Expression profile of long noncoding RNAs and comprehensive analysis of lncRNA-cisTF-DGE regulation in condyloma acuminatum.

OBJECTIVE: To identify differentially expressed long noncoding RNAs (lncRNAs) in condyloma acuminatum (CA) and to explore their probable regulatory mechanisms by establishing coexpression networks. METHODS: High-throughput RNA sequencing was performed to assess genome-wide lncRNA expression in CA and paired adjacent mucosal tissue. The expression of candidate lncRNAs and their target genes in larger CA specimens was validated using real-time quantitative reverse transcriptase polymerase chain reaction (RT‒qPCR). Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for the functional enrichment analysis of these candidate lncRNAs and differential mRNAs. The coexpressed mRNAs of the candidate lncRNAs, calculated by Pearson's correlation coefficient, were also analysed using GO and KEGG analysis. In addition, the interactions among differentially expressed lncRNAs (DElncRNAs)-cis-regulatory transcription factors (cisTFs)-differentially expressed genes (DEGs) were analysed and their network was constructed. RESULTS: A total of 546 lncRNAs and 2553 mRNAs were found to be differentially expressed in CA compared to the paired control. Functional enrichment analysis revealed that the DEGs coexpressed with DElncRNAs were enriched in the terms of cell adhesion and keratinocyte differentiation, and the pathways of ECM-receptor interaction, local adhesion, PI3K/AKT and TGF-ß signaling. We further constructed the network among DElncRNAs-cisTFs-DEGs and found that these 95 DEGs were mainly enriched in GO terms of epithelial development, regulation of transcription or gene expression. Furthermore, the expression of 3 pairs of DElncRNAs and cisTFs, EVX1-AS and HOXA13, HOXA11-AS and EVX1, and DLX6-AS and DLX5, was validated with a larger number of specimens using RT‒qPCR. CONCLUSION: CA has a specific lncRNA profile, and the differentially expressed lncRNAs play regulatory roles in mRNA expression through cis-acting TFs, which provides insight into their regulatory networks. It will be useful to understand the pathogenesis of CA to provide new directions for the prevention, clinical treatment and efficacy evaluation of CA.

Alteration of RNA m6A methylation mediates aberrant RNA binding protein expression and alternative splicing in condyloma acuminatum.

Background: Condyloma acuminatum (CA) is caused by low-risk human papillomavirus, and is characterized by high recurrence after treatment. The RNA modification N6-methyladenosine (m6A) plays an important role during diverse viral infections, including high-risk HPV infection in cervical cancer. However, it is unclear whether low-risk HPV infection changes the RNA m6A methylation in CA. Methods: High-throughputm6A-sequencing was performed to profile the transcriptome-wide mRNA modifications of CA tissues infected by LR-HPVs and the paired normal tissues from CA patients. We further investigated the regulation of alternative splicing by RNA binding proteins (RBPs) with altered m6A modification and constructed a regulatory network among these RBPs, regulated alternative splicing events (RASEs) and regulated alternative splicing genes (RASGs) in CA. Results: The results show that the m6A level in CA tissues differed from that in the paired controls. Furthermore, cell cycle- and cell adhesion- associated genes with m6A modification were differentially expressed in CA tissues compared to the paired controls. In particular, seven RNA binding protein genes with specific m6A methylated sites, showed a higher or lower expression at the mRNA level in CA tissues than in the paired normal tissues. In addition, these differentially expressed RNA binding protein genes would regulate the alternative splicing pattern of apoptotic process genes in CA tissue. Conclusions: Our study reveals a sophisticated m6A modification profile in CA tissue that affects the response of host cells to HPV infection, and provides cues for the further exploration of the roles of m6A and the development of a novel treatment strategy for CA.

Injectable Zn2+ and Paeoniflorin Release Hydrogel for Promoting Wound Healing.

As more and more superbugs emerge, wounds are struggling to heal due to the inflammation that accompanies infection. Therefore, there is an urgent need to reduce the abuse of antibiotics and find nonantibiotic antimicrobial methods to counter infections to accelerate wound healing. In addition, common wound dressings struggle to cover irregular wounds, causing bacterial invasion or poor drug release, which reduces the wound healing rate. In this study, Chinese medicinal monomer paeoniflorin which can inhibit inflammation is loaded in mesoporous zinc oxide nanoparticles (mZnO), while Zn2+ released from mZnO degradation can kill bacteria and facilitate wound healing. The drug-loaded mZnO was encapsulated by a hydrogel formed from oxidized konjac glucomannan and carboxymethyl chitosan via rapid Schiff base reaction to obtain an injectable drug-releasing hydrogel wound dressing. The immediate-formation hydrogel allows the dressing to cover any wound shape. In vitro and in vivo studies have demonstrated that the dressing has good biocompatibility and superior antibacterial properties, which can promote wound healing and tissue regeneration by promoting angiogenesis and collagen production, providing a promising perspective for the further development of multifunctional wound dressings.

Regenerated silk fibroin and alginate composite hydrogel dressings loaded with curcumin nanoparticles for bacterial-infected wound closure.

It is important to treat a bacterial-infected wound with a hydrogel dressing due to its excellent biocompatibility and extracellular matrix mimicking structure. In this work, the antibacterial curcumin nanoparticles (Cur-NPs) loaded silk fibroin and sodium alginate (SF/SA) composite hydrogels have been developed as dressings for bacterial-infected wound closure. The as-prepared composite hydrogel dressings exhibited excellent biocompatibility and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro. In addition, the composite hydrogel dressings showed good tissue adhesive strength because of their high viscosity and abundance of amino groups distributed on SF, which can form multi-aldehyde polysaccharides with the tissue surface. The porous 3D structure of the composite hydrogel dressings facilitated the absorption of exudate from the wound site and promoted the fusion of cellular nutrients and metabolites. In the full-thickness skin defect model with and without bacterial infection, the Cur-NPs loaded SF/SA composite hydrogel dressings prominently improves the closure of bacterial-infected wounds by improving cell proliferation, anti-inflammatory properties, vascular remodeling, and collagen deposition.

Design of 3D polycaprolactone/ε-polylysine-modified chitosan fibrous scaffolds with incorporation of bioactive factors for accelerating wound healing.

Electrospun nanofibrous scaffolds show great application potentials for wound healing owing to their effective simulation of extracellular matrix (ECM). Three-dimensional (3D) nanofibrous dressings exhibit relatively high specific surface areas, better mimicry of native ECM, adjustable hydrophilicity and breathability, good histocompatibility, enhanced wound healing, and reduced inflammation. In the present work, we designed the 3D polycaprolactone/ε-polylysine modified chitosan (PCL/PCS) nanofibrous scaffolds by an electrospinning and gas foaming process. Then, gelatin and heparin (Gel/Hep) were assembled onto the surface of PCL/PCS nanofibers by electrostatic adsorption, and vascular endothelial growth factors (VEGFs) were also synchronously incorporated into Gel/Hep layer to form a multifunctional 3D nanofibrous scaffold (PCL/PCS@Gel/Hep+VEGF) for accelerating wound healing. The as-fabricated 3D PCL/PCS@GEL/Hep+VEGF nanofibrous scaffold showed excellent antibacterial ability, hemocompatibility and biocompatibility in vitro and wound healing ability in vivo. Immunological analysis showed that the as-fabricated nanofibrous scaffold inhibited inflammation at the wound sites while promoting angiogenesis during the wound healing process. STATEMENT OF SIGNIFICANCE: The electrospun 3D fibrous scaffolds using polycaprolactone/ε-polylysine modified chitosan (PCL/PCS) have been fabricated as backbone for mimicking the extracellular matrix (ECM). Gelatin and heparin (Gel/Hep) were wrapped onto the surface of PCL/PCS fibers by electrostatic adsorption and vascular endothelial growth factors (VEGFs) were also synchronously incorporated into surface Gel/Hep layer to form multifunctional 3D fibrous scaffolds. The as-fabricated multifunctional 3D fibrous scaffolds with good antibacterial ability and biocompatibility have been used as dressings for accelerating wound healing by inhibiting inflammation at the wound sites while promoting angiogenesis during the wound healing process.

Fabrication of Curcumin-Loaded Silk Fibroin and Polyvinyl Alcohol Composite Hydrogel Films for Skin Wound Healing.

Skin regeneration of full-thickness wounds remains a challenge, requiring a well-regulated interplay of cell-cell and cell-matrix signaling. Herein, the composite hydrogel films composed of silk fibroin (SF) and polyvinyl alcohol (PVA) as scaffolds loaded with curcumin nanoparticles (Cur NPs) were developed for skin wound healing. The structure and physicochemical properties of hydrogel films were first evaluated by scanning electron microscopy (SEM), water contact angle, and chemical and mechanical measurements. In addition, the as-fabricated composite hydrogel films have a unique 3D structure and excellent biocompatibility that facilitates the adhesion and growth of cells. Antimicrobial tests in vitro showed that they could inhibit the growth of bacteria due to the incorporation of Cur NPs into composite hydrogel films. The efficacy of the curcumin-loaded SF/PVA composite hydrogel films for skin wound healing was investigated on the skin defect model in vivo. Immunological analysis showed that the as-fabricated Cur NP-loaded SF/PVA composite hydrogel films inhibited inflammation at the wound sites, while promoting angiogenesis during the wound healing process.

Elevated estradiol levels in frozen embryo transfer have different effects on pregnancy outcomes depending on the stage of transferred embryos.

Supplementation with estradiol (E2) is routinely used in frozen embryo transfer (FET) cycles and embryo age plays an important role in conceiving. This study was to compare the effects of serum E2 levels on pregnancy outcomes between cleavage- and blastocyst-stage FET cycles using hormone replacement therapy. A total of 776 FET cycles (669 couples) performed from January 2016 to December 2019 were included in the present retrospective cohort study. Regarding cleavage-stage embryo transfers, E2 levels on progesterone initiation day were significantly lower in the ongoing pregnancy/live birth (OP/LB) group than in the non-OP/LB group (214.75 ± 173.47 vs. 253.20 ± 203.30 pg/ml; P = 0.023). In addition, there were downward trends in implantation, clinical pregnancy and OP/LB rates with increasing E2 levels. However, in blastocyst-stage embryo transfers, such trends were not observed, and E2 levels were not significant difference between the OP/LB group and the non-OP/LB group (201.66 ± 182.14 vs. 197.89 ± 212.83 pg/ml; P = 0.884). The results suggests that elevated progesterone-initiation-day E2 levels may negatively affect pregnancy outcomes during artificial cleavage-stage embryo transfers. However, it is not necessary to monitor E2 levels when transferring blastocysts in artificial FET cycles.

[Analysis of genetic variant in a Chinese pedigree affected with neurofibromatosis type I].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with neurofibromatosis type I (NF1). METHODS: Target capture high-throughput sequencing and Sanger sequencing were carried out to detect the pathological variant in a NF1 patient and his parents. RESULTS: The proband and his similarly affected father have both harbored a novel nonsense variant of c.2511G>A (p.trp837x) in the NF1 gene. The same variant was not found in his mother and 200 healthy controls. CONCLUSION: The heterozygous nonsense variant of c.2511G>A (p.trp837x) of the NF1 gene probably underlay the pathogenesis of NF1 in this pedigree.

Electrospun Scaffold of Collagen and Polycaprolactone Containing ZnO Quantum Dots for Skin Wound Regeneration.

Nanofibers (NFs) have been widely used in tissue engineering such as wound healing. In this work, the antibacterial ZnO quantum dots (ZnO QDs) have been incorporated into the biocompatible poly (ε-caprolactone)/collagen (PCL/Col) fibrous scaffolds for wound healing. The as-fabricated PCL-Col/ZnO fibrous scaffolds exhibited good swelling, antibacterial activity, and biodegradation behaviors, which were beneficial for the applications as a wound dressing. Moreover, the PCL-Col/ZnO fibrous scaffolds showed excellent cytocompatibility for promoting cell proliferation. The resultant PCL-Col/ZnO fibrous scaffolds containing vascular endothelial growth factor (VEGF) also exhibited promoted wound-healing effect through promoting expression of transforming growth factor-ß (TGF-ß) and the vascular factor (CD31) in tissues in the early stages of wound healing. This new electrospun fibrous scaffolds with wound-healing promotion and antibacterial property should be convenient for treating wound healing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42235-021-00115-7.

Transdermal delivery of multifunctional CaO2@Mn-PDA nanoformulations by microneedles for NIR-induced synergistic therapy against skin melanoma.

The development of multifunctional nanoformulations (NFs) include several features in a single nanosystem for these devices to overcome the disadvantages of inefficiency and undesirable toxicity of traditional therapies and provide new opportunities in the management of tumors. Herein, multifunctional CaO2@Mn-PDA NFs with a core-shell structure, integrating the photothermal conversion properties of Mn-PDA, the chemodynamic properties of doped Mn ions, and relieving hypoxia in the tumor microenvironment (TME) were developed. The as-fabricated CaO2@Mn-PDA NFs were embedded in microneedles (MNs) for transdermal delivery into tumor sites, leading to the generation of a new minimally invasive and synergistic therapeutic strategy against skin melanoma. Under near-infrared (NIR) light irradiation, the CaO2@Mn-PDA NFs exhibited a synergistic therapeutic effect, including photothermal therapy (PTT), chemodynamic therapy (CDT), and modulating hypoxia due to their high photothermal conversion efficiency, boosted intracellular production of reactive oxygen species, excellent chemodynamic reactions, etc. Therefore, the developed MN platform, which can build implanted multifunctional characteristics for on-demand NIR-induced synergistic therapy, have a bright future in tumor suppression.

Microbiome in Healthy Women Between Two Districts With Different Air Quality Index.

Although the diversity and abundance of skin microbiome are mainly determined by intrinsic factors, including gender, age, anatomical site, and ethnicity, we question whether facial microbiome could be affected by long-term exposure to airborne pollution. Using 16S ribosomal RNA (rRNA) gene amplicon sequencing, we analyzed the facial bacterial microbiome of healthy and young Chinese women (25-35 years old) between two districts with different air quality indices (AQIs) in Zhejiang Province. The overall microbiome structure was obviously different between these two districts. It revealed an increase in both the abundance and diversity of facial bacterial microbiome in Hangzhou (HZ) with higher AQI compared with those in Yunhe (YH) with lower AQI. Linear discriminant analysis (LDA) and Lefse analysis identified a total of 45 genera showing significant overrepresentation in the HZ group. Furthermore, PICRUSt analysis showed that functional pathways associated with metabolism of saturated fatty acid were relatively more predominant in the HZ group, whereas those with DNA repair or mitochondrial DNA replication were more predominant in the YH group. Our present data can provide useful information for further researches on the composition and function of the skin microbiome related to air pollution factors as well as for the development of therapeutic agents targeting the microbes and their metabolites to resist damages of airborne pollutants.

Effect of gonadotropins and endometrial thickness on pregnancy outcome in patients with unexplained infertility or polycystic ovarian syndrome undergoing intrauterine insemination.

OBJECTIVE: The purpose of this study was to investigate the effect of gonadotropin dose and endometrial thickness (EMT) on pregnancy outcome in patients undergoing intrauterine insemination (IUI). METHODS: We retrospectively analyzed data from 361 patients with unexplained infertility or polycystic ovarian syndrome (PCOS) who underwent 930 IUI cycles treated with gonadotropins. Then, we measured the effects of gonadotropins and EMT on the clinical pregnancy rate. Finally, we assessed the association of various doses of gonadotropins on EMT. RESULTS: The dose of gonadotropins given and thickness of the endometrium were higher in the pregnancy group than in the nonpregnancy group (636.0 vs. 600.0 IU for gonadotropin dose; 9.15 vs. 8.70 mm for EMT). Clinical pregnancy rates were significantly improved by increasing the dose of gonadotropins (9.1%, <450 IU; 16.2%, 450-599 IU; 18.6%, 600-749 IU, and 17.3%, ≥750 IU), or by increased EMT (0%, <5.0 mm; 12.2%, 5.0-6.9 mm; 15.5%, 7.0-14.0 mm; and 33.3%, >14.0 mm). CONCLUSION: Increasing the dose of gonadotropins to stimulate one follicle to develop may benefit endometrial proliferation and improve IUI outcomes.

Rapid gelation of oxidized hyaluronic acid and succinyl chitosan for integration with insulin-loaded micelles and epidermal growth factor on diabetic wound healing.

In this work, poly(ethylene glycol)-b-poly[3-acrylamidophenylboronic acid-co-styrene] (PEG-b-P(PBA-co-St) has been firstly synthesized for loading of insulin to form insulin-loaded micelles. Insulin-loaded micelles (ILM) and epidermal growth factor (EGF) are further embedded into the composite hydrogels that can be rapidly gelled by mixing of oxidized hyaluronic acid (OHA) and succinyl chitosan (SCS). Then, the morphology, rheology, degradation, swelling and cytotoxicity properties of the as-prepared composite hydrogels are further investigated to evaluate their physical properties and biocompatibility of as the wound dressing. The as-prepared composite hydrogels show the excellent cell compatibility and low toxicity. To evaluate the wound healing ability of as-prepared composite hydrogels, the tests of wound healing in vivo are conducted on streptozotocin-induced rat models. And the as-prepared composite hydrogels with ILM and EGF show an excellent wound healing performance for promotion of fibroblast proliferation and tissue internal structure integrity, as well as the deposition of collagen and myofibrils. These results suggest that the as-prepared composite hydrogels with loading of ILM and EGF could be a promising candidate for wound healing applications.

Integrated Analysis Identifies an Immune-Based Prognostic Signature for the Mesenchymal Identity in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) has been divided into four molecular subtypes, of which the mesenchymal subtype has the poorest survival. Our goal is to develop a prognostic signature by integrating the immune system and molecular modalities involved in the mesenchymal subtype. METHODS: The gene expression profiles collected from 6 public datasets were applied to this study, including 1,221 samples totally. Network analysis was applied to integrate the mesenchymal modalities and immune signature to establish an immune-based prognostic signature for GC (IPSGC). RESULTS: We identified six immune genes as key factors of the mesenchymal subtype and established the IPSGC. The IPSGC can significantly divide patients into high- and low-risk groups in terms of overall survival (OS) and relapse-free survival (RFS) in discovery (OS: P < 0.001) and 5 independent validation sets (OS range: P = 0.05 to P < 0.001; RFS range: P = 0.03 to P < 0.001). Further, in multivariate analysis, the IPSGC remained an independent predictor of prognosis and performed better efficiency compared to clinical characteristics. Moreover, macrophage M2 was significantly enriched in the high-risk group, while plasma cells were enriched in the low-risk group. CONCLUSIONS: We propose an immune-based signature identified by network analysis, which is a promising prognostic biomarker and help for the selection of GC patients who might benefit from more rigorous therapies. Further prospective studies are warranted to test and validate its efficiency for clinical application.

A tetrahedral DNA nanostructure-decorated electrochemical platform for simple and ultrasensitive EGFR genotyping of plasma ctDNA.

Genotyping of the epidermal growth factor receptor (EGFR) mutation status is of great importance in the screening of appropriate patients with advanced non-small cell lung carcinoma (NSCLC) to receive superior tyrosine kinase inhibitor (TKIs) therapy. Yet conventional assays are generally costly with a relatively long turnaround time for obtaining results, which can lead to a bottleneck for immediately starting TKI therapy in late-staged patients. In this study, we propose an on-site electrochemical platform for sensitive simultaneous genotyping of the two major EGFR mutations (19del and L858R) through plasma ctDNA based on tetrahedral DNA nanostructure decorated screen-printed electrodes (SPE). Linear-after-the-exponential (LATE)-PCR combined with the amplification refractory mutation system (ARMS) was adopted to produce abundant biotin-labeled single-stranded DNA with high amplification efficiency and specificity. Disposable SPE decorated with self-assembled tetrahedral nanostructured DNA probes that showed ordered orientation and good target accessibility enabled the highly efficient hybridization of the specific amplicons through a sandwich-type and quantitatively translated the interfacial hybridization event into electrochemical signals via enzymatic amplification. Taking advantage of the ARMS-based LATE-PCR and the tetrahedral nanostructure-decorated SPE platform, we achieved the accurate detection of around 30 pg DNA of 19del or L858R, or as low as 0.1% of them in the presence of wild-type DNA. Moreover, the EGFR mutation profiles of 13 NSCLC patients we enlisted were accurately genotyped by our electrochemical platform, the results of which were in good agreement with those of commercial genetic detection methods.

Forward Wound Closure with Regenerated Silk Fibroin and Polylysine-Modified Chitosan Composite Bioadhesives as Dressings.

Wound dressing has been used for decades to be effective for accelerating skin wound healing. However, practical applications are still limited due to their lower cell affinity, tissue adhesiveness, and biocompatibility. Natural polymers are the important biomaterials because of their excellent biodegradability, biocompatibility, and low immunogenicity. In this work, the composite bioadhesives (PLS-CS/RSF) were prepared from regenerated silk fibroin (RSF) and polylysine-modified chitosan (PLS-CS) that were cross-linked by Ca2+ ions. The adhesion property tests showed that the PLS-CS/RSF exhibited excellent bonding potentials for various substrates, and the adhesive strength was up to 70 kPa for isolated porcine skin by the extension test. The as-prepared PLS-CS/RSF was nontoxic, displayed obvious antibacterial effects against Staphylococcus aureus and Escherichia coli in vitro, and their bacteriostasis rates were 100% after 120 min treatment. In addition, the PLS-CS/RSF exhibited favorable cytocompatibility by cell counting kit-8 assay. The animal model of wound closure results showed that PLS-CS/RSF can promote wound closure and the integrity of wound healing, inhibiting the secretion of inflammatory factor and tumor necrosis factor and stimulating vascular factor and α-smooth muscle actin to the release of vascular growth factor and promote angiogenesis during the process of wound healing by immunohistochemical assay.

Near-field radiative heat transfer in multilayered graphene system considering equilibrium temperature distribution.

In the present work, the near-field radiative heat transfer of a multilayered graphene system is investigated within the framework of the many-body theory. For the first time, the temperature distribution corresponding to the steady state of the system is investigated. Unique temperature steps are observed near both boundaries of the system, especially in the strong near-field regime. By utilizing the effective radiative thermal conductance, the thermal freedom of heat flux in different regions of the system is analyzed quantitatively, and the cause of various temperature distributions is explained accordingly. To characterize the heat transfer ability of the whole system, we evaluate the system with two heat transfer coefficients (HTC), transient heat transfer coefficient (THTC), and steady heat transfer coefficient (SHTC). A unique many-body enhancement is observed, which causes a red-shift of resonance peak corresponding to graphene surface plasmon polaritons. Furthermore, a three-body enhancement of SHTC emerges thanks to the relay effect and the complexity of the system. The regime of heat transport can be tuned by changing the chemical potentials of graphene and undergoes a transition from diffusive to quasi-ballistic transport in the strong near-field regime.

MicroRNA-146b Overexpression Promotes Human Bladder Cancer Invasion via Enhancing ETS2-Mediated mmp2 mRNA Transcription.

Although microRNAs have been validated to play prominent roles in the occurrence and development of human bladder cancer (BC), alterations and function of many microRNAs (miRNAs) in bladder cancer invasion are not fully explored yet. miR-146b was reported to be a tumor suppressor or oncomiRNA in various types of cancer. However, its accurate expression, function, and mechanism in bladder cancer remain unclear. Here we discovered that miR-146b was frequently upregulated in bladder cancer tissues compared with adjacent non-cancerous tissues. Inhibition of miR-146b resulted in a significant inhibitory effect on the invasion of bladder cancer cells by reducing mmp2 mRNA transcription and protein expression. We further demonstrated that knockdown of miR-146b attenuated ETS2 expression, which was the transcription factor of matrix metalloproteinase (MMP)2. Moreover, mechanistic studies revealed that miR-146b inhibition stabilized ARE/poly(U)-binding/degradation factor 1 (auf1) mRNA by directly binding to its mRNA 3' UTR, further reduced ets2 mRNA stability, and finally inhibited mmp2 transcription and attenuated bladder cancer invasion abilities. The identification of the miR-146b/AUF1/ETS2/MMP2 mechanism for promoting bladder cancer invasion provides significant insights into understanding the nature of bladder cancer metastasis. Targeting the pathway described here may be a novel approach for inhibiting invasion and metastasis of bladder cancer.

Retrieval of fractal dimension and size distribution of non-compact soot aggregates from relative intensities of multi-wavelength angular-resolved light scattering.

A new technique is developed to retrieve the fractal dimension and size distribution of soot aggregates simultaneously from the relative intensities of multi-wavelength angular-resolved light scattering. Compared with other techniques, the main advantage of this method is its independence of knowing complex refractive index, number density of aggregate, fractal prefactor and primary particle diameter. The forward light scattering procedure of soot aggregate is described by Rayleigh-Debye-Gans polydisperse fractal aggregate (RDG-PFA) scattering theory, and the retrieval process is performed by using the covariance matrix adaption-evolution strategy algorithm (CMA-ES). Three different measurement models, i.e. absolute scattering and transmittance, absolute scattering, relative scattering (RS), are investigated in present research. Numerical experiments have been performed to test the feasibility of the CMA-ES algorithm. Combined with the multi-wavelength RDG-PFA strategy, the retrieval accuracy of soot aggregate size distribution is proved to be more effectively by using the RS model. Satisfactory results under 10% Gaussian measurement noise have demonstrated the feasibility of the proposed method.

Loss of miR-143 and miR-145 in condyloma acuminatum promotes cellular proliferation and inhibits apoptosis by targeting NRAS.

The expression profile of miRNAs and their function in condyloma acuminatum (CA) remains unknown. In this study, we aimed to detect the effects of miR-143 and miR-145, the most downregulated in CA samples using high-throughput sequencing, on cell proliferation and apoptosis, to determine a novel therapeutic target for CA recurrence. RT-qPCR was used to validate the lower expression of miR-143 and miR-145 in a larger size of CA samples, and the expression of NRAS in CA samples was significantly higher than self-controls as determined by western blotting assay. Luciferase assay was performed to confirm that miR-143 or miR-145 targeted NRAS directly. Transduction of LV-pre-miR-143 or LV-pre-miR-145 to human papilloma virus (HPV)-infected SiHa cells led to reduced proliferation, greater apoptosis and inhibition of expression of NRAS, PI3 K p110α and p-AKT. However, knockout of miR-143 or miR-145 in human epidermal keratinocytes by delivery of CRISPR/CAS9-gRNA for target miRNAs protected cells from apoptosis and upregulated expression of target genes as described above. MiR-143 and miR-145 sensitized cells to nutlin-3a, a p53 activator and MDM2 antagonist, while their loss protected cells from the stress of nutlin-3a. Furthermore, siRNA targeting NRAS showed similar effects on proliferation and apoptosis as miR-143 or miR-145. Taken together, our results suggest that loss of miR-143 or miR-145 in CA protects HPV-infected cells from apoptosis induced by environmental stress, in addition to promoting cellular proliferation and inhibiting apoptosis by targeting NRAS/PI3 K/ATK. Restoration of miR-143 or miR-145 might provide an applicable and novel approach to block the recurrence and progression of CA.