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The synthesis of stable polynitrogen compounds with high-energy density has long been a major challenge. The cyclo-pentazolate anion (cyclo-N5 -) is successfully converted into aromatic and structurally symmetric bipentazole (N10) via electrochemical synthesis using highly conductive multi-walled carbon nanotubes (MWCNTs) as the substrate and sodium pentazolate hydrate ([Na(H2O)(N5)]·2H2O) as the raw material. Attenuated total refraction Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and density functional theory calculations confirmed the structure and homogeneous distribution of N10 in the sidewalls of the MWCNTs (named MWCNT-N10-n m). The MWCNT-N10-2.0 m is further used as a catalyst for electrochemical oxygen reduction to synthesize hydrogen peroxide from oxygen with a two-electron selectivity of up to 95%.
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RATIONALE: At present, there is still insufficient understanding of the progression from persistent allergic reactions to severe reactions. Adrenaline remains the preferred medication for severe allergic reactions, and intramuscular injection of adrenaline can also be considered for patients with grade I reactions that are difficult to alleviate gastrointestinal symptoms. It is worth further discussing whether it is possible to break the conventional intramuscular injection recommended by the guidelines when the effect of intramuscular injection is not ideal for persistent grade I severe allergic reactions. PATIENT CONCERNS: A young male, 20 years of age, was admitted to emergency department because of repeated rash for 3 days and abdominal pain for 6 hours after taking traditional Chinese medicine. After hormone therapy, the rash continued to recur and secondary gastrointestinal symptoms occurred on the 3th day. Adrenaline intramuscular injection was given to temporarily relieve the rash and abdominal pain, but symptoms still persisted. DIAGNOSIS: The patient was diagnosed with persistent severe allergic reaction (grade I). INTERVENTIONS: Continuous intravenous infusion of low-dose adrenaline under electrocardiographic monitoring, real-time monitoring of heart rate and blood pressure, and routine treatment with methylprednisolone, diphenhydramine, calcium gluconate, and cetirizine. During this period, adrenaline intramuscular injection is temporarily added when abdominal pain symptoms are obvious. The entire treatment process used a total of 6.8 mg of adrenaline. OUTCOMES: During the entire period of adrenaline intervention, the patient did not experience any new discomfort, and there were no abnormal fluctuations in heart rate, rhythm, or blood pressure. The symptoms of rash and abdominal pain gradually improved. LESSONS: For patients with persistent grade I severe allergic reactions, intravenous administration of low-dose adrenaline under close vital sign monitoring is safe, feasible, and highly effective in preventing biphasic, persistent, or worsening allergic reactions.
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Epinephrine , Humans , Male , Epinephrine/administration & dosage , Young Adult , Injections, Intramuscular , Infusions, Intravenous , Abdominal Pain/drug therapy , Abdominal Pain/etiology , Drug Hypersensitivity/etiology , Drug Hypersensitivity/drug therapy , Drug Hypersensitivity/diagnosis , Severity of Illness IndexABSTRACT
RATIONALE: Splenic abscess is relatively rare in clinical practice as an invasive disease. However, during the continuous prevalence of coronavirus disease 2019 (COVID-19), the incidence rate of splenic abscess showed an upward trend. However, because the etiology of splenic abscess is not specific, it is easy to be covered by the respiratory symptoms of COVID-19, resulting in omission or delay in diagnosis. If splenic abscesses cannot be treated in a timely manner, the mortality rate can reach 100%. Therefore, it is important to fully understand the correlation between COVID-19 and the development of splenic abscesses. PATIENT CONCERNS: A female patient, 71 years of age, was admitted to our hospital because of cough and sputum for 1 week and fever for 2 days. According to the positive results of novel coronavirus nucleic acid and chest computed tomography, novel coronavirus pneumonia was diagnosed. On the 4th day after treatment, abdominal distension and vomiting were observed. Abdominal ultrasound indicated splenomegaly and mixed echo masses in the spleen and abdominal computed tomography indicated 2 new round low-density lesions were found in the spleen. DIAGNOSES: The patient was diagnosed with secondary splenic abscess after COVID-19 infection. INTERVENTIONS: The patient and her family members refused to undergo ultrasound-guided splenic puncture drainage and splenectomy. In terms of treatment, she was given meropenem combined with vancomycin to continue anti-infection treatment. OUTCOMES: The patient's body temperature and infection indicators gradually increased, and the scope of splenic abscess continued to expand. The infection worsened and progressed to septic shock. The patient abandoned rescue drugs and invasive treatment, and died on the 9th day after admission. LESSONS: This case introduces the clinical characteristics of secondary splenic abscess caused by COVID-19 from the aspects of etiology, disease course, clinical manifestations, auxiliary examinations, and treatment methods. The focus is on improving the understanding of clinical doctors about secondary splenic abscesses caused by COVID-19, providing reference for early diagnosis and timely treatment.
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COVID-19 , SARS-CoV-2 , Splenic Diseases , Humans , COVID-19/complications , COVID-19/diagnosis , Female , Splenic Diseases/etiology , Aged , Abscess/etiology , Meropenem/therapeutic use , Tomography, X-Ray ComputedABSTRACT
Decreased collagen synthesis by fibroblasts is a key aspect of skin aging. Poly-L-Lactic Acid (PLLA) is a bioabsorbable material that can release lactate continuously, stimulating endogenous collagen synthesis in the skin. Herein, this study aimed to investigate the impact of PLLA-released lactate on collagen production in fibroblasts for skin rejuvenation. Human fibroblasts were exposed to varying concentrations of PLLA in vitro, while PLLA was injected into the back skin of aged mice in vivo. Safety and efficacy of PLLA on collagen synthesis and skin rejuvenation were evaluated through Calcein-AM/PI staining, EdU proliferation assay, and analysis of collagen I and collagen III expression in fibroblasts using western blotting and immunofluorescence. To elucidate the underlying mechanisms, lactate contents in cell-free supernatant and cell lysates from PLLA-treated fibroblasts, as well as total lysine lactylation (Pan Kla) levels were measured. Additionally, we found that fibroblasts can uptake extracellular lactate released from PLLA through monocarboxylate transporter-1 (MCT1) to facilitate latent-transforming growth factor beta-binding protein 1 (LTBP1) lactylation at lysine 752 (K752) via a KAT8-dependent mechanism, then increases the protein levels of collagen I and collagen III in fibroblasts. Overall, this study highlights a valuable insight into lactylation modification of non-histone protein for skin rejuvenation.
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OBJECTIVE: The Surgical Apgar Score quantifies three intraoperative parameters: lowest heart rate, lowest mean arterial pressure, and estimated blood loss (EBL). This scoring system predicts postoperative complications based on these measured factors. The aim of this study was to investigate the value of modified Surgical Apgar Score (mSAS) in predicting postoperative complications in patients with rectal cancer treated with robotic surgery in order to improve the survival and quality of life of rectal cancer patients. METHODS: The study included patients with rectal cancer who underwent robotic surgery in the Department of Gastrointestinal Surgery at the First Affiliated Hospital of Nanchang University from January 2015 to December 2023. In minimally invasive surgery, we developed a modified Surgical Apgar Score (mSAS) tailored for robotic rectal cancer surgery, incorporating an adjusted threshold for EBL. This threshold was derived from quartile analysis of a cohort of 524 patients, with a median EBL of 100 mL (IQR 80-130 mL). We analyzed the association of postoperative complications with low mSAS. RESULTS: This study included 524 patients, of which 91 (17.4%) experienced complications and 22 (4.2%) suffered severe complications. mSAS of 6 provided maximal Youden index and were determined as the cut-off values. The area under the ROC curve for predicting complications using the mSAS was 0.740. Univariate and multivariate analyses indicated that an older age, lower tumor localization, longer operation time, radiotherapy alone, combined chemoradiotherapy, and lower mSAS as independent risk factors for complications. The AUC of the prediction nomogram was 0.834 (95% CI 0.774-0.867). The calibration curve demonstrated excellent concordance with the nomogram, indicating the prediction curve ft the diagonal well. CONCLUSION: This study suggests that mSAS might be a valuable predictive indicator for postoperative complications following robotic rectal cancer surgery, with potentially higher clinical utility.
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An unprecedented Pd-catalyzed CO-free double carbonylation using Mo(CO)6 as a safe carbonyl source for the efficient synthesis of 1,4-ketoesters in an atom- and step-economic manner has been developed. The current method features operational safety, a wide substrate range, good functional group compatibility and easy scale-up. The application of carbonylation using a safe carbonyl source for the synthesis of biologically and synthetically useful carbonyl-containing molecules is underway in our lab.
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Avermectin is a highly effective insecticide that has been widely used in agriculture since the 1990s. In recent years, the safety of avermectin for non-target organisms has received much attention. The vasculature is important organs in the body and participate in the composition of other organs. However, studies on the vascular safety of avermectin are lacking. The vasculature of zebrafish larvae is characterized by ease of observation and it is a commonly used model for vascular studies. Therefore, zebrafish larvae were used to explore the potential risk of avermectin on the vasculature. The results showed that avermectin induced vascular damage throughout the body of zebrafish larvae, including the head, eyes, intestine, somite, tail and other vasculature. The main forms of damage are reduction in vascular diameter, vascular area and vascular abundance. Meanwhile, avermectin induced a decrease in the number of endothelial cells and apoptosis within the vasculature. In addition, vascular damage may be related to impairment of mitochondrial function and mitochondria-mediated apoptosis. Finally, exploration of the molecular mechanisms revealed abnormal alterations in the expression of genes related to the VEGF/Notch signaling pathway. Therefore, the VEGF/Notch signaling pathway may be an important mechanism for avermectin-induced vascular damage in zebrafish larvae. This study demonstrates the vascular toxicity of avermectin in zebrafish larvae and reveals the possible molecular mechanism, which would hopefully draw more attention to the safety of avermectin in non-target organisms.
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Apoptosis , Ivermectin , Larva , Mitochondria , Receptors, Notch , Signal Transduction , Vascular Endothelial Growth Factor A , Zebrafish , Animals , Ivermectin/analogs & derivatives , Ivermectin/toxicity , Apoptosis/drug effects , Signal Transduction/drug effects , Larva/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Receptors, Notch/metabolism , Insecticides/toxicity , Blood Vessels/drug effectsABSTRACT
BACKGROUND: Malva sylvestris L. (commonly known as mallow) has been widely used in traditional Tibetan formulations to treat allergic rhinitis (AR), and malvidin is a key anti-inflammation constituent of this plant. OBJECTIVE: The present study aimed to evaluate the potential therapeutic effect and mechanism of malvidin in an AR mouse model. METHODS: Malvidin's efficacy was evaluated in an AR mouse model induced by ovalbumin (OVA) sensitization and challenge. The factors, such as nasal symptoms, serum OVA-specific immunoglobulin E (IgE) levels, histological changes in the nasal mucosa, and expressions of Th1, Th2, Th17, and Tregs and their cytokines, were assessed. Western blotting was used to analyze the effect of malvidin on signal transducer and activator of transcription 6 (STAT6) and GATA3 expression levels. RESULTS: Malvidin reduced the allergic symptoms and serum levels of OVA-specific IgE in the AR model. Histological analysis indicated that malvidin alleviates nasal mucosal edema, eosinophil infiltration, and goblet cell proliferation. In addition, it altered the expression of Th1/Th2/Th17-related cytokines, enhanced the Treg population, and reduced Th2-mediated immunity by suppressing the phosphorylation of STAT6 and expression of the GATA3 protein. CONCLUSIONS: Malvidin significantly improved allergic symptoms in an OVA-induced AR mouse model by modulating Th1/Th2 immune responses and suppressing the STAT6/GATA3 pathway, indicating its potential as a naturally sourced agent for AR management.
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Background: The triglyceride-glucose index (TyG) is a reliable indicator for predicting the prognosis of patients with coronary heart disease (CAD) after percutaneous coronary intervention (PCI). However, its influence on patients with in-stent restenosis (ISR) is unclear. This study was designed to evaluate the association between the TyG index and the occurrence of major adverse cardiovascular events (MACEs) after PCI in patients with ISR. Methods: This retrospective study included 1654 patients who underwent PCI between 2016 and 2022 at Nanjing First Hospital. Patients were stratified into three groups based on the quantile level of the TyG index. The TyG index was determined as Ln (triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Results: Individuals with the highest TyG index showed an increased risk of MACEs compared to those with the lowest level of the TyG index (HR 1.60; 95% CI 1.11-2.30; P = 0.01). When analyzing the TyG index as a continuous variable, each standard deviation increase was associated with an HR of 1.51 (95% CI: 1.11-2.05; P = 0.01). For the male subgroup and the diabetes subgroup, this trend was even more pronounced (HR 1.269; 95% CI 1.055-1.527; P = 0.011; HR 1.385; 95% CI 1.125-1.706; P = 0.002). Additionally, the landmark analysis showed that patients with the highest level of TyG had an increased risk of MACEs 6 months after the PCI (P = 0.019). Conclusion: Elevated TyG index is associated with increased risk of adverse cardiovascular events in patients with ISR, and the extent of increase in the risk is more significant in male patients with diabetes.
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W-band (75-110 GHz) is a potential radio frequency band to provide long-distance wireless links for mobile data transmission. This paper proposes and experimentally demonstrates high-speed wireless transmission at W-band using photonics-aided method, including optical heterodyne, photonics-aided down-conversion without RF oscillator and coherent detection. A comparison between the photonics-aided method and the conventional electronic method employing solid-state electronic devices is conducted for the first time. The photonics-aided method is shown to offer advantages such as lower harmonic components, spur, reduced nonlinearity, and no local oscillator leakage, results in a 2.5 dB better performance of the photonic-aided W-band mm-wave transmitter compared to the electronic one. In the terms of receiver, the photonics-aided method can surpass the electronic method, with the help of larger electro-optical modulator bandwidth and lower drive voltage in the photonic down-conversion stage. Ultimately, using the photonics-aided method, a recorded equivalent transmission distance of 29 km@84 GHz and 45km@75.6GHz is achieved respectively for 1Gbaud QPSK signal.
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Filamentous cell growth is a vital property of fungal pathogens. The mechanisms of filamentation in the emerging multidrug-resistant fungal pathogen Candida auris are poorly understood. Here, we show that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, which forms elongated filamentous cells after a prolonged culture period. Whole-genome sequencing analysis reveals that all RL-FC isolates harbor a mutation in the C2H2 zinc finger transcription factor-encoding gene GFC1 (Gfc1 variants). Deletion of GFC1 leads to an RL-FC phenotype similar to that observed in Gfc1 variants. We further demonstrate that GFC1 mutation causes enhanced fatty acid ß-oxidation metabolism and thereby promotes RL-FC/filamentous growth. This regulation is achieved through a Multiple Carbon source Utilizer (Mcu1)-dependent mechanism. Interestingly, both the evolved RL-FC isolates and the gfc1Δ mutant exhibit an enhanced ability to colonize the skin. Our results reveal that glycerol-mediated GFC1 mutations are beneficial during C. auris skin colonization and infection.
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Candida auris , Candidiasis , Fungal Proteins , Mutation , Candidiasis/microbiology , Fungal Proteins/genetics , Fungal Proteins/metabolism , Candida auris/genetics , Candida auris/metabolism , Mice , Animals , Glycerol/metabolism , Adaptation, Physiological , Transcription Factors/metabolism , Transcription Factors/genetics , Gene Expression Regulation, Fungal , HumansABSTRACT
Introduction: Workplace violence against healthcare workers has become a serious global public health problem. The incidence of workplace violence towards Psychiatric nurses is higher than in all other medical institutions, up to 84.2% per year. It not only negatively affects many aspects of healthcare workers' lives, but also destroys the harmony of the nurse-patient relationship and reduces the quality of nursing care. The number of psychiatric nurses in China was approximately 96,000, far lower than most other countries and unable to meet the growing demand for mental health. However, the increase in workplace violence has future exacerbates the current shortage of nurses. Therefore, it is necessary to develop effective strategies to prevent psychiatric nurses from suffering from workplace violence, thereby to reduce nurse turnover and improve the quality of nursing care. A comprehensive understanding of psychiatric nurses' preferences and priorities for preventing workplace violence is an important prerequisite before formulating strategies and taking measures. Unfortunately, to date, no research has investigated the psychiatric nurses' preferences. Therefore, a discrete choice experiment (DCE) is conducting to explore the psychiatric nurses' preferences for workplace violence prevention. This article reports on methodological details of the DCE. Methods and analysis: Six attributes were developed through a literature review, one-on-one interviews and focus group discussions. D-efficient design in NGENE was used to generate choice sets. SPSS 24.0 will be used for descriptive analysis of social Demography, and Stata 16.0 will be used for analysis of DCE data. A multinomial logit model will be used to preliminarily explore trade-offs between workplace violence prevention characteristics included in the choice tasks. Then, in a mixed logit model, we plan to choose some arbitrarily defined base violence prevention program and will use the nlcom command to evaluate the probability of an alternative violence prevention program. Ethics and dissemination: The study was approved by the relevant ethics committees. Our findings will emphasize priority intervention areas based on the preferences of psychiatric nurses and provide references for hospitals to develop and improve workplace violence prevention strategies. The results will be shared through seminars, policy briefs, peer-reviewed journal articles and online blogs.
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Psychiatric Nursing , Workplace Violence , Humans , Workplace Violence/prevention & control , Workplace Violence/psychology , Workplace Violence/statistics & numerical data , China , Focus Groups , Choice Behavior , Attitude of Health Personnel , Male , Female , Adult , Research DesignABSTRACT
Background: Previous research has demonstrated the validity of the triglyceride-glucose (TyG) index as a robust measure of insulin resistance (IR) and its association with coronary artery disease (CAD). The objective of this study is to elucidate the relationship between the TyG index and the prognosis of patients underwent percutaneous coronary intervention (PCI) through a comprehensive systematic review and meta-analysis. Our goal is to provide a thorough analysis of the available evidence to offer more clarity on this association. Methods: A systematic and thorough search was carried out in the PubMed, Embase, Cochrane Library, and Web of Science databases, covering studies published in English from the beginning until October 1, 2023. The focus of the search was to gather relevant studies pertaining to the occurrence of major adverse cardiovascular events (MACE). To address the variability among the included studies, random or fixed effect models were utilized to summarize the hazard ratios (HR). In cases where heterogeneity was detected, subgroup or sensitivity analyses were performed to explore potential sources. To evaluate publication bias, the Egger or Begg test was employed. Results: This study incorporated a total of 17 studies. Individuals with the highest TyG index exhibited an elevated risk of major adverse cardiovascular events (MACEs) compared to those with the lowest TyG index (HR = 1.69; 95% CI: 1.47-1.95; P < 0.001). When analyzing the TyG index as a continuous variable, each standard deviation increase was associated with an HR of 1.60 (95% CI: 1.48-1.73; P < 0.001). Moreover, in patients diagnosed with acute coronary syndrome (ACS), higher TyG index levels showed a trend of increased risk of MACE (HR = 1.54; 95% CI: 1.27-1.86; P < 0.001). Furthermore, an elevated TyG index was found to be associated with a higher risk of in-stent restenosis (HR = 1.62; 95% CI: 1.29-2.03; P < 0.001), new-onset atrial fibrillation (HR = 2.97; 95% CI: 2.10-4.06; P = 0.014), and a reduction in quantitative flow ratio (HR = 1.35; 95% CI: 1.101-1.592; P = 0.005). Subgroup analysis indicated the risk of MACE was comparable between varied durations of follow-up (P = 0.11). Furthermore, regression analysis revealed that the positive association between TyG index and the risk of MACE did not differ between individuals with or without diabetes (P = 0.23). Conclusion: An increase in the TyG index may lead to a higher vulnerability to major adverse cardiovascular events (MACE) in patients underwent PCI and there was no significant difference in the risk of major adverse cardiovascular events (MACE) between diabetic and non-diabetic individuals.
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OBJECT: To investigate the association of R-loop binding proteins with prognosis and chemotherapy efficacy in lung adenocarcinoma. METHODS: The data related to R-loop regulatory genes were obtained from literature of R-loop proteomics and relevant databases. We used 403 lung adenocarcinoma cases in the Cancer Genome Atlas as training set, and two datasets GSE14814 and GSE31210 in Gene Expression Omnibus as validation sets. The weighted gene co-expression network analysis (WGCNA) was employed to identify R-loop genes with a significant impact on the clinical phenotype of lung adenocarcinoma. Least absolute shrinkage and selection operator (LASSO) regression was utilized to eliminate genes exhibiting multicollinearity. A multivariate Cox proportional hazards model was employed to scrutinize clinical variables and R-loop characteristic genes that exert independent prognostic effects on patient survival. Subsequently, a risk score model was constructed. The predictive capacity of this model for the prognosis of patients was analyzed and validated. Additionally, the performance of risk model on the anti-neoplastic drug sensitivity was assessed. The mutations of R-loop gene were analyzed by maftools. The effect of PLEC expression on anti-tumor drug sensitivity was tested on non-small cell lung adenocarcinoma H1299 and A549 cells in vitro. RESULTS: A collection of 1551 R-loop genes were obtained, and 78 genes exhibited significant effects on the clinical phenotype shown on WGCNA. The LASSO regression analysis retained 14 R-loop genes. A multivariate Cox analysis further identified 3 R-loop genes (HEXIM1, GLI2, PLEC) and a clinical variable (tumor grading) that were associated with patient prognosis. Risk prediction model was established according to the regression coefficients of each parameter. Kaplan-Meier survival analysis showed that the prognosis of high-risk group patients was significantly worse than that of low-risk group (P<0.01). The time-dependent ROC curve showed that the risk model had good predictive ability in both training and validation sets. Predictive analyses of anti-neoplastic drug sensitivity indicated a diminished responsiveness to both chemotherapy and targeted treatment drugs among high-risk patients. The expression of PLEC was strongly correlated with the sensitivity of gefitinib, a classical EGFR inhibitor. CONCLUSIONS: R-loop binding proteins have been identified as significant determinants in the prognosis and therapeutic strategies for lung adenocarcinoma. The results indicates that therapeutic interventions targeting these specific R-loop binding proteins might contribute to a better survival in lung cancer patients.
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Zn/alkali metal dual-ion batteries (ZM DIBs) with highly concentrated water-in-salt (WiS) electrolytes are promising next-generation energy storage systems. This enhanced design of Zn-ion rechargeable batteries offers intrinsic safety, high operating voltage, satisfactory capacity, and outstanding cyclic stability. Herein, taking the concept of highly concentrated electrolytes one step further, we introduce water-in-salt gel biopolymer electrolytes (WiS-GBEs) by encapsulating Zn/Li or Zn/Na bisalt compositions in a cellulose membrane. WiS-GBEs inherit the electrochemical merits of highly concentrated electrolytes (i.e., wide voltage window, high ionic conductivity, etc.) and excellent durability of gel biopolymer structures. Both types of WiS-GBEs apply to coin- and pouch-cell compartments of ZM DIBs, offering a high plateau voltage (>1.8 V vs. Zn2+/Zn), good and reversible capacity (118 and 57 mAh g-1 for Zn/Li and Zn/Na cells, respectively), and outstanding cycling stability (more than 90% after 1,000 cycles). Essentially, the pouch cells with WiS-GBEs present superior durability, flexibility, and capacity endurance under various bending stress conditions (90% capacity retention under 0-180° bending modes), indicating their potential capability to power wearable electronics. The practical powering ability of Li- and Na-based pouch systems is demonstrated by the example of a wearable digital timer.
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Fc-fusion proteins are an emerging class of protein therapeutics that combine the properties of biological ligands with the unique properties of the fragment crystallizable (Fc) domain of an immunoglobulin G (IgG). Due to their diverse higher-order structures (HOSs), Fc-fusion proteins remain challenging characterization targets within biopharmaceutical pipelines. While high-resolution biophysical tools are available for HOS characterization, they frequently demand extended time frames and substantial quantities of purified samples, rendering them impractical for swiftly screening candidate molecules. Herein, we describe the development of ion mobility-mass spectrometry (IM-MS) and collision-induced unfolding (CIU) workflows that aim to fill this technology gap, where we focus on probing the HOS of a model Fc-Interleukin-10 (Fc-IL-10) fusion protein engineered using flexible glycine-serine linkers. We evaluate the ability of these techniques to probe the flexibility of Fc-IL-10 in the absence of bulk solvent relative to other proteins of similar size, as well as localize structural changes of low charge state Fc-IL-10 ions to specific Fc and IL-10 unfolding events during CIU. We subsequently apply these tools to probe the local effects of glycine-serine linkers on the HOS and stability of IL-10 homodimer, which is the biologically active form of IL-10. Our data reveals that Fc-IL-10 produces significantly more structural transitions during CIU and broader IM profiles when compared to a wide range of model proteins, indicative of its exceptional structural dynamism. Furthermore, we use a combination of enzymatic approaches to annotate these intricate CIU data and localize specific transitions to the unfolding of domains within Fc-IL-10. Finally, we detect a strong positive, quadratic relationship between average linker mass and fusion protein stability, suggesting a cooperative influence between glycine-serine linkers and overall fusion protein stability. This is the first reported study on the use of IM-MS and CIU to characterize HOS of Fc-fusion proteins, illustrating the practical applicability of this approach.
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Immunoglobulin Fc Fragments , Mass Spectrometry , Protein Unfolding , Recombinant Fusion Proteins , Immunoglobulin Fc Fragments/chemistry , Recombinant Fusion Proteins/chemistry , Mass Spectrometry/methods , Interleukin-10/chemistry , Interleukin-10/metabolism , Ion Mobility Spectrometry/methods , Protein Stability , Humans , Immunoglobulin G/chemistryABSTRACT
Broadband photodetectors have attracted much attention due to their multispectral response properties and show great potential in the fields of optical sensing, multispectral imaging, and optical communications. Palladium telluride (PdTe2) is highly competitive in broadband detection due to its tunable bandgap and nonlinear optical properties. However, the low response speed hinders further improvement in the performance of PdTe2-based broadband photodetectors. In this work, we present island-type ZnO@PdTe2 composites on Si as a heterojunction photodetector exhibiting highly sensitive photodetection capabilities in a wide band from the solar-blind region (254 nm) to the short-infrared (1.55 µm). Due to the island-type morphology of the ZnO@PdTe2 composites effectively enhancing light absorption and the ZnO@PdTe2/Si stacks forming a type-II heterojunction accelerating carrier separation, the devices have an ultrafast response (1.58/1.34 µs), a detectivity of up to 1.56 × 1013 Jones, and a sensitivity of up to 107 cm2/W. A triple-channel color imaging system and a dual-channel data transmission system were developed based on the excellent and stable performance of the device. This study demonstrates the great potential of ZnO@PdTe2/Si vertical heterojunction photodetectors for high-speed, wide-band, multiscenario optical communication.
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Objective: To evaluate the effectiveness of 3D NerveVIEW sequence with gadolinium contrast on the visualization of pelvic nerves and their branches compared to that without contrast. Methods: Participants were scanned twice using 3D NerveVIEW sequence with and without gadolinium contrast to acquire pelvic nerve images. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and contrast ratio of the nerves were calculated and compared to determine the quality of images. To subjectively assess, using a 3-point scale, branch nerves critical to therapeutic decision-making, including the pelvic splanchnic nerve and pelvic plexus, the superior gluteal nerve, and the pudendal nerve. Results: In the 32 eligible participants after using contrast, the CNRs of the images of nerve-to-bone and nerve-to-vessel significantly increased (p < 0.05). The CR of the images with contrast of all nerve-to-surrounding tissues (i.e., bone, muscle, blood vessels, and fat) were also found significantly higher (p < 0.05). The assessment of observers also shows higher scores for images with contrast compared to images without contrast. Conclusion: The 3D NerveVIEW sequence combined with gadolinium contrast improved vascular suppression, increased the contrast between pelvic nerves and surrounding tissue, and enhanced the visualization of nerves and their branches. This study may be helpful for the technically challenging preoperative planning of pelvic diseases surgery.
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Tuberculosis has affected human beings for thousands of years, and until today, tuberculosis still ranks third among 29 infectious diseases in China. However, most of the existing mathematical models consider a single factor, which is not conducive to the study of tuberculosis transmission dynamics. Therefore, this study considers the combined effects of vaccination, treatment, and contaminated environments on tuberculosis, and builds a new model with seven compartments of $ SVEITRW $ based on China's tuberculosis data. The study shows that when the basic reproduction number $ R_{0} $ is less than 1, the disease will eventually disappear, but when $ R_{0} $ is greater than 1, the disease may persist. In the numerical analysis part, we use Markov-chain Monte-Carlo method to obtain the optimal parameters of the model. Through the next generation matrix theory, we calculate that the $ R_{0} $ value of tuberculosis in China is $ 2.1102 $, that is, if not controlled, tuberculosis in China will not disappear over time. At the same time, through partial rank correlation coefficients, we find the most sensitive parameter to the basic reproduction number $ R_{0} $. On this basis, we combine the actual prevalence of tuberculosis in China, apply Pontryagin's maximum principle, and perform cost-effectiveness analysis to obtain the conditions required for optimal control. The analysis shows that four control strategies could effectively reduce the prevalence of TB, and simultaneously controlling $ u_{2}, u_{3}, u_{4} $ is the most cost-effective control strategy.