The opposite effect of tapinarof between IMQ and IL-23 induced psoriasis mouse models.

Tapinarof is an aryl hydrocarbon receptor (AHR) ligand which is used to treat plaque psoriasis in adults. However, the underlying mechanism is not yet fully understood. In this study, we applied two of the most studied psoriasis mouse models: topical application of imiquimod (IMQ) and subcutaneous injection of IL-23. Although both models successfully induced psoriasis-like lesions in mice, tapinarof had a completely opposite effect on the two models. Tapinarof decreased the expression of multiple essential cytokines involved in the pathological IL-23/IL-17/IL-22 axis and ameliorated IMQ-induced psoriatic dermatitis, inhibiting keratinocyte proliferation and abnormal differentiation. However, in the IL-23-injection-model, tapinarof instead aggravated the disease. Here, tapinarof increased epidermal thickness and differentiated epidermal dysplasia in mice. Our data suggest that tapinarof may have different effects on varied types of psoriasis.

C/EBPß isoform-specific regulation of podocyte pyroptosis in lupus nephritis-induced renal injury.

As an essential factor in the prognosis of systemic lupus erythematosus (SLE), lupus nephritis (LN) can accelerate the rate at which patients with SLE can transition to chronic kidney disease or even end-stage renal disease. Podocytes now appear to be a possible direct target in LN in addition to being prone to collateral damage from glomerular capillary lesions induces by immune complexes and inflammatory processes. The NLRP3 inflammasome is regulated by CCAAT/enhancer-binding protein ß (C/EBPß), which is involved in the pathogenesis of SLE. However, the role and mechanism of C/EBPß in LN remain unclear. In this investigation, glomerular podocytes treated with LN serum and MRL/lpr mice were employed as in vivo and in vitro models of LN, respectively. In vivo, the expression of C/EBPß isoforms was detected in kidney specimens of humans and mice with LN. Then we assessed the effect of C/EBPß inhibition on renal structure and function by injecting RNAi adeno-associated virus of C/EBPß shRNA into MRL/lpr mice. In vitro, glomerular podocytes were treated with LN serum and C/EBPß siRNA to explore the role of C/EBPß in the activation of the AIM2 inflammasome and podocyte injury. C/EBPß-LAP and C/EBPß-LIP were significantly overexpressed in kidney tissue samples from LN patients and mice, and C/EBPß inhibition significantly alleviated renal function damage and ameliorated renal structural deficiencies. Inflammatory pathways downstream from the AIM2 inflammasome could be suppressed by C/EBPß knockdown. Furthermore, the upregulation of C/EBPß-LAP could activate the AIM2 inflammasome and podocyte pyroptosis by binding to the promoters of AIM2 and CASPASE1 to enhance their expression, and the knockdown of AIM2 or (and) caspase-1 reversed the effects of C/EBPß-LAP overexpression. Interestingly, C/EBPß-LIP overexpression could transcriptionally inhibit IRAG and promote Ca2+ release-mediated activation of the AIM2 inflammasome. This finding suggests that C/EBPß is not only involved in the regulation of the expression of key proteins of the AIM2 inflammasome but also affects the polymerization of key proteins of the AIM2 inflammasome through the regulation of Ca2+ release. In conclusion, this study provides a new idea for studying the regulatory mechanism of C/EBPß and provides a theoretical basis for the early diagnosis and treatment of LN in the future. © 2023 The Pathological Society of Great Britain and Ireland.

Real-world performance of HIV low viral load values in diagnosing acute HIV infection in a tertiary care hospital in Beijing, China.

BACKGROUND: Early diagnosis of HIV infection decreases the time from HIV diagnosis to viral suppression and reduces further HIV transmission. The Chinese Guidelines for the Diagnosis and Treatment of HIV/AIDS (2021 edition) state that an HIV RNA level > 5,000 copies/mL is the threshold for diagnosing HIV infection. The impact of low viral load values on HIV diagnosis needs to be investigated. METHODS: There were 3455 human immunodeficiency virus (HIV1 + 2) antibody results (immunoblotting method) and 65,129 HIV viral load values at Beijing Youan Hospital from 2019 to 2022. A total of 2434 patients had both antibody confirmatory results and viral load results. The confirmatory antibody results and HIV viral load results of 2434 patients were analyzed to investigate the impact of low viral load values on HIV diagnosis. RESULTS: Of the 2434 patients who had both confirmatory antibody results and viral load results, the viral load values of 140 patients (5.8%) had viral loads ranging from 40 copies/mL to 5,000 copies/mL before positive confirmatory antibody result, and of these 140 patients, the sample receipt time for the viral load tests of 96 (66.7%) individuals was 1 to 6 days earlier than the corresponding sample receipt time for the confirmatory antibody test. In addition, 34 patients (1.4%) had low viral loads ranging from 40 copies/mL to 1,000 copies/mL before positive confirmatory antibody result. CONCLUSION: This study revealed that there is a risk of missed diagnosis if a threshold of 5000 copies/mL is used for the diagnosis of HIV infection. These data provide valuable information for the early diagnosis of HIV infection, and our findings have potential benefits for decreasing HIV transmission.

Different Concentrations of Albumin Versus Crystalloid in Patients with Sepsis and Septic Shock: A Meta-Analysis of Randomized Clinical Trials.

OBJECTIVE: The best type of resuscitation fluids for sepsis and septic shock patients remains unclear. The aim of this study was to evaluate the efficacy of different concentrations of albumin on reducing the mortality rate of theses patients by meta-analysis. MATERIALS AND METHODS: PubMed, EMBASE, and Web of Science databases were used for screening the relevant studies. Randomized controlled trials (RCTs) were eligible if they compared the effects of albumin with crystalloid on mortality in patients with sepsis and septic shock. Data were examined and extracted by two reviewers independently. Any disagreements were resolved by consensus with or without the help from a third reviewer. Data including mortality, sample size of the patients, and resuscitation endpoints were extracted. Meta-analysis was carried based on the corresponding odds ratios with 95% confidence intervals. RESULTS: Eight studies with a total of 5124 septic patients and 3482 septic shock patients were included in this study. Compared with crystalloid, the use of albumin may represent a trend toward reduced the 90-day mortality of septic patients (OR 0.91 [0.80, 1.02]; P = .11) and significantly improved the outcome of septic shock patients (OR 0.85 [0.74, 0.99]; P = .04). Further analysis showed a potentially beneficial role of both 4% to 5% and 20% albumin on reducing the mortality of septic patients. The use of 20% albumin significantly decreased the 90-day mortality of septic shock patients (OR 0.81 [0.67, 0.98]; P = .03), which was better than 4% to 5% albumin and crystalloid. CONCLUSIONS: Albumin treatment, particularly 20% albumin, significantly reduced the 90-day mortality in septic shock patients. Both 4% to 5% and 20% of albumin may work better than crystalloid in improving the survival rate of patients with sepsis, but more relative RCTs are required for validation.

Cucurbit[7]uril-Mediated Supramolecular Bactericidal Nanoparticles: Their Assembly Process, Controlled Release, and Safe Treatment of Intractable Plant Bacterial Diseases.

A safe, biocompatible, and stimuli-responsive cucurbit[7]uril-mediated supramolecular bactericidal nanoparticle was fabricated by encapsulating a highly bioactive carbazole-decorated imidazolium salt (A1, EC50 = 0.647 µg/mL against phytopathogen Xanthomonas oryzae pv oryzae) into the host cucurbit[7]uril (CB[7]), thereby leading to self-assembled topographies from microsheets (A1) to nanospheroidal architectures (A1@CB[7]). The assembly behaviors were elucidated by acquired single-crystal structures, 1H NMR, ITC, and X-ray powder diffraction experiments. Complex A1@CB[7] displayed lower phytotoxicity and could efficiently switch on its potent antibacterial ability via introducing a simple competitor 1-adamantanamine hydrochloride (AD). In vivo antibacterial trials against rice bacterial blight revealed that A1@CB[7] could relieve the disease symptoms after being triggered by AD and provide a workable control efficiency of 42.6% at 100 µg/mL, which was superior to bismerthiazol (33.4%). These materials can provide a viable platform for fabricating diverse stimuli-responsive supramolecular bactericides for managing bacterial infections with improved safety.

Calpain-1 mediates vascular remodelling and fibrosis via HIF-1α in hypoxia-induced pulmonary hypertension.

Calpain-1, a calcium-activated neutral cysteine proteases, has been reported to be involved in the formation of pulmonary hypertension. HIF-1α, an oxygen-sensitive transcription factor, has been reported to activate genes involved in cell proliferation and extracellular matrix recombination. This study was designed to investigate the effect of calpain-1 in hypoxic pulmonary hypertension (HPH) and to explore whether there is a relationship between calpain-1 and HIF-1α in this disease. In the hypoxia-induced model of HPH, we found that hypoxia resulted in increased right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodelling and collagen deposition in lung tissues of mice. The levels of calpain-1 and HIF-1α were up-regulated in the lung tissues of hypoxia-treated mice and pulmonary arterial smooth muscle cells (PASMCs). Knock-out of calpain-1 restrained haemodynamic and histological changes induced by chronic hypoxia in mice, and inhibition of calpain-1 also repressed the abnormal proliferation and migration of PASMCs. Besides, knock-out or inhibition of calpain-1 suppressed hypoxia-induced expression of HIF-1α, VEGF, PCNA, TGF-ß1, MMP2 and collagen I in vivo and in vitro. While inhibition of HIF-1α abolished the above effects of calpain-1. Furthermore, we found that calpain-1 mediates the expression of HIF-1α through NF-κB (P65) under hypoxia conditions. In conclusion, our results suggest that calpain-1 plays a pivotal role in hypoxia-induced pulmonary vascular remodelling and fibrosis through HIF-1α, providing a better understanding of the pathogenesis of HPH.

User Experience of the Mobile Terminal Customization System: The Influence of Interface Design and Educational Background on Personalized Customization.

The study verified the role that different interface designs and users' educational backgrounds play in the task performance and subjective evaluation of mobile terminal customization system. Interface type (based on scroll, alternative, and attribute) and user group (college students and industrial workers) were employed as the variables. A total of 72 users were included in the study, and an analysis of 3 × 2 between-participants design indicated that (1) Different interface designs of customization systems had a significant difference in task performance, the alternative based interface had the best results in the task performance, and there was no significant difference between the attribute-based and scroll-based interfaces in task performance; (2) The matching between educational background and interface type will affect the users' evaluation on system usability. Industrial workers thought that the scroll-based and alternative-based interfaces were more useable, while college students preferred attribute-based interface design; (3) Different interfaces had a significant difference in user task load. The scroll-based interface had the lowest mental demand on the users, while alternative-based had the lowest physical demand on the users, though it consumed more effort; (4) Different educational backgrounds had a significant difference in user task load. Industrial workers showed lower effort in the scroll-based and alternative-based interfaces, while college students had lower effort in the attribution-based interface; (5) A correlation analysis showed that there was a significant negative correlation between the system usability score and the effort in task load. This study results have a positive significance for interface design. With educational background and layout as two important factors in our interface design, we may obtain the most appropriate design principles for enhancing the online customization experiences of different groups of consumers. The more important is that this study is based on the actual needs of the industry. For the first time, we take suitcase as an online customized product, which may not only help local manufacturers to extend their traditional offline distribution channels to online, but also provide a constructive thinking concerning interface design for customization of a single product.

Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation.

Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer.

A highly sensitive and selective chemiluminescent probe for peroxynitrite detection in vitro, in vivo and in human liver cancer tissue.

Peroxynitrite (ONOO-) is one of the important active nitrogen/reactive oxygen species that plays various roles in biological processes, such as inducing apoptosis and necrosis. Recent studies have shown that a significant increases in ONOO- content during tumor development, which is closely related to the level of oxidative stress within the tumor. It has been found that herbicide paraquat (PQ) can significantly increase the level of ONOO- in cells. Therefore, accurate monitoring abnormal changes in ONOO- caused by environmental hazardous materials and tumors is helpful in promoting the diagnosis and treatment of oxidative stress diseases (tumors), evenly environmental detection. Currently, traditional fluorescent probes for ONOO- detection have background interference. To address this, we developed a chemiluminescent probe (CL-1) and a fluorescent probe (Flu-1), using diphenyl phosphonate as a recognition group. CL-1 shows extremely sensitivity (9.8 nM), a high signal-to-noise(S/N) ratio (502), and excellent bioimaging capabilities compared to fluorescent probe (Flu-1). We have successfully used CL-1 to detect ONOO- produced by PQ stimulated cells, as well as endogenous ONOO- in tumor cells, mice, and human liver cancer tissues. Therefore, CL-1 can not only be a valuable tool for visualizing tumor and studying the role of ONOO- in tumor pathology, but the probe has the potential to be a powerful molecular imaging tool for exploring the complex biological role of ONOO- in a variety of biological Settings.

The prognostic value of vessels encapsulating tumor clusters (VETC) in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Studies have suggested that vessels encapsulating tumor clusters (VETC) is a strong predictor of prognosis in patients with hepatocellular carcinoma (HCC). METHODS: A systematic search was conducted in PubMed, Embase, Web of Science, and Scopus databases. Overall survival (OS) and tumor efficacy (TE) were two outcome measures used to evaluate the relationship between VETC and HCC prognosis. Hazard ratios (HR) and their 95% confidence intervals (CI) were used. RESULTS: Thirteen studies with 4429 patients were included in the meta-analysis. The results showed that VETC was significantly associated with both OS (HR 2.00; 95% CI 1.64-2.45) and TE (HR 1.70; 95% CI 1.44-1.99) in HCC patients. Furthermore, recurrence-free survival (RFS) was a stronger indicator of tumor efficacy (HR 1.73; 95% CI 1.44-2.07) than disease-free survival (DFS) (HR 1.69; 95% CI 1.22-2.35). This suggests that VETC-positive HCC has a higher risk of recurrence and a lower survival rate. CONCLUSION: In conclusion, the meta-analysis suggests that VETC is a significant predictor of overall survival and tumor efficacy in HCC patients and may be a valid prognostic indicator.

A nomogram for preoperative prediction of vessels encapsulating tumor clusters (VETC) pattern and prognosis of hepatocellular carcinoma.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) pattern of hepatocellular carcinoma (HCC) are associated with unfavorable prognosis. This study aimed to establish a nomogram model to predict VETC patterns based on preoperative CT imaging features. PATIENTS AND METHODS: Patients who underwent surgical resection between January 1, 2016 and August 31, 2022 were retrospectively included. Predictors associated with VETC pattern were determined by using logistic regression analyses, and a nomogram model was constructed. Prognostic factors associated with recurrence-free survival (RFS) after surgical resection were identified by using Cox regression analyses. RESULTS: A total of 84 patients were included for CT analysis. All patients underwent radical surgical resection. AST/ALT >1.07(odds ratio [OR], 4.91; 95 â€‹% CI: 1.11, 21.68; P â€‹< â€‹0.05), intratumoral necrosis (OR, 4.99; 95 â€‹% CI: 1.25, 19.99; P â€‹< â€‹0.05) and enhancing capsule (OR, 3.32; 95 â€‹% CI: 1.27, 8.94; P â€‹< â€‹0.05) were independent predictors of VETC pattern. These features were used for the construction of nomogram model, which showed comparable prediction performance, with AUC value of 0.767 (95%CI [0.662, 0.852]). CK19 status (Hazard ratio [HR], 2.02; 95 â€‹% CI: 1.06, 3.86; P â€‹< â€‹0.05), the number of tumors (HR, 3.31; 95 â€‹% CI: 1.47, 7.45; P â€‹< â€‹0.05) and VETC pattern (HR, 2.52; 95 â€‹% CI: 1.31, 4.86; P â€‹< â€‹0.05) were independent predictors of postoperative RFS. CONCLUSION: A nomogram model based on preoperative CT imaging features could be used for the characterization of VETC pattern, and has prognostic significance for postoperative RFS in patients with HCC.

Prediction of vessels encapsulating tumor clusters pattern and prognosis of hepatocellular carcinoma based on preoperative gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid magnetic resonance imaging.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) is a novel vascular pattern distinct from microvascular invasion that is significantly associated with poor prognosis in patients with hepatocellular carcinoma (HCC). This study aimed to predict the VETC pattern and prognosis of patients with HCC based on preoperative gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI). METHODS: Patients with HCC who underwent surgical resection and preoperative Gd-EOB-DTPA MRI between January 1, 2016 and August 31, 2022 were retrospectively included. The variables associated with VETC were evaluated using logistic regression. A nomogram model was constructed on the basis of independent risk factors. COX regression was used to determine the variables associated with recurrence-free survival (RFS). RESULTS: A total of 98 patients with HCC were retrospectively included. Peritumoral hypointensity on the hepatobiliary phase (HBP) (odd ratio [OR], 2.58; 95% CI, 1.05-6.33; P = .04), tumor-to-liver signal intensity ratio on HBP of ≤0.75 (OR, 27.80; 95% CI, 1.53-502.91; P = .02), and tumor-to-liver apparent diffusion coefficient ratio of ≤1.23 (OR, 4.65; 95% CI, 1.01-21.38; P = .04) were independent predictors of VETC pattern. A nomogram was constructed by combining the aforementioned 3 significant variables. The accuracy, sensitivity, and specificity were 69.79%, 71.74%, and 68.00%, respectively, with an area under the receiver operating characteristic curve of 0.75 (95% CI, 0.65-0.83). The variables significantly associated with RFS of patients with HCC after surgery were Barcelona Clinic Liver Cancer stage (hazard ratio [HR], 2.15; 95% CI, 1.09-4.22; P = .03) and VETC pattern (HR, 2.28; 95% CI, 1.29-4.02; P = .004). CONCLUSION: The preoperative imaging features based on Gd-EOB-DTPA MRI can be used to predict the VETC pattern, which has prognostic significance for postoperative RFS of patients with HCC.

The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia.

The long-term maintenance of leukaemia stem cells (LSCs) is responsible for the high degree of malignancy in MLL (mixed-lineage leukaemia) rearranged acute myeloid leukaemia (AML). The DNA damage response (DDR) and DOT1L/H3K79me pathways are required to maintain LSCs in MLLr-AML, but little is known about their interplay. This study revealed that the DDR enzyme ATM regulates the maintenance of LSCs in MLLr-AML with a sequential protein-posttranslational-modification manner via CBP-DOT1L. We identified the phosphorylation of CBP by ATM, which confers the stability of CBP by preventing its proteasomal degradation, and characterised the acetylation of DOT1L by CBP, which mediates the high level of H3K79me2 for the expression of leukaemia genes in MLLr-AML. In addition, we revealed that the regulation of CBP-DOT1L axis in MLLr-AML by ATM was independent of DNA damage activation. Our findings provide insight into the signalling pathways involoved in MLLr-AML and broaden the understanding of the role of DDR enzymes beyond processing DNA damage, as well as identigying them as potent cancer targets.

Thiol-Chromene "Click" Reaction-Activated Chemiluminescent Probe for Thiol Detection In Vitro and In Vivo.

Biothiols are biomolecules found in a higher content in cancer cells compared to normal cells, marking them useful cancer biomarkers. Chemiluminescence is widely used in biological imaging due to its excellent sensitivity and signal-to-noise ratio (SNR). In this study, we designed and prepared a chemiluminescent probe that is activated by a thiol-chromene "click" nucleophilic reaction. This probe is initially chemiluminescent but turned off and releases extremely strong chemiluminescence in the presence of thiols. It has high selectivity to thiol compared with other analytes. Real-time imaging of mice tumor sites showed significant chemiluminescence after the probe was injected, and the chemiluminescence of osteosarcoma tissues was also significantly stronger than that in adjacent tissues. We conclude that this chemiluminescent probe has potential to detect thiol, diagnose cancer, especially in its early stages, and aid in the development of related cancer drugs.

Differential diagnosis of lung cancer and tuberculosis based on 18 F-fluorodeoxyglucose PET/CT multi-time points imaging.

OBJECTIVE: To investigate the value of 18 F-fluorodeoxyglucose(FDG) PET/CT multi-time points imaging (MTPI) on the differential diagnosis between lung cancer (LC) and tuberculosis (TB). METHODS: Sixty-four patients underwent 18 F-FDG PET/CT MTPI. The stdSUVmax, stdSUVavg, retention index, metabolic tumor volume, total lesion glycolysis at four-time points and slope of metabolic curve were measured and calculated, and the sex, age, and uniformity of FDG uptake were recorded. The difference in each index between LC and TB was analyzed, and dynamic metabolic curves (DMCs) of LC and TB were fitted by significance indexes. Artificial neural network (ANN) prediction models were established between squamous cell carcinoma (SCC) and TB, as well as between adenocarcinomas and TB. RESULTS: Differences between SCC and TB, stdSUVmax/avg at four-time points, total lesion glycolysis, stdSUVmax/avg slope (1-2 h,1-3 h and 1-4 h), uniformity of FDG uptake and age were significant. stdSUVavg has the largest area under the 4 h curve; age was only significant between adenocarcinomas and TB. DMCs at 1-4 h fitted by stdSUVavg were more helpful in differentiating LC and TB than stdSUVmax. stdSUVavg(1 h and 4 h), stdSUVavg slope 1-4 h, age, and uniformity of FDG uptake were selected to establish an ANN prediction model between SCC and TB; the area under the curve (AUC) was 100.0%. The same indices were used to establish the prediction model between adenocarcinomas and TB; the AUC was up to 83.5, and after adding stdSUVavg (2 and 4 h) to adenocarcinomas and TB models, the AUC was 87.7%. CONCLUSION: 18 F-FDG PET/CT MTPI fitting DMCs and establishing an ANN prediction model would distinguish SCC from TB relatively accurately and provide certain help in the differentiation between adenocarcinomas and TB.

Diagnostic and predictive value of liquid biopsy-derived exosome miR-21 for breast cancer: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Studies have revealed that miR-21 is abnormally expressed in breast cancer patients, suggesting that miR-21 could be exploited as a possible diagnostic biomarker for clinical applications. In order to provide clinical evidence that is supported by research, we investigate the diagnostic utility of miR-21 in breast cancer in this study. METHODS: From their inception to 23 January 2022, the PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases were searched for all pertinent English literature. QUADAS-2 for literature quality assessment, GRADE for evidence grading. Statistical analyses were performed using the R 4.0.1 and Revman 5.3. The results were validated using Stata 15.1 software. Subgroup analysis was also performed according to the source of miR-21 and miR-21 combinations. RESULTS: Nine publications with 2048 patients were reviewed for inclusion. All of the included studies are of moderate-high quality. Meta-analysis was performed using a mixed-effects model. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), negative likelihood ratio (NLR) and positive likelihood ratio (PLR) were 0.91 [95% CI (0.86, 0.95)], 0.85 [95% CI (0.77, 0.91)], 56.62 [95% CI (21.00, 184.83)], 0.11 [95% CI (0.05, 0.18)] and 6.35 [95% CI (3.66, 11.16)], respectively. The GRADE classification for miR-21 was A, indicating a strong recommendation for breast cancer screening. CONCLUSIONS: The available evidence suggests that miR-21 has sufficient diagnostic value as a biomarker for breast cancer. Its diagnostic precision can be further improved by combining it with other miRNAs. Based on the GRADE review, miR-21 is strongly recommended for breast cancer screening.

Memory and threshold resistance switching in Ni/NiO core-shell nanowires.

We report on the first controlled alternation between memory and threshold resistance switching (RS) in single Ni/NiO core-shell nanowires by setting the compliance current (I(CC)) at room temperature. The memory RS is triggered by a high I(CC), while the threshold RS appears by setting a low I(CC), and the Reset process is achieved without setting a I(CC). In combination with first-principles calculations, the physical mechanisms for the memory and threshold RS are fully discussed and attributed to the formation of an oxygen vacancy (Vo) chain conductive filament and the electrical field induced breakdown without forming a conductive filament, respectively. Migration of oxygen vacancies can be activated by appropriate Joule heating, and it is energetically favorable to form conductive chains rather than random distributions due to the Vo-Vo interaction, which results in the nonvolatile switching from the off- to the on-state. For the Reset process, large Joule heating reorders the oxygen vacancies by breaking the Vo-Vo interactions and thus rupturing the conductive filaments, which are responsible for the switching from on- to off-states. This deeper understanding of the driving mechanisms responsible for the threshold and memory RS provides guidelines for the scaling, reliability, and reproducibility of NiO-based nonvolatile memory devices.

Inhibition of DEK Enhances Doxorubicin-Induced Apoptosis and Cell Cycle Arrest in T-Cell Acute Lymphoblastic Leukemia Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is a serious hematological tumor derived from early T-cell progenitors, which is extremely resistant to chemotherapy. Classically, doxorubicin (DOX) is an effective first-line drug for the treatment of T-ALL; however, DOX resistance limits its clinical effect. The DEK proto-oncogene (DEK) has been involved in neoplasms but remains unexplored in T-ALL. We silenced DEK on Jurkat cells and detected cell proliferation with cell counting and colony formation assay. Then, we detected DEK's drug sensitivity to DOX with CCK-8, cell cycle, and apoptosis with DOX treatment. Western blot analysis was performed to determine protein expression of apoptosis and cell cycle-related genes, including BCL2L1, caspase-3, and cyclin-dependent kinases (CDK). Finally, the tumorigenic ability of DEK was analyzed using a BALB/C nude mouse model. In this study, DEK was highly expressed in Jurkat cells. Inhibition of DEK can lead to decreased cell proliferation and proportion of S-phase cells in the cell cycle and more cell apoptosis, and the effect is more obvious after DOX treatment. Western blot results showed that DOX treatment leads to cell cycle arrest, reduction of cyclin-dependent kinase 6 (CDK6) protein, accumulation of CDKN1A protein, and DOX-induced apoptosis accompanied by reductions in protein levels of BCL2L1, as well as increases in protein level of caspase-3. Furthermore, DEK-silenced Jurkat cells generated a significantly smaller tumor mass in mice. Our study found that DEK is a novel, potential therapeutic target for overcoming DOX resistance in T-ALL.