Digital, Crowdsourced, Multilevel Intervention to Promote HIV Testing Among Men Who Have Sex With Men: Cluster Randomized Controlled Trial.

BACKGROUND: Despite great efforts in HIV prevention worldwide, HIV testing uptake among men who have sex with men (MSM) remains suboptimal. The effectiveness of digital, crowdsourced, multilevel interventions in improving HIV testing is still unclear. OBJECTIVE: The aim of this study was to evaluate the effect of a digital, crowdsourced, multilevel intervention in improving HIV testing uptake among MSM in China. METHODS: We conducted a 2-arm cluster randomized controlled trial among MSM in 11 cities in Shandong province, China, from August 2019 to April 2020. Participants were men who were HIV seronegative or had unknown serum status, had anal sex with a man in the past 12 months, and had not been tested for HIV in the past 3 months. Participants were recruited through a gay dating app and community-based organizations from preselected cities; these cities were matched into 5 blocks (2 clusters per block) and further randomly assigned (1:1) to receive a digital, crowdsourced, multilevel intervention (intervention arm) or routine intervention (control arm). The digital multilevel intervention was developed through crowdsourced open calls tailored for MSM, consisting of digital intervention images and videos, the strategy of providing HIV self-testing services through digital tools, and peer-moderated discussion within WeChat groups. The primary outcome was self-reported HIV testing uptake in the previous 3 months. An intention-to-treat approach was used to examine the cluster-level effect of the intervention in the 12-month study period using generalized linear mixed models and the individual-level effect using linear mixed models. RESULTS: A total of 935 MSM were enrolled (404 intervention participants and 531 controls); 751 participants (80.3%) completed at least one follow-up survey. Most participants were younger than 30 years (n=601, 64.3%), single (n=681, 72.8%), had a college degree or higher (n=629, 67.3%), and had an HIV testing history (n=785, 84%). Overall, the proportion of testing for HIV in the past 3 months at the 3-, 6-, 9-, and 12-month follow-ups was higher in the intervention arm (139/279, 49.8%; 148/266, 55.6%; 189/263, 71.9%; and 171/266, 64.3%, respectively) than the control arm (183/418, 43.8%; 178/408, 43.6%; 206/403, 51.1%; and 182/397, 48.4%, respectively), with statistically significant differences at the 6-, 9-, and 12-month follow-ups. At the cluster level, the proportion of participants who had tested for HIV increased 11.62% (95% CI 0.74%-22.5%; P=.04) with the intervention. At the individual level, participants in the intervention arm had 69% higher odds for testing for HIV in the past 3 months compared with control participants, but the result was not statistically significant (risk ratio 1.69, 95% CI 0.87-3.27; P=.11). CONCLUSIONS: The intervention effectively improved HIV testing uptake among Chinese MSM. Our findings highlight that digital, crowdsourced, multilevel interventions should be made more widely available for HIV prevention and other public health issues. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024350; http://www.chictr.org.cn/showproj.aspx?proj=36718. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-020-04860-8.

Flexoelectric Domain Walls Originated from Structural Phase Transition in Epitaxial BiVO4 Films.

Polar domain walls in centrosymmetric ferroelastics induce inhomogeneity that is the origin of advantageous multifunctionality. In particular, polar domain walls promote charge-carrier separation and hence are promising for energy conversion applications that overcome the hurdles of the rate-limiting step in the traditional photoelectrochemical water splitting processes. Yet, while macroscopic studies investigate the materials at the device scale, the origin of this phenomenon in general and the emergence of polar domain walls during the structural phase transition in particular has remained elusive, encumbering the development of this attractive system. Here, it is demonstrated that twin domain walls arise in centrosymmetric BiVO4 films and they exhibit localized piezoelectricity. It is also shown that during the structural phase transition from the tetragonal to monoclinic, the symmetry reduction is accompanied by an emergence of strain gradient, giving rise to flexoelectric effect and the polar domain walls. These results not only expose the emergence of polar domain walls at centrosymmetric systems by means of direct observation, but they also expand the realm of potential application of ferroelastics, especially in photoelectrochemistry and local piezoelectricity.

HIV testing frequency and associated factors among five key populations in ten cities of China: a cross-sectional study.

BACKGROUND: Regular HIV testing is the best way to detect people living with HIV promptly, yet not much is known about the characteristics of frequent, voluntary testers. This study explores factors related to HIV testing frequency among five key populations in China including men who have sex with men (MSM), female sex workers (FSWs), people who use drugs (PWUD), men who have casual sex with women (MCSW) and sero-negative partners among sero-discordant couples (SNPs). METHODS: We conducted a cross-sectional study in ten cities of China from November 2018 to September 2019 using convenience sampling to recruit participants. Univariate and multivariate partial proportional odds models were adopted to compare socio-behavioral factors associated with HIV testing frequencies among the five key populations. RESULTS: Among the 2022 recruited participants, 36.6% reported not testing for HIV in the past year, whereas 37.0% tested once and 26.4% tested twice. Compared with MSM, FSWs (AOR = 1.97, 95% CI: 1.36-2.86) and SNPs (AOR = 3.63, 95% CI: 2.40-5.49) were more likely to test for HIV, but MCSW (AOR = 0.23, 95% CI: 0.17-0.32) were less likely. Additionally, SNPs (AOR = 4.02, 95% CI: 2.78-5.83) were more likely to be frequent HIV testers, while FSWs (AOR = 0.49, 95% CI: 0.32-0.76) and MCSW (AOR = 0.29, 95% CI: 0.20-0.41) were less likely to be frequent testers. Factors identified as barriers to HIV testing include the following: higher education level and > 5000 CNY monthly income for FSWs; elder age and a married/cohabitating status for PWUD; reported alcohol use for MCSW; and non-Han ethnicity and non-local household for SNPs. Facilitators to frequent testing included the following: higher education level for MSM and SNPs; higher AIDS knowledge score for MSM and PWUD; > 5000 CNY monthly income for FSWs and PWUD; and reporting high-risk sexual behaviors for MSM, FSW and PWUD. CONCLUSIONS: HIV testing frequencies and associated factors were not equivalent across the five key populations in China. Public health officials should take heed of the identified high-risk populations reporting high testing rates, perhaps with intensive and tailored behavioral interventions or biochemical prophylaxis.

The effect of temperature on childhood hand, foot and mouth disease in Guangdong Province, China, 2010-2013: a multicity study.

BACKGROUND: Hand, foot and mouth disease (HFMD) is a serious infectious disease, which has become a public health problem. Previous studies have shown that temperature may influence the incidence of HFMD, but most only focus on single city and the results are highly heterogeneous. Therefore, a multicity study was conducted to explore the association between temperature and HFMD in different cities and search for modifiers that influence the heterogeneity. METHODS: We collected daily cases of childhood HFMD (aged 0-5 years) and meteorological factors of 21 cities in Guangdong Province in the period of 2010-2013. Distributed lag non-linear model (DLNM) with quasi-Poisson was adopted to quantify the effects of temperature on HFMD in 21 cities. Then the effects of each city were pooled by multivariate meta-analysis to obtain the heterogeneity among 21 cities. Potential city-level factors were included in meta-regression to explore effect modifiers. RESULTS: A total of 1,048,574 childhood cases were included in this study. There was a great correlation between daily childhood HFMD cases and temperature in each city, which was non-linear and lagged. High heterogeneity was showed in the associations between temperature and HFMD in 21 cities. The pooled temperature-HFMD association was peaking at the 79th percentile of temperature with relative risk (RR) of 2.474(95% CI: 2.065-2.965) as compared to the median temperature. Latitude was the main modifier for reducing the heterogeneity to 69.28% revealed by meta-analysis. CONCLUSIONS: There was a strong non-linear and lagged correlation between temperature and HFMD. Latitude was strongly associated with the relationship between temperature and HFMD. Meanwhile, it had an effect on modifying the relationship. These findings can conducive to local governments developing corresponding preventive measures.

Impacts of tropical cyclones and accompanying precipitation and wind velocity on childhood hand, foot and mouth disease in Guangdong Province, China.

OBJECTIVE: Guangdong province is one of the provinces most frequently hit by tropical cyclones in China. Hand, foot and mouth disease (HFMD) continues to severely affect public health across the world. Our study aimed to evaluate the impacts of different grades of tropical cyclones and accompanying precipitation and wind velocity on HFMD among children younger than 6 years old in Guangdong province from 2009 to 2013. METHODS: A time-stratified case-crossover design was used to examine the association between tropical cyclones and childhood HFMD. Principal component analysis (PCA) was first used to eliminate multicollinearity among meteorological variables. Conditional Poisson regression was then applied to calculate odds ratios (ORs) and the 95% confidence intervals (CIs). RESULTS: Tropical storms increased the risk of HFMD among children below 6 years of age on lag 4 days (OR = 1.55, 95%CI: 1.28-1.88). Tropical storms were also a risk factor for boys below 3 years of age, boys between 3 and 6 and girls below 3 years of age with the largest OR = 1.52 (95%CI:1.15-2.00), OR = 1.81 (95%CI = 1.21-2.71) and OR = 1.51 (95%CI = 1.04-2.19), respectively. Precipitation during tropical cyclones had an adverse effect on childhood HFMD when reaching 25-49.9 mm or above 100 mm with OR = 1.20 (95%CI = 1.00-1.43) on lag 0 day and OR = 1.25 (95%CI = 1.04-1.49) on lag 7 days, respectively. For extreme wind velocity during tropical cyclones, the impact on childhood HFMD was largest on the day tropical cyclones landed (OR = 1.25, 95%CI: 1.06-1.48) with winds up to 13.9-24.4  m/s. CONCLUSIONS: Tropical storms can increase the risk of HFMD among children younger than 3 years old, especially boys between 3 and 6 years old. Precipitation during tropical cyclones is a risk factor for childhood HFMD when it is between 25 and 49.9 mm or above 100 mm. As extreme wind velocity reaches 13.9-24.4  m/s, it has an adverse effect on children's health. Children below 3 years old and boys between 3 and 6 should be given more consideration during tropical storms.

Nanoparticles Based on Poly (ß-Amino Ester) and HPV16-Targeting CRISPR/shRNA as Potential Drugs for HPV16-Related Cervical Malignancy.

Persistent high-risk HPV infection is the main cause of cervical cancer. The HPV oncogene E7 plays an important role in HPV carcinogenesis. Currently, HPV vaccines do not offer an effective treatment for women who already present with cervical disease, and recommended periodical cervical screenings are difficult to perform in countries and areas lacking medical resources. Our aim was to develop nanoparticles (NPs) based on poly (ß-amino ester) (PBAE) and HPV16 E7-targeting CRISPR/short hairpin RNA (shRNA) to reduce the levels of HPV16 E7 as a preliminary form of a drug to treat HPV infection and its related cervical malignancy. Our NPs showed low toxicity in cells and mouse organs. By reducing the expression of HPV16 E7, our NPs could inhibit the growth of cervical cancer cells and xenograft tumors in nude mice, and they could reverse the malignant cervical epithelium phenotype in HPV16 transgenic mice. The performance of NPs containing shRNA is better than that of NPs containing CRISPR. HPV-targeting NPs consisting of PBAE and CRISPR/shRNA could potentially be developed as drugs to treat HPV infection and HPV-related cervical malignancy.

An effective and biocompatible polyethylenimine based vaginal suppository for gene delivery.

Gene therapy targeted human papillomavirus (HPV) is a promising treatment for cervical cancer, and the key for clinical application depends on an effective gene delivery method. Our aim was to formulate a new pharmaceutical formula for appropriate gene delivery intravaginally. For the first time, we here developed a new polyethylenimine (PEI) based vaginal suppository. The sectional immunofluorescence results confirmed the delivery efficacy both in vivo and in vitro. The quenching fluorescence and decreased gene expression in topical epithelium of green fluorescence protein (GFP) transgenic mice demonstrated the efficient targeting potential of the suppository. The other aim of this study was to evaluate the biocompatibility of the PEI based transfer. To our knowledge, this was also the first study to explore the toxicity in vivo systematically and comprehensively. Our study provided novel ideas for the translational application of PEI based suppository to the prevention and treatment of cervical cancer.

Alterations of plant architecture and phase transition by the phytoplasma virulence factor SAP11.

As key mediators linking developmental processes with plant immunity, TCP (TEOSINTE-BRANCHED, CYCLOIDEA, PROLIFERATION FACTOR 1 and 2) transcription factors have been increasingly shown to be targets of pathogenic effectors. We report here that TB/CYC (TEOSINTE-BRANCHED/CYCLOIDEA)-TCPs are destabilized by phytoplasma SAP11 effectors, leading to the proliferation of axillary meristems. Although a high degree of sequence diversity was observed among putative SAP11 effectors identified from evolutionarily distinct clusters of phytoplasmas, these effectors acquired fundamental activity in destabilizing TB/CYC-TCPs. In addition, we demonstrate that miR156/SPLs and miR172/AP2 modules, which represent key regulatory hubs involved in plant phase transition, were modulated by Aster Yellows phytoplasma strain Witches' Broom (AY-WB) protein SAP11. A late-flowering phenotype with significant changes in the expression of flowering-related genes was observed in transgenic Arabidopsis plants expressing SAP11AYWB. These morphological and molecular alterations were correlated with the ability of SAP11 effectors to destabilize CIN (CINCINNATA)-TCPs. Although not all putative SAP11 effectors display broad-spectrum activities in modulating morphological and physiological changes in host plants, they serve as core virulence factors responsible for the witches' broom symptom caused by phytoplasmas.

Clinical effects of autologous follicular unit extraction transplantation in the treatment of secondary cicatricial alopecia after infections.

OBJECTIVE: To explore the clinical effects of autologous follicular unit extraction (FUE) transplantation in the treatment of secondary scarring alopecia caused by infections, and to evaluate its effectiveness. METHODS: A retrospective observational study has been conducted, which included nine patients with secondary scarring alopecia caused by infections. All patients underwent initial autologous FUE hair transplantation surgery, and the occurrence of postoperative complications was monitored. Patient satisfaction was evaluated after 12 months post-surgery. RESULTS: At the follow-up, postoperative satisfaction was 88.9% in nine patients, with only one case of postoperative infection and no incidence of skin necrosis, significant bruising and swelling, unnatural appearance or temporary hair loss. CONCLUSIONS: Autologous FUE hair transplantation is an effective method for treating secondary scarring alopecia caused by infections. This procedure is minimally invasive, resulting in high patient satisfaction and minimal complications postoperatively.

Eruptive xanthomas in a patient with severe hypertriglyceridemia: A case report.

BACKGROUND: Xanthomatosis, a metabolic disorder causing yellow growths (xanthomas), poses challenges in lipid metabolism. This case study introduces the first documented instance within China's Yi population, emphasizing the need to explore dietary habits and treatment strategies tailored to this specific community. CASE SUMMARY: Xanthomatosis is a metabolic disorder where lipid metabolism goes awry, resulting in the development of yellowish growths called xanthomas. A male patient, 47 years of age, from China's Yi population, who is obese, visited our dermatology clinic complaining of widespread, non-painful rashes that have been present for two weeks. The patient works as a chef and has a diet that frequently includes oily and greasy foods. This case represents the initial documentation of xanthomatosis within the Yi population in China, offering a theoretical foundation for understanding dietary patterns and treatment options specific to the Yi community. CONCLUSION: The first report of xanthomatosis in the Yi population in China lays a theoretical foundation for understanding Yi dietary patterns and treatment.

Autologous follicular unit extraction transplant for postburn cicatricial alopecia: A single-center's retrospective case series.

BACKGROUND AND RATIONALE: Cicatricial alopecia not only affects patients' appearance but also has negative effects on their physical and mental well-being, as well as their daily lives. Therefore, it is essential to provide proactive treatment to patients. OBJECTIVE: To explore the clinical effects of autologous follicular unit extraction (FUE) transplantation in the treatment of secondary scarring alopecia caused by burn, and to evaluate its effectiveness. METHODS: A retrospective observational study has been conducted, which included 41 patients with secondary scarring alopecia caused by burn. All patients underwent initial autologous FUE hair transplantation surgery, and the occurrence of postoperative complications was monitored. Patient satisfaction was evaluated after 12 months post-surgery. RESULTS: Satisfaction assessments were conducted for all 41 patients. Out of the total, 31 individuals expressed being very satisfied, 7 individuals reported being satisfied, and 3 individuals indicated being not very satisfied. Among the patients, 3 experienced complications, including herpes in the donor area for one patient, temporary hair loss for another patient, and thick scab for the third patient. CONCLUSION: FUE hair transplantation yields positive results for secondary scarring alopecia caused by burn. It offers natural hair growth patterns, minimal trauma, quick recovery, high patient satisfaction, and few complications.

PIBF1 regulates multiple gene expression via impeding long-range chromatin interaction to drive the malignant transformation of HPV16 integration epithelial cells.

INTRODUCTION: Human papillomavirus (HPV) integration can induce gene expression dysregulation by destroying higher-order chromatin structure in cervical cancer. OBJECTIVES: We established a 13q22 site-specific HPV16 gene knock-in cell model to interrogate the changes in chromatin structure at the initial stages of host cell malignant transformation. METHODS: We designed a CRISPR-Cas9 system with sgRNA targeting 13q22 site and constructed the HPV16 gene donor. Cells were cotransfected, screened, and fluorescence sorted. The whole genome sequencing (WGS) was used to confirm the precise HPV16 gene integration site. Western blot and qRT-PCR were used to measure gene expression. In vitro and in vivo analysis were performed to estimate the tumorigenic potential of the HPV16 knock-in cell model. Combined Hi-C, chromatin immunoprecipitation and RNA sequencing analyses revealed correlations between chromatin structure and gene expression. We performed a coimmunoprecipitation assay with anti-PIBF1 antibody to identify endogenous interacting proteins. In vivo analysis was used to determine the role of PIBF1 in the tumor growth of cervical cancer cells. RESULTS: We successfully established a 13q22 site-specific HPV16 gene knock-in cell model. We found that HPV integration promoted cell proliferation, invasion and stratified growth in vitro, and monoclonal proliferation in vivo. HPV integration divided the affected topologically associated domain (TAD) into two smaller domains, and the progesterone-induced blocking factor 1 (PIBF1) gene near the integration site was upregulated, although PIBF1 was not enriched at the domain boundary by CUT-Tag signal analysis. Moreover, PIBF1 was found to interact with the cohesin complex off chromatin to reduce contact domain formation by disrupting the cohesin ring-shaped structure, causing dysregulation of tumorigenesis-related genes. Xenograft experiments determined the role of PIBF1 in the proliferation in cervical cancer cells. CONCLUSION: We highlight that PIBF1, a potential chromatin structure regulatory protein, is activated by HPV integration, which provides new insights into HPV integration-driven cervical carcinogenesis.

HfO2-based ferroelectric thin film and memory device applications in the post-Moore era: A review.

The rapid development of 5G, big data, and Internet of Things (IoT) technologies is urgently required for novel non-volatile memory devices with low power consumption, fast read/write speed, and high reliability, which are crucial for high-performance computing. Ferroelectric memory has undergone extensive investigation as a viable alternative for commercial applications since the post-Moore era. However, conventional perovskite-structure ferroelectrics (e.g., PbZr x Ti1- x O3) encounter severe limitations for high-density integration owing to the size effect of ferroelectricity and incompatibility with complementary metal-oxide-semiconductor technology. Since 2011, the ferroelectric field has been primarily focused on HfO2-based ferroelectric thin films owing to their exceptional scalability. Several reviews discussing the control of ferroelectricity and device applications exist. It is believed that a comprehensive understanding of mechanisms based on industrial requirements and concerns is necessary, such as the wake-up effect and fatigue mechanism. These mechanisms reflect the atomic structures of the materials as well as the device physics. Herein, a review focusing on phase stability and domain structure is presented. In addition, the recent progress in related ferroelectric memory devices and their challenges is briefly discussed.

A high throughput bispecific antibody discovery pipeline.

Bispecific antibodies (BsAbs) represent an emerging class of immunotherapy, but inefficiency in the current discovery has limited their broad clinical availability. Here we report a high throughput, agnostic, single-cell-based functional screening pipeline, comprising molecular and cell engineering for efficient generation of BsAb library cells, followed by functional interrogation at the single-cell level to identify and sort positive clones and downstream sequence identification and functionality characterization. Using a CD19xCD3 bispecific T cell engager (BiTE) as a model, we demonstrate that our single-cell platform possesses a high throughput screening efficiency of up to one and a half million variant library cells per run and can isolate rare functional clones at a low abundance of 0.008%. Using a complex CD19xCD3 BiTE-expressing cell library with approximately 22,300 unique variants comprising combinatorially varied scFvs, connecting linkers and VL/VH orientations, we have identified 98 unique clones, including extremely rare ones (~ 0.001% abundance). We also discovered BiTEs that exhibit novel properties and insights to design variable preferences for functionality. We expect our single-cell platform to not only increase the discovery efficiency of new immunotherapeutics, but also enable identifying generalizable design principles based on an in-depth understanding of the inter-relationships between sequence, structure, and function.

LncRNA HCP5 enhances the proliferation and migration of cervical cancer via miR-216a-5p/CDC42 axis.

To investigate the important roles of the cancer-promoting long non-coding RNAs (lncRNAs) in cervical cancer, the up-regulated lncRNAs and prognostic analysis were identified through Lnc2Cancer and Lncar. LncRNA-regulated miRNA and miRNA-target mRNA were analyzed based on starBase v2.0 and miTarbase to predict the lncRNA-miRNA-mRNA ceRNA network. Based on the above findings, the abnormally expressed histocompatibility leukocyte antigen complex P5 (HCP5) was identified in 31 cervical cancer patients through RT-qPCR. The stable cell lines were constructed to explore the effect of HCP5 on the promotion of cervical cancer and the regulatory role on the expression of miR-216a-5p and CDC42. Cell Counting Kit-8 (CCK8) assay, cell clone formation, and transwell assay were used to examine proliferation and migration ability of cervical cancer cells. The results displayed that the overexpression of HCP5 promoted cervical cancer cell proliferation and migration in vitro, and the elevated HCP5 can also promote tumor growth in vivo. Besides, RT-qPCR and western blot assay revealed that elevated HCP5 suppressed miR-216a-5p expression and then up-regulated the expression of CDC42. In contrast, knocking down HCP5 resulted in increased expression of miR-216a-5p and then downregulated the expression of CDC42. Rescue experiments also demonstrated that miR-216a-5p could in part intercept in promotion impact caused by HCP5 on cervical cancer cells. Above all, HCP5, as an oncogene, can promote proliferation and migration ability of cervical cancer via the regulation of the miR-216a-5p/CDC42 axis.

Enhanced Energy Density at a Low Electric Field in PVDF-Based Heterojunctions Sandwiched with High Ion-Polarized BTO Films.

Inorganic/organic dielectric composites with outstanding energy storage properties at a low electric field possess the advantages of low operating voltage and small probability of failure. Composites filled with two-dimensional inorganic nanosheets have attracted much attention owing to their fewer interfacial defects caused by the agglomeration of fillers. Continuous oxide films with a preferred orientation can play a significant role in enhancing energy storage. The challenge is to prepare large-sized, freestanding, single-crystal, ferroelectric oxide films and to combine them with polymers. In this work, a well-developed water-dissolvent process was used to transfer millimeter-sized (100)-oriented BaTiO3 (BTO) films. Poly(vinylidene fluoride) (PVDF)-based heterojunctions sandwiched with the single-crystal films were synthesized via the transferring process and an optimized hot-pressing technique. By virtue of high ion displacement polarization and inhibited conductive path formation of single-crystal BTO films, the energy storage density and efficiency of BTO/PVDF heterojunctions reach 1.56 J cm-3 and 71.2% at a low electric field of 120 MV m-1, which are much higher than those of pure PVDF and BTO nanoparticles/PVDF composite films, respectively. A finite-element simulation was employed to further confirm the experimental results. This work provides an effective approach to enhance energy storage properties in various polymer-based composites and opens the door to advanced dielectric capacitors.

The role of lattice dynamics in ferroelectric switching.

Reducing the switching energy of ferroelectric thin films remains an important goal in the pursuit of ultralow-power ferroelectric memory and logic devices. Here, we elucidate the fundamental role of lattice dynamics in ferroelectric switching by studying both freestanding bismuth ferrite (BiFeO3) membranes and films clamped to a substrate. We observe a distinct evolution of the ferroelectric domain pattern, from striped, 71° ferroelastic domains (spacing of ~100 nm) in clamped BiFeO3 films, to large (10's of micrometers) 180° domains in freestanding films. By removing the constraints imposed by mechanical clamping from the substrate, we can realize a ~40% reduction of the switching voltage and a consequent ~60% improvement in the switching speed. Our findings highlight the importance of a dynamic clamping process occurring during switching, which impacts strain, ferroelectric, and ferrodistortive order parameters and plays a critical role in setting the energetics and dynamics of ferroelectric switching.

Systematic analysis of the long noncoding RNA (lncRNA)-miRNA-mRNA competing endogenous RNA network to identify prognostic biomarkers and the potential regulatory axis in glioblastoma multiforme.

BACKGROUND: Glioblastoma (GBM) is an intracranial brain tumor characterized by a high final lethality rate and recurrence rate, and limited available therapies. With the development of high-throughput sequencing technology, the genomic and transcriptomic features of GBM have been fully characterized. Therefore, our study aimed to identify its underlying genetic mechanisms, thus facilitating the development of novel therapies for GBM. METHODS: Based on the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, differential expression of RNAs in GBM and control group was analyzed. After constructing the long noncoding RNA (lncRNA)-miRNA-mRNA regulatory network of GBM, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) were performed to analyze related key nodes and the lncRNAs interacting with them. Further univariate Cox regression was conducted to explore independent factors, and then multivariate Cox regression was performed to construct risk prediction models. RESULTS: We first constructed the lncRNA-miRNA-mRNA regulatory network of GBM and two effective prediction models that included 2 mRNAs [transcription factor 12 (TCF12) and discoidin, CUB and LCCL domain containing 2 (DCBLD2)] and 5 lncRNAs (C10orf25, LINC00343, HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1), FGF12 antisense RNA 2 (FGF12-AS2) and H19). Additionally, we identified several key molecules [TCF12, integrin ß3 (ITGB3), high mobility group AT-hook 2 (HMGA2), C10orf25 and LINC00336] closely associated with GBM prognosis. C10orf25/miR-218/DCBLD2 may be an important regulatory pathway in GBM. CONCLUSIONS: Key molecules (TCF12, ITGB3, HMGA2, C10orf25, LINC00336 and H19) that are independent prognostic factors may be possible biomarkers to further optimize GBM prognosis. Two effective prognostic risk models that include 2 mRNAs (TCF12 and DCBLD2) and 5 lncRNAs (C10orf25, LINC00343, HOTAIRM1, FGF12-AS2 and H19) were constructed. C10orf25/miR-218/DCBLD2 may be an important regulatory pathway associated with the pathogenesis of GBM. Our findings contribute to further understanding the pathogenesis of GBM and finding possible candidate genes for prognostic and therapeutic usage with GBM.

Detection of HPV and Human Chromosome Sites by Dual-Color Fluorescence In Situ Hybridization Reveals Recurrent HPV Integration Sites and Heterogeneity in Cervical Cancer.

Human papillomavirus (HPV) integration in the human genome is suggested to be an important cause of cervical cancer. With the development of sequencing technologies, an increasing number of integration "hotspots" have been identified. However, this HPV integration information was derived from analysis of whole cervical cancer tissue, and we know very little about the integration in different cancer cell subgroups or individual cancer cells. This study optimized the preparation of probes and provided a dual-color fluorescence in situ hybridization (FISH) method to detect HPV integration sites in paraffin-embedded cervical cancer samples. We used both HPV probes and site-specific probes: 3p14 (FHIT), 8q24 (MYC), 13q22 (KLF5/KLF12), 3q28 (TP63), and 5p15 (TERT). We detected HPV signals in 75 of the 96 cases of cervical cancer; 62 cases showed punctate signals, and 13 cases showed diffuse punctate signals. We identified 3p14 as a high-frequency HPV integration site in 4 cervical cancer cases. HPV integration at 8p14 occurred in 2 cases of cervical cancer. In the same cervical cancer tissue of sample No.1321, two distinct subgroups of cells were observed based on the HPV probe but showed no difference in cell and nucleus morphology. Our study provides a new method to investigate the frequent HPV integration sites in cervical cancer and reports the heterogeneity within cervical cancer from the perspective of HPV integration.

E7-Targeted Nanotherapeutics for Key HPV Afflicted Cervical Lesions by Employing CRISPR/Cas9 and Poly (Beta-Amino Ester).

INTRODUCTION: Persistent HR-HPV (high-risk human papillomavirus) infection is the main cause of cervical cancer. The HPV oncogene E7 plays a key role in HPV tumorigenesis. At present, HPV preventive vaccines are not effective for patients who already have a cervical disease, and implementation of the recommended regular cervical screening is difficult in countries and regions lacking medical resources. Therefore, patients need medications to treat existing HPV infections and thus block the progression of cervical disease. METHODS: In this study, we developed nanoparticles (NPs) composed of the non-viral vector PBAE546 and a CRISPR/Cas9 recombinant plasmid targeting HPV16 E7 as a vaginal treatment for HPV infection and related cervical malignancies. RESULTS: Our NPs showed low toxicity and high biological safety both in vitro (cell line viability) and in vivo (various important organs of mice). Our NPs significantly inhibited the growth of xenograft tumors derived from cervical cancer cell lines in nude mice and significantly reversed the cervical epithelial malignant phenotype of HPV16 transgenic mice. CONCLUSION: Our NPs have great potential to be developed as a drug for the treatment of HPV-related cervical cancer and precancerous lesions.