Analyzing psychological resilience in college students: A decision tree model.

In the evolving landscape of higher education, particularly in the post-pandemic era, it is crucial for college students to face societal challenges and achieve success by understanding and predicting psychological resilience. To deepen our understanding of psychological resilience, this study used a decision tree model to explore influencing factors. We surveyed 776 college students and collected data on demographic information, self-esteem, sense of school belonging, pro-environmental behavior, subjective well-being, internet game addiction, life autonomy, and academic procrastination using several scales. The decision tree model identified eight key predictors of psychological resilience, which are as follows in order of importance: self-esteem, sense of school belonging, pro-environmental behavior, subjective well-being, academic procrastination, life autonomy, internet game addiction, and academic achievement. This model's accuracy reached 73.985 %, emphasizing its potential utility in educational settings. The findings not only provide a novel and data-driven perspective to understand psychological resilience in college students compared to existing research but also provide practical guidance for educational practitioners and policymakers on how to develop psychological resilience in college students.

Biparatopic anti-PCSK9 antibody enhances the LDL-uptake in HepG2 cells.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 µM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.

Base-resolution m5C profiling across the mammalian transcriptome by bisulfite-free enzyme-assisted chemical labeling approach.

5-methylcytosine (m5C) is a prevalent RNA modification crucial for gene expression regulation. However, accurate and sensitive m5C sites identification remains challenging due to severe RNA degradation and reduced sequence complexity during bisulfite sequencing (BS-seq). Here, we report m5C-TAC-seq, a bisulfite-free approach combining TET-assisted m5C-to-f5C oxidation with selective chemical labeling, therefore enabling direct base-resolution m5C detection through pre-enrichment and C-to-T transitions at m5C sites. With m5C-TAC-seq, we comprehensively profiled the m5C methylomes in human and mouse cells, identifying a substantially larger number of confident m5C sites. Through perturbing potential m5C methyltransferases, we deciphered the responsible enzymes for most m5C sites, including the characterization of NSUN5's involvement in mRNA m5C deposition. Additionally, we characterized m5C dynamics during mESC differentiation. Notably, the mild reaction conditions and preservation of nucleotide composition in m5C-TAC-seq allow m5C detection in chromatin-associated RNAs. The accurate and robust m5C-TAC-seq will advance research into m5C methylation functional investigation.

Response of changes in lake area to drought and land use change.

The lake area is a crucial parameter that characterizes the state of a lake. Under the dual pressures of climate change and human activity, the magnitude and frequency of changes in lake areas become more pronounced. This process poses a serious threat to the local ecological environment. In this study, we constructed a lake water extraction model (LakeNet) based on a fully convolutional neural network. We extracted and analyzed the spatiotemporal characteristics of the area of nine major lakes from 1987 to 2022, as well as the driving factors behind these changes. Our results indicate that: 1) LakeNet exhibits high extraction accuracy and can remove some clouds. 2) The area of the nine major lakes shows a fluctuating downward trend (-8.11km2/10a), with drought and land use changes identified as significant driving forces behind the changes in lake boundaries, drought events caused the lake area to decrease, and the expansion of cropland further reduced the lake area. 3) Due to variations in lake area, the impact of drought on the area of the nine major lakes exhibits a lag effect, smaller lakes are likely to respond more quickly to drought.

Exploring the Roles of m6A-Modified circRNAs in Myasthenia Gravis Based on Multi-Omics Analysis.

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies. The important roles of circRNAs modified by m6A methylation have been reported in the pathogenesis of other autoimmune diseases, but remain unclear in MG. To address this point, we collected peripheral blood mononuclear cells from six MG patients and six healthy controls and performed m6A­circRNA epitranscriptomic microarray and RNA sequencing. Differentially m6A-modified circRNAs and differentially expressed genes (DEGs) were analyzed. A network was constructed containing 17 circRNAs, 30 miRNAs, and 34 DEGs. The GSE85452 dataset was downloaded. DEGs that were differentially expressed in the GSE85452 dataset were selected as seed genes. Finally, four candidate m6A-modified circRNAs (hsa_circ_0084735, hsa_circ_0018652, hsa_circ_0025731, and hsa_circ_0030997) were identified through a random walk with restart. We found that they had different degree correlations with different immune cells. The results of MeRIP-qPCR showed that the m6A methylated levels of hsa_circ_0084735 and hsa_circ_0025731 were downregulated in MG patients, while the other two circRNAs were not significantly different between MG and control group. For the first time, we explored the pathogenesis of MG at the epigenetic transcriptome level. Our results will open new perspectives for MG research and identify potential biomarkers and therapeutic targets for MG.

Dietary supplementation of vitamin B1 prevents the pathogenesis of osteoarthritis.

As the primary cause for chronic pain and disability in elderly individuals, osteoarthritis (OA) is one of the fastest-growing diseases due to the aging world population. To date, the impact of microenvironmental changes on the pathogenesis of OA remains poorly understood, greatly hindering the development of effective therapeutic approaches against OA. In this study, we profiled the differential metabolites in the synovial fluid from OA patients and identified the downregulation of vitamin B1 (VB1) as a metabolic feature in the OA microenvironment. In a murine destabilization of medial meniscus-induced OA model, supplementation of VB1 significantly mitigated the symptoms of OA. Cytokine array analysis revealed that VB1 treatment remarkably reduced the production of a pro-OA factor-C-C Motif Chemokine Ligand 2 (CCL2), in macrophages. Further evidence demonstrated that exogenous CCL2 counteracted the anti-OA function of VB1. Hence, our study unveils a unique biological function of VB1 and provides promising clues for the diet-based treatment of OA.

Tirofiban mediates neuroprotective effects in acute ischemic stroke by reducing inflammatory response.

Growing evidence suggests that neuroinflammation is a critical driver of the development, worsening, and cell death observed in acute ischemic stroke (AIS). While prior research has demonstrated that tirofiban enhances functional recovery in AIS patients by suppressing platelet aggregation, its impact and underlying mechanisms in AIS-related neuroinflammation remain elusive. The current study established an AIS mouse model employing photochemical techniques and assessed neurological function and brain infarct size using the modified neurological severity scale (mNSS) and 2,3,5-Triphenyltetrazolium chloride (TTC) staining, respectively. Tirofiban significantly reduced the volume of cerebral infarction in AIS mice, accompanied by an enhancement in their neurological functions. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays along with experiments assessing oxidative stress showed that tirofiban mitigated oxidative damage and apoptosis in the ischemic penumbra post-AIS. Additionally, DNA microarray analysis revealed alterations in gene expression patterns in the ischemic penumbra after tirofiban treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that most gene-level downregulated signaling pathways were closely related to the inflammatory response. Moreover, the protein microarray analysis revealed that tirofiban diminished the expression levels of inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha, in the ischemic penumbra. Additionally, immunofluorescence staining showed that tirofiban regulated inflammatory responses by altering the state and phenotype of microglia. In conclusion, this study suggests that tirofiban reduces inflammatory response by regulating microglial state and phenotype and lowering the levels of inflammatory factors, providing neuroprotection in acute ischemic stroke.

Mechanism of acupuncture and moxibustion in ameliorating liver injury induced by cisplatin by regulating IRE-1 signaling pathway. / "扶正益肝"é’ˆç¸ç©´æ–¹åŸºäºŽè‚Œé†‡éœ€æ±‚é ¶1ä¿¡å·é€šè·¯æ”¹å–„é¡ºé“‚è‡´å°é¼ è‚æŸä¼¤çš„æœºåˆ¶.

OBJECTIVES: To investigate the mechanism of the effect of acupuncture and moxibustion on improving liver injury in cisplatin (DDP) induced liver injury model mice by observing the changes of inositol-requiring enzyme (IRE) -1 signaling pathway. METHODS: Forty KM mice were randomly divided into control, model, acupuncture and moxibustion groups, with 10 mice in each group. The liver injury model was replicated by intraperitoneal injection of DDP (10 mg/kg). In the acupuncture group and the moxibustion group, acupuncture and moxibustion were performed at "Dazhui"(GV14), and bilateral "Ganshu"(BL18), "Shenshu" (BL23), and "Zusanli"(ST36), respectively for 6 min, once per day for 7 d. The apoptosis of hepatocytes was detected by TUNEL staining. The expression of phosphorylation(p)-IRE-1α, glucose-regulated protein (Grp) 78 and cysteine aspartic protease (Caspase) -12 in liver tissue were detected by immunohistochemistry and Western blot, respectively. The expression levels of Grp78 and Caspase-12 mRNA in liver tissue were detected by quantitative real-time PCR. RESULTS: Compared with the control group, the apoptosis rate of hepatocytes was increased (P<0.05), the positive expression and protein expression of p-IRE-1α, Grp78, and Caspase-12 were increased (P<0.05), the expression levels of Grp78 and Caspase-12 mRNA were increased (P<0.05) in the model group. Compared with the model group, all these indicators showed opposite trends (P<0.05) in the acupuncture and moxibustion groups. CONCLUSIONS: Acupuncture and moxibustion can reduce liver injury due to DDP chemotherapy by modulating IRE-1 signaling pathway, inhibiting the excessive activation of endoplasmic reticulum stress, and reducing liver cell apoptosis.

Indirect and sensitive determination of microRNAs by magnetic field-assisted capillary sieving electrophoresis combined with catalytic hairpin assembly.

To determine multiple microRNAs (miRNAs) from cells simultaneously is essential for understanding biological functions. Capillary electrophoresis (CE) can simultaneously determine multiple miRNAs by separation. Nevertheless, similar lengths and low concentrations in cells make miRNAs hard to separate and detect. In this study, CE with laser-induced fluorescence detection was combined with catalytic hairpin assembly (CHA) to determine three miRNAs, miR-21, miR-31, and miR-122. The amplification products of CHA, which were DNA duplexes, were designed to have different lengths for different miRNAs. This allowed for easy separation of the duplexes of different miRNAs by CE. The indirect determination of miRNAs was then achieved by separating and detecting these duplexes. A magnetic field was first applied on the capillary sieving electrophoresis to assist in the separation of the duplexes. Under the optimal conditions, the three duplexes could be completely separated within 2.5 min with the detection limits of miRNAs in the range 1.12-4.05 × 10-15 M. MiR-21 and miR-31 were successfully determined from Hela cells, while miR-122 was determined from chicken livers by this method. The recoveries ranged from 97.5% to 118%. The developed method was sensitive and reliable for miRNA determination.

Irisflorentin improves functional recovery after spinal cord injury by protecting the blood-spinal cord barrier and promoting axonal growth.

Spinal cord injury (SCI) induces the disruption of the blood-spinal cord barrier (BSCB) and the failure of axonal growth. SCI activates a complex series of responses, including cell apoptosis and endoplasmic reticulum (ER) stress. Pericytes play a critical role in maintaining BSCB integrity and facilitating tissue growth and repair. However, the roles of pericytes in SCI and the potential mechanisms underlying the improvements in functional recovery in SCI remain unclear. Recent evidence indicates that irisflorentin exerts neuroprotective effects against Parkinson's disease; however, whether it has potential protective roles in SCI or not is still unknown. In this study, we found that the administration of irisflorentin significantly inhibited pericyte apoptosis, protected BSCB integrity, promoted axonal growth, and ultimately improved locomotion recovery in a rat model of SCI. In vitro, we found that the positive effects of irisflorentin on axonal growth were likely to be mediated by regulating the crosstalk between pericytes and neurons. Furthermore, irisflorentin effectively ameliorated ER stress caused by incubation with thapsigargin (TG) in pericytes. Meanwhile, the protective effect of irisflorentin on BSCB disruption is strongly related to the reduction of pericyte apoptosis via inhibition of ER stress. Collectively, our findings demonstrate that irisflorentin is beneficial for functional recovery after SCI and that pericytes are a valid target of interest for future SCI therapies.

Tanning wastewater restructured nitrogen-transforming bacteria communities and promoted N2O emissions in receiving river riparian sediments.

Physicochemical and toxicological characterization of leather tanning wastewater has been widely documented. However, few reports have examined the response of denitrification N2 and N2O emissions in riparian sediments of tannery wastewater-receiving rivers. In this study, 15N-nitrate labeling was used to reveal the effects of tanning wastewater on denitrification N2 and N2O emission in a wastewater-receiving river (the old Mang River, OMR). OMR riparian sediments were highly polluted with total organic carbon (93.39 mg/kg), total nitrogen (5.00 g/kg) and heavy metals; specifically, Cr, Zn, Cd, and Pb were found at concentrations 47.3, 5.8, 1.6, 4.3, and 2.8 times that in a nearby parallel river without tanning wastewater input (the new Mang River, NMR), respectively. The denitrification N2 emission rates (0.0015 nmol N · g-1 h-1) of OMR riparian sediments were significantly reduced by 2.5 times compared with those from the NMR (p < 0.05), but the N2O emission rates (0.31 nmol N · g-1 h-1) were significantly increased (4.1 times, p < 0.05). Although the dominant nitrogen-transforming bacteria phylum was Proteobacteria in the riparian sediments of both rivers, 11 nitrogen-transforming bacteria genera in the OMR were found to be significantly enriched; five of these were related to pollutant degradation based on linear discriminant analysis (LDA >3). The average activity of the electron transport system in the OMR was 6.3 times lower than that of the NMR (p < 0.05). Among pollution factors, heavy metal complex pollution was the dominant factor driving variations in N2O emissions, microbial community structure, and electron transport system activity. These results provide a new understanding and reference for the treatment of tanning wastewater-receiving rivers.

The regulation of postharvest strawberry quality mediated by abscisic acid under elevated CO2 stress.

Elevated CO2 was a potential strategy for strawberry preservation. However, the regulatory mechanism remained unclear. In current study, transcriptome analysis showed that elevated CO2 played important roles in regulating strawberry fruit quality at the transcriptional level, and plant hormones metabolism at least partially involved in the regulatory process. Further, ABA was demonstrated to play important roles in the response to elevated CO2. Elevated CO2 inhibited the accumulation of ABA, which was 61% lower than that in control. Elevated CO2 repressed ABA synthesis by inhibiting NCED activity and the expression of FaNCED1/2, leading to the reduction of ABA accumulation as a result. Meanwhile, elevated CO2 also decreased ABA sensitivity by down-regulating FaSnRK2.4/2.6 and FaABI5 expression. The dual down-regulation of ABA signaling accounted for the regulation of fruit quality under elevated CO2 treatment. These results provide new insights into the mechanism of strawberry fruit response to elevated CO2.

Effect of acupuncture on post-stroke dysphagia: a randomized controlled trial.

Introduction: Post-stroke dysphagia (PSD) is associated with various complications that increase morbidity and mortality rates. Acupuncture has been used extensively in China to treat these complications; however, its therapeutic efficacy remains uncertain. We therefore aimed to study the clinical effects of acupuncture on PSD. Methods: Patients (n = 101) were randomly divided into acupuncture (n = 50) and rehabilitation training control (n = 51) groups based on the treatment used. Both groups were treated once daily, 6 days a week, for a total of 4 weeks. Pulse oxygen saturation (SpO2) and standardized swallowing assessment (SSA) were performed before the intervention, 2 weeks into treatment, after the intervention (4 weeks post-intervention), and at a 6-month follow-up (28 weeks). The levels of hemoglobin (Hb) and albumin (ALB), and 5-hydroxytryptamine (5-HT) and dopamine (DA) were measured before the intervention, 2 weeks into treatment, and after the intervention (4 weeks), as nutrition and swallowing function indices, respectively. Results: Following the intervention, significant differences were observed between the acupuncture and control groups. The acupuncture group exhibited considerably superior enhancements in SpO2 and SSA scores at 4 weeks (p < 0.001). Moreover, this group demonstrated significantly greater improvements in Hb, ALB, 5-HT, and DA values 4 weeks post-treatment (p < 0.001). However, sex-based differences were not observed (P > 0.005). Conclusion: Acupuncture treatment can improve the swallowing function and nutritional status of patients with PSD, and increase the levels of 5-HT and DA. These findings strongly support the efficacy of acupuncture as a therapeutic intervention in patients with PSD.Clinical trial registration: identifier, ChiCTR2100052201. (https://www.chictr.org.cn/).

Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report.

Castleman disease (CD) is a relatively rare lymphoproliferative disorder. Lesions predominantly originate on the chest and neck and rarely occur on the abdomen. A 34-year-old female presented to our hospital with an unexplained 10-year history of anemia. A pathological diagnosis of plasma cell-type CD was established. One cycle of chemotherapy (thalidomide, cyclophosphamide, and prednisolone) improved her anemia significantly. Prompt etiological diagnosis and early intervention are essential to address systemic manifestations in patients with CD, and it is crucial to consider CD as a differential diagnosis when intra-abdominal masses are detected.

Cardiovascular disease therapeutics via engineered oral microbiota: Applications and perspective.

Engineering bacteria are considered as a potential treatment for cardiovascular diseases and related risk factors. Oral bacteria are closely related to the occurrence and development of cardiovascular diseases, and their engineering has broad prospects and potential in the treatment of cardiovascular diseases. Oral pathogenic bacteria undergo protein and genetic engineering, including the incorporation of exogenous plasmids to yield therapeutic effects; genetically engineered oral probiotics can be harnessed to secrete cytokines and reactive oxygen species, offering novel therapeutic avenues for cardiovascular diseases.

CD39 transforming cancer therapy by modulating tumor microenvironment.

CD39 is a pivotal enzyme in cancer, regulating immune response and tumor progression via extracellular ATP and adenosine in the tumor microenvironment (TME). Beyond its established immunoregulatory function, CD39 influences cancer cell angiogenesis and metabolism, opening new frontiers for therapeutic interventions. Current research faces gaps in understanding CD39's full impact across cancer types, with ongoing debates about its potential beyond modulating immune evasion. This review distills CD39's multifaceted roles, examining its dual actions and implications for cancer prognosis and treatment. We analyze the latest therapeutic strategies, highlighting the need for an integrated approach that combines molecular insights with TME dynamics to innovate cancer care. This synthesis underscores CD39's integral role, charting a course for precision oncology that seeks to unravel controversies and harness CD39's therapeutic promise for improved cancer outcomes.

SCARB2 associates with tumor-infiltrating neutrophils and predicts poor prognosis in breast cancer.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in various aspects of breast cancer development and metastasis. Nevertheless, the expression, prognostic significance, and correlation with clinical features of SCARB2 in breast cancer, as well as the infiltrative characteristics of TME, remain largely unknown. METHODS: We analyzed the differential presentation of SCARB2 mRNA in breast cancer tissues and nontumorous breast tissues and prognosis by The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Additionally, the Tumor Immunity Estimation Resource (TIMER) was taken to evaluate the correlation between SCARB2 mRNA presence and tumor-infiltrating immune cells and immune checkpoints in the TME in breast cancer. We performed multiple immunohistochemical staining to verify the SCARB2 protein expression in breast cancer tissues and its relationship to immune cells and checkpoints and clinicopathological features. RESULTS: We identified elevated SCARB2 expression in breast cancer tissues, and high SCARB2 protein presentation was associated with advanced clinical stage and unfavorable prognosis. In addition, enhanced SCARB2 protein presence was closely correlated with up-regulation CD66b+ neutrophils infiltration in tumor tissues (r = 0.210, P < 0.05) and CD68 + CD163+ M2 macrophages in the interstitium (r = 0.233, P < 0.05), as well as the immune checkpoints, including PD-1 (r = 0.314, P < 0.01) protein expression. CONCLUSION: SCARB2 holds promise for predicting the clinical outcome of breast cancer patients and could serve as a potential therapeutic target.

Control strategies for trunk exoskeletons based on motion intent recognition: A review.

BACKGROUND: Wearable trunk exoskeletons hold immense potential in fields such as healthcare and industry. Previous research has indicated that intention recognition control plays a crucial role in users' daily use of exoskeletons. OBJECTIVE: This review aims to discuss the characteristics of intention recognition control schemes for intelligent trunk exoskeletons under different control objectives over the past decade. METHODS: Considering the relatively late development of active trunk exoskeletons, we selected papers published in the last decade (2013 to 2023) from the Web of Science, PubMed, and IEEE Xplore databases. In total, 50 articles were selected and examined based on four control objectives. RESULTS: In general, we found that researchers focus on trunk exoskeleton devices designed for assistance and motor augmentation, which rely more on body movement signals as a source for intention recognition. CONCLUSION: Based on these results, we identify and discuss several promising research directions that may help to attain a widely accepted control methods, thereby advancing further development of trunk exoskeleton technology.

Organic Reactions Enabled by Mechanical Force-Induced Single Electron Transfer.

Mechanochemical reactions, achieved through milling, grinding, or other mechanical actions, have emerged as a solvent-free alternative to traditional solution-based chemistry. Mechanochemistry not only provides the opportunity to eliminate bulk solvent use, reducing waste generation, but also unveils a new reaction strategy which enables the realization of reactions previously inaccessible in solution. While the majority of organic reactions facilitated by mechanical force traditionally follow two-electron transfer pathways similar to their solution-based counterparts, the field of mechanochemically induced single-electron transfer (SET) reactions has witnessed rapid development. This review outlines examples of mechanochemical reactions facilitated by the SET process, focusing on the reagents that initiate SET, thereby positioning mechanochemistry as a burgeoning field within the realm of single-electron chemistry.

Dual-Targeted Self-Adjuvant Heterocyclic Lipidoid@Polyester Hybrid Nanovaccines for Boosting Cancer Immunotherapy.

Tumor vaccines have demonstrated a modest response rate, primarily attributed to their inefficient delivery to dendritic cells (DCs), low cross-presentation, DC-intrinsic immunosuppressive signals, and an immunosuppressive tumor microenvironment (TME). Here, draining lymph node (DLN)-targeted and tumor-targeted nanovaccines were proposed to address these limitations, and heterocyclic lipidoid (A18) and polyester (BR647) were synthesized to achieve dual-targeted cancer immunotherapy. Meanwhile, oligo hyaluronic acid (HA) and DMG-PEG2000-Mannose were incorporated to prepare dual-targeted nanovaccines encapsulated with STAT3 siRNA and model antigens. The nanovaccines were designed to target the DLN and the tumor, facilitating the delivery of cargo into the cytoplasm. These dual-targeted nanovaccines improved antigen presentation and DC maturation, activated the stimulator of interferon genes (STING) pathway, enhanced the pro-apoptotic effect, and stimulated antitumor immune responses. Additionally, these dual-targeted nanovaccines overcame immunosuppressive TME, reduced immunosuppressive cells, and promoted the polarization of tumor-associated neutrophils from N2 to N1. Among the four dual-targeted nanovaccines that induced robust antitumor responses, the heterocyclic lipidoid@polyester hybrid nanovaccines (MALO@HBNS) demonstrated the most promising results. Furthermore, a combination strategy involving MALO@HBNS and an anti-PD-L1 antibody exhibited an immensely powerful anticancer role. This work introduced a dual-targeted nanovaccine platform for antitumor treatment, suggesting its potential combination with an immune checkpoint blockade as a comprehensive anticancer strategy.