase our current understanding of the acetic acid resistance (AAR) mechanisms in A. pasteurianus and provide opportunities for strain improvement and scaled-up vinegar production.Key Points• TCS and TAS are responsive to the acid stress and constitute the regulating networks.• Adaptive expression changes of cell envelope elements help cell resist acid stress.• Cells promote genome stability and diversify ATP production to withstand acid stress.

15.
Eur J Med Chem ; : 112982, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33158578

RESUMO

A pre-trained self-attentive message passing neural network (P-SAMPNN) model was developed based on our anti-osteoclastogenesis dataset for virtual screening purpose. Validation processes proved that P-SAMPNN model was significantly superior to the other base line models. A commercially available natural product library was virtually screened by the P-SAMPNN model and resulted in confirmed 5 hits from 10 selected virtual hits. Among the confirmed hits, compounds AP-123/40765213 and AE-562/43462182 are the nanomolar inhibitors against osteoclastogenesis with a new scaffold. Further studies indicate that AP-123/40765213 and AE-562/43462182 significantly suppress the mRNA expression of RANK and downregulate the expressions of osteoclasts-related genes Ctsk, Nfatc1, and Tracp. Our work demonstrated that P-SAMPNN method can guide phenotype-based drug discovery.

16.
J Hazard Mater ; : 124359, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33158653

RESUMO

Pyrisoxazole is a chiral fungicide that is routinely applied to agricultural plant protection, but the potential environmental risk may be under- or over-estimated because the risk induced by stereoisomers have never been evaluated individually. Thus, we carried out a systemic evaluation of pyrisoxazole at the stereoisomeric level, including absolute configuration, stereoselective bioactivity, acute toxicity, and stereoselective dissipation behavior. There were 99.0-3545.3 fold difference in bioactivity toward six target pathogens (e.g., Alternaria solani) and 1.3-4.0 times difference in toxicity against aquatic organisms (Selenastrum capricornutum and Daphnia magna) between the best and worst stereoisomer. There appeared to be no significant stereoselective dissipation in all three kinds of soil under aerobic and anaerobic conditions. Stereoselective dissipation in buffer solution and river water only observed between diastereomers rather than between enantiomers. In addition, photolysis played a central role in the dissipation of pyrisoxazole in river water. RS-pyrisoxazole was 2.2- to 6.9-times more bioactive and 1.2- to 2.1-times more toxic than Rac-pyrisoxazole, and what is more, RS-pyrisoxazole degraded faster than other stereoisomers in river water. The result implicated that developing pure RS-pyrisoxazole as commercial product could reduce the input of inactive isomer on the basis of guaranteeing the efficacy against the target pathogens.

17.
Theranostics ; 10(26): 12204-12222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204338

RESUMO

Rationale: Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating inflammatory bowel disease (IBD) due to their immunomodulatory and trophic functions. However, their efficacy is influenced by tissue origin, donator condition, isolation, and expansion methods. Here, we generated phenotypically uniform MSCs from human embryonic stem cells (T-MSCs) and explored the molecular mechanisms involved in promoting mucosal integrity and regeneration in colitis mice. Methods: T-MSCs were injected intravenously into mice with dextran sulfate sodium (DSS)-induced colitis, and the in vivo distribution and therapeutic efficacy were evaluated. We performed serum cytokine antibody microarrays to screen potentially effective proteins and examined the therapeutic effect of insulin-like growth factor-1 (IGF-1). Colon epithelial regeneration potential was evaluated, and RNA sequencing was employed to determine the underlying molecular mechanisms. Finally, in vitro IGF-1 stimulation was performed to assess its effect on cell functions and organoid growth. Results: Intravenous administration of T-MSCs alleviated colitis in both acute and chronic DSS mouse models. Labeled T-MSCs were mainly distributed in the lungs, liver, and spleen after systemic infusion. The antibody array analysis of serum cytokines indicated that the IGF-1 level was increased in the treatment group, and serum ELISA further confirmed its elevation in the regeneration stage. Intraperitoneal injection of IGF-1 receptor inhibitors abrogated the anti-inflammatory activity of T-MSCs. The colonic epithelium of the treatment group showed greater regenerative potency than the controls and the IGF1R-PI3K-AKT pathway was up-regulated. RNA sequencing showed that T-MSC treatment contributed to colonic cell integrity and promoted xenobiotic metabolism. In vitro IGF-1 stimulation promoted the growth and proliferation of colon cells and organoids. Conclusions: Intravenous infusion of T-MSCs alleviated colitis in mice by elevating the circulating IGF-1 level. Increased IGF-1 maintained the integrity of epithelial cells and contributed to their repair and regeneration. Our study has identified T- MSCs as a potential cell resource for IBD treatment.

18.
Sci Adv ; 6(47)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33208361

RESUMO

Advances in treating ß cell loss include islet replacement therapies or increasing cell proliferation rate in type 1 and type 2 diabetes, respectively. We propose developing multiple proliferation-inducing prodrugs that target high concentration of zinc ions in ß cells. Unfortunately, typical two-dimensional (2D) cell cultures do not mimic in vivo conditions, displaying a markedly lowered zinc content, while 3D culture systems are laborious and expensive. Therefore, we developed the Disque Platform (DP)-a high-fidelity culture system where stem cell-derived ß cells are reaggregated into thin, 3D discs within 2D 96-well plates. We validated the DP against standard 2D and 3D cultures and interrogated our zinc-activated prodrugs, which release their cargo upon zinc chelation-so preferentially in ß cells. Through developing a reliable screening platform that bridges the advantages of 2D and 3D culture systems, we identified an effective hit that exhibits 2.4-fold increase in ß cell proliferation compared to harmine.

19.
PLoS Genet ; 16(11): e1009194, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33137136

RESUMO

Sex determination pathways are astoundingly diverse in insects. For instance, the silk moth Bombyx mori uniquely use various components of the piRNA pathway to produce the Fem signal for specification of the female fate. In this study, we identified BmGTSF1 as a novel piRNA factor which participates in B. mori sex determination. We found that BmGtsf1 has a distinct expression pattern compared to Drosophila and mouse. CRISPR/Cas9 induced mutation in BmGtsf1 resulted in partial sex reversal in genotypically female animals by shifting expression of the downstream targets BmMasc and Bmdsx to the male pattern. As levels of Fem piRNAs were substantially reduced in female mutants, we concluded that BmGtsf1 plays a critical role in the biogenesis of the feminizing signal. We also demonstrated that BmGTSF1 physically interacted with BmSIWI, a protein previously reported to be involved in female sex determination, indicating BmGTSF1 function as the cofactor of BmSIWI. BmGtsf1 mutation resulted in piRNA pathway dysregulation, including piRNA biogenesis defects and transposon derepression, suggesting BmGtsf1 is also a piRNA factor in the silkworm. Furthermore, we found that BmGtsf1 mutation leads to gametogenesis defects in both male and female. Our data suggested that BmGtsf1 is a new component involved in the sex determination pathway in B. mori.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33143450

RESUMO

SIGNIFICANCE: Genomic instability, a hallmark of cancer, renders cancer cells susceptible to genomic stress from both endogenous and exogenous origins, result in the increased tendency to accrue DNA damage, chromosomal instability or aberrant DNA localization. Apart from the cell autonomous tumor-promoting effects, genomic stress in cancer cells could have a profound impact on the tumor microenvironment. Recent Advances: Recently, it is increasingly appreciated that harnessing genomic stress could provide a promising strategy to revive antitumor immunity, and thereby offer new therapeutic opportunities in cancer treatment. CRITICAL ISSUES: Genomic stress is closely intertwined with antitumor immunity via mechanisms involving the direct crosstalk with DNA damage response components, upregulation of immune-stimulatory/inhibitory ligands, release of damage-associated molecular patterns (DAMPs), increase of neoantigen repertoire, and activation of DNA sensing pathways. A better understanding of these mechanisms will provide molecular basis for exploiting the genomic stress to boost antitumor immunity. FUTURE DIRECTIONS: Future research should pay attention to the heterogeneity between individual cancers in the genomic instability and the associated immune response, and how to balance the toxicity and benefit by specifying the types, potency and treatment sequence of genomic stress inducer in therapeutic practice.

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