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Tourism, as an activity that satisfies people's desire for diverse life experiences and knowledge, has had profound impacts on the economy, culture, and other fields. However, with the rapid development of technologies, such as the Internet of Things and multimodal large language models, traditional tourism is unable to meet the demand for intelligent and personalized travel experiences. To address this, this paper proposes an interactive personalized tourism service system based on the concept of parallel intelligence, utilizing the ACP approach and multimodal large language models. The system constructs a comprehensive tourism model and leverages retrieval-augmented generation and multi-agent collaboration systems to create a new paradigm for personalized tourism services. Additionally, this paper explores the application ecosystem of parallel tourism, expanding the tourism ecosystem from four aspects: clothing, food, accommodation and transportation. This paper analyzes the integration of other industries with personalized tourism services. Parallel tourism is poised to bring new possibilities for the development of the tourism service industry.

Background: Ghrelin is widely distributed in an animal's body, playing important biological roles. In mammals, Ghrelin can stimulate food intake and weight gain, but in poultry, it inhibits food intake and drinking. We aimed to determine the effect of Ghrelin on feeding, drinking, body weight and growth hormone (GH) content of African ostrich chicks. Methods: Sixteen 40-day-old African ostrich chicks were randomly divided into four groups and injected intravenously with saline (control) or Ghrelin (10, 50 and 100 µg/kg) for 7 days. The feeding, drinking and growth hormone (GH) levels using measurement method and radioimmunoassay were determined. Result: The results show that exogenous Ghrelin increased the feed intake rate, the drinking rate and the secretion of GH in the ostriches. [ABSTRACT FROM AUTHOR]

In response to the issue of suboptimal thermal performance in traditional data centers, four distinct airflow management structures, namely, composite, linear, convex, and concave diversion plates, were proposed. With Airpak 3.0, numerical simulations were conducted on five different data centers, including the original configuration of the computer room air conditioner (CRAC). The objective was to assess the impact of various airflow management structures on the thermal performance of data centers, with experimental validation of the model. The findings demonstrate that these airflow management structures significantly enhance the thermal performance of data centers. Among them, the composite diversion plate yielded moderate improvements, the convex diversion plate effectively optimized velocity distribution, in spite of limitations on temperature optimization, and the concave diversion plate exhibited non-uniform temperature distribution. Overall, the linear diversion plate proved to be the most effective.

Objective: Cage rearing has critical implications for the laying duck industry because it is convenient for feeding and management. However, caging stress is a type of chronic stress that induces maladaptation. Environmental stress responses have been extensively studied, but no detailed information is available about the comprehensive changes in plasma metabolites at different stages of caging stress in ducks. We designed this experiment to analyze the effects of caging stress on performance parameters and oxidative stress indexes in ducks. Methods: Liquid chromatography tandem mass spectrometry (LC/MS-MS) was used to determine the changes in metabolites in duck plasma at 5 (CR5), 10 (CR10), and 15 (CR15) days after cage rearing and traditional breeding (TB). The associated pathways of differentially altered metabolites were analyzed using Kyoto encyclopedia of genes and genomes (KEGG) database. Results: The results of this study indicate that caging stress decreased performance parameters, and the plasma total superoxide dismutase levels were increased in the CR10 group compared with the other groups. In addition, 1,431 metabolites were detected. Compared with the TB group, 134, 381, and 190 differentially produced metabolites were identified in the CR5, CR10, and CR15 groups, respectively. The results of principal component analysis (PCA) show that the selected components sufficiently distinguish the TB group and CR10 group. KEGG analysis results revealed that the differentially altered metabolites in duck plasma from the CR5 and TB groups were mainly associated with ovarian steroidogenesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism. Conclusion: In this study, the production performance, blood indexes, number of metabolites and PCA were compared to determine effect of the caging stress stage on ducks. We inferred from the experimental results that caging-stressed ducks were in the sensitive phase in the first 5 days after caging, caging for approximately 10 days was an important transition phase, and then the duck continually adapted. [ABSTRACT FROM AUTHOR]

Background: The African ostrich is the largest herbivorous bird in the world, which has high economic value. However, the brooding period of African ostrich is long. During this period, the various organs of the body are not fully developed, the resistance is low and it is easy to get sick, thus affecting the growth and development. Therefore, it is of great significance to enhance the digestion and absorption capacity of ostrich chicks and improve its growth speed in shortening the incubation period of ostrich, improving the survival rate of ostrich and the economic benefits of ostrich breeding. Methods: Sixteen 40-day-old African ostrich chicks (male or female) were randomly divided into four groups and injected intravenously of Metatarsal vein with saline (control) or ghrelin (10, 50 and 100 µg/kg) for 6 days. The morphology, gastrin and pepsin levels in the duodenum were measured using stereology, HE staining and radioimmunoassay. Result: The 10, 50 and 100 µg/kg of ghrelin administered groups showed lower duodenal length and length index than the control group (P<0.05). Villus length increased in the 50 µg/kg and 100 µg/kg ghrelin administered groups (P<0.05). Crypt depth decreased in the 10 µg/kg ghrelin administered group (P<0.05). The ratio of villus length to crypt depth in each group increased and the difference was significant in the 50 µg/kg and 100 µg/kg ghrelin administered groups (P<0.05). Pepsin content in the duodenum slightly increased in the 10 µg/kg ghrelin administered group (P>0.05) and it significantly decreased in the 50 µg/kg and 100 µg/kg ghrelin administered groups (P<0.05). Gastrin content in the duodenum increased significantly (P<0.05) in the 10 µg/kg ghrelin administered group and decreased in the 100 µg/kg ghrelin administered group (P<0.05). [ABSTRACT FROM AUTHOR]

Objective: The oxidative stress status and changes of chicken ovary tissue after shading were studied, to determine the mechanism of the effect of shading on follicular development. Methods: Twenty healthy laying hens (40 weeks old) with uniform body weight and the same laying rate were randomly divided into two groups (the shading group and normal light group). In the shading group, the cage was covered to reduce the light intensity inside the cage to 0 without affecting ventilation or food intake. The normal lighting group received no additional treatment. After 7 days of shading, oxidative stress related indicators and gene expression were detected. Results: Analysis of paraffin and ultrathin sections showed that apoptosis of ovarian granulosa cells (GCs) increased significantly after light shading. Enzyme linked immunosorbent assay results revealed that the levels of total antioxidant capacity, malondialdehyde, superoxide dismutase (SOD), glutathione, catalase (CAT), and other substances in the sera, livers, ovaries, and follicular GCs of laying hens increased significantly after shading for 7 days; and reactive oxygen species (ROS) levels in the livers of laying hens also increased significantly. ROS in the serum, ovarian and GCs also increased. After shading for 7 days, the levels of 8hydroxy2 deoxyguanosine in the sera and ovarian tissues of laying hens increased significantly. Cell counting kit8 detection showed that the proliferation activity of GCs in layer follicles decreased after shading for 7 days; the expression level of the antiapoptotic gene Bcell lymphoma2 in ovarian tissue and follicular GCs was significantly reduced, and the expression levels of proapoptotic caspase 3 (casp3), and SOD, glutathione peroxidase 2 (GPX2), and CAT were all significantly increased. Conclusion: Oxidative stress induced by shading light has a serious inhibitory effect on follicular development during reproduction in laying hens. [ABSTRACT FROM AUTHOR]

Background Immunotherapy represented by programmed death protein-1 (PD-1) inhibitors has gradually become the standard treatment of advanced non-small cell lung cancer (NSCLC) in recent years, changing the treatment landscape of advanced NSCLC. However, most PD-1-related studies excluded patients with NSCLC more than 70 or 75 years, resulting in relatively limited data about the efficacy and safety of PD-1 inhibitors in elderly patients. Objective This study aims to evaluate the efficacy and safety of PD-1 inhibitors in elderly patients with advanced NSCCL. Methods This study selected elderly patients with advanced NSCLC over 65 years who received PD-1 inhibitors monotherapy in Department of Thoracic Surgery and Oncology of the Fourth Affiliated Hospital of Gansu University of Traditional Chinese Medicine from October 2018 to November 2021. A total of 63 elderly patients with NSCLC were included. The PD-1 inhibitors of the study were approved in Chinese market, including camrelizumab, sintilimab and pembrolizumab. The data about efficacy and safety of PD-1 inhibitors were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until 2022-03-15. The efficacy data of PD-1 inhibitors, the prognosis of elderly patients with advanced NSCLC and the toxicity and side effects of PD-1 inhibitors were collected. Cox comparative risk model was used to explore the influencing factors of the prognosis of elderly patients with advanced NSCLC. Results The median age of the 63 elderly patients with advanced NSCLC was 71 (65, 89) years. The best response assessment during PD-1 inhibitors therapy showed that no patients had complete response, 14 patients had partial responses, 21 patients had stable status, and 28 patients had progressive status. The objective response rate (ORR) of patients with advanced NSCLC treated with PD-1 inhibitors monotherapy was 22.2% (14/63) , and the disease control rate (DCR) was 66.7% (14/21) . Prognostic data showed that the median progression free survival (PFS) of the 63 patients with advanced NSCLC was 3.3 (2.0, 4.6) months and the median overall survival (OS) was 10.2 (6.1, 14.3) months. Among 63 elderly patients with NSCLC, 46 of them (73.0%) had treatment related adverse reaction during PD-1 inhibitors monotherapy, and the rate of grade 3 or above adverse reactions was 14.3%. The most common adverse reactions were fatigue, diarrhea, rash and abnormal liver function with the rates of 23.8% (15/63) , 19.1% (12/63) , 15.9% (10/63) and 14.3% (9/63) , respectively. Cox comparative risk model analysis suggested that ECOG performance status and number of metastatic lesions might be independent factors of PFS in patients with advanced NSCLC treated with PD-1 inhibittors. Conclusion PD-1 blockades monotherapy demonstrated potential efficacy and acceptable safety for elderly patients with NSCLC. ECOG performance status and number of metastatic lesions might be potential risk factors that predict the PFS of the patients.

Extracellular vesicles (EVs), products released by cells in multiple biological activities, are currently widely accepted as functional particles and intercellular communicators. From the orthodox perspective, EVs derived from apoptotic cells (apoEVs) are responsible for cell debris clearance, while recent studies have demonstrated that apoEVs participate in tissue regeneration. However, the underlying mechanisms and particular functions in tissue regeneration promotion of apoEVs remain ambiguous. Some molecules active during apoptosis also function in tissue regeneration triggered by apoptosis, such as caspases. ApoEVs are generated in the process of apoptosis, carrying cell contents to manifest biological effects and possess biomarkers to target phagocytes. The regenerative effect of apoEVs might be due to their abilities to facilitate cell proliferation and regulate inflammation. Such regenerative effect has been observed in various tissues, including skin, bone, cardiovascular system, and kidneys. Engineered apoEVs are produced to amplify the biological benefits of apoEVs, rendering them optional for drug delivery. Meanwhile, challenges exist in thorough mechanistic exploration and standardization of production. In this review, we discussed the link between apoptosis and regeneration, current comprehension of the origination and investigation strategies of apoEVs, and mechanisms in tissue regeneration of apoEVs and their applications. Challenges and prospects are also addressed here.

In this paper, poly(ether ether ketone) (PEEK) scaffold was manufactured using the fused deposition modeling (FDM) technology with a modified platform. The effect of processing parameters of FDM on the porosity and compressive strength of PEEK scaffold with uniform pores (0.8 mm of diameter) was optimized through Taguchi methodology. With the determined parameters, four kinds of PEEK scaffolds with gradient pores (0.4–0.8 mm, 0.6–1.0 mm, 0.8–1.2 mm, and 1.2–2.0 mm) were manufactured. The scaffolds were investigated using scanning electron microscopy. The results showed that the pores of scaffolds were interconnected with rough surface, which can allow the attachment, migration, and differentiation of cells for bone forming. The tensile strength, compressive max strength, and compressive yield strength of scaffolds were between 18 and 35 MPa, 197.83 and 370.42 MPa, and 26 and 36 MPa, respectively. The mechanical properties of the scaffolds can satisfy the loading requirements of human bones. Therefore, the PEEK scaffolds have a potential to be used in tissue engineering as implants.

Objective: Vascular dementia is the second leading cause of dementia, which is strongly associated with diabetes. Ectopic expression of miR-133a in endothelial cells is involved in endothelial dysfunction in diabetes. Whether berberine, as a natural product in Coptis chinensis, improves vascular dementia induced by diabetes remains unknown. Methods: Diabetes and subsequent vascular dementia were induced in rats by injecting streptozotocin (50 mg/kg/day) for five consecutive days. The expression of miR-133a was determined by fluorescence in situ hybridization. The learning and memory were evaluated by step-down, step-through, and morris water maze (MWM) tests. Results: In streptozotocin-injected rats, hyperglycemia dramatically induced miR-133a ectopic expressions in vascular endothelium, reduced GTPCH1 gene expressions and BH4 levels, which were reversed by berberine administration (1.0 g/kg/day, 8 weeks). Hyperglycemia also inhibited acetylcholine-induced vasorelaxation in middle cerebral artery and reduced blood supply to the brain, which were bypassed by berberine. Ex vivo studies indicated that miR-133a agomirs abolished these beneficial effects of berberine on acetylcholine-induced vasorelaxation, while supplement of L-sepiapterin prevented endothelial dysfunction in middle cerebral artery isolated from rats. By performing step-down, step-through, and MWM tests, we observed that hyperglycemia significantly caused the impairments of learning and memory in streptozotocin-injected rats. Importantly, these aberrant phenotypes in diabetic rats were normalized by berberine therapy. Finally, berberine reduced miR-133a expression, and increased both BH4 levels and NO production in cultured endothelial cells treated with high glucose. Conclusion: Berberine improves vascular dementia in diabetes, which is possibly related to the suppression of miR-133a ectopic expression in endothelial cells.

The aim of this study was to explore the correlation between psychological resilience and social support and anxiety in obstetric nurses and to provide theoretical basis for improving the mental health of obstetric nurses.

Background: We have previously reported that the long-term exposure of organophosphorus induces vascular dementia (VD) in rats. As a coenzyme, vitamin B6 is mainly involved in the regulation of metabolisms. Whether vitamin B6 improves VD remains unknown. Methods: The model of VD was induced by feeding rats with isocarbophos (0.5 mg/kg per two day, 12 weeks). The blood flow of the posterior cerebral artery (PCA) in rat was assessed by transcranial Doppler (TCD). The learning and memory were evaluated by the Morris Water Maze (MWM) test. Results: Administration of vitamin B6 increased the blood flow in the right and left posterior cerebral arteries and improved the functions of learning and memory in isocarbophos-treated rats. Vitamin B6 increased the protein levels of N-methyl-D-aspartate receptor (NMDAR) 2B, postsynaptic densities (PSDs) protein 95, and calmodulin-dependent protein kinase II (CaMK-II) in the hippocampus, which were decreased by isocarbophos in rats. Morphological analysis by light microscope and electronic microscope indicated disruptions of the hippocampus caused by isocarbophos were normalized by vitamin B6. Importantly, the antagonist of NMDAR signaling by eliprodil abolished these beneficial effects produced by vitamin B6 on PCA blood flow, learning, memory, and hippocampus structure in rats, as well as the protein expression of NMDAR 2B, PSDs protein 95, and CaMK-II in the hippocampus. Conclusion: Vitamin B6 activates NMDAR signaling to prevent isocarbophos-induced VD in rats.

Background: Berberine has several preventive effects on cardiovascular diseases. Increased expression of miR-29b has been reported to attenuate cardiac remodeling after myocardial infarction (MI). We hypothesized that berberine via an miR-29b-dependent mechanism promotes angiogenesis and improves heart functions in mice after MI. Methods: The MI model was established in mice by ligation of left anterior descending coronary artery. The expression of miR-29b was examined by RT-qPCR. Angiogenesis was assessed by immunohistochemistry. Results: Berberine increased miR-29b expression and promoted cell proliferations and migrations in cultured endothelial cells, which were abolished by miR-29b antagomir or AMP-activated protein kinase inhibitor compound C. In mice following MI, administration of berberine significantly increased miR-29b expressional level, promoted angiogenesis, reduced infarct size, and improved heart functions after 14 postoperative days. Importantly, these in vivo effects of berberine were ablated by antagonism of miR-29b. Conclusion: Berberine via upregulation of miR-29b promotes ischemia-induced angiogenesis and improves heart functions.

Background: Hypertension is an increased risk of heart failure and acute myocardial infarction (MI). Tert-butylhydroquinone (tBHQ), as an antioxidant, shows multiple cardioprotective actions including the reduction in blood pressure. The aim of this study was to investigate whether and how tBHQ improves heart functions in rats. Methods: The MI model was established in WKY and spontaneously hypertensive rats (SHRs) by ligation of left anterior descending coronary artery. Akt phosphorylation was examined by western blot in human umbilical vein endothelial cells (HUVECs) or in rats. Angiogenesis was assessed by immunohistochemistry and immunofluorescence. Heart function was determined by echocardiography. Results: tBHQ increased Akt phosphorylation, promoted cell proliferations and migrations in HUVECs, which were abolished by Akt inhibitor wortmannin. In SHRs following MI, administration of tBHQ significantly increased Akt phosphorylation, promoted angiogenesis, reduced infarct size, and improved heart functions after 14 postoperative days. Importantly, these in vivo effects of tBHQ were ablated by wortmannin in SHRs. Conclusion: tBHQ via Akt activation promotes ischemia-induced angiogenesis and improves heart functions in hypertensive rats. In perspectives, the application of tBHQ should be considered in patients with ischemic diseases such as MI and stroke.

The available extraction methods for the determination of Br and I in geological samples, include semifusion, aqua ammoniae closed digestion and pyrohydrolysis. The sample digestion and extraction of Br and I are the major error sources, due to the low content and volatization of Br and I. A pyrohydrolysis method with liquid nitrogen trap has been developed and used to extract Br and I in geological samples using liquid nitrogen condensation absorption replacing alkaline solution absorption. Br and I are measured by Inductively Coupled Plasma-Mass Spectrometry. The detection limits of Br and I are 0.06 μg/g and 0.01 μg/g, respectively, calculated as 10 times standard deviation using dilution times of 50. These detection limits are lower than those of traditional pyrohydrolysis and semifusion methods and slightly higher than those of aqua ammoniae closed digestion method. The precision is 6.4%-21.0% RSD. The proposed method reduces the use of alkaline solution, lowers the blank and dilution times, and improves the precision. This method is much simpler than the semifusion method and can serve as a complementary method for aqua ammoniae closed digestion method. For soils and stream sediments, aqua ammoniae closed digestion method is preferred. For rocks and samples that cannot be completely digested by aqua ammoniae closed digestion method, the proposed method may be more suitable.

A suppression strategy of circulating current of modular multilevel converter based on proportional complex integral controller was proposed according to double fundamental frequency negative sequence property of phase-to-phase circulating current of modular multilevel converter, which achieved circulating current suppression by setting resonant frequency of proportional complex integral controller to voltage frequency of power grid of double fundamental frequency negative sequence. In the strategy, there are no system parameters, no conversion of rotational coordinate and no current feedforward decoupling control in the proportional complex integral controller, so as to avoid the matter of poor control effect caused by changing system parameters. The simulation in Matlab/Simulink verifies correctness and effectiveness of the strategy.

The paper researched primary cause of increasing of switching frequency of modular multilevel converter led by traditional capacitor voltage sorting algorithm according to operation principle of the converter. It proposed an improved sorting algorithm of capacitor voltage in order to decrease the switching frequency and improve system running efficiency. The algorithm optimizes and improves the traditional sorting algorithm, gives three voltage references, and compares switched capacitor voltage in sub-module with the references, so as to judge whether the switched sub-module is going to keep running in the next time. It constructed a MMC simulation model contained 60 sub-modules with the optimized algorithm in Matlab. The simulation results verify that the optimized algorithm can significantly reduce switching frequency of power devices, and decrease power consumption of the converter.

An electromagnetic transient mathematical model of MMC based on switch state function was built and an improved MMC passive controller based on EL model was designed. The controller adopts error control method, namely using zero control error to make actual output track given reference value of MMC control system. In order to make error energy decay to zero rapidly and speed up dissipative characteristics, the damping matrix was introduced; To eliminate steady state residual voltage, MMC DC voltage was introduced to control system, and compared with reference direct voltage, the voltage is regulated by PI control and is added to active current reference component to get ultimate active current reference component. The simulation results show that the controller can completely track reference value, reduce voltage fluctuation range, and has good dynamic response.

In the Post-Exxon Era of sequence stratigraphy, various sequence models for the complex stratigraphic records with their response mechanisms are developed. All the models with strong pertinence are endowed, which lead to misapprehension in the conceptual system. Therefore, the standardization of sequence stratigraphy with the aim to provide consistency in the terminology has become an important motive of modern sequence. During the development of sequence stratigraphy, the identification and distinction between normal and forced regression have laid important foundation for the system description of sequence development. This becomes the first step towards the standardization because of model-independent nature. The introduction of model-independent unconventional system tracts in fluvial sequence models, which are low- and high-accommodation system tracts, which turn out to be another successful attempt of towards the standardization of sequence stratigraphy. The four parts of stratigraphic records, which include the complexity and cyclicity in the stratigraphic accumulation process; the non-gradual change and the non-integrity of the stratigraphic records; the variability represented by the diversity of the sequence models and the nature of standardization including variability, will provide more clues and approaches for further sequence stratigraphy development

The paper analyzed influence of dead time on single sub-module of modular multilevel converter and reached conclusions that the sub-module will produce positive dead voltage from inserted state to cut-off state when arm current is positive and negative dead voltage from cut-off state to inserted state when arm current is negative. It analyzed influence of dead time on ideal fundamental voltage of modular multilevel converter, and deduced formulas of equivalent amplitude of output fundamental wave of dead voltage, actual amplitude of fundamental wave and offset of angle of output voltage, so as to reach conclusions that when voltage of DC side is fixed value, influence of dead time on modular multilevel converter relates to carrier wave ratio, dead time and phase-difference between output voltage and output current and unrelates to numbers of input module, improving modulation depth of voltage and reducing dead time can reduce influence of dead time on modular multilevel converter effectively. Simulation result validates effectiveness of the above conclusions.

For delay problem brought by asymmetric drop of traditional control strategy based on double dq and PI regulator, a control strategy based on PR regulator was proposed, namely use closed-loop power to get positive sequence current quantitative required by rotor-side converter, and calculate negative sequence current quantitative by inhibiting the second harmonic of electromagnetic torque. Matlab/Simulink simulation results show that the control strategy based on PR regulator solves delay problem effectively, and has better control performance than control strategy based on double dq and PI regulator.

In view of the problem of common-mode current existed in topology of single-phase transformerless type photovoltaic grid-connected inverter, several topologies were introduced which can restrain common-mode current effectively, namely single-phase full-bridge topology with double-polarity modulation, full-bridge topology with AC bypass, H5 topology and NPC topology. Principle of restraining common-mode current of these topologies were analyzed in details, and these topologies were compared in terms of switching loss and system efficiency. Finally, it was pointed out that H5 topology has best performance.

In view of the problems existed in traditional photovoltaic grid-connected power system such as low output voltage, big fluctuation range, high energy consumption and bad reliability, the paper proposed a design scheme of Z-source photovoltaic grid-connected inverter based on one-cycle control. It analyzed circuit structure and characteristics of Z-source inverter, introduced implementation of one-cycle control strategy of Z-source inverter in details, and built simulation model with Matlab/Simulink. The experiment result showed that the Z-source inverter has good boost effect which reduces requirement of photovoltaic cells' voltage level, and using one-cycle control technology can track network voltage well which realizes unity power factor.

Novel hybrid magnetic cross-linked enzyme aggregates of phenylalanine ammonia lyase (HM-PAL-CLEAs) were developed by co-aggregation of enzyme aggregates with magnetite nanoparticles and subsequent crosslinking with glutaraldehyde. The HM-PAL-CLEAs can be easily separated from the reaction mixture by using an external magnetic field. Analysis by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) indicated that PAL-CLEAs were inlayed in nanoparticle aggregates. The HM-PAL-CLEAs revealed a broader limit in optimal pH compared to free enzyme and PAL-CLEAs. Although there is no big difference in Km of enzyme in CLEAs and HM-PAL-CLEAs, Vmax of HM-PAL-CLEAs is about 1.75 times higher than that of CLEAs. Compared with free enzyme and PAL-CLEAs, the HM-PAL-CLEAs also exhibited the highest thermal stability, denaturant stability and storage stability. The HM-PAL-CLEAs retained 30% initial activity even after 11 cycles of reuse, whereas PAL-CLEAs retained 35% of its initial activity only after 7 cycles. These results indicated that hybrid magnetic CLEAs technology might be used as a feasible and efficient solution for improving properties of immobilized enzyme in industrial application.

Based on energy release rate criterion,a reliability analysis model is presented for the gear fracture. Firstly,the formula of gear fracture energy release rate is deduced,then the material parameter,crack size,load which affecting on gear fracture are regarded as random variables. The performance function of the crack structure failure is built by taking advantage of the energy release rate criterion. The first- order second-moment method and stochastic finite element method are used to calculate the reliability. The computation results show that this suggested method has advantages of high accuracy and efficiency.

Abstract The use of biotechnological techniques to introduce novel proteins into food crops (transgenic or GM crops) has motivated investigation into the properties of proteins that favor their potential to elicit allergic reactions. As part of the allergenicity assessment, bioinformatic approaches are used to compare the amino-acid sequence of candidate proteins with sequences in a database of known allergens to predict potential cross reactivity between novel food proteins and proteins to which people have become sensitized. Two criteria commonly used for these queries are searches over 80-amino-acid stretches for >35% identity, and searches for 8-amino-acid contiguous matches. We investigated the added value provided by the 8-amino-acid criterion over that provided by the >35%-identity-over-80-amino-acid criterion, by identifying allergens pairs that only met the former criterion, but not the latter criterion. We found that the allergen-sequence pairs only sharing 8-amino-acid identity, but not >35% identity over 80 amino acids, were unlikely to be cross reactive allergens. Thus, the common search for 8-amino-acid identity between novel proteins and known allergens appears to be of little additional value in assessing the potential allergenicity of novel proteins.

Background: Calciphylaxis is a rare disorder characterized by skin necrosis caused by calcium deposition within vessels, thrombosis, and subsequent tissue ischemia. Penile involvement may rarely occur., Objective: To identify risk factors, diagnosis, management, and mortality of patients with penile calciphylaxis., Methods: A retrospective medical record review was conducted of 16 patients with penile calciphylaxis treated at 2 large urban tertiary care centers between January 2001 and December 2019. A control group of 44 male patients with nonpenile calciphylaxis at the same institution was included., Results: The median survival of patients with penile calciphylaxis was 3.8 months (interquartile range, 27.0 months). Mortality was 50% at 3 months and 62.5% at 6 months for penile calciphylaxis, and 13.6% at 3 months and 29.5% at 6 months for controls (P = .008). Patients with penile calciphylaxis were less likely to be obese (P = .04) but more likely to have hyperparathyroidism (P = .0003) and end-stage renal disease (P = .049)., Limitations: Retrospective study design and small sample size., Conclusions: This study further defines the disease course of penile calciphylaxis, which has high mortality. Imaging may be used to aid diagnosis. Risk factors include end-stage renal disease, hyperparathyroidism, and normal body mass index., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Patient outcomes are improved when dermatologists provide inpatient consultations. Inpatient access to dermatologists is limited, illustrating an opportunity to use teledermatology. Little is known about the ability of dermatologists to accurately diagnose disease and manage inpatients with teledermatology, particularly when using nondermatologist-generated clinical data., Methods: This prospective study assessed the ability of teledermatology to diagnose disease and manage 41 dermatology consultations from a large urban tertiary care center, using internal medicine referral documentation and photographs. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the κ statistic., Results: There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median κ = 0.83), substantial agreement in laboratory evaluation decisions (median κ = 0.67), almost perfect agreement in imaging decisions (median κ = 1.0), and moderate agreement in biopsy decisions (median κ = 0.43). There was almost perfect agreement in treatment (median κ = 1.0), but no agreement in follow-up planning (median κ = 0.0). There was no association between raw photograph quality and the primary plus differential diagnosis or primary diagnosis alone., Limitations: Selection bias and single-center nature., Conclusions: Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions., (Copyright © 2020. Published by Elsevier Inc.)

Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression. Here, we demonstrate that APE1 accelerates pancreatic cancer cell proliferation through glial cell line-derived neurotrophic factor (GDNF)/glial factor receptor α1 (GFRα1)/Src/ERK axis-cascade signaling. The proliferation of endogenous APE1 expressed-MIA PaCa-2, a human pancreatic carcinoma cell line, was increased by treatment with GDNF, a ligand of GFRα1. Either of downregulated APE1 or GFRα1 expression using small interference RNA (siRNA) inhibited GDNF-induced cancer cell proliferation. The MEK-1 inhibitor PD98059 decreased GDNF-induced MIA PaCa-2 cell proliferation. Src inactivation by either its siRNA or Src inhibitor decreased ERK-phosphorylation in response to GDNF in MIA PaCa-2 cells. Overexpression of GFRα1 in APE1-deficient MIA PaCa-2 cells activated the phosphorylation of Src and ERK. The expression of both APE1 and GFRα1 was gradually increased as progressing pancreatic cancer grades. Our results highlight a critical role for APE1 in GDNF-induced pancreatic cancer cell proliferation through APE1/GFRα1/Src/ERK axis-cascade signaling and provide evidence for future potential therapeutic drug targets for the treatment of pancreatic cancer.

Scavenger receptors typically bind to multiple ligands on a cell surface, including endogenous and modified host-derived molecules and microbial pathogens. They promote the elimination of degraded or harmful substances such as non-self or altered-self targets through endocytosis, phagocytosis, and adhesion. Currently, scavenger receptors are subdivided into eight classes based on several variations in their sequences due to alternative splicing. Since recent studies indicate targeting scavenger receptors has been involved in cancer prognosis and carcinogenesis, we will focus on the current knowledge about the emerging role of scavenger receptor classes A to E in cancer progression., Competing Interests: CONFLICT OF INTEREST STATEMENT: None declared., (© Chonnam Medical Journal, 2020.)

Psoriasis is a chronic, recurrent, heterogeneous, cutaneous inflammatory skin disease for which there is no cure. It affects approximately 7.5 million people in the United States. Currently, several biologic agents that target different molecules implicated in the pathogenic processes of psoriasis are being assessed in diverse clinical studies. However, relapse usually occurs within weeks or months, meaning there is currently no cure for psoriasis. Therefore, recent studies have discovered diverse new potential treatments for psoriasis: inhibitors of bacteria such as Staphylococcus aureus , tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and neuropilin 1 (NRP1). A promising approach that has recently been described involves modifying antimicrobial peptides to develop new cutaneous anti-bacterial agents that target inflammatory skin disease induced by Staphylococcus . Increased expression of TRAIL and its death receptors DR4 and DR5 has been implicated in the pathogenesis of plaque psoriasis. In addition, TRAIL has the ability to inhibit angiogenesis by inducing endothelial cell death and by negative regulation of VEGF-induced angiogenesis via caspase-8-mediated enzymatic and non-enzymatic functions. Since NRP1 regulates angiogenesis induced by multiple signals, including VEGF, ECM and semaphorins, and also initiates proliferation of keratinocytes through NF-κB signaling pathway in involved psoriatic skin, targeting NRP1 pathways may offer numerous windows for intervention in psoriasis. In this review, we will focus on the current knowledge about the emerging role of synthetic antimicrobial peptides, TRAIL and NRP1 blocking peptides in the pathogenesis and treatment of psoriasis., Competing Interests: CONFLICT OF INTEREST STATEMENT: None declared.

Over recent years, several new molecular and immunogenic therapeutic approaches to melanoma treatment have been approved and implemented in clinical practice. Mechanisms of resistance to these new therapies have become a major problem. Mutation-specific pharmacotherapy can result in simultaneous emergence of resistant clones at many separate body sites despite an initially positive therapeutic response. Additionally, treatments aimed at inducing apoptosis are subject to resistance due to escape through other known mechanisms of regulated cell death (RCD). In this review, we discuss the complexity in pharmacological manipulation of melanoma with c-Kit, BRAF, MEK, and/or mTOR mutant cell lines. This study also addresses melanoma evasion of cell death through modalities of RCD such as apoptosis, autophagy, and necroptosis. This study also examines new combination therapies which have been approved to target both cell cycle dysregulation and cell death pathways. Lastly, we recognize the importance of immunomodulation though manipulation of the body's natural killing mechanisms with CTLA4, PD1, and CSF1 inhibition. As we begin to recognize tumor cell activation of alternate pathways, evasion of programmed cell death, and manipulation of the tumor microenvironment, it is increasingly important to grasp the complexity of personalized therapy in melanoma treatment., Competing Interests: CONFLICT OF INTEREST STATEMENT: None declared.

Background: Multiple trials have attempted to demonstrate the effective induction of cell death in TRAIL-resistant cancer cells, including using a combined treatment of recombinant TRAIL and various proteasome inhibitors. These studies have yielded limited success, as the mechanism of cell death is currently unidentified. Understanding this mechanism's driving forces may facilitate the induction of cell death in TRAIL-resistant cancer cells., Methods: Three kinds of recombinant soluble TRAIL proteins were treated into TRAIL-resistant cells and TRAIL-susceptible cells, with or without bortezomib, to compare their respective abilities to induce cell death. Recombinant TRAIL was treated with bortezomib to investigate whether this combination treatment could induce tumor regression in a mouse syngeneic tumor model. To understand the mechanism of combined treatment-induced cell death, cells were analyzed by flow cytometry and the effects of various cell death inhibitors on cell death rates were examined., Results: ILz:rhTRAIL, a recombinant human TRAIL containing isoleucine zipper hexamerization domain, showed the highest cell death inducing ability both in single treatment and in combination treatment with bortezomib. In both TRAIL-resistant and TRAIL-susceptible cells treated with the combination treatment, an increase in cell death rates was dependent upon both the dose of TRAIL and its intrinsic properties. When a syngeneic mouse tumor model was treated with the combination of ILz:rhTRAIL and bortezomib, significant tumor regression was seen as a result of the effective induction of cancer cell death. The combination treatment-induced cell death was both inhibited by TRAIL blocking antibody and caspase-dependent. However, it was not inhibited by various ER stress inhibitors and autophagy inhibitors., Conclusions: The combination treatment with ILz:rhTRAIL and bortezomib was able to induce cell death in both TRAIL-susceptible and TRAIL-resistant cancer cells through the intracellular TRAIL signaling pathway. The efficiency of cell death was dependent on the properties of TRAIL under the environment provided by bortezomib. The combination treatment-induced cell death was not regulated by bortezomib-induced ER stress response or by autophagy.

Melanoma is one of the most aggressive cancers in the world and is responsible for the majority of skin cancer deaths. Recent advances in the field of immunotherapy using active, adoptive, and antigen-specific therapeutic approaches, have generated the expectation that these technologies have the potential to improve the treatment of advanced malignancies, including melanoma. Treatment options for metastatic melanoma patients have been dramatically improved by the FDA approval of new therapeutic agents including vemurafenib, dabrafenib, and sorafenib. These kinase inhibitors have the potential to work in tandem with MEK, PI3K/AKT, and mTOR to inhibit the activity of melanoma inducing BRAF mutations. This review summarizes the effects of the new therapeutic agents against melanoma and the underlying biology of these BRAF inhibitors., Competing Interests: CONFLICT OF INTEREST STATEMENT: None declared.

Background: The diagnosis of Lyme disease relies on the accurate diagnosis of erythema chronicum migrans (ECM) because serologic tests, culture, and polymerase chain reactions are often inaccurate. Although ECM is classically associated with a targetoid rash, there are many variants of this lesion. These variants of ECM are often initially diagnosed as cellulitis or spider bite reactions and treated with oral antibiotics. Inappropriate treatment further delays the diagnosis of Lyme disease, leading to late complications., Methods: We present four cases of vesiculobullous and hemorrhagic ECM, a less common variant of ECM., Results: All four patients had a history of exposure to wooded areas in Massachusetts during the summer months. In these patients, ECM presented with central vesicles and bullae with hemorrhage, crusting, and in some cases necrosis. Serologic testing was positive in three of the four cases at presentation. In one case, microscopic examination of a skin biopsy showed epidermal spongiosis with parakeratosis, focal necrosis, papillary dermal edema, erythrocyte extravasation, and a superficial and deep perivascular lymphocytic infiltrate with neutrophils and eosinophils of the dermis. No fungal organisms or bacteria were identified. All four patients were treated with doxycycline with complete resolution of symptoms., Conclusions: It is important to recognize the vesiculobullous and hemorrhagic variants of ECM in order to minimize the provision of inappropriate antibiotic treatment for other diagnoses. Early diagnosis of ECM and the initiation of appropriate antibiotics may prevent late complications of Lyme disease., (© 2015 The International Society of Dermatology.)

Alpha-melanocyte stimulating hormone (α-MSH) is a highly conserved 13-aa neuropeptide derived from pro-opiomelanocortin by post-translational processing, which has been reported to exhibit potent anti-inflammatory activity and a wide range of immunosuppressive activities in the skin. However, the regulatory effect of α-MSH is not completely clear in cutaneous innate immunity. In this study, we investigate the functional regulation of α-MSH in TLR2-mediated inflammatory responses in normal human keratinocytes (HKs). α-MSH pretreatment down-regulated the Staphylococcus aureus LTA-induced expression of both TLR2 and IL-8 as well as NF-κB nuclear translocation in HK cells. The inhibitory effect of α-MSH was blocked by agouti signaling protein (ASP), an α-MSH receptor-1 antagonist. To investigate the mechanism of this response in more detail, siRNA of IRAK-M, a negative regulator of TLR signaling, was utilized in these studies. The α-MSH suppressive effect on IL-8 production and NF-κB transactivation was inhibited by IRAK-M siRNA transfection in HK cells. These results indicate that α-MSH is capable of suppressing keratinocyte TLR2-mediated inflammatory responses induced by S. aureus-LTA, thus demonstrating another novel immunomodulatory activity of α-MSH in normal human keratinocytes.

Transcription factor SOX4 has been implicated in skeletal myoblast differentiation through the regulation of Cald1 gene expression; however, the detailed molecular mechanism underlying this process is largely unknown. Here, we demonstrate that SOX4 acetylation at lysine 95 by KAT5 (also known as Tip60) is essential for Cald1 promoter activity at the onset of C2C12 myoblast differentiation. KAT5 chromodomain was found to facilitate SOX4 recruitment to the Cald1 promoter, which is involved in chromatin remodeling at the promoter. Chromatin occupancy analysis of SOX4, KAT5, and HDAC1 indicated that the expression of putative SOX4 target genes during C2C12 myoblast differentiation is specifically regulated by the molecular switching of the co-activator KAT5 and the co-repressor HDAC1 on SOX4 transcriptional activation.

The cutaneous inflammation associated with acne vulgaris is caused by the anaerobic bacterium Propionibacterium acnes through activation of the innate immune system in the skin. Current standard treatments for acne have limitations that include adverse effects and poor efficacy in many patients, making development of a more effective therapy highly desirable. In the present study, we demonstrate the protective effects of a novel customized α-helical cationic peptide, P5, against P. acnes-induced inflammatory responses in vitro and in vivo. Application of P5 significantly reduced expression of two inflammatory cytokines IL-8 and TNF-α in P. acnes-treated primary human keratinocytes, where P5 appeared to act in part by binding to bacterial lipoteichoic acid, thereby suppressing TLR2-to-NF-κB signaling. In addition, in a mouse model of acne vulgaris, P5 exerted both anti-inflammatory and antimicrobial effects against P. acnes, but exerted no cytotoxic effects against skin cells. These results demonstrate that P5, and perhaps other cationic antimicrobial peptides, offer the unique ability to reduce numbers P. acnes cells in the skin and to inhibit the inflammation they trigger. This suggests these peptides could potentially be used to effectively treat acne without adversely affecting the skin.