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Aim: To identify DNA methylation and transcription biomarkers in the psoriatic epidermis. Materials & methods: Gene transcription and DNA methylation datasets of psoriatic epidermal tissue were obtained from the Gene Expression Omnibus. Machine learning algorithm analysis and weighted gene coexpression network analysis were carried out to screen hub genes. Results: Differentially methylated and expressed genes were identified in the psoriatic epidermis. Six hub genes were selected – GZMB, CRIP1, S100A12, ISG15, CRABP2 and VNN1 – whose transcript levels showed a significant correlation with Psoriasis Area and Severity Index scores and immune infiltration. Conclusion: Psoriatic epidermis is primarily in a hypermethylated status. Epidermis-specific hub differentially methylated and expressed genes are potential biomarkers to help judge the condition of psoriasis. more...

This article investigates the time-dependent sensitivity of structural reliability assessment to multisource uncertainties using Lamb wave. To precisely model the influence of local damage on the structure in the course of damage growth, a surface damage effect model is proposed to obtain the equivalent elasticity modulus, which can be coupled with the structure model. The evolution of the surface damage is modeled using the fatigue crack propagation model. Furthermore, by setting up the component and structure failure criteria, the time-dependent reliability model of the structure under multisource uncertainties from Lamb wave detection and material properties is established. The method of score function is employed to evaluate the sensitivity index, which is defined as the derivative of the reliability with respect to the distribution parameters of uncertain variables. A spatial truss structure is used to demonstrate the overall procedure. Numerical results show that the sensitivities indices are time and damage size dependent. The sensitivity contributions from Lamb wave quantification model and the material properties are comparable when the crack size is relatively small. When the crack grows to a larger size, the reliability assessment result is much more sensitive to uncertainties associated with material properties. more...

Locking compression plates (LCP) with asymmetrical holes and polyaxial screws are effective for treating mid-femoral fractures, but are prone to failure in cases of bone nonunion. To understand the failure mechanism of the LCP, this study assessed the material composition, microhardness, metallography, fractography and biomechanical performance of a retrieved LCP used for treating a bone fracture of AO type 32-A1. For the biomechanical assessment, a finite element surgical model implanted with the intact fixation-plate system was constructed to understand the stresses and structural stiffness on the construct. Also, to avoid positioning screws around the bone fracture, different working lengths of the plate (the distance between the two innermost screws) and screw inclinations (±5°, ±10° and ±15°) were investigated. The fracture site of the retrieved LCP was divided into a narrow side and broad side due to the asymmetrical distribution of holes on the plate. The results indicated that the chemical composition and microhardness of the LCP complied with ASTM standards. The fatigue failure was found to originate on the narrow side of the hole, while the broad side showed overloading characteristics of crack growth. When the screws were inserted away from the region of the bone fracture by increasing the working length, the stress of the fixation-plate system decreased. Regardless of the screw insertion angle, the maximum stress on the LCP always appeared on the narrow side, and there was little change in the structural stiffness. However, angling the screws at -10° resulted in the most even stress distribution on the fixation-plate system. In conclusion, the LCP assessed in this study failed by fatigue fracture due to bone nonunion and stress concentration. The narrow side of the LCP was vulnerable to failure and needs to be strengthened. When treating an AO type 32-A1 fracture using an LCP with asymmetrical holes and polyaxial screws, inserting the screws at -10° may reduce the risk of implant failure and positing screws around the fractured area of the bone should be avoided. more...

Actinic keratosis (AK) is a common premalignant lesion induced by chronic exposure to ultraviolet radiation and may develop into invasive cutaneous squamous carcinoma (cSCC). The identification of specific biomarkers in AK are still unclear. Long non-coding RNAs (lncRNAs), as transcripts of more than 200 nucleotides, significantly involving in multiple biologic processes, especially in the development of tumors.In our study, we obtained data from RNA-sequencing analysis using two AK lesion tissues and three normal cutaneous tissues to comparatively analyze the differentially expressed (DE) lncRNAs and messenger RNAs (mRNAs). Firstly, we used microarray analyses to identify DE lncRNAs and DE mRNAs. Secondly, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to analyze the primary function and find out significant pathways of these DE mRNA and lncRNAs. Finally, we used the top ten DE lncRNAs to construct a lncRNA-mRNA co-expression network.Our results showed that there were a total of 2,097 DE lncRNAs and 2,043 DE mRNAs identified. GO and KEGG analysis and the lncRNA-mRNA co-expression network (using the top 10 DE lncRNAs comprises 130 specific co-expressed mRNAs to construct) indicated that lncRNAlncRNA more...

We demonstrate a high-performance graphene-silicon slot-waveguide electro-optic micro-ring modulator featuring a record modulation efficiency of 10.99 V-1µm-1 with a 33-dB extinction ratio, 8-µm-long graphene and a modulation bandwidth of >40 GHz. more...

A light emitting diode (LED), with a wavelength of 308 nm, has been utilized in the dermatologic treatment of vitiligo.We investigated the efficacy and safety of 308-nm LED for use in the treatment of vitiligo.We conducted a retrospective study of 70 stable-stage vitiligo patients (with a total of 99 lesions) who received 308-nm LED treatment at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College from June 2018 to June 2020. Treatment efficacy was evaluated after 8 treatment sessions, 16 treatment sessions, and the final treatment session, to estimate the percentage of re-pigmentation in the treated area. The Kruskal-Wallis test was used for data analysis.Based on the final treatment session analysis of all 99 lesions, 0 lesions showed no response, 21 lesions showed poor response, 29 lesions showed moderate response, 23 lesions showed good response, and 26 lesions showed excellent response. The efficacy rate was 49.49%, and there was a significant correlation between the six distinct anatomical regions treated and re-pigmentation grade (χThe clinical efficacy of 308-nm LED treatment is limited based on the treatment area. It demonstrated significant practical application in the treatment of vitiligo. more...

Giant condyloma acuminatum (GCA) which is also called Buschke-Lowenstein tumor. It is a rare tumor of the anorectal area and external genitalia associated with low-risk HPV types 6 or 11. GCA has a high-rate of recurrence (66%) and malignant transformation (56%). The clinical features of GCA are progression of exophytic, ulcerative, and cauliflower-shaped tumors, it has significant dimensions and may undergo malignant transformation such as squamous cell carcinoma or cervical cancer. It is difficult to treat GCA, and it may be impossible for GCA to self-healing, but we herein report a rare case of a 19-year-old female with self-healing GCA. more...

Background Baicalin, a natural product isolated from Scutellaria radix, has been reported to exert anti-oxidant and anti-apoptotic effects on skin, but the underlying mechanism remains poorly understood. This study aimed to investigate the possible mechanism of anti-UVB effect of baicalin in human skin fibroblasts. Methods Cell proliferation was estimated by CCK-8 Kit. Apoptotic incidence was detected by flow cytometry with Annexin V-PE/PI apoptosis detection kit. Autophagy was determined by the evaluation of fluorescent LC3 puncta and Western blotting. Cell signalling was analysed by Western blotting. Results Baicalin exerted cytoprotective effects in UVB-induced HSFs. Moreover, baicalin increased autophagy and suppressed UVB-induced apoptosis of HSFs. Pretreatment with 3-MA, an autophagy inhibitor, attenuated baicalin-induced HSFs autophagy and promoted apoptosis. Baicalin activated AMPK, which leads to suppression of basal mTOR activity in cultured HSFs. Administration of compound C, an AMPK inhibitor, abrogated AMPK phosphorylation and increased mTOR phosphorylation and apoptosis compared with baicalin alone. Conclusion Taken together, these results indicate the important role of mTOR inhibition in UVB protection by baicalin and provide a new target and strategy for better prevention of UV-induced skin disorders. more...

Psoriasis is a systemic inflammatory disease, associated with metabolic disorders, including high level of low-density lipoprotein. PCSK9, which promotes the degradation of low-density lipoprotein receptors and, there-fore, the increased concentration of circulating low-density lipoprotein, is also involved in inflammation. This study aims to examine the role of PCSK9 in psoriasis and to investigate the potential of topically applying small interfering RNA targeting Pcsk9 as a psoriasis treatment. We investigated the expression of PCSK9 in lesions of psoriasis patients and imiquimod-induced psoriatic reactions in Pcsk9-knockout and Pcsk9 small interfering RNA-treated mice, and we also used cultured human keratinocytes to investigate the role of PCSK9 in regulating cell proliferation and apoptosis. We found that PCSK9 is overexpressed in psoriatic lesions and that suppressing Pcsk9 can decrease the inflammatory reaction induced by imiquimod treatment and inhibit hyperproliferation of keratinocytes. We also found that suppressing PCSK9 can significantly alter the cell cycle and induce apoptosis of human keratinocytes. Taken together, our findings indicate that PCSK9 plays an important role in psoriasis and may be a therapeutic target. more...

Cutaneous basal cell carcinoma (BCC) is a common subtype of malignant skin tumor with low invasiveness. Early diagnosis and treatment of BCC and the identification of specific biomarkers are particularly urgent. Long non-coding RNAs (lncRNAs) have been shown to be associated with the development of various tumors, including BCC. The present study conducted a comparative analysis of the differential expression of lncRNAs and mRNAs through whole-genome technology. Microarray analyses were used to identify differentially expressed (DE) lncRNAs and DE mRNAs. Reverse transcription-quantitative (RT-q) PCR confirmed the differential expression of 10 lncRNAs in BCC. Subsequently, a lncRNA-mRNA co-expression network was constructed using the top 10 DE lncRNAs. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the possible biological effects of the identified mRNAs and to speculate on the possible biological effects of the lncRNAs. A total of 1,838 DE lncRNAs and 2,010 DE mRNAs were identified and 10 of the DE lncRNAs were confirmed by RT-qPCR. A lncRNA-mRNA co-expression network comprising 166 specific co-expressed lncRNAs and mRNAs was constructed using the top 10 DE lncRNAs. According to the results of the GO and KEGG analyses, lncRNA {"type":"entrez-nucleotide","attrs":{"text":"XR_428612.1","term_id":"578818152","term_text":"XR_428612.1"}}XR_428612.1 may serve an important role in mitochondrial dysfunction and the progression of BCC by modulating TICAM1, USMG5, COX7A2, FBXO10, ATP5E and TIMM8B. The present study provided whole-genome identification and a systematic analysis of lncRNA-mRNA co-expression profiles in BCC. more...

Background: the wear of tibial insert is still one of primary factors leading to failure of total knee arthroplasty (TKA). Dodecyl gallate (DG) has shown improvements in the oxidation stability of highly cross-linked polyethylene (HXLPE). This study aimed to assess the application of HXLPE supplemented with DG (HXLPE-DG) on the tibial insert in TKA concerning the wear resistance and the potential impact on implant fixation, Methods: tibial inserts made of HXLPE-DG were subjected to a 3 million loading-cycle wear test following ISO 14243-1:2009. The loss of mass and wear rate of the tibial inserts were calculated. The quantity, size,- and shape of wear particles were recorded, Results: the test specimens lost an average mass of 16.00 mg ± 0.94 mg, and were on an average wear rate of 3.92 mg/million cycles ± 0.19 mg/million cycles. The content of wear particles in the calf serum medium was 3.94 × 108 particles/mL ± 3.93 × 107 particles/mL, 96.66% ± 0.77% of the particles had an equivalent circular diameter less than 0.5 μm. The aspect ratio of wear particles was 1.40 (min: 1.01, max: 6.42). Conclusions: HXLPE-DG displayed advantages over the commonly used materials for tibial inserts and presented the potential of application in TKA. more...

Melanoma remains a potentially deadly malignant tumor. The incidence of melanoma continues to rise. Immunotherapy has become a new treatment method and is widely used in a variety of tumors. Original melanoma data were downloaded from TCGA. ssGSEA was performed to classify them. GSVA software and the "hclust" package were used to analyze the data. The ESTIMATE algorithm screened DEGs. The edgeR package and Venn diagram identified valid immune-related genes. Univariate, LASSO and multivariate analyses were used to explore the hub genes. The "rms" package established the nomogram and calibrated the curve. Immune infiltration data were obtained from the TIMER database. Compared with that of samples in the high immune cell infiltration cluster, we found that the tumor purity of samples in the low immune cell infiltration cluster was higher. The immune score, ESTIMATE score and stromal score in the low immune cell infiltration cluster were lower. In the high immune cell infiltration cluster, the immune components were more abundant, while the tumor purity was lower. The expression levels of TIGIT, PDCD1, LAG3, HAVCR2, CTLA4 and the HLA family were also higher in the high immune cell infiltration cluster. Survival analysis showed that patients in the high immune cell infiltration cluster had shorter OS than patients in the low immune cell infiltration cluster. IGHV1-18, CXCL11, LTF, and HLA-DQB1 were identified as immune cell infiltration-related DEGs. The prognosis of melanoma was significantly negatively correlated with the infiltration of CD4+ T cells, CD8+ T cells, dendritic cells, neutrophils and macrophages. In this study, we identified immune-related melanoma core genes and relevant immune cell subtypes, which may be used in targeted therapy and immunotherapy of melanoma. more...

We demonstrated a passively Q-switched Nd: LuAG laser at 1064 nm based on few-layered MoS2 saturable absorber (SA) for the first time. The output pulses with a pulse duration of 280 ns and a repetition rate of 210 kHz were obtained at an incident pump power of 7.3 W, corresponding to a maximum output power of 290 mW. The experimental results show that MoS2 is a promising SA for solid-state lasers at 1 μ m. more...

In this paper, a sub-nanosecond KTiOPO4 (KTP)-based intracavity optical parametric oscillator (IOPO) pumped by a dual-loss modulated Q-switched and mode-locked (QML) laser with an acousto-optic modulator (AOM) and a Cr4+:YAG saturable absorber (Cr4+:YAG-SA) has been demonstrated. By changing the initial transmission of Cr4+:YAG-SA and the transmission of the output coupler at the signal wavelength, the signal pulse width compression can be realized. At an incident pump power of 8.3 W and an AOM repetition rate of 15 kHz, a single signal pulse underneath Q-switched envelope with the shortest pulse width of 220 ps was obtained. The experimental results reveal that this is a simple and effective way to obtain the sub-nanosecond OPO signal pulses. In addition, the related coupled rate equations have been set up and the simulation results agreed with the experimental results well. more...

We experimentally demonstrate a thermo-optic phase shifter based on a densely distributed silicon spiral waveguide, with power consumption, insertion loss, footprint and modulation bandwidth of 3 mW/π, 0.9 dB, 28×67 μm2 and 39 kHz respectively. more...

We show in simulation a 2-um graphene on silicon suspended electro-optic (E/O) modulator based on slot microring resonator working at critical coupling that shows dramatically increased speed while keeping big modulation depth. more...

The market for orthopedic implants is growing rapidly with the increasing prevalence of orthopedic diseases in an aging society. Different designs and materials have been developed over the years and have, in general, shown excellent results in pre-clinical testing. However, there have been incidences of serious complications when novel implants or materials are put into clinical use, with some well-known cases being metallosis in patients implanted with metal-on-metal hip replacements and osteolysis from polyethylene wear debris generated in hip and knee joint replacements. Unforeseen factors related to new designs, materials and surgical techniques can lead to different outcomes for pre-clinical testing and clinical use. While often an excellent indicator of a device's performance in clinical settings, pre-clinical testing does sometime fail to predict critical flaws in implant development. This article aims to explore the gaps in the current approach to testing. The ISO international standard of pre-clinical testing should be modified to more adequately capture actual clinical use of the implant and simulate daily activities. This article will also introduce modern methods for implant development, such as FEM, 3D printing and computer-aided orthopedic surgery, which can be widely applied to improve pre-clinical testing procedures and reduce the incidence of surgical malalignment by analyzing biomechanical performance, planning surgical procedure and providing surgical guide. more...

Cobalt-chromium-molybdenum alloy (CoCrMo) and ceramic are the two most common materials for the femoral head in hip joint prostheses, and the acetabular liner is typically made from ultra-high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (XLPE), or highly cross-linked polyethylene blended with Vitamin E (VEXLPE). The selection of suitable materials should consider both wear performance and cost-effectiveness. This study compared the wear rate between different friction pairs using a hip joint simulator and then recommended a suitable prosthesis based on the corresponding processing technology and cost. All wear simulations were performed in accordance with ISO 14242, using the same hip joint simulator and same test conditions. This study found that when using the same material for the femoral head, the XLPE and VEXLPE liners had a lower wear rate than the UHMWPE liners, and the wear rate of the XLPE liners increased after blending with Vitamin E (VEXLPE). There was no significant difference in the wear rate of XLPE when using a CoCrMo or ceramic head. Considering the wear rate and cost-effectiveness, a CoCrMo femoral head with an accompanying XLPE liner is recommended as the more suitable combination for hip prostheses. more...

Solid-state passively Q-switched Nd:LuAG laser at 1.3 μm with few layered MoS 2 as saturable absorber has been experimentally realized and demonstrated. The shortest pulse width of 188 ns and pulse repetition rate of 73 kHz were obtained. The experimental results verified the broadband saturable absorption characteristics of MoS 2 and indicated its ability to generate short pulses. more...

The passive Q-switching characteristics of a diode-pumped Tm,Ho:YAP laser at 2 μm based on a MoS2 saturable absorber (SA) is presented for the first time. Pulses as short as 435 ns under a repetition rate of about 55 kHz were generated at the incident pump power of 8.4 W, corresponding to the pulse peak power up to 11.3 W. This is, to the best of our knowledge, the highest pulse peak power, ever obtained from MoS2 based passively Q-switched 2-μm lasers. The experimental results sufficiently validated the feasibility of MoS 2 as SA for solid-state 2-μm lasers. more...

By simultaneously using an acousto-optic modulator (AOM) and a single-walled carbon nanotube saturable absorber, an intracavity optical parametric oscillation (IOPO) in KTiOPO 4 pumped by a dual-loss-modulated Q-switched laser has been demonstrated. With an incident pump power of 8.3 W and an AOM modulation rate of 20 kHz, the maximum output power of 375 mW for signal waves was obtained, corresponding to an optical-conversion efficiency of 4.5%. In comparison with IOPO pumped by a singly Q-switched laser with an AOM, the IOPO pumped by doubly Q-switched laser can generate signal light with shorter pulse width and higher peak power as well as better pulse stability. more...

Antigen specific B cells undergo a process termed affinity maturation in the germinal centers of secondary lymphoid organs where B cells with high affinity receptors are selected to mature into antibody-producing cells or to the memory B cell pool. It is known that B cell antigen receptor (BCR) signaling plays pivotal role in this selection process. Calcium influx is an essential component of BCR signaling. The current report is to determine the effect of calcium influx on antibody affinity maturation. In our studies, mice deficient for both endoplasmic reticulum calciumsensor Stim1 and Stim2 was immunized with T-cell dependent and independent antigens. Antibody affinity was measured by ELISA. We demonstrated that Stim1 &Stim2 deficient B cells exhibit accelerated pace of affinity maturation compared to wild type controls while the overall antibody production was not dramatically impaired to T-independent antigen immunization. In conclusion, calcium influx plays an important role in antibody affinity maturation in humoral immune responses. The knowledge can be used in manipulate humoral immune response for the design of effective vaccines. more...

Silicon photonic integrated circuits (PICs) show great potential for many applications. The phase tuning technique is indispensable and of great importance in silicon PICs. An optical phase shifter with balanced overall performance on power consumption, insertion loss, footprint, and modulation bandwidth is essential for harnessing large-scale integrated photonics. However, few proposed phase shifter schemes on various platforms have achieved a well-balanced performance. In this Letter, we experimentally demonstrate a thermo-optic phase shifter based on a densely distributed silicon spiral waveguide on a silicon-on-insulator platform. The phase shifter shows a well-balanced performance in all aspects. The electrical power consumption is as low as 3 mW to achieve a π phase shift, the optical insertion loss is 0.9 dB per phase shifter, the footprint is 67 × 28 µ m 2 under a standard silicon photonics fabrication process without silicon air trench or undercut process, and the modulation bandwidth is measured to be 39 kHz. more...

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By simultaneously using a multi-walled carbon nanotube (MWCNT) and a monolayer graphene saturable absorber (SA) in the cavity, a laser-diode-pumped dual-loss-modulated passively Q-switched Tm:LuAG laser at 2 mu m is demonstrated for the first time. In comparison with the singly passively Q-switched laser with MWCNT or monolayer graphene SA, the doubly passively Q-switched laser with both MWCNT and monolayer graphene SA can generate shorter pulse width and higher peak power. A maximum pulse width compression ratio of 2.8 and a highest peak power enhancement factor of 4 were obtained at the incident pump power of 5.8 W, respectively. The experimental results show that the dual-loss modulation is an efficient method to compress the pulse widths and improve the peak powers of the Q-switched lasers at 2 mu m. more...

By using monolayer graphene as saturable absorber, a passively Q-switched Tm:LuAG laser with high efficiency at 2 μm is demonstrated. At the incident pump power of 5.8 W, pulses with duration of 235 ns and maximum average output power of 873 mW were obtained at a repetition rate of 72 kHz. This is, to the best of our knowledge, the highest average output power, as well as the narrowest pulse width, ever obtained among graphene-based passively Q-switched solid-state bulk lasers at 2 μm regime. more...

Noncollinear optical parametric amplifiers (NOPAs) have become the leading technique for the amplification of carrier-envelope phase (CEP)-stable, few-cycle pulses at high repetition rate and high average power. In this Letter, a NOPA operating at a repetition rate of 100 kHz delivering more than 24 W of average power before compression is reported. The amplified bandwidth supports sub-7 fs pulse durations and pulse compression close to the transform limit is realized. CEP stability after amplification is demonstrated. The system paves the way to attosecond pump-probe spectroscopy with electron-ion coincidence detection. more...

Antigen specific B cells undergo a process termed affinity maturation in the germinal centers of secondary lymphoid organs where B cells with high affinity receptors are selected to mature into antibody-producing cells or to the memory B cell pool. It is known that B cell antigen receptor (BCR) signaling plays pivotal role in this selection process. Calcium influx is an essential component of BCR signaling. The current report is to determine the effect of calcium influx on antibody affinity maturation. In our studies, mice deficient for both endoplasmic reticulum calciumsensor Stim1 and Stim2 was immunized with T-cell dependent and independent antigens. Antibody affinity was measured by ELISA. We demonstrated that Stim1 &Stim2 deficient B cells exhibit accelerated pace of affinity maturation compared to wild type controls while the overall antibody production was not dramatically impaired to T-independent antigen immunization. In conclusion, calcium influx plays an important role in antibody affinity maturation in humoral immune responses. The knowledge can be used in manipulate humoral immune response for the design of effective vaccines. more...