Search

Background: Pain associated with aminolevulinic acid photodynamic therapy (ALA-PDT) for the treatment of facial dermatoses results in low patient compliance. Two-step photodynamic therapy (two-step PDT) may improve comfort by optimizing light amplitude and exposure time. Objective: To investigate the efficacy of two-step PDT in reducing the pain generated during the treatment of facial skin disorders. Methods: Twenty-six patients with AK were randomly divided into two groups; the experimental group was treated with two-step photodynamic therapy and the control group was treated with conventional photodynamic therapy. The pain intensity of the patients at different times was assessed using the pain numerical rating scale (NRS). Results: A total of 26 patients completed three ALA-PDT treatments, 13 and 13 patients in each group, respectively. The mean NRS scores of patients in the experimental group (3.28±1.41, 3.33±1.43, 3.42±1.78) were lower than those of the control group (5.00±1.94, 5.09±1.86, 4.86±1.64) on each occasion. The incidence of certain adverse reactions was lower in the experimental group than in the control group. There was no difference between the two groups in terms of clinical outcome, recurrence rate and patient satisfaction. Conclusion: Two-step photodynamic therapy can reduce pain and the incidence of some adverse reactions, but does not affect clinical efficacy, recurrence rate and patient satisfaction.

On-Load Tap-Changer (OLTC) is the only core equipment in the ultra-high voltage (UHV) converter transformer that moves frequently, and flexible connection structure (FCS) is the moveable actuating part of the vacuum interrupter drive mechanism of OLTC. Minimizing the transient stress during the movement of FCS is essential for prolonging its fatigue life, thus is pursued by optimizing the shape of the flexible sheet in this paper. Peak transient stress of FCS is defined as the optimization objective, and eight geometrical parameters controlling the shape of flexible sheet are defined as the optimization variables. A progressive three-stage shape optimization strategy is proposed by combing four techniques: Multi-body Dynamic (MBD), Finite Element Analysis (FEA), Correlation Coefficient Analysis (CCA) and Adaptive Single-objective Optimization (ASO). MBD analysis of the vacuum interrupter drive mechanism and FEA of the FCS are utilized for calculating the transient stress distribution. Spearman CCA is performed to quantitively determine the correlation and sensitivity between the optimization variables and the optimization objective. Shape optimization of FCS using ASO is carried out, and results show that the stress concentration is basically eliminated and the peak transient stress decrease by 34.35% after shape optimization. Further analysis of the FCS with multi-layered flexible sheet is conducted, again demonstrating the effectiveness of the shape optimization on minimizing transient stress.

Introduction: Chylothorax is caused by lymphatic chyle fluid leaking back through the thoracic duct and accumulating in the pleural cavity. It is related to a thoracic duct injury or occlusion. It is rare to have bilateral chylothorax after cervical lymph node dissection for thyroid cancer diagnosis. Case report: A 28-year-old woman was admitted to our hospital with bilateral hypoechoic thyroid nodules and cervical lymph node abnormalities. She underwent thyroidectomy and lymphadenectomy but developed chylothorax 3 days after surgery. She was treated with bilateral thoracic drainage, electrolyte supplementation, and somatostatin, and was discharged 17 days post-treatment. Conclusion: Bilateral chylothorax is a rare complication of thyroid cancer surgery. Early diagnosis and treatment, especially the detection of dyspnea, are key. Also, unobstructed bilateral thoracic drainage, improved surgical skills, and reduced thoracic duct injuries can help reduce complications.

Background: Immune status is widely acknowledged as a valuable marker for predicting cancer prognosis and therapy response. However, there has been a limited understanding of the stromal landscape in cancer. Methods: By employing ESTIMATE, stromal- and immune-scores were inferred for 6193 tumor samples spanning 12 cancer types sourced from The Cancer Genome Atlas (TCGA). Subsequently, the samples were categorized into seven groups based on their stromal and immune scores. A comparison of prognosis, lymphocyte and stromal cell infiltration, and the response to programmed death ligand 1 (PD-L1) therapy was conducted among these subtypes. Results: It was unveiled by the analysis that, in the majority of cancer types, stromal score exhibited a more potent predictive capability for outcomes compared to the immune score. Furthermore, it was observed that in four cancer types, intermediate immune infiltration coupled with low stromal infiltration correlated with the most favorable overall survival, whereas an unfavorable outcome was predicted in colorectal cancer (CRC) and stomach adenocarcinoma (STAD) when high immune infiltration coexisted with intermediate or high stromal infiltration. Conclusion: In summary, while high immune scores frequently correlate with a positive prognosis, such correlation is not universal. A potential strategy to address the current limitations of the immune score in specific circumstances could involve a focus on stromal scores or a subtle integration of stromal and immune status.

The natural gas compressibility factor is a vital parameter in petroleum engineering calculation. Currently, the calculation models for calculating natural gas compressibility factors in engineering are not accurate and efficient enough. To solve this problem, multivariate nonlinear regression is used to fit the 6988 data of the Standing–Katz chart, a novel empirical formula of natural gas compressibility factors is obtained, which is suitable for the pseudo-reduced pressure range of 0.2 to 30. The mean absolute error, mean relative error and root mean square error between the fitted values and the Standing–Katz chart values are 0.01140, 0.01282 and 0.01663 respectively, hence the fitted values accord well with the chart values. The proposed correlation is verified by 270 measured data of natural gas compressibility factors under low and medium pressure conditions and 219 measured data under high pressure conditions and compared with the other five representative calculation models. The verification result shows that the mean absolute error, mean relative error and root mean square error between the calculated values and the measured values are 0.01962, 0.01626 and 0.02511 respectively, and the proposed correlation is superior to the other five methods because of its higher calculation accuracy. The new correlation is practical and accurate for predicting the natural gas compressibility factor under an extensive range of pressure conditions.

Objective: The mechanistic target of rapamycin complex 1 (mTORC1) is a key molecule that links nutrients, hormones, and growth factors to cell growth/function. Our previous studies have shown that mTORC1 is required for β-cell functional maturation and identity maintenance; however, the underlying mechanism is not fully understood. This work aimed to understand the underlying epigenetic mechanisms of mTORC1 in regulating β-cell functional maturation. Methods: We performed Microarray, MeDIP-seq and ATAC-seq analysis to explore the abnormal epigenetic regulation in 8-week-old immature βRapKO islets. Moreover, DNMT3A was overexpressed in βRapKO islets by lentivirus, and the transcriptome changes and GSIS function were analyzed. Results: We identified two major epigenetic silencing mechanisms, DNMT3A-dependent DNA methylation and PRC2-dependent H3K27me3 modification, which are responsible for functional immaturity of Raptor-deficient β-cell. Overexpression of DNMT3A partially reversed the immature transcriptome pattern and restored the impaired GSIS in Raptor-deficient β-cells. Moreover, we found that Raptor directly regulated PRC2/EED and H3K27me3 expression levels, as well as a group of immature genes marked with H3K27me3. Combined with ATAC-seq, MeDIP-seq and ChIP-seq, we identified β-cell immature genes with either DNA methylation and/or H3K27me3 modification. Conclusion: The present study advances our understanding of the nutrient sensor mTORC1, by integrating environmental nutrient supply and epigenetic modification, i.e., DNMT3A-mediated DNA methylation and PRC2-mediated histone methylation in regulating β-cell identity and functional maturation, and therefore may impact the disease risk of type 2 diabetes.

As a novel member of the ultra-high temperature ceramic family, which have extremely high melting points and remarkable hardness, Ta1-xHfxC solid solution ceramics are promising for applications in thermal protection systems. Ta1-xHfxC (x = 0, 0.2, 0.5, 0.8, and 1.0) with 2 vol% Cr3C2, were densified up to 98.8% at 2000 °C using a two-step spark plasma sintering process. Effect of Cr3C2 on the linear shrinkage of Ta1-xHfxC was investigated. Possible ‘eutectic’ reaction within TaCCr3C2 ceramic was inferred to contribute to the shrinkage at 1462 °C. High-angle annular dark-field scanning transmission electron microscopy combined with energy-dispersive spectroscopy was employed to further confirm the mutual diffusion between rock-salt structured ‘CrCx’ and TaC. Flexural strength, fracture toughness and Vicker’s hardness of Ta1-xHfxC ceramics were in the range of 439–492 MPa, 4.0–5.8 MPa∙m1/2 and 14.9–19.9 GPa respectively. The coefficient of thermal expansion (in the temperature range of 25–1000 °C) and thermal conductivity (at 1000 °C) of Ta1-xHfxC varied from 7.17 to 7.51 × 10−6 K−1 and 31.9–42.9 W/m·K, respectively. The high-temperature strength of Ta0.5Hf0.5C decreased to 165 MPa up to 1600 °C, approximately 34% of room-temperature strength, and a ‘zig-zag’ load-displacement curve was observed.

Polycationic vectors are a promising class of gene delivery systems. To improve delivery efficiency and reduce cytotoxicity, hydrophobic modification has been proposed as an effective way. Herein, we synthesized a class of terpolymer vectors with various hydrophobicities as well as multiple biodegradable disulfide bonds and cationic side chains. The chemical structure and hydrophobic modification ratio of polymers were characterized. The amphiphilic vectors were able to condense pDNA to form flexible and uniform nanoparticles with a size of 60–85 nm. The shielding effect of hydrophobic side chains led to a lower zeta potential and reduced cytotoxicity. The endocytosis efficiency of amphiphilic vectors was significantly increased and the endocytosis pathway shifted from mainly via the clathrin pathway to clathrin/caveolae/lipid raft co-mediated endocytosis. The amphiphilic vectors demonstrated significantly higher transfection efficiency. In addition, the hydrophobic structural domain of polymers could improve serum stability, alleviating the serum inhibition commonly seen in cationic polymers. Then, we tested the tumor-suppressor gene wtp53 delivered by the amphiphilic vectors in triple-negative breast cancer models both in vitro and in vivo. Tumor cell cycle arrest and apoptosis were triggered through the regulation of downstream cell cycle proteins and apoptosis proteins, inhibiting tumor growth with an excellent safety profile.

The Hedgehog (HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment (TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance. The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6 (IL-6) and interferon-γ (IFN-γ), macrophages, and T cell-dependent immune responses, play a vital role in tumor growth by affecting the HH signaling pathway. Moreover, inhibition of proliferating cancer-associated fibroblasts (CAFs) and inflammatory factors can normalize the TME by suppressing HH signaling. Furthermore, aberrant HH signaling activation is favorable to both the proliferation of cancer stem cells (CSCs) and the drug resistance of gastrointestinal tumors. This review discusses the current understanding of the role and mechanism of aberrant HH signaling activation in gastrointestinal carcinogenesis, the gastrointestinal TME, tumor immune tolerance and drug resistance and highlights the underlying therapeutic opportunities.

Individuals with Netherton syndrome (NTS) have increased serine protease activity, which strongly impacts the barrier function of the skin epidermis and leads to skin inflammation. Here, we investigated how serine protease activity in NTS correlates with changes in the stratum corneum (SC) ceramides, which are crucial components of the skin barrier. We examined two key enzymes involved in epidermal ceramide biosynthesis, β-glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) SC ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided with increased ASM activity, particularly in areas with increased serine protease activity. NTS patients with scaly erythroderma exhibited more pronounced anomalies in GBA and ASM activities than patients with ichthyosis linearis circumflexa. They also displayed a stronger increase in SC ceramides processed via ASM. We conclude that changes in the localization of active GBA and ASM correlate with i) altered SC ceramide composition in NTS patients, ii) local serine protease activity, and iii) the clinical manifestation of NTS.

Summary: Ammonia is one of the most important bulk chemicals in modern society. However, the highly energy-extensive contemporary industrial production of ammonia was developed in the early 20th century and requires extensive heating of highly pressurized flammable hydrogen gas, whose global production still relies heavily on non-sustainable petroleum. The development of “sustainable” nitrogen fixation process represents a grand aspirational chemical pursuit concerning our future human well-being. Herein, we report an ultra-stable nitride-based photosensitizing semiconductor that enables efficient, sustainable, and mild photochemical nitrogen fixation. The catalyst exhibits strong chemisorption of nitrogen and enables immediate electron donation from its surface vacancy to nitrogen. In addition, it was also demonstrated that the nitride-based semiconductor possesses the potential to minimize electron-hole recombination. : Chemical Reaction; Catalysis; Density Functional Theory (DFT); Nanostructure Subject Areas: Chemical Reaction, Catalysis, Density Functional Theory (DFT), Nanostructure

China experiences severe particulate pollution, especially in winter, and determining the characteristics of particulate matter (PM) during pollution events is imperative for understanding the sources and causes of the pollution. However, inconsistencies have been found in the aerosol composition, sources and secondary processing among reported studies. Modern meta-analysis was used to probe the PM chemical characteristics and processing in winter at four representative regions of China, and the first finding was that secondary aerosol formation was the major effect factor for PM pollution. The secondary inorganic species behaved differently in the four regions: sulfate, nitrate, and ammonium increased in the Beijing–Tianjin–Hebei (BTH) and Guanzhong (GZ) areas, but only nitrate increased in the Pearl River Delta (PRD) and Yangtze River Delta (YRD) regions. The increased production of secondary organic aerosol (SOA) was probably caused by aqueous-phase processing in the GZ and BTH regions and by photochemical reactions in the PRD. Finally, we suggest future AMS/ACSM observations should focus on the aerosol characteristics in rural areas in winter in China. Keywords: Secondary aerosols, Aqueous-phase reactions, Photochemical reactions, Polluted days, Winter

Recent studies point to the evolution of drug resistance in lung cancer as being centered, at least in part, on the upregulation of various genes involved in controlling efflux or drug inactivation. Among the most important of these genes is Nuclear Factor Erythroid 2-Related Factor (NRF2), considered the master regulator of 100–200 target genes involved in cellular responses to oxidative and/or electrophilic stress. With increased focus on the development of combinatorial approaches for cancer treatment, we utilized CRISPR/Cas9 to disable the NRF2 gene in lung cancer cells by disrupting the NRF2 nuclear export signal (NES) domain; phenotypically, the protein is largely blocked from transiting into the nucleus after translation. In tissue culture, cells with this gene knockout were found to have a reduced proliferation phenotype and are more sensitive to chemotherapeutic agents, such as cisplatin and carboplatin. These observations were confirmed in xenograft mouse models wherein the homozygous knockout cells proliferate at a slower rate than the wild-type cells, even in the absence of drug treatment. Tumor growth was arrested for a period of 16 days, with a dramatic decrease in tumor volume being observed in samples receiving the combined action of CRISPR-directed gene editing and chemotherapy. Keywords: CRISPR, Cas9, gene editing, NRF2, lung cancer, chemoresistance, NSCLC

Summary: Netherton syndrome (NS) is a monogenic skin disease resulting from loss of function of lymphoepithelial Kazal-type-related protease inhibitor (LEKTI-1). In this study we examine if bacteria residing on the skin are influenced by the loss of LEKTI-1 and if interaction between this human gene and resident bacteria contributes to skin disease. Shotgun sequencing of the skin microbiome demonstrates that lesional skin of NS subjects is dominated by Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). Isolates of either species from NS subjects are able to induce skin inflammation and barrier damage on mice. These microbes promote skin inflammation in the setting of LEKTI-1 deficiency due to excess proteolytic activity promoted by S. aureus phenol-soluble modulin α as well as increased bacterial proteases staphopain A and B from S. aureus or EcpA from S. epidermidis. These findings demonstrate the critical need for maintaining homeostasis of host and microbial proteases to prevent a human skin disease. : Williams et al. show how an abnormal skin microbiome promotes inflammation associated with Netherton syndrome, a monogenic disorder in the human protease inhibitor SPINK5. Subjects with Netherton syndrome have excess colonization by S. aureus or S. epidermidis that then produce and promote increased protease production in the epidermis. Keywords: Netherton syndrome, S. aureus, S. epidermidis, proteases, epidermal barrier, skin inflammation, skin microbiome

Objective: To explore the effectiveness and safety of cardiac rehabilitation qigong exercise in stable coronary artery disease (CAD) patients undergoing phase III rehabilitation. Methods: This was a randomized controlled trial. A total of 59 stable CAD patients undergoing phase III rehabilitation treated in Sports Medicine Hospital from March 2017 to September 2017 were enrolled after meeting the inclusion criteria and then divided into cardiac rehabilitation qigong exercise group (n = 30) receiving a 12-week intervention and control group (n = 29). All participants were assessed at baseline and at 12-week intervention for the primary outcome, that was treadmill test parameter and the secondary outcomes including physical fitness, body composition, bone mineral density, and cardiac ultrasound B-mode imaging. Results: There were no significant differences in baseline demographics between the two groups. After a 12-week cardiac rehabilitation qigong exercise intervention, compared with the control group, ΔVO2 (initial 1352.63 ± 340.95 vs 12 weeks 1594.57 ± 467.14) vs (initial 1363.83 ± 322.90 vs 12 weeks 1323.76 ± 318.92) (P = .003), ΔVO2/kg (initial 21.23 ± 3.56 vs 12 weeks 24.75 ± 5.11) vs (initial 21.01 ± 3.71 vs 12 weeks 20.35 ± 3.66) (P = .002), ΔMETS (initial 6.19 ± 1.12 vs 12 weeks 7.16 ± 1.60) vs (initial 6.00 ± 1.19 vs 12 weeks 5.86 ± 1.23) (P = .001), ΔVO2/HR (P = .027), ΔSV (P = .014), ΔOUES (P = .012), Δhand-grip strength (P = .002), Δflexibility (P = .001), Δbalance (P = .002), ΔT-score (P = .042), ΔBQI (P = .018). However, Δresting systolic blood pressure (P = .004) and Δresting diastolic pressure (P = .012) decreased in the cardiac rehabilitation qigong exercise group. Conclusion: Cardiac rehabilitation qigong exercise can improve cardiopulmonary aerobic capacity, physical fitness, bone mineral density in patients with stable CAD, suggesting that certain effect and safety for stable CAD patients undergoing phase III rehabilitation can be obtained. Keywords: Stable coronary artery disease, Rehabilitation, Cardiac rehabilitation qigong exercise, Cardiopulmonary aerobic capacity

Objective: The aim of this study was to evaluate the effects of traditional Chinese exercises (TCEs) on stroke risk factors in patients with pre-hypertension or mild-to-moderate essential hypertension. Methods: We performed searches of seven electronic databases for studies published from their inception until July 2017. We included randomized controlled trials (RCTs) of the effects of TCEs with or without health education on stroke risk factors in patients with pre-hypertension or mild-to-moderate essential hypertension. Outcomes were independently extracted from each study by two authors and were pooled to determine risk ratios and standardized mean differences.materials-methods Results: We included 15 RCTs, involving 1272 hypertensive participants. Compared with no intervention, TCEs were associated with a clinically meaningful amelioration of stroke risk factors, including reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose, blood lipids, and waist-to-hip ratio, and improved quality of life. Compared with health education, TCEs reduced SBP but had no effect on DBP. Compared with health education alone, TCEs plus health education resulted in an amelioration of stroke risk factors. No serious adverse events were reported.results Conclusion: TCEs may be effective alongside health education in ameliorating stroke risk factors in individuals with pre-hypertension or mild-to-moderate essential hypertension. However, the current evidence is insufficient due to poor methodology and lack of adequate safety data. Further rigorously-designed RCTs are warranted.conclusion Keywords: Hypertension, Stroke risk factor, Tai Chi, Baduanjin, Yijinjin

Skeletal muscle atrophy induced by aging (sarcopenia), inactivity, and prolonged fasting states (starvation) is predominantly restricted to glycolytic type II muscle fibers and typical spares oxidative type I fibers. However, the mechanisms accounting for muscle fiber-type specificity of atrophy have remained enigmatic. In the current study, although the Fyn tyrosine kinase activated the mTORC1 signaling complex, it also induced marked atrophy of glycolytic fibers with relatively less effect on oxidative muscle fibers. This was due to inhibition of macroautophagy via an mTORC1-independent but STAT3-dependent reduction in Vps34 protein levels and decreased Vps34/p150/Beclin1/Atg14 complex 1. Physiologically, in the fed state endogenous Fyn kinase activity was increased in glycolytic but not oxidative skeletal muscle. In parallel, Y705-STAT3 phosphorylation increased with decreased Vps34 protein levels. Moreover, fed/starved regulation of Y705-STAT3 phosphorylation and Vps34 protein levels was prevented in skeletal muscle of Fyn null mice. These data demonstrate a Fyn/STAT3/Vps34 pathway that is responsible for fiber-type-specific regulation of macroautophagy and skeletal muscle atrophy.