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Objective Due to the increase of metro operation mileages and track conditions complexity, abnormal bogie vibrations caused by wheel-rail wear often occur. Bogie frame serves as an important load-bearing component, requiring research on its structural integrity and vibration failure mechanism under abnormal vibration conditions. Method Taking a metro bogie frame as example, based on vibration transmission tests and dynamic stress data, a study is conducted on the abnormal vibration and beam fatigue failure causes of metro vehicles on a line during operation, analyzing the source of disturbance and vibration transmission path. Based on the results of frame working modal tests, the vibration acceleration and dynamic stress time-frequency characteristics at beam failure points when vehicle passing typical sections are analyzed. By analyzing influencing factors such as wheel polygon, rail corrugation, and vehicle operating speed, the amplitude and spectrum characteristics of beam dynamic stress are investigated. Result & Conclusion Before wheel reprofiling, the main measuring points where equivalent stress amplitude exceeds the limit are concentrated at the connections between beams and side beams, beams and small longitudinal beams, and the upper cable supports of beams. After wheel reprofiling, the equivalent stress amplitudes at all measuring points significantly decrease, far below the allowable stress amplitude. The main external excitation source causing beam cracking is the 5 to 8 order wheel polygon, and the exacerbated vehicle vibration caused by wheel off-roundness is the direct cause for fatigue failure of beam cable supports.

PurposeThis study aims to develop a assessment system for evaluating shoulder joint muscle strength in patients with varying degrees of upper limb injuries post-stroke, using surface electromyographic (sEMG) signals and joint motion data.MethodsThe assessment system includes modules for acquiring muscle electromyography (EMG) signals and joint motion data. The EMG signals from the anterior, middle, and posterior deltoid muscles were collected, filtered, and denoised to extract time-domain features. Concurrently, shoulder joint motion data were captured using the MPU6050 sensor and processed for feature extraction. The extracted features from the sEMG and joint motion data were analyzed using three algorithms: Random Forest (RF), Backpropagation Neural Network (BPNN), and Support Vector Machines (SVM), to predict muscle strength through regression models. Model performance was evaluated using Root Mean Squared Error (RMSE), R-Square (R2), Mean Absolute Error (MAE), and Mean Bias Error (MBE), to identify the most accurate regression prediction algorithm.ResultsThe system effectively collected and analyzed the sEMG from the deltoid muscles and shoulder joint motion data. Among the models tested, the Support Vector Regression (SVR) model achieved the highest accuracy with an R2 of 0.8059, RMSE of 0.2873, MAE of 0.2155, and MBE of 0.0071. The Random Forest model achieved an R2 of 0.7997, RMSE of 0.3039, MAE of 0.2405, and MBE of 0.0090. The BPNN model achieved an R2 of 0.7542, RMSE of 0.3173, MAE of 0.2306, and MBE of 0.0783.ConclusionThe SVR model demonstrated superior accuracy in predicting muscle strength. The RF model, with its feature importance capabilities, provides valuable insights that can assist therapists in the muscle strength assessment process.

IntroductionThe composition and subsets of skin cells continuously change in a dynamic manner. However, the specific microcosmic alterations of human photoaged skin, independent of chronologic aging, remain unclear and have been infrequently analyzed. This study aimed to evaluate the biological processes and mechanisms underlying cell-subgroup alterations in skin photoaging.MethodsWe utilized single-cell sequencing and biological analysis from a single case to investigate the effects of photoaging. Skin punch biopsies were taken from sun-exposed forearm skin and unexposed buttock skin from the same individual for comparative analysis.ResultsOur analysis identified 25 cell clusters and 12 skin cell types, revealing significant changes in unique gene expressions between the sun-exposed and unexposed skin samples. A comparison of cell numbers within each cluster revealed 9 dominant cell clusters in sun-exposed skin and 16 dominant cell clusters in unexposed skin. Enrichment analysis indicated that PD-L1 expression and the PD-1 checkpoint pathway were more prominent in sun-exposed skin, while MAPK, TNF-alpha, TGF-beta, and apoptosis pathways were more enriched in hair follicle cells of sun-exposed skin.DiscussionThis study reveals changes in cell components in photoaged skin from a single case and provides novel insights into cellular subpopulations and pathology during repeated UVA-induced skin damage. These findings enhance our understanding of the complex interplay between different cells in photoaged skin and offer potential targets for preventing human skin photoaging and UV-induced skin cancers.

The conventional TO-247-3 packages with single-sided cooling limit the thermal and electrical performances of discrete SiC MOSFET devices. In this paper, a double-sided cooling press-pack (PP) packaging approach for the discrete SiC MOSFET device is proposed to optimize its thermal and electrical performances. First, a double-sided cooling PP structure for the discrete SiC MOSFET devices is designed with a copper foam gate pin and an embedded fixture. Then, based on finite element simulations, the steady-state thermal and electrical performances of the discrete SiC MOSFET device with the double-sided cooling PP package are analyzed, and the parasitic inductance of the designed SiC MOSFET device is extracted by the ANSYS Q3D software. Finally, a prototype of the double-sided cooling PP SiC MOSFET device is fabricated, and test platforms are established to verify its performance. The research findings demonstrate that the designed double-sided cooling PP SiC MOSFET device can reduce thermal resistance and switching loss by 47.4 % and 42.3%, respectively.

Erlec1 gene has been suggested to be involved in the regulation of bone development. However, the underlying mechanism remains largely unknown. In this study, we showed that loss of Erlec1 leads to growth retardation in mice. Erlec1−/− mice exhibited increased proliferation, delayed differentiation and mineralization in osteoblasts accompanied by decreased production of collagen I. Our data demonstrated that Erlec1 regulates bone formation through modulating proliferation and differentiation of osteoblasts by affecting the synthesis of collagen I, suggesting that Erlec1 may serve as a potent target for bone metabolism diseases.

Abstract Common bile duct (CBD) exploration and T-tube drainage are the main surgical methods for the removal of bile duct stones (BDSs), which can now be completed by laparoscopy. However, the feasibility and safety of primary closure of the CBD (PCCBD) in laparoscopic CBD exploration (LCBDE) without biliary drainage are still uncertain. From January 1, 2021, to June 30, 2022, patients who were diagnosed with BDSs and underwent LCBDE and primary closure of the CBD without biliary drainage in our hospital were included. The clinical and prognostic data of the patients were retrospectively analyzed to determine the feasibility and safety of PCCBD in LCBDE without biliary drainage. Forty-nine patients successfully underwent PCCBD in LCBDE without biliary drainage. The operation time was 158.8 ± 50.3 (90–315,150) minutes, the bile duct suture time was 17.6 ± 4.46 (10–26, 18) minutes, the intraoperative blood loss volume was 70.4 ± 52.6 (5–200, 80) ml, the hospitalization cost was 28,141.2 ± 7011.3 (15,005.45–52,959.34, 26,815.14) CNY Yuan, the hospitalization time was 13.22 ± 5.16 (8–32, 12) days, and the postoperative hospitalization time was 7.31 ± 1.94 (3–15, 7) days. There were 3 cases of postoperative bile leakage (3/49, 6.12%), all of them healed by nonsurgical treatment. During the follow-up of 17.2 ± 11.01 (10–26, 17) months, no residual BDSs, biliary stricture or other complications classified as Clavien-Dindo grade I or higher occurred. For some selected patients who meet certain criteria, PCCBD in LCBDE without biliary drainage is feasible and safe and is more conducive to the rapid postoperative recovery of patients.

Objective To evaluate the therapeutic efficacy of a combination of compound middle-layer acid and 30% supramolecular salicylic acid for melasma. Methods Five female patients with melasma who were admitted to our hospital from May 2022 to December 2022 were enrolled in this study. A self-parallel controlled study was carried out. The patients' treated side was treated with compound middle-layer acid while the control side was treated with 30% supramolecular salicylic acid at weeks 0 and 4. On week 8, the treated side and control side were treated with 30% supramolecular salicylic acid and compound middle-layer acid, respectively. We compared the area score of facial lesions, skin color, sebum, water content and the severity of melasma-related psychological stress between the two sides. Results The combination therapy significantly decreased the area scores on the forehead, cheek and chin (P0.10). Moreover, the combination therapy decreased both SAS (from 21.62±5.99 to 20.86±6.44, P

Abstract The existence of causal relationship between dietary factors and respiratory diseases is uncertain. We comprehensively investigated the association between dietary factors and respiratory diseases by using Mendelian randomization (MR). Genetic variants linked to dietary factors were selected as instrumental variables with genome-wide significance. These instrumental variables were obtained from large GWAS databases. These databases include Biobank, the FinnGen study, and other large consortia. We used multivariate MR analyses to control the effects of smoking and education. Median analysis was conducted to evaluate whether body mass index (BMI) played a role in dietary factors in respiratory diseases. Dried fruit intake was found to be associated with a decreased risk of chronic obstructive pulmonary disease (COPD) (OR: 0.211; 95% CI 0.117–0.378; P

ABSTRACT: Objectives: To investigate the gene mutations associated with ceftriaxone (CRO) resistance among gonococcal isolates, and to determine the effects of the mutated genes on CRO minimum inhibitory concentrations (MICs) with transformation assays and antisense peptide nucleic acids (asPNAs). Methods: Ceftriaxone-resistant (CROR) and ceftriaxone-susceptible (CROS) isolates were identified using EUCAST and paired according to similarity in their MICs to other antimicrobials. The two groups of gonococci were sequenced and analysed. Mutated genes that showed a statistical difference between the two groups were transformed into gonococcal reference strains to determine their functions. AsPNAs were designed and transformed into the former transformant to further confirm the effects of the mutated genes. Results: Twenty-two paired CROR and CROS isolates were obtained. The incidence of the penA-A501T and penA-G542S mutations individually, as well as combined mutations (penA-A501T and ftsX-R251H, penA-G542S and ftsX R251H), was statistically different between the two groups. The MIC of ATCC43069 (A43) increased 2 times following transformation with penA-A501T, and the MICs of A43 and ATCC49226 (A49) increased 32 times and 2 times following transformation with penA-A501T and ftsX-R251H, respectively. Antisense PNA-P3 reduced the MIC of the A43 transformant most significantly when transformed individually. PNA-P3 and PNA-F1 (asPNAs of the penA and ftsX) restored CRO susceptibility. Conclusions: PenA-A501T and penA-G542S mutations are important in CRO resistance among gonococci isolates. The ftsX-R251H mutation is also related to CRO resistance, and combined mutations of ftsX-R251H and penA-A501T comediate a significant reduction in CRO susceptibility. The combined application of PNA-P3 and PNA-F1 could effectively reverse the resistance to CRO in N. gonorrhoeae.

Objective To evaluate the efficacy and safety of autologous platelet-rich plasma (PRP) in the treatment of androgenetic alopecia and to investigate the correlation between concentrations of growth factors and efficacy. Methods Seven male patients with AGA were included in this prospective study. In each subject, one side of the alopecia area was randomly injected with PRP while the opposite side was injected with saline once every other week for 3 times, followed by follow-up at 1, 2, and 3 months. Clinical pictures and dermoscopy images were taken for assessment of efficacy by patients and doctors. ELISA was used to measure the levels of PDGF, TGF-β and VEGF in PRP and peripheral blood. Relationship between efficacy and concentration of growth factors was also determined. Results After the treatment, both hair density hair/follicle ratio were increased on the PRP side compared with the placebo side (P

Purpose: To determine whether individuals with subjective cognitive decline (SCD) have changes in whole-brain network characteristics and intracerebral node characteristics in the structural network, and whether there is a difference between SCD with and without Apolipoprotein E4 (APOEε4). Methods: This cross-sectional study included 36 individuals without SCD without APOEε4 (healthy control, HC group), 21 individuals with SCD with APOEε4 (APOEε4+ group), and 33 individuals with SCD without APOEε4 (APOEε4- group). The white matter structural network was constructed using the fractional anisotropy (FA) based deterministic fiber tracking method. Graph theory was used to analyze the whole-brain network characteristics and intracerebral node characteristics of the three groups. Results: Regarding the whole-brain network characteristics, all three groups exhibited small-worldness in their structural networks. The clustering coefficient (Cp) and local efficiency (Eloc) in the APOEε4+ and APOEε4- groups were significantly lower than in the HC group (p < 0.05), but no significant difference in Cp or Eloc was observed between the APOEε4+ and APOEε4- groups. Regarding intracerebral node characteristics, there were significant differences in some brain regions, mainly the default mode network (DMN), the occipital lobe, the temporal lobe, and subcortical regions. The change in intracerebral node characteristics was different between the APOEε4+ group and the APOEε4- group. Conclusions: Individuals with SCD demonstrate changes in whole-brain network characteristics and intracerebral node characteristics in the structural network. Moreover, differences exist between APOEε4+ and APOEε4- individuals.

Abstract Press‐pack insulated gate bipolar transistor modules (PP‐IGBTs) have been widely used in high‐voltage and high‐power‐density applications, such as high‐voltage direct‐current (HVDC) converters, because of their advantages of low thermal resistance, double side cooling, and short‐circuit failure mode. Package failure is one of the main reasons for IGBT module failure. Package condition monitoring is the key to realizing modules fault diagnosis, condition prediction, and intelligent operation and maintenance. At present, a variety of characteristic parameters, such as on voltage and junction temperature, are used in package condition monitoring. However, the characteristic parameters show different variation laws under different package degradation modes. Therefore, the relationship between package degradation modes and characteristic parameters is the key to realizing the condition monitoring, so as to improve the reliability of the power electronic system. In this paper, first, the package structure of a PP‐IGBT is analyzed. Second, the mechanisms of fretting wear degradation, gate‐oxide degradation, spring degradation, lid warping degradation, micro arcing degradation, short‐circuit failure, and open‐circuit failure are reviewed. The variation laws of characteristic parameters under each degradation and failure mode are then investigated. Finally, three difficult problems including characteristic parameter measurement, especially pressure monitoring, high‐sensitivity detection, and characterization and evaluation, are discussed and analyzed.

Abstract Introduction Neuroendocrine differentiation (NED) in colorectal cancer (CRC) cells has been known for decades, and our previous meta-analysis indicated that CRC patients with neuroendocrine differentiation have a lower 5-year survival rate. In recent years, an increasing number of studies have found that exosome-derived long non-coding RNAs (lncRNAs) play important roles in cancer progression and metastasis. However, the functions and mechanism of exosome-derived lncRNAs in CRC with neuroendocrine differentiation are not yet fully clear. Materials and methods The clinical significance of NED was assessed in a retrospective study of 105 patients. Next-generation sequencing and bioinformatics analysis were conducted to select lnc-HOXB8-1:2 for further study. Using immunohistochemistry, qRT–PCR, western blot, transwell assay, immunofluorescence assay, fluorescence in situ hybridization assay and dual-luciferase reporter assay, the oncogenic role of exosome-derived lnc-HOXB8-1:2 was determined in CRC with NED. The mechanism underlying the lnc-HOXB8-1:2/hsa-miR-6825-5p/CXCR3 axis was also explored. Results NED was a risk factor for the progression and mortality of CRC. lnc-HOXB8-1:2, derived from exosomes secreted by neuroendocrine differentiated colon cancer cells, was identified in our study. The proportion of M2 macrophages and the migration and invasion capacities of tumor-associated macrophages (TAMs) markedly increased after the addition of neuroendocrine differentiated CRC cell-derived exosomes. More excitingly, the expression of lnc-HOXB8-1:2 and the protein level of CXCR3 were also upregulated in TAMs. The lnc-HOXB8-1:2/hsa-miR-6825-5p/CXCR3 axis was predicted via miRanda software and confirmed by the dual-luciferase reporter assay. Furthermore, the increased expression of lnc-HOXB8-1:2 was accompanied by downregulation of hsa-miR-6825-5p expression and upregulation of CXCR3 protein levels. Overexpression of hsa-miR-6825-5p also reduced CXCR3 expression. Conclusion lnc-HOXB8-1:2 in exosomes derived from neuroendocrine differentiated CRC cells acted as a ceRNA competitively binding hsa-miR-6825-5p to upregulate CXCR3 expression and leading to TAM infiltration and M2 polarization, which promotes neuroendocrine differentiated CRC progression.

MHC-peptide multimers are important reagents for detecting antigen specific T cells. Here the authors show that DNA scaffolds can be used to make MHC-peptide multimers and the avidity controlled so that low abundance or T cells with low affinity TCR can be detected using these reagents.

Incorporation of organometallic catalysts within macromolecular scaffolds is a promising approach to constructing biocompatible catalytic systems. Here, we report our recent progress in establishing a modular synthetic platform to prepare di-block brush-arm star copolymers (DBSPs), which were further used as scaffolds to construct catalytic systems that can function in complex biological media. First, a novel convergent graft-to approach based on ring-opening metathesis polymerization (ROMP) and enyne metathesis mediated conjugation was developed to synthesize DBSPs. By introducing active esters, functional DBSPs can be rapidly accessed through post-polymerization modification. DBSPs with fluorescent or radial probes were prepared, enabling structure-property study of the DBSPs. Further incorporation of organometallic catalysts into the DBSPs via either covalent conjugation or physical encapsulation afforded catalytic systems that are active in cellular environments.

Abstract Background Psoriasis is a chronic relapsing immunological skin disease characterized by multiple cross-talk inflammatory circuits which are relevantly associated with abnormal cross-reactivity between immune cells and keratinocytes (KCs). It may be inadequate to eradicate complicated pathogenesis only via single-mode therapy. To provide optimal combinatory therapeutics, a nanocomposite-based hydrogel was constructed by loading methotrexate (MTX) into ZnO/Ag to realize combined multiple target therapy of psoriasis. Results In this composite hydrogel, ZnO hybrid mesoporous microspheres were utilized both as drug carriers and reactive oxygen species (ROS)-scavenging nanoparticles. A proper amount of Ag nanoparticle-anchored ZnO nanoparticles (ZnO/Ag) was functionalized with inherent immunoregulatory property. The experiments showed that ZnO/Ag nanoparticles could exhibit a self-therapeutic effect that was attributed to reducing innate cytokine profiles by inactivating p65 in proinflammatory macrophages and abrogating secretion of adaptive cytokines in KCs by downregulating ROS-mediated STAT3-cyclin D1 signaling. A preferable antipsoriatic efficacy was achieved via topical administration of this hydrogel on the imiquimod (IMQ)-induced psoriasis mice model, demonstrating the superior transdermal delivery and combined enhancement of therapeutic efficacy caused by intrinsic nanoparticles and extrinsic MTX. Conclusion This composite hydrogel could serve as a multifunctional, nonirritating, noninvasive and effective transcutaneous nanoagent against psoriasis. Graphical Abstract

Abstract Background Abnormal hypermethylation of the septin 9 gene was an inchoate incident in some cancers. Though latest several researches had paid attention to its value in prognosis, the consequences were not distinctly, especially in colorectal cancer (CRC) with stage II and stage III. Purpose The aim of this research was to pick up the prognostic value of the methylated septin 9 gene (mSEPT9) in CRC patients, particularly in TNM stage II—III. Methods Blood samples before surgery were obtained from 144 CRC patients, of which there were 94 with stage II and stage III. mSEPT9 was considered positive when the cycle number of the peak reaction (Ct) was lower than the threshold value (41.0) for two times during three times PCR test. mSEPT9 and other relative factors of prognosis were estimated by survival analysis. The level of septin 9 in tissues was tested by immunohistochemical (IHC). Results Stage II and stage III patients with mSEPT9 positive (mSEPT9+) had a lower disease-free survival (DFS) rate than those with mSEPT9 negative (mSEPT9-) (2-year DFS rates, 52.1% vs 73.9%, P = 0.014). In multivariate regression analysis, mSEPT9 was also an independent predictor of prognosis (HR = 2.741, P = 0.009). The risk of local recurrence or distant metastasis in CRC patients after surgery was mSEPT9+ with stage III, mSEPT9- with stage III/mSEPT9+ with stage II, and mSEPT9- with stage II (P = 0.001), from highest to lowest. In addition, mSEPT9 was strongly associated with TNM staging, tumor immersion depth, distant metastasis, differentiation degree, vascular invasion and microsatellite. When we explored the associations between septin 9 protein level revealed by IHC and other elements, recurrence/progression (R = − 0.523, P = 0.001), mSEPT9 status (R = − 0.451, P = 0.004) and T stage (R = − 0.375, P = 0.017) showed significant correlations. Conclusions Positive mSEPT9 is a poor prognostic marker for CRC patients in stage II and III. It is also a powerful complement to TNM staging in predicting postoperative DFS of CRC patients of stage II and III.

Taking the rotor system supported by angular contact ball bearing as the research object, the dynamic model of rotor bearing system is established by using Lagrange equation. Based on the Archard wear model, the calculation model of wear depth of bearing raceways considering lubrication effects is presented. The wear depth is introduced into the system dynamics model as the bearing clearance. The dynamic characteristics of rotor-bearing system and the evolution of bearing wear are carefully analyzed taking into account the rotor speed, bearing preload and disc position. The results show that the influence of bearing wear on dynamic characteristics of rotor-bearing system is closely related to rotor speed and bearing preload. Changing disc position does not lead to the significant variation of dynamic characteristics of rotor-bearing system with wear depth of bearing raceways. The rotor speed significantly affects the bearing wear, the bearing preload has very limited effect on bearing wear, and the variation of the disc position results in the weak difference of wear depth of bearings.

Allium fistulosum (Welsh onion) is a perennial onion species that originates in eastern Asia. It is an important cooking ingredient in eastern countries, such as China, Japan, and Korea. In western countries, it is primarily used as a scallion or salad onion. According to the dictionary of Chinese drugs, the seeds of A. fistulosum, a traditional Chinese medicine, are used as tonic and aphrodisiac. The purpose of this study was to evaluate the protective effect of the seeds of A. fistulosum extract (SAFE) against acute myocardial ischemia. Rat and dog acute myocardial ischemia models were used, the model of acute myocardial ischemia in rats were divided into six groups: control group (saline, 10 mL·kg−1), model group (saline, 10 mL·kg−1), SAFE low, medium and high dose groups（50, 150, 300 mg·kg−1）and the positive control group (Xingling granule, 900 mg·kg−1), and the model of acute myocardial ischemia in dogs were also divided into the control group （saline, 2 mL·kg−1）, SAFE low, medium and high dose groups（15, 45, 90 mg·kg−1）and the positive control group (Xingling granule, 300 mg·kg−1). Myocardial ischemia degree was measured by epicardium electrocardiogram, the range of myocardial infarction was determined by quantitative histology （N-BT staining), and serum creatine kinase (CK）and lactate dehydrogenase（LDH) content were detected by biochemical assay. Compared with the control group, the results showed that SAFE could reduce the degree of myocardial ischemia, infarcted area, and elevation of serum CK and LDH levels in rats and dogs after coronary ligation. In conclusion, SAFE can improve acute myocardial ischemia and reduce myocardial infarction in rats and dogs, and which suggests that it can achieve prevention effects of myocardial ischemia.

Carbapenem-resistant Enterobacteriaceae (CRE) infections constitute a threat to public health, and KPC and NDM are the major carbapenemases of concern. Rapid diagnostic tests are highly desirable in point-of-care (POC) and emergency laboratories with limited resources. Here, we developed a multiplex lateral flow assay based on asymmetric PCR and barcode capture probes for the simultaneous detection of KPC-2 and NDM-1. Biotinylated barcode capture probes corresponding to the KPC-2 and NDM-1 genes were designed and cast onto two different sensing zones of a nitrocellulose membrane after reacting with streptavidin to prepare a multiplex lateral flow strip. Streptavidin-coated gold nanoparticles (SA-AuNPs) were used as signal reporters. In response to the target carbapenemase genes, biotin-labelled ssDNA libraries were produced by asymmetric PCR, which bond to SA-AuNPs via biotin and hybridise with the barcode capture probe via a complementary sequence, thereby bridging SA-AuNPs and the barcode capture probe to form visible red lines on the detection zones. The signal intensities were proportional to the number of resistance genes tested. The strip sensor showed detection limits of 0.03 pM for the KPC-2 and 0.07 pM for NDM-1 genes, respectively, and could accurately distinguish between KPC-2 and NDM-1 genes in CRE strains. For the genotyping of clinical isolates, our strip exhibited excellent consistency with real-time fluorescent quantitative PCR and gene sequencing. Given its simplicity, cost-effectiveness, and rapid analysis accomplished by the naked eye, the multiplex strip is promising auxiliary diagnostic tool for KPC-2 and NDM-1 producers in routine clinical laboratories.

Abstract. Rosacea is a chronic inflammatory skin disease that primarily affects the centrofacial areas and mainly manifests as recurrent flushing and erythema. In recent years, there has been progress in the understanding of the diagnosis and treatment of rosacea. Therefore, a group of dermatological experts updated the guidelines based on the 2016 expert consensus statement on rosacea diagnosis and treatment in China. These new guidelines propose diagnostic criteria for rosacea at different sites to further standardize the diagnosis and treatment of rosacea in China.

Abstract Background The main cause of death in colorectal cancer patients is metastasis. Accumulating evidences suggest that circRNA plays pivotal roles in cancer initiation and development. However, the underlying molecular mechanisms of circRNAs that orchestrate cancer metastasis remain vague and need further clarification. Methods Two paired CRC and adjacent normal tissues were used to screen the upregulated circRNAs by circRNA-seq; then, cell invasion assay was applied to confirm the functional invasion-related circRNAs. According to the above methods, circHERC4 (hsa_circ_0007113) was selected for further research. Next, we investigated the clinical significance of circHERC4 in a large cohort of patients with CRC. The oncogenic activity of circHERC4 was investigated in both CRC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying circHERC4 as a malignant driver. Results We demonstrated that circHERC4 was aberrantly elevated in CRC tissues (P

Owing to the advantages of short-circuit failure mode, double-sided heat dissipation, and low thermal resistance, press-pack insulated gate bipolar transistors (PP-IGBTs) are widely used in high-power-density applications, such as high-voltage direct-current converters. As the core device of large-capacity power equipment, the reliability of a PP-IGBT is directly related to the security of the power system. In recent years, a silver-sintered package has been proposed to improve the electro-thermal performance of PP-IGBTs. However, the long-term reliability of this package has not been proven. In response to this problem, 3300-V/50-A silver-sintered PP-IGBT (SPP-IGBT) modules are used in long-reliability research. First, electro-thermal-stress finite-element models of PP-IGBTs and SPP-IGBTs were proposed and the accuracy of models verified by experiments. Through a simulation comparison, the results show that under the rated operating conditions, the on-voltage and maximum temperature of SPP-IGBTs dropped by 9.3% and 3.7%, respectively. In addition, the temperature and stress of each component were reduced, among which the surface stress of the IGBT chip emitter dropped by as much as 24.7%. Subsequently, a power-cycle test platform was established, and three PP-IGBTs and three SPP-IGBTs were tested. Finally, the experimental results were compared and analyzed, and the reasons for the sharp increase of on-voltage and metal melt were explored. The results show that the silver-sintered package improves the electrical-thermal performance and long-term reliability of the module.

Background: Recent studies have reported that the incidence of sensitive skin is increasing. Skin sensitivity and skin barrier functions were related to many skin diseases including atopic dermatitis, psoriasis, rosacea, and so on. Mesenchymal stem cell (MSC)-derived exosomes (hMSC) might be considered as a new effective therapeutic scheme.Aims: This study aims to investigate the safety and efficacy of hMSC exosomes as a novel topical treatment for sensitive skin.Patients/Methods: Exosomes were extracted from primary hMSC via ultracentrifugation method. The morphology of hMSC exosomes was studied via transmission electron microscope. Expression of exosome specific surface marker was detected via Western blot. 22 subjects (female, aged 18–55) diagnosed with sensitive skin were enrolled. Follow-up was conducted before, 7-day, 14-day, and 28-day after hMSC exosomes use. Transepidermal water loss (TEWL), surface hydration, sebum secretion, and L*a*b* value were simultaneously tested at the same time point in an environment-controlled room.Results: Under transmission electron microscopy, the extracted hMSC exosomes were circular or elliptical with intact membrane structure, and their diameters ranged mainly from 40 to 80 nm. Western blot showed that the expression of markers CD63, CD9, and Tsg101 was positive. Brownian motion based nanoparticle trajectory analysis (NTA) showed that the main peak of particle size distribution occurred around 96 nm, the average particle size was 122 nm, and the main peak accounted for 96.7%. All this conformed to the biological characteristics of exosomes standardized by the International Society for Extracellular Vesicles. In the clinical trial, scores of objective symptoms including roughness, scales, erythema, and subjective symptoms including tension, burning, or itching, were improved after 7-, 14-, and 28- day using hMSC-exosomes. TEWL, hydration, sebum, pH, and a* values were tended to return to the level of healthy skin.Conclusion: The hMSC-exosomes, with the advantages of biocompatibility and biodegradability, could improve clinical symptoms and eruptions in sensitive skin patients, and might be as an MSC cell-free novel therapy in sensitive skin-related disease treatment.

Abstract Background Liver metastasis is the most common cause of death in patients with colorectal cancer (CRC). Phosphatase of regenerating liver-3 induces CRC metastasis by epithelial-to-mesenchymal transition, which promotes CRC cell liver metastasis. Mesenchymal-to-epithelial transition (MET), the opposite of epithelial-to-mesenchymal transition, has been proposed as a mechanism for the establishment of metastatic neoplasms. However, the molecular mechanism of MET remains unclear. Methods Using Immunohistochemistry, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, human miRNA arrays, and xenograft mouse model, we determined the role of hepatocyte exosome-derived miR-203a-3p in CRC MET. Results In our study, we found that miR-203a-3p derived from hepatocyte exosomes increased colorectal cancer cells E-cadherin expression, inhibited Src expression, and reduced activity. In this way miR-203a-3p induced the decreased invasion rate of CRC cells. Coclusion MiR-203a-3p derived from hepatocyte exosomes plays an important role of CRC cells to colonize in liver.

Abstract. Acne inversa/hidradenitis suppurativa is a chronic, recurrent, inflammatory skin disease that affects the pilosebaceous units, causinfollicular occlusion. The etiology and pathogenesis of acne inversa/hidradenitis suppurativa involves internal and external factors such as genetic susceptibility, inflammation and immunity, microorganisms, obesity, and smoking. acne inversa/hidradenitis suppurativa is difficult to treat, and the current aim of treatment is to control the frequency and duration of disease flares and improve the quality of life. Treatment protocols for acne inversa/hidradenitis suppurativa should be selected based on the disease severity grade. Medical treatments include antibiotics, retinoids, biologics, immunosuppressive agents, and antiandrogen agents. Adjuvant treatments include surgery and laser/light therapies. This consensus aims to further standardize the diagnosis and treatment procedures of acne inversa/hidradenitis suppurativa in China to facilitate its diagnosis and treatment.

Objective: To investigate the role of LncRNAs that regulate cathepsin D in chronic light-damaged skin cells and explore their role in the mechanism of skin photoaging. Methods: Cultured human dermal fibroblasts were induced to a photoaging cells model by repetitive UVA radiation (UVA radiation group), which was evaluated by CCK8 assay, β-galactosidase staining and flow cytometry detection of apoptosis rate. High-throughput sequencing was used to detect LncRNA expression profiles. Functional annotation analysis was preformed to identify the LncRNAs that could regulate cathpeisn D. miRanda and TargetScan were preformed to analyze the miRNA that can target binding to LncRNA-cathpeisn D. Results: Compared with cells in the control group, the proliferative activity of cells in the UVA radiation group significantly decreased [(60.02±5.13)% vs (89.06±4.21)%, t=2.31, P

Macamides are a class of amide alkaloids that are only found in maca and are widely considered to be its bioactive marker compounds. More than thirty macamide monomers have been identified in recent years; however, it is difficult to obtain a single macamide monomer from the maca plant because of their similar structures and characteristics. We used the carbodiimide condensation method (CCM) to efficiently synthesize five typical macamides, including N-benzyl-hexadecanamide (NBH), N-benzyl-9Z,12Z,15Z-octadecenamide, N-(3-methoxybenzyl)-9Z,12Z-octadecenamide, N-benzyl-9Z,12Z-octadecenamide, and N-(3-methoxybenzyl)-9Z,12Z,15Z-octadecadienamide. All the synthesized macamides were purified by a one-step HPLC with a purity of more than 95%. NBH is the most abundant macamide monomer in natural maca, and it was selected to evaluate the anti-fatigue effects of macamides. The results indicated that NBH could enhance the endurance capacity of mice by increasing liver glycogen levels and decreasing blood urea nitrogen, lactate dehydrogenase, blood ammonia, and blood lactic acid levels. Macamides might be the active substances that give maca its anti-fatigue active function.

BackgroundThe AIFM1 gene is located on chromosome Xq26.1 and encodes a flavoprotein essential for nuclear disassembly in apoptotic cells. Mutations in this gene can cause variable clinical phenotypes, but genotype-phenotype correlations of AIFM1-related disorder have not yet been fully determined because of the clinical scarcity.Case PresentationWe describe a 4-month-old infant with mitochondrial encephalopathy, carrying a novel intronic variant in AIFM1 (NM_004208.4: c.1164 + 5G > A). TA cloning of the complementary DNA (cDNA) and Sanger sequencing revealed the simultaneous presence of an aberrant transcript with exon 11 skipping (89 bp) and a normal transcript through analysis of mRNA extracted from the patient’s fibroblasts, which is consistent with direct RNA sequencing results.ConclusionWe verified the pathogenic effect of the AIFM1 c.1164 + 5G > A splicing variant, which disturbed normal mRNA splicing. Our findings expand the mutation spectrum of AIFM1 and point out the necessity of intronic sequence analysis and the importance for integrative functional studies in the interpretation of sequence variants.

This study investigates whether Mandarin listeners integrate a prosody-covarying phonological variable, the Chinese Tone 3 sandhi (T3S), into auditory sentence disambiguation. The T3S process changes the first of two consecutive low tones (T3) into a rising tone. It applies obligatorily within a foot and optionally across feet. When T3S is optional, it is more likely to apply to Tone 3 syllables across smaller prosodic boundaries than larger ones; the smaller the boundary, the sharper the T3S pitch rise. Participants listened to twenty-seven structurally ambiguous sentences and identified from two written interpretations the one consistent with what they heard. Each sentence contains two consecutive Tone 3 syllables, and posing different prosodic boundaries between the Tone 3 syllables would result in different interpretations. The first Tone 3 syllable was manipulated into three tone shapes (sharp-rising, shallow-rising, low) and two duration types (long, short). The results show higher major-juncture interpretation rates when the first Tone 3 is long than short, when T3S does not apply than when it applies, and when T3S has a shallower than sharper pitch slope. The tone effect further interacts with the foot formation of Tone 3 syllables in each sentence. We propose that listeners have sophisticated knowledge of prosodic variables and use it efficiently in linguistically meaningful contexts.

The recognition of tooth-marked tongues has important value for clinical diagnosis of traditional Chinese medicine. Tooth-marked tongue is often related to spleen deficiency, cold dampness, sputum, effusion, and blood stasis. The clinical manifestations of patients with tooth-marked tongue include loss of appetite, borborygmus, gastric distention, and loose stool. Traditional clinical tooth-marked tongue recognition is conducted subjectively based on the doctor’s visual observation, and its performance is affected by the doctor’s subjectivity, experience, and environmental lighting changes. In addition, the tooth marks typically have various shapes and colors on the tongue, which make it very challenging for doctors to identify tooth marks. The existing methods based on deep learning have made great progress for tooth-marked tongue recognition, but there are still shortcomings such as requiring a large amount of manual labeling of tooth marks, inability to detect and locate the tooth marks, and not conducive to clinical diagnosis and interpretation. In this study, we propose an end-to-end deep neural network for tooth-marked tongue recognition based on weakly supervised learning. Note that the deep neural network only requires image-level annotations of tooth-marked or non-tooth marked tongues. In this method, a deep neural network is trained to classify tooth-marked tongues with the image-level annotations. Then, a weakly supervised tooth-mark detection network (WSTDN) as an architecture variant of the pre-trained deep neural network is proposed for the tooth-marked region detection. Finally, the WSTDN is re-trained and fine-tuned using only the image-level annotations to simultaneously realize the classification of the tooth-marked tongue and the positioning of the tooth-marked region. Experimental results of clinical tongue images demonstrate the superiority of the proposed method compared with previously reported deep learning methods for tooth-marked tongue recognition. The proposed tooth-marked tongue recognition model may provide important syndrome diagnosis and efficacy evaluation methods, and contribute to the understanding of ethnopharmacological mechanisms.

This paper provides a distributed control strategy for battery energy storage systems (BESS) based on multi-agent system. The proposed control laws can guarantee that the state of charge (SoC) is synchronized, and BESS active power can be shared proportionally. Moreover, the heterogeneous characteristics of BESS are considered in modeling BESS and designing control laws, while they are not carefully considered in the existed literature. Besides, the proposed control laws are robust to the changing communication topologies and link broken since they can be applied over the time-varying directed unbalanced communication networks. Simulation studies, which are carried out on matlab/simulink, validate the effectiveness of the control strategy and laws.

Abstract. Allergic contact dermatitis is a common clinical allergic disease. The patch test is the gold standard for finding and clarifying contact allergens. With the deepening understanding of the epidemiology, pathogenesis, and clinical manifestations of contact dermatitis, as well as the increased requirements for the standardized application of patch tests, the relevant consensus needs to be continuously updated. This consensus is updated on the basis of the version issued in 2015. In this revised version, it refines the selection of clinical indications, improves the judgment and interpretation of results, adds delayed detection and patient education, and so on, which aims to further standardize clinical applications and improve the value of patch test.

Perceptual learning is when listeners hear novel speech input and shift their subsequent perceptual behavior. In this paper we consider the relationship between sound change and perceptual learning. We spell out the connections we see between perceptual learning and different approaches to sound change and explain how a deeper empirical understanding of the properties of perceptual learning might benefit sound change models. We propose that questions about when listeners generalize their perceptual learning to new talkers might be of of particular interest to theories of sound change. We review the relevant literature, noting that studies of perceptual learning generalization across talkers of the same gender are lacking. Finally, we present new experimental data aimed at filling that gap by comparing cross-talker generalization of fricative boundary perceptual learning in same-gender and different-gender pairs. We find that listeners are much more likely to generalize what they have learned across same-gender pairs, even when the different-gender pairs have more similar fricatives. We discuss implications for sound change.

The authors report that near-infrared light induces an irreversible accumulated Surface-enhanced Raman scattering (SERS) behavior of a molecule/metal–semiconductor hybrid system. They investigate the underlying mechanism and show that it is attributed to crystallinity, charge transfer and reorientation.

Skin cutaneous melanoma (SKCM) is a skin cancer type characterized by a high degree of immune cell infiltration. The potential function of lactate, a main metabolic product in the tumor microenvironment (TME) of SKCM, remains unclear. In this study, we systemically analyzed the predictive value of lactate-related genes (LRGs) for prognosis and response to immune checkpoint inhibitors (ICIs) in SKCM patients included from The Cancer Genome Atlas (TCGA) database. Cluster 3, by consensus clustering for 61 LRGs, manifested a worse clinical outcome, attributed to the overexpression of malignancy marks. In addition, we created a prognostic prediction model for high- and low-risk patients and verified its performance in a validation cohort, GSE65904. Between TME and the risk model, we found a negative relation of the immunocyte infiltration levels with patients’ risk scores. The low-risk cases had higher ICI expression and could benefit better from ICIs relative to the high-risk cases. Thus, the lactate-related prognosis risk signature may comprehensively provide a basis for future investigations on immunotherapeutic treatment for SKCM.

Most of the existing quantum-inspired models are based on amplitude-phase embedding to model natural language, which maps words into Hilbert space. In quantum-computing theory, the vectors corresponding to quantum states are all complex values, so there is a gap between these two areas. Presently, complex-valued neural networks have been studied, but their practical applications are few, let alone in the downstream tasks of natural language processing such as sentiment analysis and language modeling. In fact, the complex-valued neural network can use the imaginary part information to embed hidden information and can express more complex information, which is suitable for modeling complex natural language. Meanwhile, quantum-inspired models are defined in Hilbert space, which is also a complex space. So it is natural to construct quantum-inspired models based on complex-valued neural networks. Therefore, we propose a new quantum-inspired model for NLP, ComplexQNN, which contains a complex-valued embedding layer, a quantum encoding layer, and a measurement layer. The modules of ComplexQNN are fully based on complex-valued neural networks. It is more in line with quantum-computing theory and easier to transfer to quantum computers in the future to achieve exponential acceleration. We conducted experiments on six sentiment-classification datasets comparing with five classical models (TextCNN, GRU, ELMo, BERT, and RoBERTa). The results show that our model has improved by 10% in accuracy metric compared with TextCNN and GRU, and has competitive experimental results with ELMo, BERT, and RoBERTa.

In terms of solving the financing difficulties, supply chain financing plays a role in lowering the financing threshold of upstream and downstream enterprises, breaking the bottleneck of upstream and downstream financing, and improving the competitiveness of core enterprises and supporting enterprises, which is of great significance in accelerating the capital operation and making commercial transactions more efficient and convenient. This article takes the supervision game in game theory research methods, to supply chain financing risk supervision game model is established, from the third party logistics enterprises to participate in, the third party logistics enterprise and financing enterprises union and government security three aspects analyzes the different roles of regulatory policy, and for financing enterprise, financial institution, third party logistics enterprise and government,. The conclusion shows that each party should enhance its own credibility and ability, and increase the opportunities for communication and cooperation with other parties, so as to promote the long-term operation and development of supply chain financing.

Objective: To investigate the characteristics of blood lipid in acne patients with oral isotretinoin. Methods: 89 acne patients with complete data diagnosed in the dermatology clinic from August 2018 to February 2019 were analyzed retrospectively. Results: A total of 89 acne patients were included. All patients received 20-30 mg isotretinoin daily. At the initial diagnosis, all blood lipid tests were within the normal range. After taking the medicine, 35 patients (39.32%) had dyslipidemia, including 6 patients (17.14%) with TC combined with abnormal LDL-C, 29 patients (82.85%) with abnormal LDL-C, and 5 patients (14.28%) with significantly elevated blood lipid. Among them, 34 (97.14%) patients had dyslipidemia in the 8th week and only 1 (2.86%) patient had dyslipidemia in the 16th week. The levels of TC, TG and LDL-C in all patients were higher than those before at week 8 and 16 (all P