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Despite the advances in contraceptives, there is still a high rate of unintended pregnancies worldwide, due in large part to the lack of effective, convenient, and safe birth control methods. Compared with short-acting contraceptives, approaches that offer long-term pregnancy protection have attracted greater interest because of the reduced dosing frequency and improved patient compliance. As a novel transdermal drug delivery system, the microneedle (MN) patch has been widely used for a variety of biomedical applications, including long-acting contraception, due to unique properties, such as painless self-administration and elimination of biohazardous waste. In this review we provide a systemic review of MN patches that have been utilized for long-term contraception, including dissolvable MN patches, polymeric biodegradable MN patches, and silk fibroin-based biodegradable MN patches. The acceptability and biosafety of these contraceptive MN patches are also discussed. Finally, we give our perspectives on the future clinical translation of MN patches for long-acting contraception.

Transition metal carbides are promising candidates for thermal protection materials due to their high melting points and excellent mechanical properties. However, the relatively high thermal conductivity is still a major obstacle to its application in an ultra-high-temperature insulation system. In this work, the low thermal conductivity of dense (TiZrHfVNbTa)Cx (x = 0.6–1) high-entropy carbides has been realized by adjusting the carbon stoichiometry. The thermal conductivity gradually decreases from 10.6 W·m−1·K−1 at room temperature to 6.4 W·m−1·K−1 with carbon vacancies increasing. Due to enhanced scattering of phonons and electrons by the carbon vacancies, nearly full-dense (97.9%) (TiZrHfVNbTa)C0.6 possesses low thermal conductivity of 6.4 W·m−1·K−1, thermal diffusivity of 2.3 mm2·s−1, as well as electrical resistivity of 165.5 μΩ·cm. The thermal conductivity of (TiZrHfVNbTa)C0.6 is lower than that of other quaternary and quinary high-entropy carbide ceramics, even if taking the difference of porosity into account in some cases, which is mainly attributed to compositional complexity and carbon vacancies. This provides a promising route to reduce the thermal conductivity of high-entropy carbides by increasing the number of metallic elements and carbon vacancies.

The growing number of renewable energy replacing conventional generators results in a loss of the reserve for frequency control in power systems, while many industrial power grids often have excess energy supply due to abundant wind and solar energy resources. This paper proposes a secondary frequency control (SFC) strategy that allows industrial power grids to provide emergency high-voltage direct current (HVDC) power support (EDCPS) for emergency to a system requiring power support through a voltage source converter (VSC) HVDC link. An architecture including multiple model predictive control (MPC) controllers with periodic communication is designed to simultaneously obtain optimized EDCPS capacity and minimize adverse effects on the providing power support (PPS) system. Moreover, a model of a virtual power plant (VPP) containing aluminum smelter loads (ASLs) and a high penetration of wind power is established for the PPS system. The flexibility and controllability of the VPP are improved by the demand response of the ASLs. The uncertainty associated with wind power is considered by chance constraints. The effectiveness of the proposed strategy is verified by simulation results using the data of an actual industrial power grid in Inner Mongolia, China. The DC voltage of the VSCs and the DC in the potlines of the ASLs are also investigated in the simulation.

This paper mainly focuses on the impact of inclined static air gap eccentricity (ISAGE) on the electromagnetic characteristics and mechanical performances (vibration, deformation, strain and stress). Considering different ISAGE fault types in the theoretical and finite element analysis (FEA) model of synchronous generators, the effects of intersection position of the rotor center axis and stator center axis, rotor inclined angle, and the combination of the previous two fault types on MFD, phase current and radial magnetic pulling per unit area (MPPUA) are analyzed and compared. Then, based on the stator model used uniformly in three physical fields, the harmonic response and mechanical response are investigated with loads imported by the electromagnetic field. Finally, the stator radial vibration measurement experiments are carried out to verify the results obtained by theoretical analysis and FEA. It is shown that ISAGE will considerably enlarge the fluctuation of MPPUA and intensify the radial vibration of the stator, especially at the 2nd harmonic. The probability of failure at tooth tip and inner slot wall of the stator will increase.

Abstract Background Stress hyperglycemia ratio (SHR) is a novel biomarker of true acute hyperglycemia condition and is associated with a worse prognosis in patients with myocardial infarction (MI). However, the effects of SHR in the setting of MI with non-obstructive coronary arteries (MINOCA) have not been investigated. This study aimed to explore the association between SHR and long-term clinical outcomes among MINOCA patients. Methods A total of 410 MINOCA patients were included in the final analysis of this study. The patients were divided into three groups based on the SHR tertiles: [SHR1 group (SHR ≤ 0.73), (n = 143); SHR2 group (SHR 0.73–0.84), n = 131; and SHR3 group (SHR ≥ 0.84), n = 136]. Follow-up for major adverse cardiovascular events (MACE) was conducted on all patients. Cox regression and Kaplan–Meier curve analysis were used to evaluate the relationship between SHR and MACE. The receiver operating curve (ROC) analysis was applied to obtain the optimal cut-off value of SHR for predicting clinical MACE. Results A total of 92 patients developed MACE during the mean 34 months of follow-up. A significant increase in MACE was observed in the SHR3 group compared to the SHR1 and SHR2 groups (35.3% vs. 15.4% and 16.8%, respectively; P

Abstract Background/aims Cavernous transformation of the portal vein (CTPV) in cirrhotic patients with extrahepatic portal vein obstruction (EHPVO) was a relatively rare disease and had no consensus on the treatment. Our study aimed to explore the value of anticoagulation with warfarin treatment for CTPV cirrhotic patients with EHPVO. Methods: From January 2015 to December 2019, the clinical characteristics of cirrhotic patients who were diagnosed as CTPV with EHPVO were retrospectively analyzed. Eligible patients were distributed into the anticoagulation group (n = 46) and control group (n = 38). The change of portal vein thrombosis, hepatic decompensation, survival and adverse events were evaluated between the two groups. Results The median follow-up of our patients was 51 months in the anticoagulation group and 44 months in the control group. The progress rate of the portal vein was higher in patients from the control groups (n = 12) than in patients from the anticoagulation group (n = 4, p = 0.008). There was no significant difference between the partial recanalization rate and stable rate between the two groups. Patients in anticoagulation group developed less hepatic decompensation than those in control group (13.0% vs 34.2%, p = 0.021). The Kaplan-Meier curve showed that patients in the anticoagulation group had a better prognosis than patients in the control group (P

In order to explore the adsorption characteristics and influencing factors of bongkrekic acid by Lactobacillus plantarum X1. High performance liquid chromatography was used to determine the adsorption rate of bongkrekic acid. Factors that affect the ability of the strain to remove bongkrekic acid included time, temperature, pH, bacterial concentration, bongkrekic acid concentration and simulated gastrointestinal environment. Thermodynamic and kinetic equations were used to fit the analysis results. Results showed that the strain adsorbed bongkrekic acid quickly and efficiently and the adsorption reached saturation at 1 h. The increase of temperature, bacterial concentration and bongkrekic acid concentration enhanced the adsorption and desorption was difficult after adsorption. The optimum adsorption conditions were the temperature of 37 ℃, bacterial concentration of 6 g·L−1 and bongkrekic acid concentration of 10 mg·L−1, the adsorption rates were 52.70%, 54.12% and 48.53%, respectively. Acidic environment was favorable for BA adsorption, but the adsorption effect in simulated gastrointestinal environment was reduced due to the action of protease. The adsorption capacity reached the maximum at pH3. The adsorption process conformed to Langmuir equation and Lagergren pseudo-second order equation, and it was monolayer adsorption. The thermodynamic data were analyzed and it was found that both physical adsorption and chemical adsorption existed in the adsorption process. The whole process was spontaneous and exothermic. Therefore, Lactobacillus plantarum X1 should be potential candidates as a biological detoxification agent for the remove of bongkrekic acid via their physical binding.

Abstract Objectives Immunoglobulin-G4-related disease (IgG4-RD) is a distinct systemic autoimmune-mediated disease manifesting as chronic inflammation and tissue fibrosis. Since the role of DNA methylation in the pathogenesis of IgG4-RD is still unclear, we conduct this study to investigate epigenetic modifications in IgG4-RD. Methods A genome-wide DNA methylation study was conducted with B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients and matched controls by using the Illumina HumanMethylation 850K BeadChip. We further performed pyrosequencing and immunohistochemistry assays to validate the methylation status of some targets of interest. Results We identified differentially methylated CpG sites including 44 hypomethylated and 166 hypermethylated differentially methylated probes (DMPs) in B cells and 260 hypomethylated and 112 hypermethylated DMPs in CD4+ T cells from 10 IgG4-RD patients compared with 10 healthy controls. We also identified 36945 hypomethylated and 78380 hypermethylated DMPs in salivary gland tissues of 4 IgG4-RD patients compared with 4 controls. DPM2 (cg21181453), IQCK (cg10266221), and ABCC13 (cg05699681, cg04985582) were hypermethylated and MBP (cg18455083) was hypomethylated in B cells, CD4+ T cells, and salivary gland tissues of IgG4-RD patients. We also observed the hypomethylated HLA-DQB2 in CD4+ T cells from IgG4-RD patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DMPs in salivary gland tissues of IgG4-RD patients revealed enrichment of pathways involved in the regulation of immune cell responses and fibrosis. Conclusion This is the first DNA methylation study in peripheral B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients. Our findings highlighted the role of epigenetic modification of DNA methylation and identified several genes and pathways possibly involved in IgG4-RD pathogenesis.

Fatigue resistance is a key criterion for new material that would be applied as an implant. As a “smart” implant material with good biodegradability and high strength, Mg–2Zn–0.5Zr–0.5Nd alloy has been recognized as a promising candidate for bone implant. A series of tests on fatigue properties of extruded Mg–2Zn–0.5Zr–0.5Nd alloy are carried out in this study. Alternating cyclic dynamic loads at frequencies of 5 Hz and 10 Hz both in air and in 0.9 wt% NaCl solution were loaded on extruded Mg–2Zn–0.5Zr–0.5Nd alloy respectively. In air condition, the fatigue life variational trends of Mg–2Zn–0.5Zr–0.5Nd alloy at different frequencies are similar according to the stress-life (S–N) curves. However, under high fatigue cycles, the lower loading frequency prolongs the loading time of repetitive stresses and reduces the fatigue life of the samples. In 0.9 wt% NaCl solution, the S–N curves under different frequencies show different changing trends due to the synergistic effect of corrosion environment and loading frequency. It is also found that the fatigue resistance of the alloy in 0.9 wt% NaCl solution is poorer than that in air due to the significant promotion of the formation and growth of corrosion pits by the NaCl environment. In addition, according to the fatigue fracture morphology analysis, it can be found that the failed samples show different fracture patterns in air and 0.9 wt% NaCl solution.

Diamond and graphene are considered to be one of the most promising thermal interface materials (TIMs) for electronic devices benefited from their highest thermal conductivity in the natural world. However, orientated fabrication of high thermal conductivity diamond and graphene hybrid arrays with three dimensions (3 D) thermal conductive networks are still problematic. Here, we used a unique one-step microwave plasma chemical vapor deposition, n-butylamine, as the liquid source to prepare a novel high thermal conductivity 3 D vertical diamond/graphene (VDG) hybrid arrays films. The orientated 3 D thermal conduction path of the VDG is regulated by the growth temperature, and the through-plane thermal conductivity value of the VDG700 films up to 97 W m−1 K−1. In the actual TIM performance measurement, the system cooling efficiency with our VDG as TIM is higher than the state-of-the-art commercial TIM, demonstrating the superior ability to solve the inter-facial heat transfer issues in electronic systems.

In the research of automatic interpretation of remote sensing images, semantic segmentation based on deep convolutional neural networks has been rapidly developed and applied, and the feature segmentation accuracy and network model generalization ability have been gradually improved. However, most of the network designs are mainly oriented to the three visible RGB bands of remote sensing images, aiming to be able to directly borrow the mature natural image semantic segmentation networks and pre-trained models, but simultaneously causing the waste and loss of spectral information in the invisible light bands such as near-infrared (NIR) of remote sensing images. Combining the advantages of multispectral data in distinguishing typical features such as water and vegetation, we propose a novel deep neural network structure called the multispectral semantic segmentation network (MSNet) for semantic segmentation of multi-classified feature scenes. The multispectral remote sensing image bands are split into two groups, visible and invisible, and ResNet-50 is used for feature extraction in both coding stages, and cascaded upsampling is used to recover feature map resolution in the decoding stage, and the multi-scale image features and spectral features from the upsampling process are fused layer by layer using the feature pyramid structure to finally obtain semantic segmentation results. The training and validation results on two publicly available datasets show that MSNet has competitive performance. The code is available: https://github.com/taochx/MSNet.

Abstract Background The aim of this study is to investigate the prevalence of myopia and high myopia and the associated risk factors in key schools in Xi'an, China. Methods This cross-sectional study started in September 2021 and was conducted for one month. A total of 11,011 students from 10 key primary schools, five key junior high schools and five key high schools in Xi'an were randomly selected to undergo visual acuity measurement and non-cycloplegic autorefraction. The questionnaire was completed by the students and their parents together. Results The prevalence of myopia and high myopia in key schools were 75.7% and 9.7%, respectively. The prevalence of myopia and high myopia rose significantly as grade or age increased (all P < 0.001), and the prevalence of myopia and high myopia in females was higher than that in males (P < 0.001, P < 0.5). According to the multivariable logistic regression analysis, older age (OR=1.42), female compared with male (OR=1.43), having one myopic parent (OR=1.64), having two myopic parent (OR=2.30) and often taking extracurricular tuition (OR=1.35) were more likely to be associated with develop myopia (P < 0.001). Older age (OR=1.39), having one myopic parent (OR=2.29), having two myopic parent (OR= 3.69), and often taking extracurricular tuition (OR=1.48) were more likely to be associated with high myopia (P < 0.001). Conclusions The overall rate of myopia and high myopia in key schools in Xi'an, China, is extremely high. Myopia and high myopia are associated with increasing age, parents’ myopia, few outdoor exercises, and extracurricular tuition. Myopia is also associated with female and not having the habit of "one punch, one foot, one inch (when reading and writing, 10 cm from the chest to the table, 33 cm from the eye to the book and 3.3 cm from the tip of the pen to the finger)".

Abstract Background The pathogenesis of immunoglobulin G4-related disease (IgG4-RD) remains unclear. IgG4-RD often mimics other diseases, including pancreatic cancer (PC) and Sjogren’s syndrome (SS), which may easily lead to misdiagnosis. This study was performed to explore the metabolite changes and potential biomarkers of IgG4-RD and other misdiagnosed diseases. Methods Untargeted liquid chromatography–tandem mass spectrometry metabolomics profiling of plasma samples from a cohort comprising healthy controls (HCs) and patients with IgG4-RD (n = 87), PC (n = 33), and SS (n = 31) was performed. A random forest machine learning model was used to verify the relevance of the identified metabolites in the diagnosis of different diseases and the prediction of disease prognosis. Results The ATP-binding cassette transporter pathway was found to be most closely related to IgG4-RD, which was significantly up-regulated in the IgG4-RD group than in all the matched groups. Five metabolites were proved to be valuable biomarkers for IgG4-RD. Caftaric acid, maltotetraose, d-glutamic acid, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphoserine, and hydroxyproline were useful in distinguishing between IgG4-RD, PC, SS, and HC [area under the curve (AUC) = 1]. A combination of phenylalanine betaine, 1-(1z-hexadecenyl)-sn-glycero-3-phosphocholine, Pi 40:8, uracil, and N1-methyl-2-pyridone-5-carboxamide showed a moderate value in predicting relapse in patients with IgG4-RD (AUC = 0.8). Conclusions Our findings revealed the metabolite changes of IgG4-RD and provide new insights for deepening our understanding of IgG4-RD despite the lack of validation in external cohorts. Metabolomic biomarkers have significance in the clinical diagnosis and disease prognosis of IgG4-RD.

Immunoglobulin G4 (IgG4)-related autoimmune pancreatitis (AIP), also known as “type 1 AIP,” is a rare, chronic, and fibroinflammatory disease manifested as obstructive jaundice and enlargement of the pancreas, usually accompanied by extra-pancreatic organ involvement. The understanding of IgG4-related AIP is gradually deepening. In this review, we summarized the basic concepts, common clinical manifestations, and new progress of the disease including diagnostic, therapeutic strategies, and prognosis mainly based on published case reports, cohort studies, meta-analyses, and guidelines in the past 5 years. Issues such as diagnostic markers, risk factors for relapse, and more effective treatment still need to be further studied.

The United Nations Secretary-General Mechanism (UNSGM) for investigation of the alleged use of chemical and biological weapons is the only established international mechanism of this type under the UN. The UNGSM may launch an international investigation, relying on a roster of expert consultants, qualified experts, and analytical laboratories nominated by the member states. Under the framework of the UNSGM, we organized an external quality assurance exercise for nominated laboratories, named the Disease X Test, to improve the ability to discover and identify new pathogens that may cause possible epidemics and to determine their animal origin. The “what-if” scenario was to identify the etiological agent responsible for an outbreak that has tested negative for many known pathogens, including viruses and bacteria. Three microbes were added to the samples, Dabie bandavirus, Mammarenavirus, and Gemella spp., of which the last two have not been taxonomically named or published. The animal samples were from Rattus norvegicus, Marmota himalayana, New Zealand white rabbit, and the tick Haemaphysalis longicornis. Of the 11 international laboratories that participated in this activity, six accurately identified pathogen X as a new Mammarenavirus, and five correctly identified the animal origin as R. norvegicus. These results showed that many laboratories under the UNSGM have the capacity and ability to identify a new virus during a possible international investigation of a suspected biological event. The technical details are discussed in this report.

A study for human gut microbiota composition in 7 healthy Chinese adult subjects across several years provides a valuable perspective on the dynamics of microbiota composition over time.

Anxiety is thought to be evolutionarily rooted in predator defense. Yan et al. show that GABAergic neurons in the anterior hypothalamic nucleus (AHN), a node in the predator defense network, play an essential role in anxiety-like behaviors.

Chinese sweet lily (Lilium davidii var. unicolor), the only edible lily in the world, has high nutritional value. At present, the application of preservation technology is relatively backward, resulting in a large loss of lily. Therefore, the preservation has become one of the key factors limiting the development of the edible lily bulbs industry. This paper reviews the various application of pretreatment and storage technologies for the preservation of lily bulbs. It is considered that irradiation and proper preservative can be used for pretreatment. Vacuum packaging can be used for short-term storage and transportation. Phase temperature storage could be as a long-term storage mode of lily bulbs.

Tuberculosis (TB) is the leading infectious disease caused by Mycobacterium tuberculosis (Mtb). Clarithromycin (CTY), an analog of erythromycin (ERY), is more potent against multidrug-resistance (MDR) TB. ERY and CTY were previously reported to bind to the nascent polypeptide exit tunnel (NPET) near peptidyl transferase center (PTC), but the only available CTY structure in complex with D. radiodurans (Dra) ribosome could be misinterpreted due to resolution limitation. To date, the mechanism of specificity and efficacy of CTY for Mtb remains elusive since the Mtb ribosome-CTY complex structure is still unknown. Here, we employed new sample preparation methods and solved the Mtb ribosome-CTY complex structure at 3.3Å with cryo-EM technique, where the crucial gate site A2062 (E. coli numbering) is located at the CTY binding site within NPET. Two alternative conformations of A2062, a novel syn-conformation as well as a swayed conformation bound with water molecule at interface, may play a role in coordinating the binding of specific drug molecules. The previously overlooked C–H hydrogen bond (H-bond) and π interaction may collectively contribute to the enhanced binding affinity. Together, our structure data provide a structural basis for the dynamic binding as well as the specificity of CTY and explain of how a single methyl group in CTY improves its potency, which provides new evidence to reveal previously unclear mechanism of translational modulation for future drug design and anti-TB therapy. Furthermore, our sample preparation method may facilitate drug discovery based on the complexes with low water solubility drugs by cryo-EM technique.

Emamectin benzoate (EMB) is one of the high-efficacious pesticide commonly used to control the ferocious economic crop pest S. exigua in the field. The results of S. exigua life table treated with three lethal doses of EMB (LC5, LC20 and LC50) indicated that three lethal doses of EMB could all inhibited the proliferation of S. exigua population effectively by long-lasting inhibit the survival of the S. exigua larvae and per female fecundity significantly (p

Abstract Background Since viral metagenomic approach was applied to discover plant viruses for the first time in 2006, many plant viruses had been identified from cultivated and non-cultivated plants. These previous researches exposed that the viral communities (virome) of plants have still largely uncharacterized. Here, we investigated the virome in 161 species belonging to 38 plant orders found in a riverside ecosystem. Results We identified 245 distinct plant-associated virus genomes (88 DNA and 157 RNA viruses) belonging to 27 known viral families, orders, or unclassified virus groups. Some viral genomes were sufficiently divergent to comprise new species, genera, families, or even orders. Some groups of viruses were detected that currently are only known to infect organisms other than plants. It indicates a wider host range for members of these clades than previously recognized theoretically. We cannot rule out that some viruses could be from plant contaminating organisms, although some methods were taken to get rid of them as much as possible. The same viral species could be found in different plants and co-infections were common. Conclusions Our data describe a complex viral community within a single plant ecosystem and expand our understanding of plant-associated viral diversity and their possible host ranges.

Abstract It has been a decade since the first extensive study on the internet's adoption and use was conducted. Circumstances have changed in the last decade internet has become an essential need for every human being. Socio-psychological, economic, and personal factors play a significant role in shaping human behaviour. But their role in shaping consumer behaviour toward 5G is still unexplored. In order to determine the impact of socio-psychological elements on 5G technology adoption intention, the study integrated curiosity, perceived value, functional value, and environmental awareness into UTAUT2 and analyzed how they interact. Instead of relying on linear models, this study employed a dual-stage SEM-ANN approach because customers' decision-making process to adopt new technology is complex. Valid responses from 840 respondents were collected, investigated, and ranked using the deep learning ANN approach. All predictors were found statistically significant except social influence. ANN sensitivity analysis revealed that newly integrated predictors (environmental awareness, curiosity) are surprisingly the most important predictors, followed by facilitating conditions and perceived satisfaction. SEM-ANN hybrid two-step deep learning approach explained 83.6% variance higher than the baseline model (UTAUT2). The study improved UTAUT2 by adding new variables and expanding its canvas to predict user technology adoption. This will show how consumers react to 5G services and help telecoms grow into new markets.

Abstract Background Antineutrophil Cytoplasmic Antibodies (ANCA) associated glomerulonephritis (AGN) is a group of autoimmune diseases and mono-macrophages are involved in its glomerular injuries. In this study, we aim to investigate the role of CD206+ mono-macrophages in AGN. Methods 27 AGN patients (14 active AGN, 13 remissive AGN) together with healthy controls (n = 9), disease controls (n = 6) and kidney function adjusted controls (n = 9) from Department of Nephrology, Ruijin hospital were recruited. Flow cytometry was used to study proportion of CD206+ cells in peripheral blood. Immunohistochemistry for CD206 staining was performed and CD206 expression was scored in different kidney regions. Serum soluble CD206 (sCD206) was measured by enzyme-linked immunosorbent assay (ELISA). We also generated murine myeloperoxidase (MPO) (muMPO) ANCA by immunizing Mpo −/− mice. Mouse bone marrow-derived macrophages (BMDMs) from wild C57BL/6 mice and peripheral blood mononuclear cell (PBMC) derived macrophages from healthy donors were treated with MPO ANCA with or without its inhibitor AZD5904 to investigate the effects of MPO-ANCA on CD206 expression. Results The proportion of peripheral CD206+CD68+ cells in active AGN patients were significantly higher than that in remissive patients (p

Abstract Lysophosphatidylcholine (LPC) was previously found to show neuroprotective effect on nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) induced signalings. Also, numerous studies reported the emerging roles of long noncoding RNAs (LncRNAs) involved in neurodegenerative disease. However, the biological mechanism of LPC and expression profile of lncRNAs has not been reported. Here, lncRNAs in PC12 cells under LPC and NGF treatment were analyzed using high throughput sequencing technology for the first time. We identified 564 annotated and 1077 novel lncRNAs in PC12 cells. Among them, 121 lncRNAs were differentially expressed in the PC12 cells under LPC stimulation. KEGG analysis showed that differentially expressed mRNAs co-expressed with lncRNAs mainly enriched in ribosome, oxidative phosphorylation, Parkinson’s disease, Huntington’s disease and Alzheimer’s disease etc. LncRNA-mRNA network analysis showed that lncRNA ENSRNOT00000082515 had interactions with 626 different mRNAs suggesting that lncRNA ENSRNOT00000082515 probably play vital role. Finally, sequencing data were validated by qRT-PCR for ENSRNOT00000084874, ENSRNOT00000082515, LNC_001033 forward Fgf18, Vcam1, and Pck2.

Abstract This article has conducted a comprehensive study on the stator and rotor vibration characteristics of the doubly‐fed induction generator (DFIG) in the case of radial air gap eccentricity (RAGE). Differently from other previous studies, this paper not only investigates the vibration characteristics of stator and rotor in radial static air gap eccentricity (RSAGE) and radial dynamic air‐gap eccentricity (RDAGE) fault but also takes the radial hybrid air gap eccentricity (RHAGE) into account. Through theoretical derivation, the detailed expressions of stator magnetic pull per unit area (MPPUA) and rotor unbalanced magnetic pull (UMP) are obtained. The finite element analysis (FEA) and experiment based on a two pairs of poles DFIG, and the results are consistent with theoretical calculations. It is shown that RAGE will enlarge the magnitude of stator MPPUA/vibration and rotor UMP/vibration. Specifically, RSAGE will not change the frequency components of stator MPPUA/vibration but will bring new frequency components to rotor UMP/vibration. However, both stator MPPUA/vibration and rotor UMP/vibration will generate new frequency components during RDAGE fault. In addition, the effect of RHAGE is the superposition of RSAGE and RDAGE. The research conclusions obtained in this paper can be used as a supplementary criterion for diagnosing the eccentricity of DFIG.

Martensitic transformations are structural phase transition that usually bring about stimuli-responsive phenomena. Here authors present a 1D hybrid perovskite ferroelastic martensite that shows thermoelastic actuation behaviour with a significant photoelectric response around room temperature.

Abstract Background The combination of oncolytic viruses (OVs) with immune checkpoint blockades is a research hotspot and has shown good efficacy. Here, we present the first attempt to combine oncolytic herpes simplex virus 2 (OH2) with an anti-SIRPα antibody as an antitumour treatment. Our results provide unique insight into the combination of innate immunity with OV. Methods We verified the polarization and activation of OH2 in RAW264.7 cells in vitro. Subsequently, we evaluated the antitumour ability of OH2 and anti-SIRPα combined therapy in a tumour-bearing mouse model. RNA-seq and Single-cell RNA-seq were used to characterize the changes in the tumour microenvironment. Results The OH2 lysates effectively stimulated RAW264.7 cells to polarize towards the M1 but not the M2 phenotype and activated the function of the M1 phenotype in vitro. In the macrophage clearance experiment, OH2 therapy induced polarization of M1 macrophages and participated in the antitumour immune response in a tumour-bearing mouse model. Treatment with a combination of OH2 and anti-SIRPα effectively inhibited tumour growth and significantly prolonged the survival time of the mice, and this result was more obvious in the mouse model with a larger tumour volume at the beginning of the treatment. These results suggest that combination therapy can more profoundly reshape the TME and activate stronger innate and adaptive immune responses. Conclusions Our data support the feasibility of oncolytic virus therapy in combination with anti-SIRPα antibodies and suggest a new strategy for oncolytic virus therapy.

Abstract Background Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS). Methods CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE. Results Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR

Abstract Background Patients with obstructive sleep apnoea (OSA), male sex, obesity, older age or hypertension are prone to hypoxemia during flexible bronchoscopy. This study investigated whether using a high-flow nasal cannula (HFNC) could reduce the incidence of oxygen desaturation during bronchoscopy under deep sedation in patients at risk of hypoxemia. Methods A total of 176 patients at risk of hypoxemia who underwent flexible bronchoscopy under deep sedation were randomly assigned to two groups: the HFNC group (humidified oxygen was supplied via a high-flow nasal cannula at a rate of 60 L/min and a concentration of 100%, n = 87) and the facemask group (oxygen was supplied via a tight-fitting facemask at a rate of 6 L/min and a concentration of 100%, n = 89). Results Oxygen desaturation occurred in 4 (4.6%) patients in the HFNC group and 26 (29.2%) patients in the facemask group (P

Abstract Background An over-expression of the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer and is associated with aggressive disease and poor prognosis. SCT200 is a newly developed recombinant, fully humanized, anti-EGFR monoclonal antibody. This study aimed to evaluate its safety, tolerability, pharmacokinetics (PK), and efficacy in patients with wild-type KRAS/NRAS/BRAF metastatic colorectal cancer (mCRC). Methods This phase I study comprising dose-escalation phase and dose-expansion phase. SCT200 was administrated intravenously to groups of three to six patients. An every 3-week dosing cycle (0.5–15.0 mg/kg) and multiple dosing schedule were evaluated. Blood samples were collected at preset intervals for PK assessment, radiological imaging was used for efficacy assessment, and continuous safety monitoring was performed in each group during the study. Results From December 16, 2014 to December 31, 2018, fifty-six patients with wild-type K RAS/NRAS/BRAF mCRC receiving ≥ 1 dose of SCT200 were evaluated. Among them, 44.6% (25/56) of the patients failed at least two prior lines of chemotherapy. No dose-limiting toxicities occurred in any group. All of the patients experienced treatment-emergent adverse events (TEAEs). 96.4% (54/56) of patients experienced treatment-related adverse events (TRAEs), and 26.8% (15/56) of patients with Grade ≥ 3 TRAEs. No serious TRAEs were observed. The most common TRAEs were dermotoxicity and hypomagnesemia. PK analysis showed non-linear PK in the range of 0.5 - 8.0 mg/kg of single dose SCT200, the clearance decreased, and the elimination half-life (T1/2) prolonged following dose increase. In the multiple-dose period, the clearance decreased, peak concentration increased, and T1/2 prolonged during prolonged drug administration, and a steady state was reached after five consecutive dose of 6.0 mg/kg quaque week (QW). The objective response rate (ORR) was 30.4% (17/56, 95% confidence interval [CI], 18.8%–44.1%). The ORR in the dose-expansion group (6.0 mg/kg QW) was 48.0% (12/25, 95% CI, 27.8%–68.7%), the median progression-free survival was 5.2 months (95%CI, 3.6–5.5), and the median overall survival was 20.2 months (95%CI, 12.1-not reached). Conclusions SCT200 showed favorable safety, PK profile, and preliminary efficacy for patients with wild-type KRAS/NRAS/BRAF mCRC. Trial registration This study was registered with ClinicalTrials.gov ( NCT02211443 ).

Abstract. Background:. The association between sex hormone-binding globulin (SHBG) and renal function has rarely been reported in men. We aimed to investigate the above association in a community-based Chinese population. Methods:. A total of 5027 men were included from the survey on prevalence for metabolic diseases and risk factors, which is a population-based study conducted from 2014 to 2016 in Eastern China. The estimated glomerular filtration rate (eGFR) was calculated according to the chronic kidney disease Epidemiology Collaboration equation. Low eGFR was defined as eGFR

In the study, pumpkin peel polysaccharide was extracted by hot water extraction, and a novel pumpkin peel polysaccharide chromium (III) [PPP-Cr(III)] complex was synthesized combined with trivalent chromium ions. Using the chelation rate as the evaluation index, the effects of the mass fraction between chromium and polysaccharide, reaction pH, reaction temperature and reaction time on the synthesis of PPP-Cr(III) complex were studied, the extraction conditions of PPP-Cr(III) complex was optimized by the response surface methodology, and the bioaccessibility of trivalent chromium ions in the PPP-Cr(III) complex was determined by in vitro simulated gastrointestinal digestion. The response surface analysis results showed that the optimum preparation conditions were as follows: The mass fraction between chromium and polysaccharide was 0.08:1, the reaction temperature was 60 ℃ and the reaction pH was 6.8, respectively, with the experimental chelation rate was 99.23%±0.12%. In addition, in vitro simulated gastrointestinal digestion studies showed that the solubility of PPP-Cr(III) complex in synthetic stomach conditions were stable and the dialysis rate of PPP-Cr(III) complex were higher than those of chromium chloride. Therefore, PPP-Cr(III) complex was a new potential type of chelate due to its high bioaccessibility of trivalent chromium ions.

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

Glioblastoma (GBM) therapy is severely impaired by the blood–brain barrier (BBB) and invasive tumor growth in the central nervous system. To improve GBM therapy, we herein presented a dual-targeting nanotheranostic for second near-infrared (NIR-II) fluorescence imaging-guided photo-immunotherapy. Firstly, a NIR-Ⅱ fluorophore MRP bearing donor-acceptor-donor (D-A-D) backbone was synthesized. Then, the prodrug nanotheranostics were prepared by self-assembling MRP with a prodrug of JQ1 (JPC) and T7 ligand-modified PEG5k-DSPE. T7 can cross the BBB for tumor-targeted delivery of JPC and MRP. JQ1 could be restored from JPC at the tumor site for suppressing interferon gamma-inducible programmed death ligand 1 expression in the tumor cells. MRP could generate NIR-II fluorescence to navigate 808 nm laser, induce a photothermal effect to trigger in-situ antigen release at the tumor site, and ultimately elicit antitumor immunogenicity. Photo-immunotherapy with JPC and MRP dual-loaded nanoparticles remarkably inhibited GBM tumor growth in vivo. The dual-targeting nanotheranostic might represent a novel nanoplatform for precise photo-immunotherapy of GBM.

Building construction are attaching greater importance to decrease carbon emissions in order to mitigate greenhouse effects. Precast pile foundation and cast-in-situ pile foundation are main types of foundations. This paper calculates carbon emissions from prestressed pipe pile foundation and cast-in-situ pile foundation under the same bearing capacity, as well as the carbon emissions from different rectifications to battered piles. Prestressed concrete pipe pile foundation demonstrates comparatively less carbon emissions than cast-in-situ pile foundation. The latter releases 1.4 times more carbon than the former. In the rectifications of battered piles, prestressed concrete pipe pile foundation has significantly lowered carbon emissions, to as much as one third of other solutions. This paper also reveals that measures to reduce carbon emissions involve two raw materials, concrete and steel. Carbon emissions should be listed as the fourth parameter in the design of foundation on the basis of bearing capacity, settlement and economical cost. Green, low-carbon, regenerable raw materials are to be explored and selected for building industry.

Peptide drugs play an important role in diabetes mellitus treatment. Oral administration of peptide drugs is a promising strategy for diabetes mellitus because of its convenience and high patient compliance compared to parenteral administration routes. However, there are a series of formidable unfavorable conditions present in the gastrointestinal (GI) tract after oral administration, which result in the low oral bioavailability of these peptide drugs. To overcome these challenges, various nanoparticles (NPs) have been developed to improve the oral absorption of peptide drugs due to their unique in vivo properties and high design flexibility. This review discusses the unfavorable conditions present in the GI tract and provides the corresponding strategies to overcome these challenges. The review provides a comprehensive overview on the NPs that have been constructed for oral peptide drug delivery in diabetes mellitus treatment. Finally, we will discuss the rational application and give some suggestions that can be utilized for the development of oral peptide drug NPs. Our aim is to provide a systemic and comprehensive review of oral peptide drug NPs that can overcome the challenges in GI tract for efficient treatment of diabetes mellitus.

Abstract Objective To figure out the functions of thymic stromal lymphopoietin (TSLP) in IgG4-related disease (IgG4-RD). Methods Plasma TSLP levels were tested by Elisa, and its receptors were detected by flow cytometry. Expressions of TSLP and TSLPR in involved tissues were stained by immunohistochemistry and immunofluorescence. Proliferation, apoptosis, and B subsets of TSLP stimulated-B cells were analyzed by flow cytometry. TSLP-stimulated B cells were co-cultured with CD4+ Naïve T cells. Signaling pathway was identified by RNA-sequencing and western blot. Anti-TSLP therapy was adapted in LatY136F knock-in mice (Lat, IgG4-RD mouse model). Results Plasma TSLP level was increased in IgG4-RD patients and was positively correlated with serum IgG4 level and responder index (RI). TSLPR was co-localized with CD19+ B cells in the submandibular glands (SMGs) of IgG4-RD. TSLP promoted B cell proliferation, and TSLP-activated B cells polarized CD4+ naive T cells into follicular helper T (Tfh) cells through OX40L. RNA-sequencing identified JAK-STAT signaling pathway in TSLP-activated B cells and it was verified by western blot. Anti-TSLP therapy alleviated the inflammation of lung in Lat mice. Conclusion Elevated TSLP in IgG4-RD promoted B cells proliferation and polarized Tfh cells and might be served as a potential therapeutic target.

Abstract Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes that reduce COVID-19 host susceptibility is a critical next step. Using a translational genomics approach that integrates COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX), and perturbagen signatures, we identified IL10RB as the top candidate gene target for COVID-19 host susceptibility. In a series of validation steps, we show that predicted GReX upregulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes and that in vitro IL10RB overexpression is associated with increased viral load and activation of disease-relevant molecular pathways.

The occurrence of recrystallization will cause catastrophic damage to the structure of metallic single crystal, which can be avoided by choosing crystal orientation reasonably. In this work, the effect of crystal orientation on the recrystallization behavior of single crystal is investigated using multi-scale characterization method. The electron backscattered diffraction analysis shows that in mesoscopic scale, the recrystallization behavior of Mo–3Nb single crystal exhibits a strong orientation dependence, which the new recrystallization grains are produced in the -oriented single crystal, while the single crystal structure is still retained in other orientations. At the micro scale, the elongated dislocation cells with certain misorientations appear in the -oriented single crystal, while only the dislocation walls and parallel dislocation cells distribute on the single crystal with the and orientations, respectively. The length of dislocation lines in deformed single crystal with orientation is calculated using molecular dynamics to be 3491.22 Å, which is much longer than that of the orientation (1133.27 Å) and the orientation (2862.68 Å), suggesting a higher crystal distortion and easier recrystallization in the orientation. In addition to the coalescence mechanism of discontinuous sub-grains, the shear band also plays an important role in promoting recrystallization nucleation. This work provides reference value for the secondary processing of molybdenum single crystal, so as to obtain more excellent products and expand its potential application.

The continuous hot rolling process induces anisotropy in the plastic yield and flow and results in an anisotropic ductile fracture. In this study, experiments, including uniaxial in-plane tension tests and shear tests of butterfly specimens along different material orientations, were performed, and microscopic observations were used to determine the differences in damage mechanisms. The Yld91 anisotropic yield stress was introduced into the extended isotropic Gurson-Tvergaard-Needleman (GTN) model, and the associated flow rule (AFR) and non-associated flow rule (NAFR) were adopted to formulate two anisotropic GTN models. Anisotropic GTN models were implemented in finite element software via user subroutines, and were used to predict the fracture initiation of Al2024-T351. For different plastic flow rules, the anisotropic parameters were calibrated using the anisotropic stress and Lankford coefficients. An inverse analysis with a two-stage optimization algorithm was adopted to calibrate the damage-related parameters. Moreover, an extended isotropic GTN model was adopted for comparison. The prediction accuracy of the proposed anisotropic GTN models was evaluated by analyzing the load responses and displacements at fracture for various specimens and material orientations. The good conformation between the experimental results and numerical predictions verifies the predictive ability of the proposed models to a certain degree. In addition, some suggestions and conclusions are provided for the formulation of an advanced anisotropic GTN model with enhanced accuracy.

Accurate prediction of cancer drug response (CDR) is a longstanding challenge in modern oncology that underpins personalized treatment. Current computational methods implement CDR prediction by modeling responses between entire drugs and cell lines, without the consideration that response outcomes may primarily attribute to a few finer-level 'subcomponents', such as privileged substructures of the drug or gene signatures of the cancer cell, thus producing predictions that are hard to explain. Herein, we present SubCDR, a subcomponent-guided deep learning method for interpretable CDR prediction, to recognize the most relevant subcomponents driving response outcomes. Technically, SubCDR is built upon a line of deep neural networks that enables a set of functional subcomponents to be extracted from each drug and cell line profile, and breaks the CDR prediction down to identifying pairwise interactions between subcomponents. Such a subcomponent interaction form can offer a traceable path to explicitly indicate which subcomponents contribute more to the response outcome. We verify the superiority of SubCDR over state-of-the-art CDR prediction methods through extensive computational experiments on the GDSC dataset. Crucially, we found many predicted cases that demonstrate the strength of SubCDR in finding the key subcomponents driving responses and exploiting these subcomponents to discover new therapeutic drugs. These results suggest that SubCDR will be highly useful for biomedical researchers, particularly in anti-cancer drug design.

ABSTRACT Clostridium perfringens is a bacterial species of importance to both public and animal health. The gene optrA is the first gene that confers resistance to the tedizolid, a last-resort antimicrobial agent in human medicine. Herein, we whole-genome sequenced and analyzed one optrA-positive C. perfringens strain QHY-2 from Tibetan sheep in Qinghai province and identified one optrA plasmid pQHY-2. The plasmid shared similar structure with the optrA-positive plasmids p2C45 and p21-D-5b previously identified in C. perfringens, demonstrating the potential horizontal transmission of the optrA plasmids among C. perfringens strains. Annotation of the optrA-positive plasmids showed optrA and erm(A) located on a segment flanked by IS element IS1216E, and fexA, optrA, and erm(A) located on a segment flanked by IS element ISVlu1, which revealed the possible dissemination mechanism. Additionally, a Tn6218-like transposon carrying aac(6′)-aph(2″) and erm(B) was also detected on pQHY-2, demonstrating the transposition of Tn6218 and spread of antibiotic resistance among Clostridium bacteria. Molecular analysis indicated the optrA-positive plasmids belonged to a plasmid type distinct from the pCW3-like plasmids, pCP13-like plasmids, or pIP404-like plasmids. Further structure analysis showed they might be formed by inserting segments into plasmid pCPCPI53k-r1_1, which coexist with two pCW3-like plasmids and one pCP13-like plasmid in C. perfringens strain CPI 53k-r1 isolated from a healthy human in Finland. IMPORTANCE Antimicrobial resistance is now a global concern posing threats to food safety and public health. The pCW3-like plasmids can encode several main toxin genes and three antibiotic resistance genes (ARGs), including tetA(P), tetB(P), and erm(B), which used to be considered as the main carrier of ARGs in Clostridium perfringens. In this study, we found the optrA plasmids, which belonged to a novel plasmid type, could also harbor many other ARGs, indicating this type of plasmid might be the potential repository of ARGs in C. perfringens. Additionally, this type of plasmid could coexist with the pCW3-like plasmids and pCP13-like plasmids that encoded toxin genes associated with gastrointestinal diseases, which showed the potential threat to public health.

Objective: The problems and challenges encountered by Chinese medical institutions in implementing the national centralized drug procurement was investigated and analyzed in order to provide reference for the regulatory agencies to formulate policies.Methods: A questionnaire survey was conducted to collect the problems encountered by 329 Chinese medical institutions in implementing the national centralized drug procurement and the corresponding suggestions provided by relevant experts. Statistical analysis was performed to identify differences in the themes and the number of collected problems, further revealing the relevance to the region in which the medical institutions is located.Result: 1360 problems and suggestions were collected from 329 Chinese medical institutions that located in North (19.15%), Northeast (5.78%), East (33.43%), Central (10.03%), South (9.73%), Southwest (14.89%), and Northwest China (6.99%). There was statistically significant difference in the number of collected problems and suggestions between regions (p < 0.001). Furthermore, the content of gathered problems and suggestions involves in 15 themes including system construction, organizational system and work responsibilities, reasonable measurement and reporting of procurement volume et al. These themes that these medical institutions are focusing on are mainly centered on the supply guarantee (15%), reasonable measurement and reporting of procurement volume (11.40%) and guarantee measures for clinical priority use (9.48%) of drugs with national centralized procurement. Meanwhile, we found that problems regarding the supply guarantee of drugs with national centralized procurement displayed significant difference between regions (p = 0.0096).Conclusion: Chinese medical institutions are facing great challenges in implementing the national centralized drug procurement. The scientific study and judgment of the current situation and the construction of corresponding solution require a precise classification of the problems encountered by medical institutions in the process of implementing the national centralized drug procurement policy, which is of great practical significance for deepening the reform of the medical and health system.

Background.Normothermic machine perfusion (NMP) could provide protection to organs from donation after circulatory death (DCD) before transplantation, and its molecular mechanism remains unclear. Our previous study discovered that the air-ventilated NMP confers a better DCD liver recovery than oxygen-ventilated NMP. The purpose in the current study was to investigate the protective mechanism of air-ventilated NMP in a rat model of DCD liver by metabolomics, and to select biomarker to predict liver function recovery.Materials and Methods.Peroxisome proliferator activator receptor-α (PPARα) agonist or antagonist was administered via the perfusion circuit in the air-ventilated NMP. Perfusate samples were taken for measurements of aminotransferases using standard biochemical methods, tumor necrosis factor-alpha and interleukin-6. Liver biopsies were allocated for detection of metabolomics, PPARα and cytochrome P450 1A2 (CYP1A2).Results.Metabolomics analysis revealed the significant increased γ-linolenic acid and decreased adrenic acid during the air-ventilated NMP, indicating linoleic acid metabolism pathway was associated with a better DCD liver recovery; as a major enzyme involved in linolenic acid metabolism, CYP1A2 was found correlated with a less inflammation and better liver function with the air-ventilated NMP; PPARα agonist could increase CYP1A2 expression and activity, decrease inflammation response, and improve liver function with the air-ventilated NMP, while PPARα antagonist played the opposite.Conclusion.Air-ventilated NMP confers a better liver recovery from DCD rats through the activated linoleic acid metabolism and CYP1A2 upregulation; CYP1A2 expression and activity might function as biomarker to predict DCD liver function recovery with NMP.

BackgroundSexually transmitted infections (STIs) remain a significant public health concern, particularly among young adults, and Chlamydia trachomatis (CT) infections are the most common STIs in young women. One of the most effective ways to prevent STIs is the consistent use of condoms during sexual intercourse. There has been no economic evaluation of the interactive web-based sexual health program, Smart Girlfriend, within the Chinese population. ObjectiveThis study aimed to evaluate the long-term cost-effectiveness of Smart Girlfriend in preventing STIs in the Chinese population. The evaluation compared the program with a control intervention that used a 1-page information sheet on condom use. MethodsA decision-analytic model that included a decision tree followed by a Markov structure of CT infections was developed since CT is the most prevalent STI among young women. The model represents the long-term experience of individuals who received either the intervention or the control. One-way and probabilistic sensitivity analyses were conducted. The main outcomes were the number of CT infections and the incremental cost as per quality-adjusted life year (QALY). ResultsA cohort of 10,000 sexually active nonpregnant young women initially entered the model in a noninfectious state (ie, “well”). In the base-case analysis, the implementation of the Smart Girlfriend program resulted in the prevention of 0.45% of CT infections, 0.3% of pelvic inflammatory disease, and 0.04% of chronic pelvic pain, leading to a gain of 70 discounted QALYs and cost savings over a 4-year time horizon, compared to the control group. With more than 4548 users, the intervention would be cost-effective, and with more than 8315 users, the intervention would be cost saving. A 99% probability of being cost-effective was detected with a willingness to pay US $17,409 per QALY. ConclusionsSmart Girlfriend is a cost-effective and possibly cost-saving program over a 4-year time horizon. This result was particularly sensitive to the number of website users; launching the website would be cost-effective if more than 4548 people used it. Further work is warranted to explore if the findings could be expanded to apply to women who have sex with women and in the context of other STIs. Trial RegistrationClinicalTrial.gov NCT03695679; https://clinicaltrials.gov/study/NCT03695679

Research objectiveTo propose a technique for placing pedicle screws in the thoracic spine using the Supraspinous ligament Arc Tangent (SLAT) as a guide to increase the safety and stability of screw placement.Content and methodsA retrospective analysis of postoperative anteroposterior and lateral x-ray images was performed for 118 patients with thoracic spine diseases who received conventional freehand technique from January 2016 to May 2020 and SLAT-guided technique since June 2020 to present. The diagnoses included thoracic spinal stenosis, deformity, fractures, infections, and tumors. The angle between the screw and the upper endplate was categorized as grade 1 (0°–5°), grade 2 (5°–10°), and grade 3 (>10°). Three surgeons with more than 10 years of experience in spinal surgery measured the angle between the screw and the upper endplate in the lateral view. Chi-square test was used for statistical analysis, and p

Background:. N6-methyladenosine (m6A), the most prevalent internal RNA modification in eukaryotic cells, is dynamically regulated in response to a wide range of physiological and pathological states. Nonetheless, the involvement of METTL14-induced m6A in liver fibrosis (LF) has yet to be established. Methods:. In vitro, HSC cell lines with knock-down and overexpression of METTL14 were constructed, and the effects of METTL14 gene on the phenotypic function of activated HSCs were observed. The proliferation rate was measured by CCK8 and EDU, the cell proliferation cycle was measured by flow detector, the migration rate was measured by Transwell, and the contractility of F-actin was observed after phalloidin staining. The downstream target gene NOVA2 of METTL14 was screened by combined sequencing of MeRIP-seq and RNA-seq, combined with signal analysis. Adeno-associated virus (AAV) was injected into the tail vein in vivo to knock down the expression of METTL14, so as to further observe the role of METTL14 in the progress of LF. Results:. our research showed that the methylase METTL14 content was decreased in hepatic tissue from patients with LF, leading to a lowered degree of m6A modification. Functionally, we discovered that knocking down m6A methyltransferase METTL14 led to increased HSC activation and a substantial worsening of LF. Mechanically, as shown in a multiomics study of HSCs, depleting METTL14 levels decreased m6A deposition onNOVA2 mRNA transcripts, which prompted the activation of YTHDF2 to detect and degrade the decrease of NOVA2 mRNA Conclusions:. METTL14 functioned as a profibrotic gene by suppressing NOVA2 activity in a mechanism dependent on m6A-YTHDF2. Moreover, knocking down METTL14 exacerbated LF, while NOVA2 prevented its development and partly reversed the damage.

Summary: Certain types of face masks are highly efficient in protecting humans from bacterial and viral pathogens, and growing concerns with high safety, low cost, and wide market suitability have accelerated the replacement of reusable face masks with disposable ones during the last decades. However, wearing these masks creates countless problems associated with personnel comfort as well as more significant issues related to the cost of fabrication, the generation of medical waste, and environmental contaminants. In this work, we present a facile spray-pressing technique for the production of P-masks with a potential scale-up prospect by adding a graphene layer on one side of meltblown fabric and a functional layer on the other side. In principle, this technique could be easily integrated into the present automatic mask production process and the masks have self-cleaning and/or self-sterilizing properties when it is exposed to solar or simulated solar irradiation.

Background: This study aims to evaluate the efficacy and safety of Danggui Niantong Decoction (DGNT) systematically on gout treating.Methods: This study was registered in PROSPERO, and the registration number was CRD42021271607. By the end of December, 2022, literature research was conducted among eight electronic databases. Main results of this study were blood uric acid (BUA) and Creactive protein (CRP). Secondary outcomes were erythrocyte sedimentation rate (ESR), serum creatinine (Scr), urinary protein quantified at 24 h (Upro), and interleukin-8 (IL-8). Study screening, data collection, as well as quality assessment were performed by two reviewers independently, and analysis was completed using Stata (SE15.0) and Review Manager (5.4).Results: A total number of 13 studies were included in our meta-analysis (n = 1,094 participants). Results showed DGNT combined with conventional western medicine (CWM) was more effective than WM alone in BUA (weighted mean differences (WMD) = −3.49, 95% confidence interval (CI) [−50.36, −32.59], p = 0.000), CRP (WMD = −41.48, 95% CI [−4.32, −2.66], p = 0.017), ESR (WMD = −6.23, 95% CI [−9.28, −3.17], p = 0.019), Scr (WMD = −18.64, 95% CI [−23.09, −14.19], p = 0.001), Upro (WMD = −0.72, 95% CI [−0.91, −0.53], p = 0.000), and IL-8 (WMD = −4.77, 95% CI [−11.48, 1.94], p = 0.000). None of the adverse effects noted were severe, and no life-threatening event was reported.Conclusion: This study shows that DGNT combined with CWM seems to have an effective clinical therapeutic potential. In addition, it also provides a scientific basis for better clinical application of DGNT in the future.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021271607; Identifier: PROSPERO, CRD42021271607.