Ultra-small, low-cost, and simple-to-control PSP projector based on SLCD technology.

Demand for ultra-small, inexpensive, and high-accurate 3D shape measurement devices is growing rapidly, especially in the industrial and consumer electronics sectors. Phase shifting profilometry (PSP) is a powerful candidate due to its advantages of high accuracy, great resolution, and insensitivity to ambient light. As a key component in PSP, the projector used to generate the phase-shifting sinusoidal fringes must be ultra-small (several millimeters), low-cost, and simple to control. However, existing projection methods make it difficult to meet these requirements simultaneously. In this paper, we present a modern technique that can be used to fabricate the desired projector. A specifically designed device based on segmented liquid crystal display (SLCD) technology is used to display the projected patterns, and a cylindrical lens is used as the projection lens. The SLCD device can display four sets of specific filled binary patterns, each yielding a sinusoidal fringe, and all four sinusoidal fringes satisfy the four-step phase shift relation. 3D shape measurement experiments verify the performance of the projector. Considering that the size of SLCD devices can be reduced to a few millimeters, the proposed technique can be easily used to manufacture ultra-small, low-cost, and simple-to-control PSP projectors.

[Retracted] MicroRNA­203 inhibits the proliferation and invasion of U251 glioblastoma cells by directly targeting PLD2.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the PLD2 western blotting data shown in Fig. 3A and the Transwell invasion assay data shown in Fig. 6 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 9: 503­508, 2014; 10.3892/mmr.2013.1814].

The regulatory role and clinical application prospects of circRNA in the occurrence and development of CNS tumors.

BACKGROUND: Central nervous system (CNS) tumors originate from the spinal cord or brain. The study showed that even with aggressive treatment, malignant CNS tumors have high mortality rates. However, CNS tumor risk factors and molecular mechanisms have not been verified. Due to the reasons mentioned above, diagnosis and treatment of CNS tumors in clinical practice are currently fraught with difficulties. Circular RNAs (circRNAs), single-stranded ncRNAs with covalently closed continuous structures, are essential to CNS tumor development. Growing evidence has proved the numeral critical biological functions of circRNAs for disease progression: sponging to miRNAs, regulating gene transcription and splicing, interacting with proteins, encoding proteins/peptides, and expressing in exosomes. AIMS: This review aims to summarize current progress regarding the molecular mechanism of circRNA in CNS tumors and to explore the possibilities of clinical application based on circRNA in CNS tumors. METHODS: We have summarized studies of circRNA in CNS tumors in Pubmed. RESULTS: This review summarized their connection with CNS tumors and their functions, biogenesis, and biological properties. Furthermore, we introduced current advances in clinical RNA-related technologies. Then we discussed the diagnostic and therapeutic potential (especially for immunotherapy, chemotherapy, and radiotherapy) of circRNA in CNS tumors in the context of the recent advanced research and application of RNA in clinics. CONCLUSIONS: CircRNA are increasingly proven to participate in decveloping CNS tumors. An in-depth study of the causal mechanisms of circRNAs in CNS tomor progression will ultimately advance their implementation in the clinic and developing new strategies for preventing and treating CNS tumors.

In Silico Identification of Therapeutic Targets and Novel Drug Candidates for Malignant Peripheral Nerve Sheath Tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive form of sarcomas with a poor prognosis and limited treatment options. Therefore, new therapeutic targets are urgently needed to identify novel drugs. METHODS: Based on the Gene Expression Omnibus database, an integrated analysis was performed to identify differentially expressed genes (DEGs) in MPNSTs compared to neurofibromas (NFs). Then functional enrichment analyses, protein-protein interaction (PPI) network construction, and hub gene selection were conducted. We explored DEG-guided repurposable drugs to treat MPNST based on the Library of Integrated Network-Based Cellular Signatures (LINCS) database. Furthermore, the binding affinity between predicted drug candidates and the MPNST-associated hub gene was calculated using molecular docking. RESULTS: We identified 89 DEGs in common with all three MPNSTs datasets. In the PPI networks, twist family bHLH transcription factor 1 (Twist1) with higher node degrees was further evaluated as a therapeutic target. Cytochalasin-d, cabozantinib, everolimus, refametinib, and BGT-226 were extracted from the LINCS database, which showed lower normalized connectivity scores (-1.88, -1.81, -1.78, -1.76, and -1.72, respectively) and was considered as drug candidates. In addition, the results of molecular docking between the five drugs and Twist1 showed a binding affinity of -6.61, -7.03, -7.73, -3.94, and -7.07 kcal/mol, respectively. CONCLUSIONS: Overall, our results describe the importance of Twist1 in MPNST pathogenesis. Everolimus was also found to be a potential therapeutic drug for MPNSTs.

Comprehensive analysis of mitochondrial dysfunction and necroptosis in intracranial aneurysms from the perspective of predictive, preventative, and personalized medicine.

Mitochondrial dysfunction and necroptosis are closely associated, and play vital roles in the medical strategy of multiple cardiovascular diseases. However, their implications in intracranial aneurysms (IAs) remain unclear. In this study, we aimed to explore whether mitochondrial dysfunction and necroptosis could be identified as valuable starting points for predictive, preventive, and personalized medicine for IAs. The transcriptional profiles of 75 IAs and 37 control samples were collected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene co-expression network analysis, and least absolute shrinkage and selection operator (LASSO) regression were used to screen key genes. The ssGSEA algorithm was performed to establish phenotype scores. The correlation between mitochondrial dysfunction and necroptosis was evaluated using functional enrichment crossover, phenotype score correlation, immune infiltration, and interaction network construction. The IA diagnostic values of key genes were identified using machine learning. Finally, we performed the single-cell sequencing (scRNA-seq) analysis to explore mitochondrial dysfunction and necroptosis at the cellular level. In total, 42 IA-mitochondrial DEGs and 15 IA-necroptosis DEGs were identified. Screening revealed seven  key genes invovled in mitochondrial dysfunction (KMO, HADH, BAX, AADAT, SDSL, PYCR1, and MAOA) and five genes involved in necroptosis (IL1B, CAMK2G, STAT1, NLRP3, and BAX). Machine learning confirmed the high diagnostic value of these key genes for IA. The IA samples showed  higher expression of mitochondrial dysfunction and necroptosis. Mitochondrial dysfunction and necroptosis exhibited a close association. Furthermore, scRNA-seq indicated that mitochondrial dysfunction and necroptosis were preferentially up-regulated in monocytes/macrophages and vascular smooth muscle cells (VSMCs) within IA lesions. In conclusion, mitochondria-induced necroptosis was involved in IA formation, and was mainly up-regulated in monocytes/macrophages and VSMCs within IA lesions. Mitochondria-induced necroptosis may be a novel potential target for diagnosis, prevention, and treatment of IA.

Oblique radiograph with methylene blue marking: A reliable technique for upper thoracic level localization.

Purpose: Traditionally, plain radiographs are used in intraoperative spinal level localization (SLL), whereas counting vertebrae is often hampered by shoulders and scapulae in lateral views, thus increasing the potential for wrong-level surgery. To improve the localization accuracy, this study evaluated the safety and feasibility of oblique radiographs with methylene blue markings for SLL and explored the optimal angle and height of oblique radiographs. Methods: The clinical data of 33 patients with upper thoracic spine lesions who were operated on in our hospital from January 2021 to April 2022 were retrospectively analyzed. Oblique radiographs with methylene blue markings were used for intraoperative SLL. Results: A total of 33 patients were included in this study. The average BMI was 24.3 ± 0.7 kg/m2. The ipsilateral lamina structures were clearly shown in all cases. The median radiographing times of all the patients was 3, and the median radiographing duration was 2 min and 25 s. The average angle of oblique radiographs was 55.1 ± 3.8°, and the average distance from the skin to the root of the spinous process was 4.9 ± 1.2 cm. Conclusions: Using oblique radiographs with methylene blue markings, not only the bone structure of an upper thoracic spine can be revealed clearly, but also the positioning deviation of traditional needle localization can be avoided. The lesion segment can be precisely located by this technology during surgery. Our angle of oblique radiographs and height determination method can be used to reduce the radiation exposure and shorten the operation time.

LINC00978 regulates metabolic rewiring to promote the malignancy of glioblastoma through AKR1B1.

Glioma is a fatal primary brain tumor. Improved glioma treatment effectiveness depends on a better understanding of its underlying mechanisms. Glioblastoma (GBM), was classified as high-grade glioma with the most lethality and therapeutic resistance. Herein, we reported LINC00978 overexpressed in high-grade gliomas. Down-regulation of LINC00978 in glioblastoma cells inhibited cell proliferation, invasion, migration, and induced apoptosis. In vivo experiments confirmed that the CamK-A siRNA of LINC00978 could effectively inhibit the proliferation of glioblastoma cells. The main pathway and genes regulated by LINC00978 were detected using RNA sequencing to elucidate the molecular mechanism. The results suggest that LINC00978 regulates the expression of genes related to metabolic pathways, including aldo-keto reductase family 1 member B (AKR1B1), which mediates the cytotoxicity of 2-deoxyglucose. LINC00978 positively regulated AKR1B1 expression, and 2-deoxyglucose induced AKR1B1 expression via a LINC00978-dependent mechanism. This research has revealed that LINC00978 promotes the sensitivity of glioblastoma cells to 2DG. LINC00978 is highly expressed in most high-grade glioma patients. Thus, understanding the anticancer mechanism identified in this study may contribute to treating the majority of glioma patients. This study clarified the function and molecular mechanism of LINC00978 in glioblastoma and provided a study basis for LINC00978 to guide the clinical treatment of glioblastoma.

Spinal extradural arachnoid cysts: A novel formation mechanism and dural defect location technology.

Purpose: The formation mechanism of spinal extradural arachnoid cysts (SEACs) remains unclear. There are several hypotheses for the formation of SEACs, but none of them can fully explain its pathological findings and surgical procedures. In this study, we retrospectively analyzed the cases of SEACs, aiming to clarify the formation mechanism of SEACs. In addition, we summarize a concise method for locating dural defects preoperatively and formulate a putative explanation of this method. Methods: The clinical data of 14 patients with SEACs underwent surgery in our hospital from January 2017 to December 2021 were retrospectively analyzed. Results: Fourteen patients were identified during the study period. The cysts all spanned the T12/L1 segment, and dural defects were also located at the T12/L1 level (2 cases not recorded) as well as the middle or the upper-middle level of the cysts. Nine cases were treated with total cyst excision, 2 cases were treated with dural defect closure only, and 3 cases were treated with total cyst excision and dural defect closure. Histopathological examination demonstrated that the cyst wall contained both the arachnoid epithelial and compact fibrous connective tissue. The symptoms were relieved in all patients, and no recurrence was observed. Conclusions: According to intraoperative and pathological findings, the dural outer layer cyst (DOLC) is a more reasonable hypothesis about SEACs formation. When CT myelography or cinematic MRI cannot determine the location of the dural defect preoperatively, it can be located according to the middle level of the SEACs with high accuracy.

Machine learning-based identification of SOX10 as an immune regulator of macrophage in gliomas.

Gliomas, originating from the glial cells, are the most lethal type of primary tumors in the central nervous system. Standard treatments like surgery have not significantly improved the prognosis of glioblastoma patients. Recently, immune therapy has become a novel and effective option. As a conserved group of transcriptional regulators, the Sry-type HMG box (SOX) family has been proved to have a correlation with numerous diseases. Based on the large-scale machine learning, we found that the SOX family, with significant immune characteristics and genomic profiles, can be divided into two distinct clusters in gliomas, among which SOX10 was identified as an excellent immune regulator of macrophage in gliomas. The high expression of SOX10 is related to a shorter OS in LGG, HGG, and pan-cancer groups but benefited from the immunotherapy. It turned out in single-cell sequencing that SOX10 is high in neurons, M1 macrophages, and neural stem cells. Also, macrophages are found to be elevated in the SOX10 high-expression group. SOX10 has a positive correlation with macrophage cytokine production and negative regulation of macrophages' chemotaxis and migration. In conclusion, our study demonstrates the outstanding cluster ability of the SOX family, indicating that SOX10 is an immune regulator of macrophage in gliomas, which can be an effective target for glioma immunotherapy.

A prognostic signature consisting of metabolism-related genes and SLC17A4 serves as a potential biomarker of immunotherapeutic prediction in prostate cancer.

Background: Prostate cancer (PCa), a prevalent malignant cancer in males worldwide, screening for patients might benefit more from immuno-/chemo-therapy remained inadequate and challenging due to the heterogeneity of PCa patients. Thus, the study aimed to explore the metabolic (Meta) characteristics and develop a metabolism-based signature to predict the prognosis and immuno-/chemo-therapy response for PCa patients. Methods: Differentially expressed genes were screened among 2577 metabolism-associated genes. Univariate Cox analysis and random forest algorithms was used for features screening. Multivariate Cox regression analysis was conducted to construct a prognostic Meta-model based on all combinations of metabolism-related features. Then the correlation between MetaScore and tumor was deeply explored from prognostic, genomic variant, functional and immunological perspectives, and chemo-/immuno-therapy response. Multiple algorithms were applied to estimate the immunotherapeutic responses of two MeteScore groups. Further in vitro functional experiments were performed using PCa cells to validate the association between the expression of hub gene SLC17A4 which is one of the model component genes and tumor progression. GDSC database was employed to determine the sensitivity of chemotherapy drugs. Results: Two metabolism-related clusters presented different features in overall survival (OS). A metabolic model was developed weighted by the estimated regression coefficients in the multivariate Cox regression analysis (0.5154*GAS2 + 0.395*SLC17A4 - 0.1211*NTM + 0.2939*GC). This Meta-scoring system highlights the relationship between the metabolic profiles and genomic alterations, gene pathways, functional annotation, and tumor microenvironment including stromal, immune cells, and immune checkpoint in PCa. Low MetaScore is correlated with increased mutation burden and microsatellite instability, indicating a superior response to immunotherapy. Several medications that might improve patients` prognosis in the MetaScore group were identified. Additionally, our cellular experiments suggested knock-down of SLC17A4 contributes to inhibiting invasion, colony formation, and proliferation in PCa cells in vitro. Conclusions: Our study supports the metabolism-based four-gene signature as a novel and robust model for predicting prognosis, and chemo-/immuno-therapy response in PCa patients. The potential mechanisms for metabolism-associated genes in PCa oncogenesis and progression were further determined.

A novel inflammation-related lncRNAs prognostic signature identifies LINC00346 in promoting proliferation, migration, and immune infiltration of glioma.

In this study, a total of 13 inflammation-related lncRNAs with a high prognostic value were identified with univariate, multivariate Cox regression analysis, and LASSO analysis. LINC00346, which is one of the 13 lncRNAs identified, was positively associated with type 2 macrophage activation and the malignant degree of glioma. Fluorescence in situ hybridization (FISH) and immunohistochemical staining showed that LINC00346 was highly expressed in high-grade glioma, while type 2 macrophages key transcription factor STAT3 and surface marker CD204 were also highly expressed simultaneously. LINC00346 high-expression gliomas were more sensitive to the anti-PD-1 and anti-CTLA-4 therapy. LINC00346 was also associated with tumor proliferation and tumor migration validated by EdU, cell colony, formation CCK8, and transwell assays. These findings reveal novel biomarkers for predicting glioma prognosis and outline relationships between lncRNAs inflammation, and glioma, as well as possible immune checkpoint targets for glioma.

CRX-527 induced differentiation of HSCs protecting the intestinal epithelium from radiation damage.

Recently, Toll-like receptors (TLRs) have been extensively studied in radiation damage, but the inherent defects of high toxicity and low efficacy of most TLR ligands limit their further clinical transformation. CRX-527, as a TLR4 ligand, has rarely been reported to protect against radiation. We demonstrated that CRX-527 was safer than LPS at the same dose in vivo and had almost no toxic effect in vitro. Administration of CRX-527 improved the survival rate of total body irradiation (TBI) to 100% in wild-type mice but not in TLR4-/- mice. After TBI, hematopoietic system damage was significantly alleviated, and the recovery period was accelerated in CRX-527-treated mice. Moreover, CRX-527 induced differentiation of HSCs and the stimulation of CRX-527 significantly increased the proportion and number of LSK cells and promoted their differentiation into macrophages, activating immune defense. Furthermore, we proposed an immune defense role for hematopoietic differentiation in the protection against intestinal radiation damage, and confirmed that macrophages invaded the intestines through peripheral blood to protect them from radiation damage. Meanwhile, CRX-527 maintained intestinal function and homeostasis, promoted the regeneration of intestinal stem cells, and protected intestinal injury from lethal dose irradiation. Furthermore, After the use of mice, we found that CRX-527 had no significant protective effect on the hematopoietic and intestinal systems of irradiated TLR4-/- mice. in conclusion, CRX-527 induced differentiation of HSCs protecting the intestinal epithelium from radiation damage.

The Protective Effects of Apigenin Against Radiation-Induced Intestinal Injury.

Radiation-induced intestinal injury (RIII) restricts the therapeutic efficacy of radiotherapy in abdominal or pelvic malignancies. Also, intestinal injury is a major cause of death following exposure to high doses of radiation in nuclear accidents. No safe and effective prophylactics or therapeutics for RIII are currently available. Here, we reported that the apigenin, a natural dietary flavone, prolonged the survival in c57 mice after lethal irradiation. Apigenin pretreatment brought about accelerated restoration of crypt-villus structure, including enhanced regenerated crypts, more differentiated epithelium cells, and increased villus length. In addition, intestinal crypt cells in the apigenin-treated group exhibited more proliferation and less apoptosis. Furthermore, apigenin increased the expression of Nrf2 and its downstream target gene HO-1, and decreased oxidative stress after irradiation. In conclusion, our findings demonstrate the radioprotective efficacy of apigenin. Apigenin has the potential to be used as a radioprotectant in cancer therapy and nuclear accidents.

Dimethyl Sulfoxide Attenuates Radiation-Induced Testicular Injury through Facilitating DNA Double-Strand Break Repair.

The testis is susceptible to ionizing radiation, and male infertility and sexual dysfunction are prevalent problems after whole-body or local radiation exposure. Currently, there is no approved agent for the prevention or treatment of radiation-induced testicular injury. Herein, we investigated the radioprotective effect of dimethyl sulfoxide (DMSO), an organosulfur compound that acts as a free radical scavenger, on testicular injury. Treatment of mice with a single dose of DMSO prior to 5 Gy irradiation restored sex hormones and attenuated the reduction in testis weight. Histological analyses revealed that DMSO alleviated the distorted architecture of seminiferous tubules and promoted seminiferous epithelium regeneration following irradiation. Moreover, DMSO provided quantitative and qualitative protection for sperm and preserved spermatogenesis and fertility in male mice. Mechanistically, DMSO treatment enhanced GFRα-1+ spermatogonial stem cell and c-Kit+ spermatogonial survival and regeneration after radiation. DMSO also alleviated radiation-induced oxidative stress and suppressed radiation-induced germ cell apoptosis in vivo and in vitro. Additionally, DMSO efficiently reduced DNA damage accumulation and induced the expression of phosph-BRCA1, BRCA1, and RAD51 proteins, indicating that DMSO facilitates DNA damage repair with a bias toward homologous recombination. In summary, our findings demonstrate the radioprotective efficacy of DMSO on the male reproductive system, which warrants further studies for future application in the preservation of male fertility during conventional radiotherapy and nuclear accidents.

The hydrogen storage nanomaterial MgH2 improves irradiation-induced male fertility impairment by suppressing oxidative stress.

OBJECTIVE: This study aimed to reveal the protective effect of hydrogen storage nanomaterial MgH2 on radiation-induced male fertility impairment. METHODS: The characterization of MgH2 were analyzed by scanning electron microscopy (SEM) and particle size analyzer. The safety of MgH2 were evaluated in vivo and in vitro. The radioprotective effect of MgH2 on the reproductive system were analyzed in mice, including sperm quality, genetic effect, spermatogenesis, and hormone secretion. ESR, flow cytometry and western blotting assay were used to reveal the underlying mechanisms. RESULTS: MgH2 had an irregular spherical morphology and a particle size of approximately 463.2 nm, and the content of Mg reached 71.46%. MgH2 was safe and nontoxic in mice and cells. After irradiation, MgH2 treatment significantly protected testicular structure, increased sperm density, improved sperm motility, reduced deformity rates, and reduced the genetic toxicity. Particularly, the sperm motility were consistent with those in MH mice and human semen samples. Furthermore, MgH2 treatment could maintain hormone secretion and testicular spermatogenesis, especially the generation of Sertoli cells, spermatogonia and round sperm cells. In vitro, MgH2 eliminated the [·OH], suppressed the irradiation-induced increase in ROS production, and effectively alleviated the increase in MDA contents. Moreover, MgH2 significantly ameliorated apoptosis in testes and cells and reversed the G2/M phase cell cycle arrest induced by irradiation. In addition, MgH2 inhibited the activation of radiation-induced inflammation and pyroptosis. CONCLUSION: MgH2 improved irradiation-induced male fertility impairment by eliminating hydroxyl free radicals. Mice fertility and function were evaluated with or without MgH2 treatment after 5 Gy irradiation. MgH2 had the ability of hydroxyl radicals scavenging and MDA suppressing in testicular tissue induced by irradiation. Further, MgH2 could participate in spermatogenesis and protect sperm development in three stages: the generation of Sertoli cells (Sox-9+), spermatogonia (Stra8+) and round sperm cells (Crem+). Moreover, MgH2 alleviated the decrease of testosterone secreted by interstitial cells after irradiation. In addition, MgH2 suppressed apoptosis, pyroptosis and inflammatory response and alleviated cell cycle arrest by mediating IR-induced ROS.

[Retracted] MicroRNA­663 inhibits the proliferation, migration and invasion of glioblastoma cells via targeting TGF­ß1.

Subsequently to the publication of the above article, an interested reader drew to the Editor's attention that they had identified several instances of overlapping data panels comparing between the scratch­wound assay data ('36 h' experiments) portrayed in Figs. 3 and 8; furthermore, there appeared to be an overlap in a pair of the data panels shown for the Transwell assay experiments with U87 cells in Fig. 9 (albeit with an inversion of one of the panels), such that these data may have been derived from the same original source, even though they were purportedly intended to show the results from differently performed experiments. Given the multiple instances of overlapping data panels that have been identified in the compilation of the figures in this article, the Editor of Oncology Reports has decided that this article should be retracted from the publication on account of a lack of overall confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 35: 1125­1134, 2016; DOI: 10.3892/or.2015.4432].

Dopamine-derived nanoparticles for the protection of irradiation-induced intestinal injury by maintaining intestinal homeostasis.

Radiotherapy of abdominal and pelvic tumors almost inevitably injures the intestine by oxidative stress and causes inflammation. Regrettably, traditional radioprotective agents for irradiation (IR) induced intestinal injury suffer from challenges such as poor solubility, unsatisfactory bioactivity and undesired adverse reactions, which significantly limit their usefulness. Polydopamine nanoparticles (PDA-NPs) have shown promising potential in scavenging reactive oxygen species (ROS) and suppressing inflammation. In this study, PDA-NPs were prepared by a simple method and their physical properties were characterized. Mice received two doses of PDA-NPs by oral gavage 22 h apart, and were irradiated with X-rays 2 h after the last gavage. The protective effect of PDA-NPs and possible mechanisms of protection against IR-induced intestinal injury were explored. The results showed that PDA-NPs were spherical and well dispersed, with good shape uniformity, compact structure, good colloid dispersion stability, concentration-dependent light absorption, and accurate quantification. Importantly, PDA-NPs reduced mortality and prolonged the average survival time of mice after IR. Furthermore, PDA-NPs protected mice from IR-induced injury to crypt-villus units and maintained intestinal barrier function in the intestine. In particular, PDA-NPs significantly inhibited the depletion of Lgr5+ intestinal stem cells (ISCs) and promoted cell regeneration after IR, which indicated that the regeneration ability of ISCs was maintained and the repair of intestinal structure and function was promoted. Finally, PDA-NPs significantly suppressed the apoptosis, inflammatory pyroptosis and DNA damage of intestinal cells induced by ionizing radiation. Altogether, our study suggested that PDA-NPs may have great potential in protecting the intestines from ionizing radiation damage.

Disulfiram Protects Against Radiation-Induced Intestinal Injury in Mice.

Radiation-induced intestinal injury (RIII) occurs after high doses of radiation exposure. RIII restricts the therapeutic efficacy of radiotherapy in cancer and increases morbidity and mortality in nuclear disasters. Currently, there is no approved agent for the prevention or treatment of RIII. Here, we reported that the disulfiram, an FDA-approved alcohol deterrent, prolonged the survival in mice after lethal irradiation. Pretreatment with disulfiram inhibited proliferation within 24 h after irradiation, but improved crypt regeneration at 3.5 days post-irradiation. Mechanistically, disulfiram promoted Lgr5+ intestinal stem cells (ISCs) survival and maintained their ability to regenerate intestinal epithelium after radiation. Moreover, disulfiram suppresses DNA damage accumulation, thus inhibits aberrant mitosis after radiation. Unexpectedly, disulfiram treatment did not inhibit crypt cell apoptosis 4 h after radiation and the regeneration of crypts from PUMA-deficient mice after irradiation was also promoted by disulfiram. In conclusion, our findings demonstrate that disulfiram regulates the DNA damage response and survival of ISCs through affecting the cell cycle. Given its radioprotective efficacy and decades of application in humans, disulfiram is a promising candidate to prevent RIII in cancer therapy and nuclear accident.

CMTM Family Genes Affect Prognosis and Modulate Immunocytes Infiltration in Grade II/III Glioma Patients by Influencing the Tumor Immune Landscape and Activating Associated Immunosuppressing Pathways.

Lower-grade glioma (LGG) is one of the most common primary tumor types in adults. The chemokine-like factor (CKLF)-like Marvel transmembrane domain-containing (CMTM) family is widely expressed in the immune system and can modulate tumor progression. However, the role of the CMTM family in LGG remains unknown. A total of 508 LGG patients from The Cancer Genome Atlas (TCGA) database were used as a training cohort, and 155 LGG patients from the Chinese Glioma Genome Atlas (CGGA) array database, 142 LGG patients from the CGGA RNA-sequencing database, and 168 LGG patients from the GSE108474 database were used as the validation cohorts. Patients were subdivided into two groups using consensus clustering. The ENET algorithm was applied to build a scoring model based on the cluster model. Finally, ESTIMATE, CIBERSORT, and xCell algorithms were performed to define the tumor immune landscape. The expression levels of the CMTM family genes were associated with glioma grades and isocitrate dehydrogenase (IDH) status. Patients in cluster 2 and the high-risk score group exhibited a poor prognosis and were enriched with higher grade, wild-type IDH (IDH-WT), 1p19q non-codeletion, MGMT promoter unmethylation, and IDH-WT subtype. Patients in cluster 1 and low-risk score group were associated with high tumor purity and reduced immune cell infiltration. Enrichment pathways analysis indicated that several essential pathways involved in tumor progression were associated with the expression of CMTM family genes. Importantly, PD-1, PD-L1, and PD-L2 expression levels were increased in cluster 2 and high-risk groups. Therefore, the CMTM family contributes to LGG progression through modulating tumor immune landscape.