SETDB1: Progress and prospects in cancer treatment potential and inhibitor research.

SET domain bifurcated methyltransferase 1 (SETDB1) serves as a histone lysine methyltransferase, catalyzing the di- and tri-methylation of histone H3K9. Mounting evidence indicates that the abnormal expression or activity of SETDB1, either through amplification or mutation, plays a crucial role in tumorigenesis and progression. This is particularly evident in the context of tumor immune evasion and resistance to immune checkpoint blockade therapy. Furthermore, there is a robust association between SETDB1 dysregulation and an unfavorable prognosis across various types of tumors. The oncogenic role of SETDB1 primarily arises from its methyltransferase function, which contributes to the establishment of a condensed and transcriptionally inactive heterochromatin state. This results in the inactivation of genes that typically hinder cancer development and silencing of retrotransposons that could potentially trigger an immune response. These findings underscore the substantial potential for SETDB1 as an anti-tumor therapeutic target. Nevertheless, despite significant strides in recent years in tumor biology research, challenges persist in SETDB1-targeted therapy. To better facilitate the development of anti-tumor therapy targeting SETDB1, we have conducted a comprehensive review of SETDB1 in this account. We present the structure and function of SETDB1, its role in various tumors and immune regulation, as well as the advancements made in SETDB1 antagonists. Furthermore, we discuss the challenges encountered and provide perspectives for the development of SETDB1-targeted anti-tumor therapy.

SLFN11 promotes clear cell renal cell carcinoma progression via the PI3K/AKT signaling pathway.

SLFN11 is abnormally expressed and associated with survival outcomes in various human cancers. However, the role of SLFN11 in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the clinical value and potential functions of SLFN11 in ccRCC. Comprehensive bioinformatics analyses were performed using online databases. Quantitative real-time PCR (qPCR) and western blotting were used to validate the expression data. CCK8, flow cytometry analysis, and EdU staining were performed to determine the level of cell proliferation. Flow cytometry analysis was also used to detect cell apoptosis. Wound-healing assay and Transwell assays were performed to assess cell migration and invasion capability, respectively. SLFN11 was overexpressed and was an independent prognostic factor in ccRCC. SLFN11 knockdown inhibited cell proliferation, migration, and invasion and promoted apoptosis. Functional and pathway enrichment analyses suggested that SLFN11 may have an impact on tumorigenesis in ccRCC through regulation of the inflammatory response, the PI3K/AKT signaling pathway and other effectors. Furthermore, SLFN11 knockdown inhibited the phosphorylation of the PI3K/AKT signaling pathway and could be activated by 740 Y-P. Finally, we demonstrated that miR-183 may specifically target SLFN11, and miR-183 expression was correlated with predicted survival. SLFN11 may play a critical role in ccRCC progression and may serve as a novel prognostic biomarker in ccRCC.

Pulmonary tumor embolism in a maintenance hemodialysis patient with hepatocellular carcinoma.

Patients with chronic kidney disease are already at an increased risk for pulmonary embolism, since loss of renal function rendered a procoagulant state. Further, malignant tumor is a well-established risk factor for pulmonary thromboembolism. Alternatively, occlusion of the pulmonary vasculature by tumor cells per se and associated thrombi may mimic thromboembolic disease. By comparison, however, report of pulmonary tumor embolism (PTE) in patients on maintenance hemodialysis (MHD) is exceedingly rare. A less vigilant clinician may have otherwise treated this situation as fluid overload or thromboembolic disorder. We herein described in an MHD patient such an unusual case of PTE, which was diagnosed by contrast-enhanced CT and PET/CT. As such, our work may expand the knowledge reserve of dialysis staffs about this rare complication of malignancy.

Iron diselenide/carbon black loaded mushroom-shaped evaporator for efficiently continuous solar-driven desalination.

Solar-driven desalination is an environmentally sustainable method to alleviate the problems of freshwater scarcity and the energy crisis. However, how to improve the synergy between the photothermal material and the evaporator to achieve high photothermal conversion efficiency simultaneously, excellent thermal management system and good salt resistance remains a challenge. Here, a mushroom-shaped solar evaporation device is designed and fabricated with iron diselenide/carbon black (FeSe2/CB) coated cellulose acetate (CA) film as mushroom surface and cotton swab as mushroom handle, which presented high solar-driven evaporation and excellent salt resistance. Thanks to the unique photothermal effect and the synergistic effect, the FeSe2/CB composites enabled a promising photothermal conversion efficiency of up to 65.8 °C after 180 s. The mushroom-shaped evaporation device effectively overcomes water transport and steam spillage channel blockage caused by salt crystallization through its unique vertical transport water channels and conical air-water interface. When exposed to real sunlight, the solar evaporation rate of the steam generation structure reached as high as 2.03 kg m-2 h-1, which is more than 13 times higher than natural evaporation. This study offered new insights into the higher solar-driven evaporation rate and salt-blocking resistance of the FeSe2/CB mushroom-shaped solar evaporation device for solar-powered water production.

Luminescent Gold Nanoparticles with Discrete DNA Valences for Precisely Controlled Transport at the Subcellular Level.

Ultrasmall luminescent gold nanoparticles (AuNPs) with excellent capabilities to cross biological barriers offer great promise in designing intelligent model nanomedicines for investigating structure-property relationships at the subcellular level. However, the strict surface controllability of ultrasmall AuNPs is challenging because of their small size. Herein, we report a facile in situ method for precisely controlling DNA aptamer valences on the surface of luminescent AuNPs with emission in the second near-infrared window using a phosphorothioate-modified DNA aptamer, AS1411, as a template. The discrete DNA aptamer number of AS1411-functionalized AuNPs (AS1411-AuNPs, ≈1.8 nm) with emission at 1030 nm was controlled in one aptamer (V1), two aptamers (V2), and four aptamers (V4). It was then discovered that not only the tumor-targeting efficiencies but also the subcellular transport of AS1411-AuNPs were precisely dependent on valences. A slight increase in valence from V1 to V2 increased tumor-targeting efficiencies and resulted in higher nucleus accumulation, whereas a further increase in valence (e.g., V4) significantly increased tumor-targeting efficiencies and led to higher cytomembrane accumulation. These results provide a basis for the strict surface control of nanomedicines in the precise regulation of in vivo transport at the subcellular level and their translation into clinical practice in the future.

Pulmonary cryptococcosis closely mimicking lung cancer in a membranous nephropathy patient taking calcineurin inhibitor.

In patients with membranous nephropathy (MN), malignancy may be either the underlying disease or results of immunosuppressive therapy which may also lead to opportunistic infections including the pulmonary cryptococcosis. On CT scan, nodule is the most common feature in pulmonary cryptococcosis and it can mimic lung cancer both clinically and radiologically. Therefore, pulmonary nodular lesions caused by cryptococcosis may be easily misdiagnosed and require unnecessary surgical treatment. As such, we herein presented an isolated subpleural solitary nodule with satellite lesion that closely mimicked lung cancer on both contrast-enhanced computed tomography (CT) scan and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT in an MN patient under long-term tacrolimus regimen. Cryptococcosis was ascertained by the finding of oval thick-walled yeast on histopathology of the lung biopsy specimen taken during the Argon-Helium cryotherapy. Further, the pulmonary lesions progressively dissipated after antifungal treatment. Arguably, our experience may help clinicians in general and nephrologists in particular with a better understanding of the cryptococcal infection manifesting as pulmonary nodule(s) in the MN patients and contribute to more efficacious differential diagnosis against the lung cancer.

An Atypical Incontinentia Pigmenti Female with Persistent Mucocutaneous Hyperinflammation and Immunodeficiency Caused by a Novel Germline IKBKG Missense Mutation.

While most missense mutations of the IKBKG gene typically result in Ectodermal Dysplasia with Immunodeficiency, there have been rare reported instances of missense mutations of the IKBKG gene causing both Incontinentia Pigmenti (IP) and immunodeficiency in female patients. In this study, we described an atypical IP case in a 19-year-old girl, characterized by hyperpigmented and verrucous skin areas over the entire body. Remarkably, she experienced recurrent red papules whenever she had a feverish upper respiratory tract infection. Immunohistochemical staining unveiled a substantial accumulation of CD68+ macrophages alongside the TNF-α positive cells in the dermis tissue of new pustules, with increased apoptotic basal keratinocytes in the epidermis tissue of these lesions. Starting from the age of 8 years old, the patient suffered from severe and sustained chronic respiratory mucous membrane scar hyperplasia and occluded subglottic lumen. In addition to elevated erythrocyte sedimentation rate values, inflammatory cells were observed in the pathologic lesions of endobronchial biopsies and Bronchoalveolar Lavage Fluid (BALF) smear. Further histological analysis revealed a destructive bronchus epithelium integrity with extensive necrosis. Simultaneously, the patient experienced recurrent incomplete intestinal obstructions and lips contracture. The patient's BALF sample displayed an augmented profile of proinflammatory cytokines and chemokines, suggesting a potential link to systemic hyperinflammation, possibly underlying the pathogenic injuries affecting the subglottic, respiratory, and digestive systems. Furthermore, the patient presented with recurrent pneumonias and multiple warts accompanied by a T+BlowNKlow immunophenotype. Next generation sequencing showed that the patient carried a novel de novo germline heterozygous missense mutation in the IKBKG gene (c. 821T>C, p. L274P), located in the highly conserved CC2 domain. TA-cloning sequencing of patient's cDNA yielded 30 mutant transcripts out of 44 clones. In silico analysis indicated that the hydrogen bond present between Ala270 and Leu274 in the wild-type NEMO was disrupted by the Leu274Pro mutation. However, this mutation did not affect NEMO expression in peripheral blood mononuclear cells (PBMCs). Moreover, patient PBMCs exhibited significantly impaired TNF-α production following Lipopolysaccharide (LPS) stimulation. X-chromosome inactivation in T cells and neutrophils were not severely skewed. Reduced levels of IκBα phosphorylation and degradation in patient's PBMCs were observed. The NF-κB luciferase reporter assay conducted using IKBKG-deficient HEK293T cells revealed a significant reduction in NF-kB activity upon LPS stimulation. These findings adds to the ever-growing knowledge on female IP that might contribute to the better understanding of this challenging disorder.

Hemophagocytic lymphohistiocytosis and histiocytic necrotizing lymphadenitis secondary to hemodialysis catheter-related bloodstream infection caused by Corynebacterium Striatum.

BACKGROUND: We herein described the coexistence of hemophagocytic lymphohistiocytosis (HLH) and histiocytic necrotizing lymphadenitis, alternatively known as the Kikuchi disease (KD), secondary to hemodialysis catheter-related bloodstream infection (BSI) caused by Corynebacterium striatum. CASE PRESENTATION: A patient on maintenance hemodialysis had developed persistent fever and Corynebacterium striatum was subsequently identified from the culture of both catheter tip and peripheral blood. During mitigation of the BSI, however, his fever was unabated and ensuing workup further found thrombocytopenia, hyperferritinemia, hypertriglyceridemia, low NK cell activity and a surge in serum CD25 levels. Moreover, biopsy of the bone marrow and lymph node detected histopathological evidence of hemophagocytosis and KD, respectively. Upon these abnormalities, the title-bound diagnosis was considered and the patient was eventually recovered from the treatment of dexamethasone instead of antibiotics. Consistently, aberrations in his serum CD25 levels and NK cell activity had subsided two months after discharge. CONCLUSIONS: Arguably, this encounter offered a unique chance to unravel the principal pathogenic cascade in immunobiology that made the three entities one disease continuum. As such, our work may add new understandings of HLH and/or KD secondary to severe infections in general and excessive release of cytokines in particular among patients with kidney diseases. The resultant early diagnosis is crucial to initiate appropriate treatment and improve the survival of patients with these challenging and potentially life-threatening disorders.

Structural characterization of an isocytosine-specific deaminase VCZ reveals its application potential in the anti-cancer therapy.

Non-natural nucleobase isocytosine (IC) is the isomer of cytosine; its chemical derivate 5-fluoroisocytosine (5-FIC) together with the isocytosine-specific deaminase (ICD) VCZ was suggested to be potential practical enzyme/prodrug pair for cancer therapy through gene-directed enzyme-prodrug therapy (GDEPT) method. In this study, we have determined the crystal structures of apo-VCZ and its complex with 5-FU. We identified the critical residues for substrate binding and catalytic reaction. We also captured the substrate-induced conformational changes of VCZ, then proposed the conjectural reaction procedures of VCZ for converting the IC into the uracil. Moreover, we evaluated the therapeutic effect of wildtype or the mutated VCZ protein in the colorectal cancer cell lines. Our studies will shed light on optimizing the ICD/5-FIC pairs by modifying either the enzyme or the prodrug based on the structural observations, thereby improving the possibility of applying the ICD/5-FIC pair in clinical trials.

Discovery of 3-(1H-benzo[d]imidazole-2-yl)-1H-pyrazol-4 -amine derivatives as novel and potent syk inhibitors for the treatment of hematological malignancies.

Spleen tyrosine kinase (Syk) is an important oncogene and signal transduction mediator that is mainly expressed in hematopoietic cells. Syk plays a key role in the B cell receptor (BCR) signaling pathway. Abnormal activation of Syk is closely related to the occurrence and development of hematological malignancies. Therefore, Syk is a potential target for the treatment of various hematologic cancers. Starting from compound 6(Syk, IC50 = 15.8 µM), we performed fragment-based rational drug design for structural optimization based on the specific solvent-accessible region, hydrophobic region, and ribose region of Syk. This resulted in the discovery of a series of novel 3-(1H-benzo [d]imidazole-2-yl)-1H-pyrazol-4-amine Syk inhibitors, which led to the identification of 19q, a highly potent Syk inhibitor that exhibited excellent inhibitory activity on Syk enzyme (IC50 = 0.52 nM) and showed potency against several other kinases. In addition, compound 19q effectively reduced phosphorylation of downstream PLCγ2 level in Romos cells. And it also exhibited antiproliferative activity in multiple hematological tumour cells. More gratifyingly, 19q showed impressive efficacy at a low dosage (1 mg/kg/day) in the MV4-11 mouse xenograft model without affecting the body weight of the mice. These findings suggest that 19q is a promising new Syk inhibitor for treating blood cancers.

Self-Assembled Bifunctional Copper Hydroxide/Gold-Ordered Nanoarray Composites for Fast, Sensitive, and Recyclable SERS Detection of Hazardous Benzene Vapors.

Volatile organic compounds (VOCs), particularly monoaromatic hydrocarbon compounds (MACHs), pose a potential risk to the atmospheric environment and human health. Therefore, the progressive development of efficient detection methodologies is a pertinent need, which is still a challenge at present. In this study, we present a rapid and sensitive method to detect trace amounts of MACHs using a bifunctional SERS composite substrate. We prepared an Au/SiO2 enhanced layer and a porous Cu(OH)2 adsorption layer via microfluidic-assisted gas-liquid interface self-assembly. The composite substrate effectively monitored changes in benzaldehyde using time-varying SERS spectra, and track-specifically identified various VOCs such as benzene, xylene, styrene, and nitrobenzene. In general, the substrate exhibited a rapid response time of 20 s to gaseous benzaldehyde, with a minimum detection concentration of less than 500 ppt. Further experimental assessments revealed an optimum Cu(OH)2 thickness of the surrounding adsorption layer of 150 nm, which can achieve an efficient SERS response to MACHs. Furthermore, the recoverable and reusable property of the composite substrate highlights its practicality. This study presents a straightforward and efficient approach for detecting trace gaseous VOCs using SERS, with significant implications in the designing of SERS substrates for detecting other VOCs.

Genetically Engineered Artificial Exosome-Constructed Hydrogel for Ovarian Cancer Therapy.

Owing to the insidious onset of ovarian cancer, most patients are in the advanced stage with extensive peritoneal metastasis when they are diagnosed. Treatment of peritoneal metastasis from advanced ovarian cancer remains a significant challenge. Inspired by the massive macrophages in the peritoneal environment, here, we reported an artificial exosome-based peritoneal-localized hydrogel to domesticate peritoneal macrophages as the therapeutic target for realizing potent ovarian cancer therapy, where artificial exosomes derived from genetically sialic-acid-binding Ig-like lectin 10 (Siglec-10)-engineered M1-type macrophages were chemically designed as gelator. Upon triggering immunogenicity with X-ray radiation, our hydrogel encapsulating efferocytosis inhibitor MRX-2843 enabled a cascade regulation to orchestrate polarization, efferocytosis, and phagocytosis of peritoneal macrophages for realizing robust phagocytosis of tumor cells and powerful antigen presentation, offering a potent approach for ovarian cancer therapy via bridging the innate effector function of macrophages with their adaptive immune response. Moreover, our hydrogel is also applicable for potent treatment of inherent CD24-overexpressed triple-negative breast cancer, providing an emerging therapeutic regimen for the most lethal malignancies in women.

Risk signature identification and NPRL2 affects sunitinib sensitivity in clear cell renal cell carcinoma.

Tumor suppressor genes (TSGs) play a crucial role in tumorigenesis and drug resistance. We analyzed the subtypes of clear cell renal cell carcinoma (ccRCC) mediated by 8 genes contained in the 3p21.3 tumor suppressor gene cluster and their effects on TME cell infiltration based on the TCGA database. The risk score model was established by principal component analysis. The hub gene NPRL2 was selected by protein-protein interactions (PPI) analysis. The effect of NPRL2 on sunitinib sensitivity of ccRCC was verified by using CCK-8, colony formation assay, wound healing assay, transwell assay and xenograft tumor model. Changes in protein expression were detected by Western blotting. We found that 8 TSGs were all differentially expressed in ccRCC samples, which could divide ccRCC into two subtypes. The constructed risk score model could predict the prognosis and drug sensitivity of ccRCC patients, and was an independent prognostic factor for ccRCC. Over-expression of NPRL2 promoted apoptosis, inhibited EMT, decreased the phosphorylation of the PI3K/AKT/mTOR signaling pathway to inhibit its activity, and promoted the sensitivity of sunitinib to ccRCC cells. Collectively, our findings increased the understanding of TSGs in ccRCC, suggesting that NPRL2 as a TSG could enhance sunitinib sensitivity to ccRCC cells.

Emetine, a small molecule natural product, displays potent anti-gastric cancer activity via regulation of multiple signaling pathways.

BACKGROUND: Gastric cancer (GC) is a life-threatening malignant tumor with high incidence rate. Despite great progress, there are still many GC sufferers that cannot benefit from the existing anti-GC treatments. Therefore, it is still necessary to develop novel medicines against GC. Emetine, a natural small molecule isolated from Psychotria ipecacuanha, has been broadly used for medicinal purposes including cancer treatment. Here, we conducted a comprehensive study on the anti-GC effects of emetine and the related mechanisms of action. METHODS: The cell viability was evaluated by MTT and colony formation assay. Cellular proliferation and apoptosis were analyzed by edu incorporation assay and Annexin V-PI staining, respectively. Moreover, wound healing assay and transwell invasion assay were conducted to detect cell migration and invasion after treatment with emetine. To elucidate the molecular mechanism involved in the anti-GC effects of emetine, RNA sequencing and functional enrichment analysis were carried out on MGC803 cells. Then, the western blot analysis was performed to further verify the anti-GC mechanism of emetine. In vivo anti-tumor efficacy of emetine was evaluated in the MGC803 xenograft model. RESULTS: MTT and colony formation assay exhibited a strong potency of emetine against GC cell growth, with IC50 values of 0.0497 µM and 0.0244 µM on MGC803 and HGC-27 cells, respectively. Further pharmacodynamic studies revealed that emetine restrained the growth of GC cells mainly via proliferation inhibition and apoptosis induction. Meanwhile, emetine also had the ability to block GC cell migration and invasion. The results of RNA sequencing and western blot showed that emetine acted through regulating multiple signaling pathways, including not only MAPKs and Wnt/ß-catenin signaling axes, but also PI3K/AKT and Hippo/YAP signaling cascades that were not found in other tumor types. Notably, the antitumor efficacy of emetine could also be observed in MGC803 xenograft models. CONCLUSION: Our data demonstrate that emetine is a promising lead compound and even a potential drug candidate for GC treatment, deserving further structural optimization and development.

Glutathione-Activated Emission of Ultrasmall Gold Nanoparticles in the Second Near-Infrared Window for Imaging of Early Kidney Injury.

Biomarker-activatable luminescent probes with high sensitivity and specificity show great promise in advanced bioimaging applications. However, the lack of stable biomarkers at an early stage is currently a major obstacle for sensitive early disease imaging. Herein, we develop a facile in vivo ligand exchange strategy to achieve renal-clearable activatable luminescent gold nanoparticles (AuNPs), which are independent of biomarkers for sensitive and long-time imaging of early kidney injury. Significantly activated emission in the second near-infrared region (∼1026 nm) is realized from the ligand exchange of triphenylphosphine-3,3',3″-trisulfonic acid (TPPTS)-coated AuNPs (∼1.4 nm, TPPTS-AuNPs) with quantitative amounts of glutathione (GSH). The abundant GSH in cells, particularly in liver sinusoids, is then demonstrated successfully to activate the emission of TPPTS-AuNPs with an extremely low background for both cell imaging and in vivo visualization of visceral organs (e.g., liver and kidneys). In addition, the in vivo GSH-exchanged TPPTS-AuNPs show enhanced interactions with acidic renal tubular epithelial cells, resulting in sensitive (contrast index, ∼3.9) and long-time (>6.5 h) noninvasive monitoring of acidosis-induced early kidney injury. This facile ligand exchange strategy opens new possibilities for designing activatable luminescent probes independent of biomarkers for earlier disease diagnosis and treatment.

Dose-effect relationship between dose-volume parameters of residual gross tumor volume and clinical prognosis in MRI-guided adaptive brachytherapy for locally advanced cervical cancer: a single-center retrospective study.

PURPOSE: To investigate the dose-effect relationship between the dose-volume parameters of residual gross tumor volume (GTVres) and clinical prognosis in MRI image-guided adaptive brachytherapy (IGABT) of patients with locally advanced cervical cancer in our center. MATERIALS AND METHOD: The clinical data of 93 patients with locally advanced cervical squamous cell cancer who received external beam radiotherapy (EBRT) combined with IGABT ± chemotherapy in our center were retrospectively analyzed. The disease stage, overall treatment time (OTT), chemotherapy, and the dose-volume parameters D90, D98, and D100 of GTVres, the intermediate-risk clinical target volume (CTVIR), and the high-risk clinical target volume (CTVHR) of the patients were statistically analyzed. Kaplan-Meier and uni- and multivariable Cox regression analyses were used to analyze 2­year overall survival (OS), progression-free survival (PFS), and local control rate (LC). A probit model was employed to assess the dose-effect relationship between the volume and dose-volume parameters of GTVres and 2­year OS, PFS, and LC. RESULTS: The median follow-up time was 19.6 months and 2­year OS, PFS, and LC were 79.6%, 68.8%, and 94.6%, respectively. CTVHR D90 was an independent influencing factor for 2­year PFS (P = 0.041); GTVresBT1 volume was an independent factor for 2­year OS, PFS, and LC (P < 0.001). The probit model showed that at GTVresBT1 volume < 32.86 cm3, the expected 2­year LC was > 90%; at GTVres D98 > 129.12 GyEQD2, the expected 2­year OS was > 90%. CONCLUSION: Both the volume and dose-volume parameters of GTVres are promising predictors in assessment of IGABT prognosis of cervical cancer.

Effects of physical exercise on the physical conditioning of college students / Efeitos do exercício físico sobre o condicionamento físico dos universitários / Efectos del ejercicio físico en la condición física de los estudiantes universitarios

ABSTRACT Introduction: The physical fitness of college students incites an alarming concern. Although the importance of fitness tests for college students has improved, the overall level and range are low. This requires colleges and universities to increase sports awareness and enrich their exercise methods. Relevant scientific articles can assist universities in promoting college students' physical and mental health. Objective: Analyze the effects of exercise on college students' physical fitness. Methods: We randomly selected 30 college students with normal cardiopulmonary function as volunteers for the research. Walking for 30 minutes was promoted, followed by a rapid walking test for college students. Factors such as breathing, heart rate, and other indicators during exercise were collected, measured, and evaluated. Results: The students in the research had good correlations with each index of oxygen uptake, CO2 exhalation, ventilation ratio, and heart rate during uniform running. The value of the indices tended to stabilize about 5 minutes after exercise. Conclusion: Active running exercise can improve aerobic endurance in college students. Physical fitness was improved in this trial. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O condicionamento físico dos estudantes universitários incita uma preocupação alarmante. Embora a importância dos testes de condicionamento físico para os estudantes universitários tenha se aprimorado, o nível geral e sua faixa de variação são baixos. Isso exige das faculdades e universidades atitudes para aumentar a consciência dos esportes e enriquecer seus métodos de exercício físico. Artigos científicos relevantes podem auxiliar as universidades em seus esforços para promover a saúde física e mental dos estudantes universitários. Objetivo: Analisar os efeitos da prática de exercícios físicos sobre o condicionamento físico dos universitários. Métodos: Selecionou-se aleatoriamente 30 estudantes universitários com função cardiopulmonar normal como voluntários para a pesquisa. Foi promovida a caminhada por 30 minutos seguida de um teste rápido de caminhada nos estudantes universitários. Fatores como a respiração, frequência cardíaca e outros indicadores durante o exercício foram coletados, medidos e avaliados. Resultados: Os estudantes da pesquisa tinham boas correlações com cada índice de absorção de oxigênio, exalação de CO2, relação de ventilação e frequência cardíaca durante a corrida uniforme. O valor dos índices tendeu a estabilizar-se cerca de 5 minutos após o exercício. Conclusão: O exercício de corrida ativa pode melhorar a resistência aeróbica dos estudantes universitários. O condicionamento físico foi aprimorado nesse experimento. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La condición física de los estudiantes universitarios suscita una alarmante preocupación. Aunque la importancia de las pruebas de aptitud física para los estudiantes universitarios ha mejorado, el nivel general y su alcance son bajos. Esto requiere que los colegios y universidades adopten actitudes para aumentar la conciencia deportiva y enriquecer sus métodos de ejercicio físico. Los artículos científicos pertinentes pueden ayudar a las universidades en sus esfuerzos por promover la salud física y mental de los estudiantes universitarios. Objetivo: Analizar los efectos del ejercicio físico en la aptitud física de los estudiantes universitarios. Métodos: Seleccionamos al azar 30 estudiantes universitarios con función cardiopulmonar normal como voluntarios para la investigación. Se promovió el caminar durante 30 minutos seguido de una prueba de marcha rápida en estudiantes universitarios. Se recogieron, midieron y evaluaron factores como la respiración, la frecuencia cardíaca y otros indicadores durante el ejercicio. Resultados: Los estudiantes de la investigación tenían buenas correlaciones con cada índice de captación de oxígeno, exhalación de CO2, relación de ventilación y frecuencia cardíaca durante la carrera uniforme. El valor de los índices tendía a estabilizarse unos 5 minutos después del ejercicio. Conclusión: El ejercicio de carrera activa puede mejorar la resistencia aeróbica de los estudiantes universitarios. En este experimento se mejoró la aptitud física. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Role of histone methyltransferase SETDB1 in regulation of tumourigenesis and immune response.

Epigenetic alterations are implicated in tumour immune evasion and immune checkpoint blockade (ICB) resistance. SET domain bifurcated histone methyltransferase 1 (SETDB1) is a histone lysine methyltransferase that catalyses histone H3K9 di- and tri-methylation on euchromatin, and growing evidence indicates that SETDB1 amplification and abnormal activation are significantly correlated with the unfavourable prognosis of multiple malignant tumours and contribute to tumourigenesis and progression, immune evasion and ICB resistance. The main underlying mechanism is H3K9me3 deposition by SETDB1 on tumour-suppressive genes, retrotransposons, and immune genes. SETDB1 targeting is a promising approach to cancer therapy, particularly immunotherapy, because of its regulatory effects on endogenous retroviruses. However, SETDB1-targeted therapy remains challenging due to potential side effects and the lack of antagonists with high selectivity and potency. Here, we review the role of SETDB1 in tumourigenesis and immune regulation and present the current challenges and future perspectives of SETDB1 targeted therapy.