High-performance transient SBS-based microwave measurement using high-chirp-rate modulation and advanced algorithms.

The transient stimulated Brillouin scattering (SBS) effect, enabled by optical chirp chain (OCC) technology, has already been proposed and demonstrated for microwave frequency identification with high temporal resolution. Through increasing the OCC chirp rate, the instantaneous bandwidth can be effectively extended without loss of the temporal resolution. However, the higher chirp rate results in more asymmetric transient Brillouin spectra, which worsens the demodulation accuracy when using the traditional fitting method. In this Letter, advanced algorithms, including image processing and artificial neural network, are employed to improve the measurement accuracy and demodulation efficiency. A microwave frequency measurement scheme is implemented with 4 GHz instantaneous bandwidth and 100 ns temporal resolution. Through the proposed algorithms, the demodulation accuracy of transient Brillouin spectra under 50 MHz/ns high chirp rate is improved from 9.85 MHz to 1.17 MHz. Moreover, owing to the matrix computations of the proposed algorithm, the time consumption is reduced by two orders of magnitude compared with the fitting method. The proposed method allows a high-performance OCC transient SBS-based microwave measurement, which provides new possibilities to realize real-time microwave tracking for diverse application fields.

High expression of AP2M1 correlates with worse prognosis by regulating immune microenvironment and drug resistance to R-CHOP in diffuse large B cell lymphoma.

BACKGROUND: First-line treatment with R-CHOP has cured 50%-60% patients of diffuse large B cell lymphoma (DLBCL), and more than one-third patients will eventually progressed to relapsed/refractory disease with dismal outcomes. Adaptor Related Protein Complex 2 Subunit Mu 1 (AP2M1) is required for the activity of a vacuolar ATPase and may also play an important role in regulating the intracellular trafficking and function of CTLA-4 protein. Herein, using both public databases and our own tumor samples, we aimed to demonstrate the prognostic role of AP2M1 and the potential tumor-promoting mechanisms in DLBCL. METHOD: Using public datasets of DLBCL from both GEO and TCGA databases, we analyzed the role of AP2M1 in mediating chemoresistance to R-CHOP and its correlation with various clinical parameters and prognosis. By using various R packages, we evaluated the role of AP2M1 on regulating tumor immune microenvironment. Moreover, tumor samples of DLBCL from Beijing TongRen Hospital were used to validate our findings by immunohistochemistry staining. RESULT: Expression of AP2M1 was significantly increased in DLBCL, which was correlated with poor prognosis and a variety of clinical indicators. On the basis of enrichment analysis, it was found that AP2M1 may be related to intracellular receptor signaling pathway. Through immune analysis and drug prediction, we found that the expression of AP2M1 affected the immune environment and drug response of DLBCL, which further revealed the important role of AP2M1 in DLBCL. By analyzing 61 patients treated uniformly with R-CHOP regimen in our center, we validated the above findings that high expression of AP2M1 correlated with inferior survival outcomes and affected sensitivity to R-CHOP treatment. CONCLUSION: Expression of AP2M1 may affect the prognosis of DLBCL patients probably by affecting the immune environment and the responses to many drugs in treating DLBCL, indicating AP2M1 as a potential therapy target in DLBCL.

Malignant clonal evolution drives multiple myeloma cellular ecological diversity and microenvironment reprogramming.

BACKGROUND: Multiple myeloma (MM) is a heterogeneous disease with different patterns of clonal evolution and a complex tumor microenvironment, representing a challenge for clinicians and pathologists to understand and dissect the contribution and impact of polyclonality on tumor progression. METHODS: In this study, we established a global cell ecological landscape of the bone marrow (BM) from MM patients, combining single-cell RNA sequencing and single-molecule long-read genome sequencing data. RESULTS: The malignant mutation event was localized to the tumor cell clusters with shared mutation of ANK1 and IFITM2 in all malignant subpopulations of all MM patients. Therefore, these two variants occur in the early stage of malignant clonal origin to mediate the malignant transformation of proplasmacytes or plasmacytes to MM cells. Tumor cell stemness index score and pseudo-sequential clonal evolution analysis can be used to divide the evolution model of MM into two clonal origins: types I and IX. Notably, clonal evolution and the tumor microenvironment showed an interactive relationship, in which the evolution process is not only selected by but also reacts to the microenvironment; thus, vesicle secretion enriches immune cells with malignant-labeled mRNA for depletion. Interestingly, microenvironmental modification exhibited significant heterogeneity among patients. CONCLUSIONS: This characterization of the malignant clonal evolution pattern of MM at the single-cell level provides a theoretical basis and scientific evidence for a personalized precision therapy strategy and further development of a potential new adjuvant strategy combining epigenetic agent and immune checkpoint blockade.

Chicken miR-126-5p negatively regulates antiviral innate immunity by targeting TRAF3.

Innate immunity plays an essential role in preventing the invasion of pathogenic microorganisms. However, innate immunity is a double-edged sword, whose excessive activation is detrimental to immune homeostasis and even leads to a "cytokine storm" of the infected host. The host develops a series of negative regulatory mechanisms to balance the immune response. Here, we report a negative regulatory mechanism of chicken innate immunity mediated by miRNA. In the GEO database, we found that miR-126-5p was markedly up-regulated in chickens infected by RNA viruses. Upregulation of miR-126-5p by RNA virus was then further shown via both a cell model and in vivo tests. Overexpression of miR-126-5p significantly inhibited the expression of interferon and inflammatory cytokine-related genes induced by RNA viruses. The opposite result was achieved after the knockdown of miR-126-5p expression. Bioinformatics analysis identified TRAF3 as candidate target gene of miR-126-5p. Experimentally, miR-126-5p can target TRAF3, as shown by the effects of miR-126-5p on the endogenous expression of TRAF3, and by the TRAF3 3'UTR driven luciferase reporter assay. Furthermore, we demonstrated that miR-126-5p negatively regulated innate immunity by blocking the MAVS-TRAF3-TBK1 axis, with a co-expression assay. Overall, our results suggest that miR-126-5p is involved in the negative regulation of chicken innate immunity, which might contribute to maintaining immune balance.

Fast Brillouin optical time-domain analysis using frequency-agile and compressed sensing.

A fast Brillouin optical time-domain analysis (BOTDA) sensor has been proposed and experimentally demonstrated based on the frequency-agile and compressed-sensing technique. The proposed scheme employs a data-adaptive sparse base obtained by the principle component analysis algorithm, enabling the sparse representation of Brillouin spectrum. Then, it can be reconstructed successfully with random frequency sampling and orthogonal matching-pursuit algorithms. In the experiment, the Brillouin gain spectrum (BGS) is mapped by the conventional fast BOTDA, where the frequency step and span are 4 MHz and 500 MHz, respectively. By using compressed-sensing technology, the BGS is successfully recovered with 37 random frequency samples, the number of which is only 30% of the full data. With fewer sampling frequencies, the compressed-sensing technology is able to improve the sensing performance of the conventional fast BOTDA, including a 3.3-time increase in sampling rate and 70% reduction in data storage.

N-doped carbon dots modified with the epithelial cell adhesion molecule antibody as an imaging agent for HepG2 cells using their ultra-sensitive response to Al3.

Carbon dots (CDs) are emerging as an ideal multifunctional materials due to their ease of preparation and excellent properties in medical imaging technology, environmental monitoring, chemical analysis and other fields. N-doped CDs modified with the epithelial cell adhesion molecule antibody (anti-EpCAM-NCDs) were synthesized in an ingenious and high-output approach. Due to the fluorescence enhancement effect of the introduced N atoms, the obtained anti-EpCAM-NCDs exhibited a strong green emission with an absolute quantum yield of up to 32.5%. Anti-EpCAM-NCDs have immunofluorescent properties and an active targeting function. The fluorescence effect and fluorescence quenching of anti-EpCAM-NCDs are used to image cells and detect Al3+, respectively. Experimental results show that this probe exhibited a wide linear response to Al3+over a concentration range of 0-100µM with a detection limit and quantification limit of 3 nM and 6 nM, respectively. Significantly, anti-EpCAM-NCDs, which have negligible cytotoxicity, excellent biocompatibility and high photostability, could be used for the intracellular imaging of HepG2 cells and the detection of Al3+in environmental and biological samples. As an efficient multifunctional material, anti-EpCAM-NCDs hold great promise for a number of applications in biological systems.

A full Bayesian partition model for identifying hypo- and hyper-methylated loci from single nucleotide resolution sequencing data.

BACKGROUD: DNA methylation is an epigenetic modification that plays important roles on gene regulation. Study of whole-genome bisulfite sequencing and reduced representation bisulfite sequencing brings the availability of DNA methylation at single CpG resolution. The main interest of study on DNA methylation data is to test the methylation difference under two conditions of biological samples. However, the high cost and complexity of this sequencing experiment limits the number of biological replicates, which brings challenges to the development of statistical methods. RESULTS: Bayesian modeling is well known to be able to borrow strength across the genome, and hence is a powerful tool for high-dimensional-low-sample-size data. In order to provide accurate identification of methylation loci, especially for low coverage data, we propose a full Bayesian partition model to detect differentially methylated loci under two conditions of scientific study. Since hypo-methylation and hyper-methylation have distinct biological implication, it is desirable to differentiate these two types of differential methylation. The advantage of our Bayesian model is that it can produce one-step output of each locus being either equal-, hypo- or hyper-methylated locus without further post-hoc analysis. An R package named as MethyBayes implementing the proposed full Bayesian partition model will be submitted to the bioconductor website upon publication of the manuscript. CONCLUSIONS: The proposed full Bayesian partition model outperforms existing methods in terms of power while maintaining a low false discovery rate based on simulation studies and real data analysis including bioinformatics analysis.

Cytosolic localization of Fox proteins in motor neurons of G93A SOD1 mice.

NeuN is a nuclear protein expressed exclusively in mature neurons and has served for many years as a reliable neuronal marker in immunohistochemical labeling studies. In 2009, NeuN was identified as Fox3, one of three closely related RNA binding proteins important in pre-mRNA splicing. During the course of a previous study using G93A SOD1 mice, a model of amyotrophic lateral sclerosis (ALS), we observed that NeuN was significantly redistributed to the cytosol. Since altered splicing may be important in the pathogenesis of ALS, we compared the localization (predominantly nuclear or cytosolic) of all three Fox proteins in the lumbar spinal cord of wild-type and G93A SOD1 mice before and after the development of clinical signs of disease. The Fox proteins regulate their own splicing, and we also examined the major Fox protein isoforms in nuclear and cytosolic fractions of lumbar spinal cord by Western blotting. We report here that Fox3 and Fox2 undergo a major cytosolic relocalization in this ALS model that increases with age and that is associated with progressive alterations in the splicing profiles of all three Fox proteins.

A comparative study on the heparin-binding proteomes of Toxoplasma gondii and Plasmodium falciparum.

Toxoplasma gondii is an obligatory intracellular apicomplexan parasite which exploits host cell surface components in cell invasion and intracellular parasitization. Sulfated glycans such as heparin and heparan sulfate have been reported to inhibit cell invasion by T. gondii and other apicomplexan parasites such as Plasmodium falciparum. The aim of this study was to investigate the heparin-binding proteome of T. gondii. The parasite-derived components were affinity-purified on the heparin moiety followed by MS fingerprinting of the proteins. The heparin-binding proteins of T. gondii and P. falciparum were compared based on functionality and affinity to heparin. Among the proteins identified, the invasion-related parasite ligands derived from tachyzoite/merozoite surface and the secretory organelles were prominent. However, the profiles of the proteins were different in terms of affinity to heparin. In T. gondii, the proteins with highest affinity to heparin were the intracellular components with functions of parasite development contrasted to that of P. falciparum, of which the rhoptry-derived proteins were prominently identified. The profiling of the heparin-binding proteins of the two apicomplexan parasites not only explained the mechanism of heparin-mediated host cell invasion inhibition, but also, to a certain extent, revealed that the action of heparin on the parasite extended after endocytosis.

Efficacy and safety analysis of combination therapy based on mitoxantrone hydrochloride liposome injection (Lipo-MIT) in relapsed/refractory NK/T-cell lymphoma.

Background: Currently, there is no standard treatment for relapsed/refractory NK/T-cell lymphoma (NKTCL). Liposomal mitoxantrone (Lipo-MIT) showed good anti-tumor effect in patients with NKTCL, breaking the limitation of natural resistance of NKTCL to anthracyclines. To further improve the efficacy, we tried a combination therapy based on Lipo-MIT in patients with relapsed/refractory NKTCL. Methods: 12 patients with relapsed/refractory NKTCL were enrolled in this retrospective study, all of whom had previously received pegaspargase-based treatments. The salvage treatment was a combination regimen based on Lipo-MIT. The efficacy was evaluated after every two cycles. Results: 11 patients had stage IV NKTCL, and all but one patients had an NRI score of ≥3. The median previous lines of treatment was two (range, 1-4), and five patients were refractory to their last line of treatment. The best response rates were as follows: complete response (CR) in five (41.7%) patients, partial response in five (41.7%) patients, stable disease in one (8.3%) patient, and progressive disease in one (8.3%) patient. At a median follow-up of four months (range, 2-14), seven patients died, with a median PFS of five months and a median OS of seven months. The six-month PFS and OS rate was 44.4% and 52.1%, respectively. All patients had suffered from side effects, among which myelosuppression was most reported. Nine patients had grade three or more myelosuppression, and the median recovery time from myelosuppression was 14 days (2-35 days). Five patients had obvious skin hyperpigmentation, and the CR rate was significantly higher compared with those without skin hyperpigmentation (80% vs. 14.3%, p=0.023). Other side effects included liver insufficiency (N=4), coagulation dysfunction (N=4), acute pancreatitis (N=2), and immunotherapy-related adverse effects (irAEs, N=2). Conclusion: Combination therapy based on Lipo-MIT has a high remission rate for relapsed/refractory NKTCL, but the duration of remission needs to be further extended. Lipo-MIT has obvious myelosuppression toxicity, and active supportive therapy should be given when combined with other cytotoxic drugs.

Ti3C2Tx MXene- and Sulfuric Acid-Treated Double-Network Hydrogel with Ultralow Conductive Filler Content for Stretchable Electromagnetic Interference Shielding.

Hydrogels are emerging as stretchable electromagnetic interference (EMI) shielding materials because of their tissue-like mechanical properties and water-rich porous cellular structures. However, achieving high-performance hydrogel shields remains a challenge because enhancing conductivity often results in a compromise in deformation adoptability. This work proposes a treatment strategy involving sulfuric acid/titanium carbide MXene, which can simultaneously enhance the conductivity and stretchability of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/poly(vinyl alcohol) (PVA) double-network hydrogels. Multiple spectroscopic characterizations reveal that sulfuric acid promotes the linear conformation transition of the PEDOT molecular chain, while MXene increases charge delocalization and hydrogen bond cross-linking sites. The hydrogels, synthesized with a combined content of 0.6 wt % of MXene and PEDOT:PSS, exhibit an average X-band EMI SE of 41 dB. This performance is sustained at 94.5%, even following stretching and release at a strain of 200%. Interestingly, the EMI SE is found to linearly increase, reaching a value of 99 dB as the frequency is increased to 26.5 GHz. This increase is attributed to the enhanced water molecular polarization process, as supported by theoretical calculations of the impedance and attenuation constant. This work introduces a post-treatment technique that optimizes double-network hydrogels, providing deep insights into their EMI shielding mechanism and enabling high-performance EMI shielding with an ultralow conductive filler content.

S-Block Metal Mg-Mediated Co─N─C as Efficient Oxygen Electrocatalyst for Durable and Temperature-Adapted Zn-Air Batteries.

In the quest to enhance Zn-air batteries (ZABs) for operating across a wide spectrum of temperatures, synthesizing robust oxygen electrocatalysts is paramount. Conventional strategies focusing on orbital hybridization of d-d and p-d aim to moderate the excessive interaction between the d-band of the transition metal active site and oxygen intermediate, yet often yield suboptimal performance. Herein, an innovative s-block metal modulation is reported to refine the electronic structure and catalytic behavior of Co─NC catalysts. Employing density functional theory (DFT) calculations, it is revealed that incorporating Mg markedly depresses the d-band center of Co sites, thereby fine-tuning the adsorption energy of the oxygen reduction reaction (ORR) intermediate. Consequently, the Mg-modified Co─NC catalyst (MgCo─NC) unveils remarkable intrinsic ORR activity with a significantly reduced activation energy (Ea) of 10.0 kJ mol-1, outstripping the performance of both Co─NC (17.6 kJ mol-1), benchmark Pt/C (15.9 kJ mol-1), and many recent reports. Moreover, ZABs outfitted with the finely tuned Mg0.1Co0.9─NC realize a formidable power density of 157.0 mW cm-2, paired with an extremely long cycle life of 1700 h, and an exceptionally minimal voltage gap decay rate of 0.006 mV h-1. Further, the Mg0.1Co0.9─NC-based flexible ZAB presents a mere 2% specific capacity degradation when the temperature fluctuates from 25 to -20 °C, underscoring its robustness and suitability for practical deployment in diverse environmental conditions.

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution.

BACKGROUND: To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution. METHODS: This retrospective study included 115 newly diagnosed patients with WR-DLBCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS). RESULTS: During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P  = 0.025 and P  = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4-99.8%) and 95.2% (95% CI: 89.0-100.0%), respectively, and 80.5% (95% CI: 69.3-93.6%) and 90.5% (95% CI: 52.8-99.8%) in the R-CHOP group. Patients without B symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11; 95% CI: 0.01-0.88) and 0.042 (HR: 0.19; 95% CI: 0.04-0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups. CONCLUSION: Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLBCL.

Development of a Universal Multi-Epitope Vaccine Candidate against Streptococcus suis Infections Using Immunoinformatics Approaches.

Streptococcus suis is a significant zoonotic pathogen that is a great threat not only to the swine industry but also to human health, causing arthritis, meningitis, and even streptococcal toxic shock-like syndrome. Owing to its many serotypes and high geographic variability, an efficacious cross-protective S. suis vaccine is not readily available. Therefore, this study aimed to design a universal multi-epitope vaccine (MVHP6) that involved three highly immunogenic proteins of S. suis, namely, the surface antigen containing a glycosaminoglycan binding domain (HP0197), endopeptidase (PepO), and 6-phosphogluconate dehydrogenase (6PGD). Forecasted T-cell and B-cell epitopes with high antigenic properties and a suitable adjuvant were linked to construct a multi-epitope vaccine. In silico analysis showed that the selected epitopes were conserved in highly susceptible serotypes for humans. Thereafter, we evaluated the different parameters of MVHP6 and showed that MVHP6 was highly antigenic, non-toxic, and non-allergenic. To verify whether the vaccine could display appropriate epitopes and maintain high stability, the MVHP6 tertiary structure was modeled, refined, and validated. Molecular docking studies revealed a strong binding interaction between the vaccine and the toll-like receptor (TLR4), whereas molecular dynamics simulations demonstrated the vaccine's compatibility, binding stability, and structural compactness. Moreover, the in silico analysis showed that MVHP6 could evoke strong immune responses and enable worldwide population coverage. Moreover, MVHP6 was cloned into the pET28a (+) vector in silico to ensure the credibility, validation, and proper expression of the vaccine construct. The findings suggested that the proposed multi-epitope vaccine can provide cross-protection against S. suis infections.

Biomarkers for predicting the efficacy of immune checkpoint inhibitors.

Immune checkpoint blockade has vastly changed the landscape of cancer treatment and showed a promising prognosis for cancer patients. However, there is still a large portion of patients who have no response to this therapy. Therefore, it's essential to investigate biomarkers to predict the efficacy of immune checkpoint inhibitors. This article summarizes the predictive value of established biomarkers, including programmed cell death ligand 1(PD-L1) expression level, tumor mutational burden, tumor-infiltrating lymphocytes, and mismatch repair deficiency. It also addresses the predictive value of tumorous mutations, circulation factors, immune-related factors, and gut microbiome with immunotherapy treatment. Furthermore, some of the emerging novel biomarkers, and potential markers for hyper progressive disease are discussed, which should be validated in clinical trials in the future.

An Immune-Related Prognostic Classifier Is Associated with Diffuse Large B Cell Lymphoma Microenvironment.

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is a life-threatening malignant tumor characterized by heterogeneous clinical, phenotypic, and molecular manifestations. Given the association between immunity and tumors, identifying a suitable immune biomarker could improve DLBCL diagnosis. METHODS: We systematically searched for DLBCL gene expression microarray datasets from the GEO database. Immune-related genes (IRGs) were obtained from the ImmPort database, and 318 transcription factor (TF) targets in cancer were retrieved from the Cistrome Cancer database. An immune-related classifier for DLBCL prognosis was constructed using Cox regression and LASSO analysis. To assess differences in overall survival between the low- and high-risk groups, we analyzed the tumor microenvironment (TME) and immune infiltration in DLBCL using the ESTIMATE and CIBERSORT algorithms. WGCNA was applied to study the molecular mechanisms explaining the clinical significance of our immune-related classifier and TFs. RESULTS: Eighteen IRGs were selected to construct the classifier. The multi-IRG classifier showed powerful predictive ability. Patients with a high-risk score had poor survival. Based on the AUC for three- and five-year survival, the classifier exhibited better predictive power than clinical data. Discrepancies in overall survival between the low- and high-risk score groups might be explained by differences in immune infiltration, TME, and transcriptional regulation. CONCLUSIONS: Our study describes a novel prognostic IRG classifier with strong predictive power in DLBCL. Our findings provide valuable guidance for further analysis of DLBCL pathogenesis and clinical treatment.

TLR4 Agonist Combined with Trivalent Protein JointS of Streptococcus suis Provides Immunological Protection in Animals.

Streptococcus suis (S. suis) serotype 2 (SS2) is the causative agent of swine streptococcosis and can cause severe diseases in both pigs and humans. Although the traditional inactive vaccine can protect pigs from SS2 infection, novel vaccine candidates are needed to overcome its shortcomings. Three infection-associated proteins in S. suis-muramidase-released protein (MRP), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and DLD, a novel putative dihydrolipoamide dehydrogenase-have been previously identified by immunoproteomic assays. In this study, the effective immune protection of the recombinant trivalent protein GAPDH-MRP-DLD (JointS) against SS2, SS7, and SS9 was determined in zebrafish. To improve the immune efficacy of JointS, monophosphoryl lipid A (MPLA) as a TLR4 agonist adjuvant, which induces a strong innate immune response in the immune cells of mice and pigs, was combined with JointS to immunize the mice. The results showed that immunized mice could induce the production of a high titer of anti-S. suis antibodies; as a result, 100% of mice survived after SS2 infection. Furthermore, JointS provides good protection against virulent SS2 strain infections in piglets. Given the above, there is potential to develop JointS as a novel subunit vaccine for piglets to prevent infection by SS2 and other S. suis serotypes.

LncRNA BCYRN1-induced autophagy enhances asparaginase resistance in extranodal NK/T-cell lymphoma.

Background: Asparaginase (ASP) is the cornerstone drug in the treatment of extranodal NK/T-cell lymphoma (ENKTCL), and the mechanisms of resistance to ASP remain largely unknown. Long non-coding RNAs play important roles in chemotherapy resistance in various cancers. However, the expression of BCYRN1 and its role in ENKTCL still remain unidentified. Methods: Lentivirus-mediated BCYRN1 overexpression and knockdown were performed in SNK-6 cells. Cell autophagy was analyzed by adenovirus expressing GFP-LC3B fusion protein. RNA pull-down and RNA Binding Protein Immunoprecipitation Assay were performed to investigate the relationship between BCYRN1 and p53. Western blot analysis was performed to assess the effect of BCYRN1 on different autophagy pathways. Finally, in vivo xenograft tumor model was constructed to analyze the effect of BCYRN1 on tumor growth and ASP resistance. Results: BCYRN1 was overexpressed in ENKTCL than normal NK cells, and patients with higher expression had significantly inferior progression-free survival (PFS). The IC50 value of ASP was significantly increased in BCYRN1-overexpressed SNK-6 cells and BCYRN1 overexpression could resist the inhibitory effect of ASP on proliferation. ASP could induce concurrent apoptosis and autophagy in ENKTCL, and the latter process was enhanced by overexpression of BCYRN1, mainly through affecting both PI3K/AKT/mTOR and p53/mTOR pathways. BCYRN1 could induce the degradation of p53 via ubiquitination, thus resulting in enhancement of autophagy and ASP resistance, which could be reversed by drug-induced autophagy inhibition. The effect of BCYRN1 on tumor growth and autophagy were confirmed in vivo xenograft model. Conclusions: It was found that BCYRN1 was a valuable prognostic biomarker in ENKTCL. BCYRN1 could promote resistance to ASP by inducing autophagy, which could be reversed by inhibition of autophagy. Our findings highlight the feasibility of combining autophagy inhibition and ASP in the treatment of ENKTCL.

MiR-624-3p Promotes Esophageal Squamous Cell Carcinoma Progression via Targeting Phosphatase and Tensin Homologue.

The emerging role of miRNA as regulators in esophageal squamous cell carcinoma (ESCC) progression has aroused great attention recently. In this study, the effects of miR-624-3p in ESCC progression were explored through cell proliferation, colony formation, cell cycle, and apoptosis analyses. Results showed that increased expression of miR-624-3p enhanced cancer cell viability, proliferation, migration, and invasion but inhibited apoptosis in ESCC. Moreover, luciferase reporter assay demonstrated that miR-624-3p bound to the 3'-untranslated region of phosphatase and tensin homologue (PTEN). Further study showed that miR-624-3p exerted its tumor promoting role through targeting PTEN. Taken together, these results elucidate the regulatory role of miR-624-3p in ESCC progression, shedding light on its possible clinical application in ESCC treatment.

Combinatorial discovery of Mo-based polyoxometalate clusters for tumor photothermal therapy and normal cell protection.

Nanomaterials with multiple functions such as precision diagnosis, therapeutic efficacy and biosafety are attractive for tumor treatment but remain a technical challenge. In this study, molybdenum (Mo)-based polyoxometalate clusters (Mo-POM) with considerable photothermal conversion efficiency (∼56.6%) and high stability (>30 days) were prepared through a modification of the Folin-Ciocalteu method. These synthetic particles accumulated at the target site, and induced thermal ablation of the tumor following near infrared (NIR) absorption. Furthermore, the Mo-POM effectively scavenged reactive oxygen species (ROS) through charge transfer between Mo(vi) and Mo(v) states, thereby avoiding off-target effects on normal cells and improving the therapeutic efficiency both in vitro and in vivo. Therefore, for the first time, we prepared Mo-POM having two key functions, i.e., photothermal therapy (PTT) for cancer cells and protection of normal cells. These exceptional features may open up the exploration of Mo-POM as new tools for PTT against tumors in clinical applications.