Serum Exosomal miRNA-125b and miRNA-451a are Potential Diagnostic Biomarker for Alzheimer's Diseases.

Aim: To explore the diagnostic value of serum-derived exosomal miRNAs and predict the roles of their target genes in Alzheimer's disease (AD) based on the expression of miRNAs in AD patients. Methods: We determined the relative concentration of exosomal miRNAs by High-throughput Second-generation Sequencing and real-time quantitative real-time PCR. Results: 71 AD patients and 71 ND subjects were collected. The study demonstrated that hsa-miR-125b-1-3p, hsa-miR-193a-5p, hsa-miR-378a-3p, hsa-miR-378i and hsa-miR-451a are differentially expressed in the serum-derived exosomes of AD patients compared with healthy subjects. According to ROC analysis, hsa-miR-125b-1-3p has an AUC of 0.765 in the AD group compared to the healthy group with a sensitivity and specificity of 82.1-67.7%, respectively. Enrichment analysis of its target genes showed that they were related to neuroactive ligand-receptor interactions, the PI3K-Akt signaling pathway, the Hippo signaling pathway and nervous system-related pathways. And, hsa-miR-451a had an AUC of 0.728 that differentiated the AD group from the healthy group with a sensitivity and specificity of 67.9% and 72.6%, respectively. Enrichment analysis of its target genes showed a relationship with cytokine-cytokine receptor interactions and the PI3K-Akt signaling pathway. Conclusion: The dysregulation of serum exosomal microRNAs in patients with AD may promote the diagnosis of AD. The target genes of miRNAs may be involved in the occurrence and development of AD through various pathways.

Development and validation of a novel nomogram for predicting overall survival patients with neuroblastoma.

PURPOSE: The aim of this study was to develop a nomogram specially for predicting overall survival (OS) for Chinese patients with neuroblastoma (NB). METHODS: Patients with pathologically confirmed NB who were newly diagnosed and received treatments at our hospital from October 2013 to October 2021 were retrospectively reviewed. The nomogram for OS were built based on Cox regression analysis. The validation of the prognostic model was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). RESULTS: A total of 254 patients with NB were included in this study. They were randomly divided into a training cohort (n = 178) and a validation cohort (n = 76) at a ratio of 7:3. Multivariate analyses revealed that prognostic variables significantly related to the OS were age at diagnosis, bone metastasis, hepatic metastasis, INSS stage, MYCN status and DNA ploidy. The nomogram was constructed based on above 6 factors. The C-index values of the nomogram for predicting 3-year and 5-year OS were 0.926 and 0.964, respectively. The calibration curves of the nomogram showed good consistency between nomogram prediction and actual survival. The DCAs showed great clinical usefulness of the nomograms. Furthermore, patients with low-risk identified by our nomogram had much higher OS than those with high-risk (p < 0.001). CONCLUSION: The nomogram we constructed exhibited good predictive performance and could be used to assist clinicians in their decision-making process.

Effects of combined sintilimab and chemotherapy on progression-free survival and overall survival in osteosarcoma patients with metastasis.

Objective: To explore the safety and efficacy of metastatic osteosarcoma treatment with combined sintilimab injection and chemotherapy. Methods: We performed a retrospective analysis of 32 patients with metastatic osteosarcoma admitted to the Affiliated Hospital of Beihua University between January 2019 and June 2020. The sample was divided into an observation group, treated with sintilimab injection combined with chemotherapy (n= 16) and a control group, treated with chemotherapy (n = 16). Clinical efficacy and adverse reactions were compared between the two groups. Results: The overall response rates were 68.75% in the observation group and 31.25% in the control group (p < 0.05). The incidences of adverse reactions were 56.25% in the observation group and 81.25% in the control group. This was not a significant difference. In the observation group, the progression-free survival time was 8.13 ± 2.50 months, and the overall survival time was 22.75 ± 4.95 months. These were both significantly longer than the respective 6.44 ± 1.93 months and 19.69 ± 2.68 months in the control group (p < 0.05). Conclusion: The treatment of metastatic osteosarcoma with combined sintilimab injection and chemotherapy was found to prolong progression-free survival and overall survival time without increasing the incidence of adverse reactions.

The anisotropic transport properties of the three-terminal ballistic junction based onα-T3lattice.

The three-terminal ballistic junction (TBJ) has promising applications in nanoelectronics. We investigate the transport properties of aα-T3-based TBJ, where two typical configurations are considered, i.e. the A- and Z-TBJ. It is found that both A- and Z-TBJ exhibit transmission anisotropy, and the transmission of the A-TBJ has stronger anisotropy than that of the Z-TBJ. The amplitude of the rectification coefficient is smaller than that of phosphorene TBJ, but larger than that of graphene TBJ. When the symmetrical input is applied, the output voltage curve exhibits symmetric behavior. While in the case of asymmetric input, the symmetric behavior is broken, and the maximum value of the output voltage can reach a positive value. Interestingly, the voltage output shows a dramatic nonlinear response which may be useful for the voltage diode application with a push-pull input voltage. In addition, the heat fluxes of the asymmetric input are much smaller than those of the symmetric input. The maximum value of the heat flux under the symmetric input exceeds twice of that under the asymmetric input. Our results are useful to design nanoelectronic devices based onα-T3TBJ.

Cost-effectiveness of the screen-and-treat strategies using HPV test linked to thermal ablation for cervical cancer prevention in China: a modeling study.

BACKGROUND: Self-sampling HPV test and thermal ablation are effective tools to increase screening coverage and treatment compliance for accelerating cervical cancer elimination. We assessed the cost-effectiveness of their combined strategies to inform accessible, affordable, and acceptable cervical cancer prevention strategies. METHODS: We developed a hybrid model to evaluate costs, health outcomes, and incremental cost-effectiveness ratios (ICER) of six screen-and-treat strategies combining HPV testing (self-sampling or physician-sampling), triage modalities (HPV genotyping, colposcopy or none) and thermal ablation, from a societal perspective. A designated initial cohort of 100,000 females born in 2015 was considered. Strategies with an ICER less than the Chinese gross domestic product (GDP) per capita ($10,350) were considered highly cost-effective. RESULTS: Compared with current strategies in China (physician-HPV with genotype or cytology triage), all screen-and-treat strategies are cost-effective and self-HPV without triage is optimal with the most incremental quality-adjusted life-years (QALYs) gained (220 to 440) in rural and urban China. Each screen-and-treat strategy based on self-collected samples is cost-saving compared with current strategies (-$818,430 to -$3540) whereas more costs are incurred using physician-collected samples compared with current physician-HPV with genotype triage (+$20,840 to +$182,840). For screen-and-treat strategies without triage, more costs (+$9404 to +$380,217) would be invested in the screening and treatment of precancerous lesions rather than the cancer treatment compared with the current screening strategies. Notably, however, more than 81.6% of HPV-positive women would be overtreated. If triaged with HPV 7 types or HPV16/18 genotypes, 79.1% or 67.2% (respectively) of HPV-positive women would be overtreated with fewer cancer cases avoided (19 cases or 69 cases). CONCLUSIONS: Screen-and-treat strategy using self-sampling HPV test linked to thermal ablation could be the most cost-effective for cervical cancer prevention in China. Additional triage with quality-assured performance could reduce overtreatment and remains highly cost-effective compared with current strategies.

Implementation of visual inspection with acetic acid and Lugol's iodine for cervical cancer screening in rural China.

OBJECTIVE: To address the value of visual inspection where HPV-based screening is not yet available, we evaluated the real-world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China. METHODS: A total of 206 133 women aged 30-59 years received two rounds of VIA/VILI screening for cervical cancer in 2006-2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures. RESULTS: The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2-year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%-83% of CIN2, 70%-86% of CIN3, and 88%-100% of cervical cancer. Over 92% of CIN2+ were found at the early stage. CONCLUSION: Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource-restricted settings.

Protection of Taohong Siwu Decoction on PC12 cells injured by oxygen glucose deprivation/reperfusion via mitophagy-NLRP3 inflammasome pathway in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (THSWD) is a traditional Chinese medicine formula used to invigorate blood circulation and resolve blood stasis. It consists of Paeonia lactiflora Pall., Conioselinum anthriscoides (H.Boissieu) Pimenov & Kljuykov, Rehmannia glutinosa (Gaertn.) DC., Prunus persica (L.) Batsch, Angelica sinensis (Oliv.) Diels, and Carthamus creticus L. in the ratio of 3:2:4:3:3:2. THSWD is a common prescription for the treatment of ischemic stroke. AIM OF THE STUDY: To study the protective effect and mechanism of Taohong Siwu Decoction (THSWD) on PC12 cells damaged by oxygen glucose deprivation/reperfusion (OGD/R). MATERIALS AND METHODS: OGD/R model of PC12 cells was used to simulate ischemia-reperfusion (I/R) injury of nerve cells in vitro. The experiment was grouped as follows: control, OGD/R and OGD/R + THSWD (5%, 10% and 15%) group. Oxygen and glucose was restored for 24 h after 4-6 h of deprivation. The severity of damage to PC12 cells was evaluated by CCK8, flow cytometry and lactate dehydrogenase (LDH). Mitochondrial morphology and function were examined by transmission electron microscopy (TEM), ATP and mitochondrial membrane potential (MMP) assay kits. Cellular autophagy and NLRP3 inflammasome-associated proteins were detected by Western blot and immunofluorescence staining. RESULTS: THSWD treatment improved the survival rate of PC12 cells injured by OGD/R, reduced cell damage and apoptosis. Moreover, ATP, MMP and the expression of autophagy marker proteins (LC3-II/LC3-I, Beclin1, Atg5) and mitophagy marker proteins (Parkin and PINK-1) was significantly elevated. The reactive oxygen species (ROS), NLRP3 inflammasome and pro-inflammatory cytokines induced by OGD/R were distinctly reduced. In contrast, these above beneficial effects of THSWD on mitochondrial autophagy and NLRP3 inflammasome were reversed by mitochondrial division inhibitory factor 1 (Mdivi-1). CONCLUSION: THSWD protects PC12 cells against OGD/R injury by heightening mitophagy and suppressing the activation of NLRP3 inflammasome.

Neuroprotective Effect of Taohong Siwu Decoction on Cerebral Ischemia/Reperfusion Injury via Mitophagy-NLRP3 Inflammasome Pathway.

Objective: Globally, cerebral ischemia has been shown to be the second leading cause of death. Our previous studies have shown that Taohong Siwu Decoction (THSWD) exhibits obvious neuroprotective effects on cerebral ischemia/reperfusion (I/R) injury (CIRI). In this study, we further explored the modulatory effect of THSWD on mitochondrial autophagy in CIRI and the relationship between modulatory effect and NLRP3 inflammatory vesicle activation, so as to further explain the mechanism of neuroprotective effect of THSWD. Methods: Middle cerebral artery occlusion reperfusion (MCAO/R) model in rats was built to simulate I/R. Adult male SD rats (220-270 g) were randomly divided into the following four groups: the sham group, the MCAO/R group, the MCAO/R + THSWD group, and the MCAO/R + THSWD + Mitochondrial division inhibitor 1 (Mdivi-1) group. Neurological defect scores were used to evaluate neurological function. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was conducted to measure cerebral infarct volume. Nissl staining, H&E staining and TUNEL staining were executed to detect ischemic cortical neuronal cell viability and apoptosis. Electron microscopy was used to observe the ultrastructural changes of mitochondria. Total Reactive Oxygen Species (ROS) in tissue were measured by fluorescence spectrophotometry, and the activation status of microglia was evaluated by Iba-1/CD16 immunofluorescence staining. The levels of mitophagy-related proteins (LC3, Parkin, PINK1), NLRP3 inflammasome-related proteins (NLRP3, ASC, Pro-caspase-1, Cleaved-caspase-1), and inflammatory cytokines (Pro-IL-18, Pro-IL-1ß, IL-18, IL-1ß) were evaluated by western blotting. Results: The studies showed that THSWD treatment alleviated cerebral infarction and neurological deficiencies. THSWD upregulated the expressions of autophagy markers (LC3-II/LC3-I and Beclin1) mitochondrial autophagy markers (Parkin and PINK1) after CIRI. Furthermore, THSWD treatment attenuated microglia activation and damage to mitochondrial structures, thereby reducing ROS production and NLRP3 inflammasome activation. In contrast, the mitochondrial autophagy inhibitor Mdivi-1 inhibited the above beneficial effects of THSWD. Conclusions: THSWD exhibits neuroprotective effects against MCAO/R in rats by enhancing mitochondrial autophagy and reducing NLRP3 inflammasome activation.

Impact of 11q Loss of Heterozygosity Status on the Response of High-Risk Neuroblastoma With MYCN Amplification to Neoadjuvant Chemotherapy.

Purpose: The aim of this study was to investigate whether 11q loss of heterozygosity (LOH) aberration would impact the response of the primary tumor to neoadjuvant chemotherapy or to the degree of surgical resection in neuroblastoma (NB) patients with MYCN amplification. Methods: The clinical data of 42 NB patients with MYCN amplification who were newly diagnosed and received treatments at our hospital from 2011 to 2020 were retrospectively analyzed. According to the results of the segmental chromosome aberration analysis, the patients enrolled were assigned to an 11qLOH positive group and an 11qLOH negative group. Results: There was no significant difference in the mean number of chemotherapy courses completed before surgery between the 11qLOH positive and 11qLOH negative groups (p = 0.242). Each of the 42 patients had metaiodobenzylguanidine (MIBG) scans both before and after neoadjuvant chemotherapy. The percentage of patients who had a clinical MIBG change in the 11qLOH positive group was lower than the percentage in the 11qLOH negative group (27.27 vs. 66.67%, p = 0.030). The 11qLOH negative group seemed to have a higher rate of surgical resection (≥90%); however, the difference between the two groups was not statistically significant (p = 0.088). Furthermore, the 11qLOH negative group did not show significantly superior event-free survival and overall survival rates compared with the 11qLOH positive group. Conclusions: This study showed that patients with NB and MYCN amplification in combination with 11qLOH might be less likely to respond to neoadjuvant chemotherapy when compared with patients with NB and MYCN amplification without 11qLOH.

Glucagon-like peptide-1 receptor activation by liraglutide promotes breast cancer through NOX4/ROS/VEGF pathway.

AIMS: Scientific evidence imply the strong correlation between diabetes and breast cancer. Glucagon-like peptide-1 (GLP-1) and its analogue liraglutide, have been widely used for diabetes treatment. However, the role of GLP-1 receptor (GLP-1R) in breast cancer requires further elucidation. This study aimed to investigate the risk and the molecular mechanisms of liraglutide using in breast cancer. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction, western blot or immunohistochemistry were used to detect the expressions of GLP-1R, NADPH oxidase 4 (NOX4) and vascular endothelial growth factor (VEGF) in human triple negative breast cancer (TNBC) cells (MDA-MB-231 and MDA-MB-468) and tissues derived from BALB/cfC3H mouse bearing 4T1 cells inoculation. Cell proliferation and migration was detected using the Cell Counting Kit-8, adenosine triphosphate assay, and transwell assay, respectively. Flow cytometry was used to measure the level of reactive oxygen species (ROS). KEY FINDINGS: We found that the expression of GLP-1R increased after liraglutide treatment in breast cancer cells and the transplanted tumors. Liraglutide, at a slightly higher concentration, accelerated breast cancer progress in vitro (100 nM) and in vivo (400µg/kg) through the NOX4/ROS/VEGF signal pathway after activating GLP-1R. The GLP-1R inhibitor, Exendin (9-39), significantly inhibited the effect of liraglutide, inducing a reversed function of GLP-1R activation. SIGNIFICANCE: Our study illustrated that in an approximately toxicology context, liraglutide may promote the malignant progression of TNBC. The dosage and the phenotype of the breast cancer should be considered as important factors for the rational administration of antidiabetic drugs, especially that of liraglutide in breast cancer patients.

Long non­coding RNA­DUXAP8 regulates TOP2A in the growth and metastasis of osteosarcoma via microRNA­635.

Osteosarcoma (OS) is a malignant disease with high morbidity and mortality rates in children and adolescents. Evidence has indicated that long non­coding RNAs (lncRNAs) may serve important roles in human cancer progression, including OS. In the present study, the role of lnc­double homeobox A pseudogene 8 (DUXAP8) in the development of OS was identified. The expression of lncRNA­DUXAP8 was determined by reverse transcription­quantitative polymerase chain reaction in OS tissues. Cell proliferation was evaluated using Cell Counting kit­8 and colony formation assays, and Transwell assays were conducted to measure cell invasion. Cell migration was evaluated using a wound healing assay. The binding site between lnc­DUXAP8 and miR­635 RNAs was investigated using a luciferase reporter assay. The expression of lnc­DUXAP8 was significantly upregulated in OS samples and OS cell lines compared with normal tissues. High expression of lncRNA DUXAP8 was associated with shorter overall survival times. Knockdown of lncRNA DUXAP8 inhibited proliferation, migration and invasion in OS cells. Notably, mechanistic investigation revealed that lncRNA DUXAP8 predominantly acted as a competing endogenous RNA in OS by regulating the miR­635/topoisomerase alpha 2 (TOP2A) axis. lncRNA DUXAP8 is upregulated in OS, and lncRNA DUXAP8­knockdown serves a vital antitumor role in OS cell progression through the miR­635/TOP2A axis. The results of the present study suggested that lncRNA DUXAP8 may be a novel, promising biomarker for the diagnosis and prognosis of OS.

Efficacy of point-of-care thermal ablation among high-risk human papillomavirus positive women in China.

Thermal ablation is a point-of-care ablative treatment technique for cervical intraepithelial neoplasia (CIN). However, limited information is available about its efficacy in low- and middle-income countries. We evaluated the efficacy of thermal ablation in treatment of CIN detected through high-risk human papillomavirus (HPV) screening in China. Women positive on high-risk HPV and having colposcopically suspected lesions eligible for ablation underwent colposcopy, biopsy and thermal ablation in one visit. Women ineligible were recalled for large loop excision of transformation zone (LLETZ) when histopathology results were high-grade CIN. Posttreatment follow-up at 6 months or more was with HPV test and cytology followed by colposcopy and biopsy for HPV and/or cytology-positive women. Cure was defined as either negative cytology and HPV test or absence of histopathology proved CIN in any positive women. Of total 218 HPV-positive women treated with thermal ablation (n = 170) or LLETZ (n = 48), 196 reported for follow-up evaluation. For women with histologically confirmed CIN at baseline (thermal ablation-104; LLETZ-38), cure rates were 84.6% for thermal ablation and 86.8% for LLETZ. Cure rates after thermal ablation were 90.3% for CIN grade one (CIN1) and 76.2% for CIN grade two or worse (CIN2+). HPV clearance rate was 80.4% in women undergoing thermal ablation, which was lower for HPV16/18 compared to other oncogenic types (67.6% vs 85.7%). HPV test had a negative predictive value (NPV) of 98.7% to detect CIN2+ at follow-up and the positive predictive value (PPV) was 40.4%. Thermal ablation is effective to treat CIN as well as to clear the high-risk HPV infection. HPV test has high PPV and NPV in following up patients posttreatment.

Sunitinib inhibits PD-L1 expression in osteosarcoma by targeting STAT3 and remodels the immune system in tumor-bearing mice.

Aim: Exploring the mechanisms of the combination therapy using VEGFR-TKI and immune checkpoint inhibitors might be useful to control the development of osteosarcoma. Materials & methods: The expression of PD-L1 and STAT3 in osteosarcoma were determined with western blot. Proliferation, migration and invasion were determined with CCK-8 and Transwell assays. Lung metastases, tumor growth, survival and immune cell populations were performed in tumor-bearing mice. Results: Sunitinib reduced the expression of PD-L1 by inhibiting the activation of STAT3 and suppressed the migration and invasion in osteosarcoma cells. Combination therapy reduced lung metastases, tumor growth, improved survival and reverse tumor microenvironment in tumor-bearing mice. Conclusion: Sunitinib inhibits PD-L1 expression by targeting STAT3 and remodels the immune system in tumor-bearing mice.

Effectiveness of Combined Immunoglobulin and Glucocorticoid Treatments in a Patient With Stiff Limb Syndrome: Case Report and Review of the Literature.

Stiff limb syndrome (SLS) is a rare autoimmune-related central nervous system disorder, resulting in stiffness and spasms of limbs since onset with rare involvement of the truncal muscles. However, SLS patients will gain notable effects by appropriate therapy focusing on symptomatic treatment and immunotherapy. We reported on a 55-year-old female who showed typical painful spasms in both lower limbs and abduction of the right eyeball that partially responded to low-dose diazepam and had high-titer anti-glutamic acid decarboxylase (anti-GAD) antibody. Electromyography (EMG) only showed continuous motor unit activity (CMUA) in the anterior tibialis and right triceps. Eventually, our patient was diagnosed with SLS and treated with intravenous immunoglobulin (IVIG) and glucocorticoid combined simultaneously. She obtained notable effects. We also review and summarize the current literature on clinical characteristics, coexisting disease, treatment, and outcome of 40 patients with SLS. We hope that this report will provide a basis for further understanding of SLS and promote the formation of more advanced diagnosis and treatment processes.

Comparative performance evaluation of different HPV tests and triaging strategies using self-samples and feasibility assessment of thermal ablation in 'colposcopy and treat' approach: A population-based study in rural China.

Human papillomavirus (HPV) test, self-sampling and thermal ablation for cervical intraepithelial neoplasia (CIN) have been developed separately to increase screening coverage and treatment compliance of cervical cancer screening programmes. A large-scale study in rural China screened 9,526 women with their combinations to explore the optimal cervical cancer-screening cascade in the real-world. Participants received careHPV and polymerase chain reaction (PCR) HPV tests on self-collected samples. Women positive on either HPV test underwent colposcopy, biopsy and thermal ablation in a single visit. Samples positive on either HPV test were retested for genotyping. Absolute and relative performance of HPV tests, triage strategies, 'colposcopy and thermal ablation' approach were statistically evaluated. PCR HPV test detected 33.3% more CIN grade two or worse (CIN2+) at a cost of 28.1% more colposcopies compared to careHPV. Sensitivities of PCR HPV and careHPV tests to detect CIN2+ were 96.7 and 72.5%. Specificities for the same disease outcome were 82.1 and 86.0%. Triaging HPV-positive women with HPV16/18 genotyping considerably improved the positive predictive value for CIN2+ (4.8-5.0 to 18.2-19.2%). Ninety-six women positive on HPV and having abnormal colposcopy were eligible for thermal ablation and all accepted same-day treatment, contributing to 64.6% being treated appropriately (CIN1+ on histopathology), which reached up to 84.8% among women positive on HPV 16/18 triage. No serious side-effects/complications were reported. The combination of PCR HPV test followed by HPV 16/18 triaging on self-collected samples and colposcopy of triage positive women followed by immediate thermal ablation might be the appropriate screening cascade for rural China.

Benzyl butyl phthalate (BBP) triggers the malignancy of acute myeloid leukemia cells via upregulation of PDK4.

Acute Myeloid Leukemia (AML) is a cancer of hematopoietic stem cells with a rapid progression. Recent studies indicated that endocrine disruptor chemicals (EDCs) are potential risk factors for AML progression. Our present data showed that an industrial endocrine disrupting chemical, Benzyl butyl phthalate (BBP), can promote the proliferation of AML cells and decrease their sensitivity to daunorubicin (DNR) and cytarabine (Ara-C) treatments. Further, BBP can increase the glucose consumption, lactate generation, and ATP levels of AML cells. Among the measured glycolysis-related genes, BBP can increase the expression of pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4), a mitochondrial protein that regulates the tricarboxylic acid cycle (TCA) cycle. The inhibitor of PDK4 or its specific siRNA can attenuate BBP-induced cell proliferation and ATP generation, which suggested the essential roles of PDK4 in BBP-induced glycolysis and proliferation. Further, BBP can increase the mRNA stability of PDK4, while had no effect on its transcription and protein stability. miR-15b-5p can bind with the 3'UTR of PDK4 to decrease its mRNA stability, while BBP can decrease the expression of miR-15b-5p in AML cells. Collectively, our data showed that BBP can trigger the malignancy of AML cells via regulation of miR-15b-5p/PDK4 signals.

Clinical Performance of Human Papillomavirus Testing and Visual Inspection With Acetic Acid in Primary, Combination, and Sequential Cervical Cancer Screening in China.

BACKGROUND: World Health Organization guidelines recommend screening with human papillomavirus (HPV) testing followed by either treatment of all HPV-positives, or by visual inspection (VIA) for triage to treatment, citing insufficient evidence to recommend either strategy over the other. METHODS: We assessed VIA and HPV testing individually, in combination (HPV-VIA cotesting), and as triage models. Three thousand women were screened in Inner Mongolia, China, concurrently with HPV testing and VIA in a real population setting. Screen-positive women underwent colposcopy, and biopsy, if indicated. Accuracy of screening algorithms for cervical intraepithelial neoplasia grade 2 or higher (CIN-2+) was calculated after controlling for verification bias. HPV testing followed by VIA triage for CIN-2+ detection was compared with Hybrid Capture 2 viral loads triage, measured in relative light units/cutoff. RESULTS: CIN-2+ prevalence was 1.0%. Corrected sensitivity, false negative rate, and specificity for CIN-2+, respectively, for primary HPV testing were 89.7%, 10.3%, and 83.3%; 44.8%, 55.2%, and 92·3% for VIA; 93.1%, 6.9%, and 80.2% for HPV-VIA cotesting; and 41.4%, 58.6, and 95.4% for HPV with VIA triage scenarios. Using relative light units/cutoff of 5 or greater to triage HPV-positive women had twice the sensitivity as VIA triage, with comparable specificity for CIN-2+. CONCLUSIONS: When VIA performs relatively poorly and HPV testing is available, adding VIA to sequential (ie, HPV followed by VIA triage) or primary (HPV-VIA cotesting) screening does not significantly improve CIN-2+ detection beyond primary HPV screening alone. Sequential screening (ie, HPV followed by VIA triage) reduces sensitivity too low for population-based screening programs. The HPV viral loads could offer an alternative low-resource country triage strategy.

Proton-Conductive Keggin-Type Clusters Decorated by the Complex Moieties of Cu(II) 2,2'-Bipyridine-4,4'-dicarboxylate/Diethyl Analogues.

Three proton-conductive decorated Keggin-type clusters, {[Cu(debpdc)(H2O)3][Cu(debpdc)(H2O)Cl][PMo12O40]} ·2CH3OH ·1.5CH3CN ·3H2O (1), {[Cu(H2bpdc)(H2O)2Cl0.5]2[PW12O40]}·10H2O (2), and {[Cu(H2bpdc)(H2O)2.5]2[SiW12O40]}·10H2O (3) (where debpdc is diethyl 2,2'-bipyridine-4,4'-dicarboxylate and H2bpdc is 2,2'-bipyridine-4,4'-dicarboxylic acid), were synthesized through electrostatic and coordination interactions between Keggin-type anions and Cu(II) H2bpdc/debpdc complex moieties. Interestingly, in the three complexes, both the H2bpdc/debpdc and the Keggin anion are covalently linked to the Cu2+ ions as polydentate organic and inorganic ligands, respectively. Notably, complexes 2 and 3 are the first examples of the functionalization of a Keggin-type cluster with Cu(II)-H2bpdc complex moieties, thereby providing a pathway to design and synthesize multifunctional hybrid materials with cluster structures based on two building units. In them, the free COOH groups of the H2bpdc ligand can act as both hydrogen bond acceptors and proton carriers. 1 has debpdc ligands with ethoxycarbonyl groups, while 2 and 3 have the H2bpdc ligands with free COOH groups; thus, the three complexes help us to understand the influence of the different substituents on the proton conductivity. The measurement results reveal that 2 and 3 have a high conductivity value of over 10-3 S cm-1 at 100 °C under 98% relative humidity, which is 2 orders of magnitude higher than that of 1 under the same conditions.

Correction to: Ready player one? Autophagy shapes resistance to photodynamic therapy in cancers.

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