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UNSTRUCTURED The release of a dialogue-based artificial intelligence language model called chatGPT (https://openai.com/blog/chatgpt/) has garnered global attention. An exploratory study published by The Journal of the American Medical Association (JAMA) demonstrated the potential of interactive AI to assist clinical workflows by augmenting patient education and patient-clinician communication. Our study was conducted in February 2023, and we formulated 37 questions that focused on perioperative patient education in the context of thoracic surgery. We made two inquiries to chatGPT for each question, one in English and the other in Chinese, and evaluated the appropriateness and comprehensiveness of the responses separately in both languages. Experienced thoracic surgical clinicians assessed the responses. Thirty-four (91.9%) responses were qualified both in English and Chinese contexts, demonstrating the potential feasibility for perioperative patient education in thoracic surgery.

Golden camellia flowers are treasured for their unique yellow color and bioactive chemical compounds. Because of its high market demand, there is strong interest in inducing early flowering in golden camellias for earlier harvest. Previously, we have successfully induced flowering in Camelia chrysantha (Hu) Tuyama juvenile grafted plants and seedlings with paclobutrazol (PBZ). During this study, we investigated the efficacy of PBZ on C. tamdaoensis juvenile rooted cuttings. C. tamdaoensis is a yellow-flowering camellia species that is native to Vietnam and valued by the local population. It was found that applications of 100 and 200 ppm PBZ generated an average of 13 and 30 flowers per 5-year-old plant, respectively. None of the control plants flowered. The average flower diameter was 17.2 cm for 100-ppm-induced flowers and 26.0 cm for 200-ppm-induced flowers. The dynamics of various phytohormones (indoleacetic acid, abscisic acid, salicylic acid, and jasmonic acid) were altered by PBZ treatment. It is suggested that low indoleacetic acid, high abscisic acid, and jasmonic acid and a gradual increase in salicylic acid benefit floral initiation of golden camellias. The study provided the first insight regarding the action mechanism of PBZ for the initiation of camellia flowering.

This study aimed to explore the protective effect of Reduning Injection(RDN) on mice infected by influenza virus A/PR/8(PR8) and its immune regulatory roles during viral infection. In in vivo experiments, female C57 BL/6 mice were randomly divided into phosphate buffered saline(PBS) group, PR8-infected group, oseltamivir treatment group(OSV) and RDN treatment group. After 2 h of PR8 infection, mice in the oseltamivir group were gavaged with oseltamivir 30 mg·kg~(-1), and those in the RDN treatment group were injected intraperitoneally with RDN 1.5 mL·kg~(-1)once per day for seven consecutive days. The body weight of mice in each group was recorded at the same time every morning for 16 consecutive days. The line chart of body weight change was created to analyze the protective effect of RDN on flu-infected mice. The relative mRNA expression of different cytokines(IL-6, TNF-α, MCP-1, IL-1β, MIP-2, IP-10 and IL-10) in lung samples of flu-infected mice was detected by PCR. Flow cytometry was utilized to analyze the composition of immune cells of mouse BALF samples on day 5 after infection. Mouse macrophage cell line RAW264.7 was planted and treated by different concentrations of RDN(150, 300, 600 μg·mL~(-1)) for 24 h or 48 h, and cell proliferation was detected by CCK-8 assay. RAW264.7 cells and mouse primary peritoneal macrophages were stimulated with synthetic single stranded RNA(R837), which elicited the inflammatory response by mimicking the infection of single-stranded RNA viruses. The expression of cytokines and chemokines in the supernatants of above culture system was detected by ELISA and qPCR. On days 4, 5, 6, 7 and 15 after infection, the body weight loss of mice in the RDN treatment group was alleviated compared with that of PR8-infected mice(Plt;0.05). RDN treatment obviously reduced lung index and the production of IL-6, TNF-α, MCP-1 and MIP-2 in lung tissues of flu-infected mice(Plt;0.05). The proportions of macrophages, neutrophils and T cells in mouse BALF samples were analyzed by flow cytometry, and compared with PR8-infected mice, RDN decreased the proportion of macrophages in BALF of flu-infected mice(Plt;0.05), and the proportion of T cells was recovered dramatically(Plt;0.001). In CCK-8 assay, the concentrations of RDN(150, 300, 600 μg·mL~(-1)) failed to cause cytotoxicity to RAW264.7 cells. In addition, RDN lowered the expression of inflammatory cytokines such as IL-6, TNF-α,MCP-1, IL-1β, RANTES, and IP-10 and even anti-inflammatory cytokine IL-10 in R837-induced macrophages. RDN reduced the infiltration of inflammatory macrophages and the production of excessive inflammatory cytokines, alleviated the body weight loss of flu-infected mice. What's more, RDN restored the depletion of T cells, which might prevent secondary infection and deteriorative progression of the disease. Taken together, RDN may inhibit cytokine production and therefore down-regulate cytokine storm during the infection of influenza virus.

Whether to use antibiotics to prevent surgical site infection in elective inguinal tension-free hernia repair has been controversial. To systematically evaluate the effect of prophylactic antibiotic application in elective inguinal tension-free hernia repair, we identified all published randomised controlled trials of the effect of prophylactic antibiotic application on elective inguinal tension-free hernia repair were collected by computer retrieval from the China National Knowledge Infrastructure; VIP Database; Wanfang Database; China Biomedical Literature Database; and PubMed, EMBASE and Cochrane Library databases. Meta-analysis was performed by RevMan 5.3 software. The meta-analysis showed that the total incidence of surgical site infections [P = 0.003] and the incidence of superficial surgical site infections [P = 0.004] in the antibiotic group (AG) were lower than those in the non-antibiotic group (NAG). There was no significant difference in the total incidence of postoperative infections [P = 0.06], deep surgical site infections [P = 0.26] and seroma [P = 0.52] between the AG and the NAG. Based on current evidence, the application of prophylactic antibiotics in elective inguinal tension-free hernia repair can prevent the total incidence of surgical site infections and that of superficial surgical site infections but cannot prevent the total incidence of postoperative infection events, incidence of deep surgical site infections and incidence of seroma.

Histone lysine crotonylation (KCR), a novel epigenetic modification, is important in regulating a broad spectrum of biological processes and various diseases. However, whether KCR is involved in neuropathic pain remains to be elucidated. We found KCR occurs in macrophages, sensory neurons, and satellite glial cells of trigeminal ganglia (TG), neurons, astrocytes, and microglia of the medulla oblongata. KCR in TG was detected mainly in small and medium sensory neurons, to a lesser extent in large neurons. Peripheral nerve injury elevated KCR levels in macrophages in the trigeminal and dorsal root ganglia and microglia in the medulla oblongata but reduced KCR levels in sensory neurons. Inhibition of histone crotonyltransferases (p300) by intra-TG or intrathecal administration of C646 significantly alleviated partial infraorbital nerve transection (pIONT)- or spinal nerve ligation (SNL)-induced mechanical allodynia and thermal hyperalgesia. Intra-TG or intrathecal administration of Crotonyl coenzyme A trilithium salt to upregulate KCR dose-dependently induced mechanical allodynia and thermal hyperalgesia in mice. Mechanismly, inhibition of p300 alleviated pIONT-induced macrophage activation and reduced the expression of pain-related inflammatory cytokines Tnfα, Il1β and chemokines Ccl2 and Cxcl10. Correspondingly, exogenous crotonyl-CoA induced macrophage activation and the expression of Tnfα, Il1β, Il6, Ccl2 and Ccl7 in TG, which C646 can repress. These findings suggest that histone crotonylation might be functionally involved in neuropathic pain and neuroinflammation regulation.

Torsades de Pointes (TdP) occurred in a 68-year-old female with epidermal growth factor receptor (EGFR) mutant lung cancer administered osimertinib, the third-generation EGFR tyrosine kinase inhibitor (TKI). Electrocardiogram (ECG) recorded at Tdp showed QT prolongation (QTc = 515 ms), to which a Traditional Chinese Medicine (TCM) named “Litsea Cubeba” may have contributed. After discontinuation of osimertinib and Litsea Cubeba, magnesium supplementation, potassium supplementation, lidocaine infusion, and the pacemaker frequency adjustment, Tdp terminated. However, QT prolongation sustained at discharge (QTc = 528 ms), partly because of the emergency use of amiodarone. Osimertinib may prolong the QT interval leading to TdP, especially when multiple risk factors to lengthen QT interval are incidentally overlapped. Thus, regular monitoring of ECG and appropriate management of concomitant drugs are highly recommended.

Background Heterotaxy syndrome (HTX) is caused by aberrant left–right patterning early in embryonic development, which results in abnormal positioning and morphology of the thoracic and abdominal organs. Currently, genetic testing discerns the underlying genetic cause in less than 20% of sporadic HTX cases, indicating that genetic pathogenesis remains poorly understood. In this study, we aim to garner a deeper understanding of the genetic factors of this disease by documenting the effect of different matrix metalloproteinase 21 (MMP21) variants on disease occurrence and pathogenesis. Methods Eighty-one HTX patients with complex congenital heart defects and 89 healthy children were enrolled, and we investigated the pathogenetic variants related to patients with HTX by exome sequencing. Zebrafish splice-blocking Morpholino oligo-mediated transient suppression assays were performed to confirm the potential pathogenicity of missense variants found in these patients with HTX. Results Three MMP21 heterozygous non-synonymous variants (c.731G > A (p.G244E), c.829C > T (p.L277F), and c.1459A > G (p.K487E)) were identified in three unrelated Chinese Han patients with HTX and complex congenital heart defects. Sanger sequencing confirmed that all variants were de novo. Cell transfection assay showed that none of the variants affect mRNA and protein expression levels of MMP21. Knockdown expression of mmp21 by splice-blocking Morpholino oligo in zebrafish embryos revealed a heart looping disorder, and mutant human MMP21 mRNA (c.731G > A, c.1459A > G, heterozygous mRNA (wild-type&c.731G > A), as well as heterozygous mRNA (wild-type& c.1459A > G) could not effectively rescue the heart looping defects. A patient with the MMP21 p.G244E variant was identified with other potential HTX-causing missense mutations, whereas the patient with the MMP21 p.K487E variant had no genetic mutations in other causative genes related to HTX. Conclusion Our study highlights the role of the disruptive heterozygous MMP21 variant (p.K487E) in the etiology of HTX with complex cardiac malformations and expands the current mutation spectrum of MMP21 in HTX.

BackgroundCrohn’s disease (CD) is characterized by repetitive phases of remission and exacerbation, the quality of life of patients with CD is strongly influenced by disease activity, as patients in the active phase experience significantly worse symptoms. To investigate the underlying mechanism of how the course of CD is exacerbated based on the bi-directionality of the brain-gut axis (BGA), we conducted a multi-modality neuroimaging study that combined resting-state functional magnetic resonance imaging (rs-fMRI) with proton magnetic resonance spectroscopy (MRS) to detect abnormalities in the anterior cingulate cortex (ACC).Materials and MethodsClinical scales including Visual Analog Scale (VAS) and Hospital Anxiety and Depression Scale (HADS) were used to evaluate the degree of abdominal pain and mood state of participants. We made a comparison between CD patients in the active phase, the remission phase and healthy controls (HCs), not only employed the innovative wavelet-transform to analyze the amplitude of low frequency fluctuation (ALFF) but also compared the sensitivity of wavelet-transform and the traditional fast Fourier transform (FFT). Brain metabolites such as glutamate (Glu), myo-inositol (mIns) and gamma-aminobutyric acid (GABA) were also detected. Then correlation analysis was made to see whether changes in the ACC correlated with CD’s clinical symptoms.ResultsCD patients in the active phase showed higher VAS scores (p = 0.025), the scores of anxiety and depression were also higher (all p < 0.05). Wavelet-transform is slightly more sensitive in the current research. Patients in the active phase exhibited higher ALFF in the left ACC and the left superior frontal gyrus, medial (SFGmed). Patients in the active phase showed increased Glu levels in the ACC than patients in the remission phase or HCs (p = 0.039 and 0.034 respectively) and lower levels of mIns than HCs (p = 0.036). There was a positive correlation between mWavelet-ALFF values of the ACC and HADS-depression scores in CD patients (r = 0.462, p = 0.006). Besides, concentrations of Glu positively correlated with mWavelet-ALFF in the ACC in all participants (r = 0.367, p = 0.006).ConclusionAbnormal spontaneous activity and metabolic levels in the ACC were detected in CD patients in the active phase along with severer abdominal pain and worse mood state, these may contribute to the exacerbation of CD. Therefore, the ACC might be a potential neural alternative for managing the exacerbation of CD.

This study evaluated the accuracy of implant placement with surgical-template guidance both in vitro and in vivo. Virtual surgical planning was performed based on the data from CBCT scans and an intraoral scanner. Surgical templates were designed according to the planned implants and manufactured with stereolithography. In vitro, 60 implants were placed in 15 resin models. In vivo, 74 implants were placed in 54 patients. The implants were scanned with CBCT postoperatively. Implant accuracy was evaluated by measuring the following parameters: central deviation at the apex and shoulder, horizontal deviation at the apex and shoulder, vertical deviation at the apex and shoulder, and angular deviation. There were statistically significant in vitro and in vivo deviations for all parameters, and the implant deviations in vivo were significantly greater than those in vitro. When using a mucosa-supported template, horizontal deviations at the apex were significantly greater than when a teeth-supported template was used. Within the limitation of the study design, inaccuracy existed in implant placement guided with a surgical template. More studies are needed to investigate the value of the procedure in future.

Background: : The appearance of antibiotic resistance caused by metallo-β-lactamases (MβLs) is a global public health threat. Developing MβLs inhibitor is an effective way to overcome antibiotic resistance. Recently, azolylthioacetamides were reported to be promising MβLs inhibitors. Methods:: Triazolylthioacetamides were synthesized and tested for inhibition activity against the purified MβL IMP-1. Antimicrobial activities of these inhibitors in combination with cefazolin were evaluated. Isothermal Titration Calorimetry (ITC) was employed to characterize the binding of the inhibitor to IMP-1, and their action mechanism was studied by molecular docking. Results: Twenty compounds exhibited specific inhibitory activity against IMP-1 with an IC50 value in the range of 3.1-62.5 μM. Eight of the compounds can restore the antibacterial efficacy of cefazolin against E. coli BL21 strain producing IMP-1 by 2-4 fold. ITC monitoring showed that 1c exhibited dose-dependent inhibition on IMP-1. Docking studies revealed that the triazole group in 1c and 2d played an essential role in the inhibition activity. Cytotoxicity assay showed that 1c and 2d have low toxicity in L929 mouse fibroblastic cells. Conclusion: : The triazolylthioacetamides are efficient inhibitors of IMP-1 in vitro and in vivo.

© 2021 American Chemical Society.The advent of three dimensionally (3D) printed customized bone grafts using different biomaterials has enabled repairs of complex bone defects in various in vivo models. However, studies related to their clinical translations are truly limited. Herein, 3D printed poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PLGA/TCP) and TCP scaffolds with or without recombinant bone morphogenetic protein -2 (rhBMP-2) coating were utilized to repair primate's large-volume mandibular defects and compared efficacy of prefabricated tissue-engineered bone (PTEB) over direct implantation (without prefabrication). 18F-FDG PET/CT was explored for real-time monitoring of bone regeneration and vascularization. After 3-month's prefabrication, the original 3D-architecture of the PLGA/TCP-BMP scaffold was found to be completely lost, while it was properly maintained in TCP-BMP scaffolds. Besides, there was a remarkable decrease in the PLGA/TCP-BMP scaffold density and increase in TCP-BMP scaffolds density during ectopic (within latissimus dorsi muscle) and orthotopic (within mandibular defect) implantation, indicating regular bone formation with TCP-BMP scaffolds. Notably, PTEB based on TCP-BMP scaffold was successfully fabricated with pronounced effects on bone regeneration and vascularization based on radiographic, 18F-FDG PET/CT, and histological evaluation, suggesting a promising approach toward clinical translation.

Catalytic gaseous ozone decomposition under high humidity is not only an urgent need but also a significant challenge because of the low stability over the available catalysts. By the pyrolysis of ZIF-67 materials, a series of cobalt nanoparticle catalysts with tunable size and supported by hydrophobic nitrogen-doped carbon are developed for the catalytic ozone decomposition under high humidity (RH = 90%). Among them, the ZIF-67-800 catalyst exhibits the highest ozone conversion (ca. 99%) after 6 h. Interestingly, it is found that metallic cobalt nanoparticles are generated during the carbonizing process. Furthermore, the size of the nanoparticle gradually increased from 38 nm to 93 nm with an increase in the carbonizing temperature from 500 °C to 900 °C. The effect of the size of cobalt nanoparticles on the catalytic activity and stability is discussed, and the results imply that only an appropriate size of metallic cobalt particles (ca. 62 nm) may be beneficial for high catalytic activity and robust stability. The surficial oxidized cobalt species and the hydrophobic carbon support (water contact angle = 129°) also play important roles in the improvement of the stability of the decomposition of gaseous ozone under high humidity. The as-prepared ZIF-67-800 catalyst also exhibits a clear advantage over the extensively investigated materials, such as OMS-2 and active carbon. Importantly, the catalytic role of cobalt nanoparticles can be confirmed by the performance comparison of ZIF-67-800 and ZIF-8-800 catalysts, which are derived from ZIF-8 without any cobalt species.

A series of MnOx catalysts supported by carbon spheres were prepared by calcining mixtures of manganese acetate and carbon spheres under a nitrogen atmosphere, and their performance for ozone decomposition under high humidity conditions (RH = 90%) was evaluated. The calcination temperature and the ratio of manganese acetate to carbon spheres have significant influences on the catalytic stability of Mn/C catalysts for ozone decomposition. Among all the Mn/C catalysts, the 1Mn/3C-900 catalyst showed the most robust catalytic stability (ozone conversion remaining 100% after 6 h) under high humidity conditions (RH = 90%). The size of MnOx particles on the surface of the Mn/C-900 catalyst increased gradually from 18 nm to 74 nm with the increase of MnOx loading, which would lead to the change of the oxygen vacancy density and Mn2+ content of MnOx species. The 1Mn/3C-900 catalyst with a MnOx particle size of 26 nm exhibited the highest surface oxygen vacancy density and Mn2+ content of MnOx species on the surface, and thus the most stable activity was observed on the 1Mn/3C-900 catalyst. The high catalytic activity of the 1Mn/3C-900 catalyst remained for even 70 h under dry conditions. However, the significant deactivation of the 1Mn/3C-900 catalyst was observed in the presence of both gaseous ozone and water vapor (RH = 90%). Besides the competitive adsorption of water vapor on active sites, the obvious decrease of oxygen vacancy density and Mn2+ content on the catalyst surface induced by water vapor during the reaction should also be responsible for remarkable deactivation.

Yue-Juan Ling,1,2 Ting-Yu Ding,1,2 Fu-Lu Dong,3 Yong-Jing Gao,1,2 Bao-Chun Jiang1,2 1Institute of Pain Medicine, Nantong University, Nantong, Jiangsu 226019, People’s Republic of China; 2Institute of Special Environmental Medicine, Nantong University, Nantong, Jiangsu 226019, People’s Republic of China; 3School of Medicine, Nantong University, Nantong, Jiangsu, People’s Republic of ChinaCorrespondence: Bao-Chun JiangInstitute of Pain Medicine, Nantong University, 9 Seyuan Road, Nantong, Jiangsu 226019, People’s Republic of ChinaTel +86-513-55003373Email jiangbaochun@ntu.edu.cnBackground: Currently, medical treatment of inflammatory pain is limited by a lack of safe and effective therapies. Triptonide (TPN), a major component of Tripterygium wilfordii Hook.f. with low toxicity, has been shown to have good anti-inflammatory and neuroprotective effects. The present study aims to investigate the effects of TPN on chronic inflammatory pain.Materials and Methods: Inflammatory pain was induced by intraplantar injection of complete Freund’s adjuvant (CFA). TPN’s three different doses were intravenously administered to compare the analgesic efficacy: 0.1 mg/kg, 0.5 mg/kg, and 2.0 mg/kg. The foot swelling was quantitated by measuring paw volume. Mechanical allodynia and thermal hyperalgesia were assessed with von Frey filament testing and Hargreaves’ test, respectively. Western blots, qRT–PCR and immunofluorescence tests were used to analyze the expression of pAKT, tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). Two AKT inhibitors, AKT inhibitor Ⅳ and MK-2206, were used to examine AKT’s effects on pain behavior and cytokines expression.Results: Intravenous treatment with TPN attenuated CFA-induced paw edema, mechanical allodynia, and thermal hyperalgesia. Western blotting and immunofluorescence results showed that CFA induced AKT activation in the dorsal root ganglion (DRG) neurons. However, these effects were suppressed by treatment with TPN. Furthermore, TPN treatment inhibited CFA-induced increase of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Consistent with the in vivo data, TPN inhibited LPS-induced Akt phosphorylation and inflammatory mediator production in ND7/23 cells. Finally, intrathecal treatment with AKT inhibitor Ⅳ or MK-2206, attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, and simultaneously decreased the mRNA expression of TNF-α, IL-1β, and IL-6 in DRG.Conclusion: These data indicate that TPN attenuates CFA-induced pain potentially via inhibiting AKT-mediated pro-inflammatory cytokines production in DRG. TPN may be used for the treatment of chronic inflammatory pain.Keywords: triptonide, AKT, DRG, inflammatory pain, pro-inflammatory factors

Background Currently, medical treatment of inflammatory pain is limited by a lack of safe and effective therapies. Triptonide (TPN), a major component of Tripterygium wilfordii Hook.f. with low toxicity, has been shown to have good anti-inflammatory and neuroprotective effects. The present study aims to investigate the effects of TPN on chronic inflammatory pain. Materials and Methods Inflammatory pain was induced by intraplantar injection of complete Freund's adjuvant (CFA). TPN's three different doses were intravenously administered to compare the analgesic efficacy: 0.1 mg/kg, 0.5 mg/kg, and 2.0 mg/kg. The foot swelling was quantitated by measuring paw volume. Mechanical allodynia and thermal hyperalgesia were assessed with von Frey filament testing and Hargreaves' test, respectively. Western blots, qRT-PCR and immunofluorescence tests were used to analyze the expression of pAKT, tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). Two AKT inhibitors, AKT inhibitor Ⅳ and MK-2206, were used to examine AKT's effects on pain behavior and cytokines expression. Results Intravenous treatment with TPN attenuated CFA-induced paw edema, mechanical allodynia, and thermal hyperalgesia. Western blotting and immunofluorescence results showed that CFA induced AKT activation in the dorsal root ganglion (DRG) neurons. However, these effects were suppressed by treatment with TPN. Furthermore, TPN treatment inhibited CFA-induced increase of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Consistent with the in vivo data, TPN inhibited LPS-induced Akt phosphorylation and inflammatory mediator production in ND7/23 cells. Finally, intrathecal treatment with AKT inhibitor Ⅳ or MK-2206, attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, and simultaneously decreased the mRNA expression of TNF-α, IL-1β, and IL-6 in DRG. Conclusion These data indicate that TPN attenuates CFA-induced pain potentially via inhibiting AKT-mediated pro-inflammatory cytokines production in DRG. TPN may be used for the treatment of chronic inflammatory pain.

Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose and resistant to therapy and has a poor prognosis. Autophagy plays a vital role in PDAC development and progression. This study aimed to establish an autophagy-related gene (ARG) signature to predict the prognosis of patients with PDAC.The expression profiles of PDAC and healthy pancreatic tissues were obtained from The Cancer Genome of Atlas (TCGA) and GTEx (Genotype-Tissue Expression) databases, respectively. Univariate and multivariate Cox regression analyses were performed on differentially expressed ARGs to identify the optimal prognosis-related genes.A total of 73 ARGs demonstrated significant differences in expression levels between PDAC and healthy pancreatic tissues. Several pathways that play crucial roles in biological processes were identified via enrichment analyses. Furthermore, an ARG signature was established based on overall survival-related ARGs (CASP4, BAK1, PIK3R4, CASP8, BIRC5, RPTOR, and CAPN1) using least absolute shrinkage and selection operator (LASSO) regression. Cox regression analysis confirmed that the 7-gene signature was an independent prognostic factor for patients with PDAC (P0.001). In addition, the GSE21501 and GSE28735 datasets were used to validate the predictive value of the prognostic model for PDAC. We also constructed a clinical nomogram with a concordance index of 0.712 to predict the overall survival of patients by integrating clinical characteristics and the ARG signature. Calibration curves substantiated fine concordance between nomogram prediction and actual observation.We constructed a new ARG-related prognostic model, which can be a prognostic biomarker and offers insights into identifying potential therapeutic targets for PDAC.

To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC.In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings.A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916.The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode.• In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

Ionic liquid (IL), 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM]PF6) as a new and environmentally friendly diluent was introduced to prepare poly(vinylidene fluoride) (PVDF) membranes via thermally induced phase separation (TIPS). Phase diagram of PVDF/[BMIM]PF6 was measured. The effects of polymer concentration and quenching temperature on the morphologies, properties, and performances of the PVDF membranes were investigated. When the polymer concentration was 15 wt%, the pure water flux of the fabricated membrane was up to nearly 2000 L·m−2·h−1, along with adequate mechanical strength. With the increasing of PVDF concentration and quenching temperature, mean pore size and water permeability of the membrane decreased. SEM results showed that PVDF membranes manufactured by ionic liquid (BMImPF6) presented spherulite structure. And the PVDF membranes were represented as β phase by XRD and FTIR characterization. It provides a new way to prepare PVDF membranes with piezoelectric properties.

It still remains a big challenge that achieving the selective oxidation of hazardous nitrogen-containing volatile organic compounds to the harmless molecular N2. Here we present the synthesis of Cu...

A series of Pt/Cr1.3Fe0.7O3 catalysts were tested for CO oxidation, and the activities are improved by the presence of H2O. Such improvement is more significant on the single atom 0.2Pt/Cr1.3Fe0.7O3 than on the 2Pt/Cr1.3Fe0.7O3 containing Pt nanoparticles, with turnover frequencies of 0.396 and 0.094 s−1 at 60 °C under 1% CO + 1% O2 + 10% CO2 + 10% H2O, respectively. In-situ diffuse reflectance infrared Fourier transform spectroscopic study on these catalysts suggests that the promoting effect of H2O is due to the facile reaction between adsorbed CO and surface hydroxyl groups via H2O dissociation. Kinetic investigation reveals that the 0.2Pt/Cr1.3Fe0.7O3 gives a higher intrinsic rate constant than the 2Pt/Cr1.3Fe0.7O3 (9.23 × 10−5 versus 4.50 × 10−5 mol g−1 s−1 at 60 °C) for the formation of formate intermediate due to its weaker CO adsorption strength, which explains the more significant H2O promotion on the single atom Pt catalyst.

Additional file 1: Table S1. Primers used for Sanger sequencing validation of MMP21 variants, mutagenesis of mutant MMP21 vectors, RT-qPCR, and construction of in situ hybridization probes.

Additional file 1. Experimental Section. Fig S1. Characterization of MPSNs. Fig S2. Fluorescence stability of MPSNs. Fig S3. The generation of singlet oxygen of MPSNs determined by the increased SOSG fluorescence. Fig S4. Cytotoxicity of MPSNs. Fig S5. 4T1 cell viability. Fig S6. CLSM images of 4T1 cells stained with Calcein-AM and PI. Fig S7. 4T1 cell viabilities after different treatments. Fig S8. A Photothermal imaging after intravenous injection of saline, MPSNs and MPSNs@R837 in tumor-bearing mice. B Photothermal heating curves. C The ex vivo fluorescence images of tumors and major organs. Fig S9. Representative H&E staining images of heart, liver, spleen, lung, and kidney. Fig S10. Change of body weights of mice after different treatments; Serum biochemistry indicators. Fig S11. A Tumor volume. B-D cytokine levels of TNF-α, INF-γ and IL-12 in sera from mice. Fig S12. Change of body weights of mice after different treatments; Serum biochemistry indicators. Fig S13. Representative H&E staining images of heart, liver, spleen, and kidney. Fig S14. Tumor volume of A primary and (B) distant tumors of each group. C the images of tumors. Fig S15. Representative immunofluorescence staining for CD8a (green) and IFN-γ (red) of spleen sections. Fig S16. A-C cytokine levels of TNF-α, INF-γ and IL-12 in sera from mice. Fig S17. Representative H&E staining images. Fig S18. Change of body weights of mice after different treatments; Serum biochemistry indicators.

Mitochondria are highly dynamic organelles that constantly undergo fission and fusion processes that closely related to their function. Disruption of mitochondrial dynamics has been demonstrated in acute kidney injury (AKI), which could eventually result in cell injury and death. Previously, we reported that augmenter of liver regeneration (ALR) alleviates renal tubular epithelial cell injury. Here, we gained further insights into whether the renoprotective roles of ALR are associated with mitochondrial dynamics. Changes in mitochondrial dynamics were examined in experimental models of renal ischemia-reperfusion (IR). In a model of hypoxia-reoxygenation (HR) injury in vitro , dynamin-related protein 1 (Drp1) and mitochondrial fission process protein 1 (MTFP1), two key proteins of mitochondrial fission, were downregulated in the Lv-ALR + HR group. ALR overexpression additionally had an impact on phosphorylation of Drp1 Ser637 during AKI. The inner membrane fusion protein, Optic Atrophy 1 (OPA1), was significantly increased whereas levels of outer membrane fusion proteins Mitofusin-1 and -2 (Mfn1, Mfn2) were not affected in the Lv-ALR + HR group, compared with the control group. Furthermore, the mTOR/4E-BP1 signaling pathway was highly activated in the Lv-ALR + HR group. ALR overexpression led to suppression of HR-induced apoptosis. Our collective findings indicate that ALR gene transfection alleviates mitochondrial injury, possibly through inhibiting fission and promoting fusion of the mitochondrial inner membrane, both of which contribute to reduction of HK-2 cell apoptosis. Additionally, fission processes are potentially mediated by promoting tubular cell survival through activating the mTOR/4E-BP1 signaling pathway.

Catalytic combustion is an effective way to eliminate volatile organic compound (VOC) pollution, such as propane. However, it is still a significant challenge to develop effective catalysts. Herein, we report NbOx-doped Pt/Al2O3 catalysts synthesized by a facile impregnation method for effective propane oxidation. New types of acidic sites are generated on the surface of Pt/Al2O3 when NbOx is added, and the acidity is gradually improved. NbOx is beneficial for the formation of Pt0 species, which obviously improves the catalytic performance. Pt-10Nb/Al2O3 gives the highest propane conversion (86.6%) at 250 °C. Furthermore, the prereduced Pt-10Nb/Al2O3-R with more Pt0 content shows higher conversion (90.1%). The specific reaction rate of Pt-Nb/Al2O3 is related to the Pt0/(Pt0 + Pt2+) ratio. Pt-10Nb/Al2O3-R with the Pt0/(Pt0 + Pt2+) value of 0.86 rather than Pt-15Nb/Al2O3 with a higher one gives the highest specific reaction rate of 76.1 μmol gPt–1 s–1, which may be attributed to the synergistic roles of Pt0...

In this paper, a multistage pressure reducing valve is presented. The main frequency of vortex-induced vibration is evaluated by monitoring the lift coefficient during vortex shedding and the pressure fluctuation formed after vortex shedding in the flow field. By comparative analysis of two different methods, the number of vortices is relatively small at small openings. Due to the limitations of the location and quantity of monitoring points, accurately locating the most active position where pressure fluctuation occurs is difficult. Monitoring the lift coefficient is more suitable to evaluate the main frequency of vortex-induced vibration. At medium and large openings, due to the increase in the number of vortices, the superposition effect of the pressure fluctuation and the influence of the flow channel shape is more obvious. Monitoring the pressure fluctuation is more appropriate to evaluate the main frequency of vortex-induced vibration the valve. Therefore, a combination of the two methods can more accurately evaluate the vortex-induced vibration characteristics of the valve. When monitoring pressure fluctuation, the position and number of monitoring points directly affect the evaluation accuracy. The pressure fluctuations around the outlet and the multilayer sleeve are more active. It is more meaningful to monitor the pressure fluctuation at these points. The main frequency of the pressure fluctuation at these points better reflects the vortex-induced vibration characteristics of the valve.

We experimentally present a tunable electromagnetically induced transparency (EIT)-like response in bright-bright mode resonators. In contrast to previous studies, we used NbN film and a gold film composite structure metamaterial. A significant slow-light effect could be observed at the transmission window, and the maximum group index could reach 100. As a variation in temperature alters the intrinsic ohmic loss of superconducting NbN film, a temperature-dependent transmittance and slow-light effect were observed. To better illustrate the physical mechanism of the two modes, a hybrid coupling model was introduced to fit the experimental transmission spectra and extract the characteristic parameters of sub-resonators. We found excellent agreement with experimental results. Our results provide deeper insight into the metamaterial analogs of an EIT-like response and offer an alternative approach for engineering slow-light devices, bandpass filters, and switches/modulators at terahertz frequencies.

BackgroundAs one of the most common stroke sequelae, poststroke cognitive impairment significantly impacts 17.6%–83% of survivors, affecting their rehabilitation, daily living and quality of life. Improving cognitive abilities among patients in stroke recovery is therefore critical and urgent. Transcutaneous auricular vagus nerve stimulation (TAVNS) is a non-invasive, safe, cost-effective treatment with great potential for improving the cognitive function of poststroke patients. This clinical research will evaluate the effectiveness, and help elucidate the possible underlying mechanisms, of TAVNS for improving poststroke cognitive function.Methods and analysisA single-centre, parallel-group, allocation concealment, assessor-blinded randomised controlled clinical trial. We will allocate 88 recruited participants to the TAVNS or sham group for an intervention that will run for 8 weeks, 5 days per week with twice daily sessions lasting 30 min each. Blood tests will be performed and questionnaires issued at baseline and 8-week and 12 week follow-ups. Primary outcomes will be changes in cognitive function scores. Secondary outcomes will be changes in activities of daily living, quality of life and serum oxidative stress indicators.Ethics and disseminationThe Ethics Committee of the First Affiliated Hospital of Hunan University of Chinese Medicine has approved the protocol (No. HN-LL-YJSLW-2022200). Findings will be published in peer-reviewed academic journals and presented at scientific conferences.Trial registration numberChiCTR2200057808.

Objective To observe the effect of cryptotanshinone on the ferroptosis of human liver cancer HepG2 cells. Methods The viability of the HepG2 cells cultured

The d , d -dipeptidase enzyme VanX is the main cause of vancomycin resistance in gram-positive bacteria because of hydrolysis of the D-Ala-D-Ala dipeptide used in cell-wall biosynthesis. Continuous assay of VanX has proven challenging due to lack of a chromophoric substrate. Here, we report a direct approach for continuous assay of VanX in vitro and in vivo from hydrolysis of D-Ala-D-Ala, based on the heat-rate changes measured with isothermal titration calorimetry (ITC). With the ITC approach, determination of kinetic parameters of VanX hydrolyzing D-Ala-D-Ala and the inhibition constant of d -cysteine inhibitor yielded KM of 0.10 mM, kcat of 11.5 s−1, and Ki of 18.8 μM, which are consistent with the data from ninhydrin/Cd(II) assays. Cell-based ITC studies demonstrated that the VanX expressed in E. coli and in clinical strain VRE was inhibited by d -cysteine with IC50 values of 29.8 and 28.6 μM, respectively. Also, the total heat from D-Ala-D-Ala (4 mM) hydrolysis decreases strongly (in absolute value) from 1.26 mJ for VRE to 0.031 mJ for E. faecalis, which is consistent with the large MIC value of vancomycin of 512 μg/mL for VRE and the much smaller value of 4 μg/mL for E. faecalis. The ITC approach proposed here could be applied to screen and evaluate small molecule inhibitors of VanX or to identify drug resistant bacteria.

Background: Chemoresistance is a major obstacle for chemotherapy failure in non-small-cell lung cancer (NSCLC). lncRNAs are a class of pivotal regulators in various cancers, and the lncRNA FOXD2-AS1 is implicated in the progression of NSCLC. However, it is still unclear whether it regulates chemosensitivity. Methods: Expression levels of FOXD2-AS1, miR185-5p, and SIX1 mRNA were identified by reverse-transcription qPCR. CCK8 assay was performed to assess cell proliferation and chemosensitivity of cisplatin-resistant A549/DDP and H1299/DDP cells. Colony-forming assay was utilized to detect colony numbers. Cell migration and invasion ability were measured by transwell assay. The protein levels of LRP, Pgp, MRP1, and SIX1 were examined by Western blot assay. The correlation between FOXD2-AS1 and miR185-5p or miR185-5p and SIX1 were validated by bioinformatic, dual-luciferase, and RNA immunoprecipitation assays. Tumor xenografts were constructed to confirm the function and mechanism of FOXD2-AS1 in chemosensitivity of DDP-resistant NSCLC. Results: FOXD2-AS1 and SIX1 were upregulated and miR185-5p downregulated in DDP-resistant NSCLC. Absence of FOXD2-AS1 enhanced drug sensitivity of A549/DDP and H1299/DDP cells, reflected by the reduced colony formation, cell proliferation, migration, invasion, and drug resistance-associated protein expression. FOXD2-AS1 acted as a molecular sponge for miR185-5p and relieved the binding of miR185-5p and its target gene SIX1, leading to the derepression of SIX1 in A549/DDP and H1299/DDP cells. Rescue experiments validated the functional interaction among FOXD2-AS1, miR185-5p, and SIX1. Moreover, FOXD2-AS1 interference receded the growth of DDP-resistant NSCLC tumors in vivo. Conclusion: FOXD2-AS1/miR185-5p/SIX1 regulates the progression and chemosensitivity of DDP-resistant NSCLC, suggesting a potential therapeutic target for cisplatin-resistant NSCLC patients.

Background: Chemoresistance is a major obstacle for chemotherapy failure in non-small-cell lung cancer (NSCLC). lncRNAs are a class of pivotal regulators in various cancers, and the lncRNA FOXD2-AS1 is implicated in the progression of NSCLC. However, it is still unclear whether it regulates chemosensitivity. Methods: Expression levels of FOXD2-AS1, miR185-5p, and SIX1 mRNA were identified by reverse-transcription qPCR. CCK8 assay was performed to assess cell proliferation and chemosensitivity of cisplatin-resistant A549/DDP and H1299/DDP cells. Colony-forming assay was utilized to detect colony numbers. Cell migration and invasion ability were measured by transwell assay. The protein levels of LRP, Pgp, MRP1, and SIX1 were examined by Western blot assay. The correlation between FOXD2-AS1 and miR185-5p or miR185-5p and SIX1 were validated by bioinformatic, dual-luciferase, and RNA immunoprecipitation assays. Tumor xenografts were constructed to confirm the function and mechanism of FOXD2-AS1 in chemosensitivity of DDP-resistant NSCLC. Results: FOXD2-AS1 and SIX1 were upregulated and miR185-5p downregulated in DDP-resistant NSCLC. Absence of FOXD2-AS1 enhanced drug sensitivity of A549/DDP and H1299/DDP cells, reflected by the reduced colony formation, cell proliferation, migration, invasion, and drug resistance–associated protein expression. FOXD2-AS1 acted as a molecular sponge for miR185-5p and relieved the binding of miR185-5p and its target gene SIX1, leading to the derepression of SIX1 in A549/DDP and H1299/DDP cells. Rescue experiments validated the functional interaction among FOXD2-AS1, miR185-5p, and SIX1. Moreover, FOXD2-AS1 interference receded the growth of DDP-resistant NSCLC tumors in vivo. Conclusion: FOXD2-AS1/miR185-5p/SIX1 regulates the progression and chemosensitivity of DDP-resistant NSCLC, suggesting a potential therapeutic target for cisplatin-resistant NSCLC patients.

A miniaturized circularly polarized (CP) metasurface (MS) antenna using capacitive loading is investigated. First, one novel miniaturized MS unit cell is proposed. By introducing a pair of capacitive-loading strips inserted along the diagonal of a corner-truncated patch, 56% size reduction is achieved for this miniaturized unit cell. Accordingly, a compact CP MS antenna of a $4\,\,\times \,\,4$ array composed by the miniaturized unit cells is designed and fed by a slot structure. Compared with the conventional CP MS antenna without capacitive-loading strips, 63% overall size reduction can be achieved. Furthermore, the CP radiation mechanism of the CP MS antenna is revealed and explained clearly using the characteristic mode analysis (CMA). For demonstration, a prototype of the proposed CP antenna was fabricated and measured. The measured 3 dB axial ratio (AR) band is from 3.33 to 3.63 GHz, and the 10 dB impedance band is from 3.02 to 3.82 GHz, while 6.5 dBi gain is realized within the CP operating band.

Pt catalysts supported on a series of CrxFe2-xO3 composite oxides with different Cr/Fe molar ratios were prepared and tested for CO oxidation. The Pt/Cr1.3Fe0.7O3 catalyst possesses the best performance (with a turnover frequency of ca. 0.2 s −1 at 80 °C under 1% CO + 1% O2 condition), due to its best reducibility which was related to the solid solution structure of the support. The catalyst also shows good stability in the presence of both 10% CO2 and 10% H2O. Detailed kinetic results and staged reaction indicate that CO2 and H2O play opposite roles in the reaction. The inhibiting role of CO2 is due to competitive adsorption of CO2 with CO and the formation of carbonate species. However, the addition of H2O could effectively decompose the carbonate and sustain the catalyst stability. Moreover, the promoting role of H2O could be mainly attributed to the weakened strength of CO adsorption and the fast interfacial reaction between CO and the surface hydroxyl groups formed via H2O dissociation, as revealed by the X-ray photoelectron spectroscopy, CO temperature-programmed desorption and the kinetic results.

Catalytic propane combustion was performed on a series of supported Pt/AlF3 catalysts. These catalysts are very active and stable in the reaction, and the 0.2Pt/AlF3 catalyst gives the highest specific reaction rate of 207.3 μmol gPt−1 s−1 at 220 °C. The 1Pt/AlF3 is much more active than the reference Pt/Al2O3 catalyst, due to its higher content of metallic Pt species than that in the Pt/Al2O3. Furthermore, turnover frequency (TOF) based on Pt dispersion increases with the surface concentration of metallic Pt0 in the catalyst, suggesting these species might be the active sites. Furthermore, synergistic roles of metallic and oxidized Pt species are found, as the TOFs calculated based on surface Pt0 concentration reaches a maximum at the Pt0/Pt2+ molar ratio of about 1. Such optimal Pt0/Pt2+ ratio implies the requirement of Pt0 Pt2+ pair in the reaction, probably due to the activation and cleavage of C H bond on metallic Pt atom and the sequential oxidation on the oxidized Pt atoms.

A series of C-AlF3 composite catalysts were prepared using a sol-gel method and different aluminum precursors (i.e. aluminum isopropoxide (Al(OiPr)3) and aluminum diacetate hydroxide (C4H7AlO5)). These catalysts were very active in gas-phase dehydrofluorination of 1, 1, 1, 3, 3-pentafluoropane. For example, a catalyst calcined at 400 °C with aluminum isopropoxide as the precursor (denoted as C-AlF3-AIP-400) gave a reaction rate of 8.30 μmol s−1 gcat-1 and a selectivity to 1, 3, 3, 3-tetrafluoropropene (HFO-1234ze) of above 99% at 340 °C. More importantly, the C-AlF3 catalysts showed excellent stability during 100 h reaction, while the pure AlF3 catalyst suffered severe deactivation owing to the coke deposition on the surface. In contrast, pre-deposited carbonaceous species formed in the catalyst due to the incomplete decomposition of organic precursors during the preparation procedure, which blocked strong acidic sites in the AlF3 and thus maintained the catalyst stability. Therefore, these findings provide useful information on the development of efficient catalyst for this reaction, particularly on the maintainance of catalyst stability.

Objectives The primary aim of this study was to determine if computed tomographic (CT) texture analysis measurements of the tumor are independently associated with progression-free survival (PFS) and overall survival (OS) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC), including both unresectable locally advanced and metastatic PDAC, who were treated with chemotherapy. Methods After an institutional review board waiver was obtained, contrast material-enhanced CT studies in 41 patients with unresectable PDAC who underwent contrast-enhanced CT before chemotherapy between 2014 and 2017 were analyzed in terms of tumor texture, with quantification of mean gray-level intensity (Mean), entropy, mean of positive pixels (MPP), kurtosis, standard deviation (SD), and skewness for fine to coarse textures (spatial scaling factor (SSF) 0–6, respectively). The association between pretreatment and posttreatment texture parameters, as well as Δ value (difference between posttreatment and pretreatment texture parameters), and survival time was assessed by using Cox proportional hazards models and Kaplan-Meier analysis. Results Findings from the multivariate Cox model indicated that tumor size, tumor SD (HR, 0.942; 95% CI: 0.898, 0.988) and skewness (HR, 0.407; 95% CI: 0.172, 0.962) measurements with SSF = 3, and tumor SD (HR, 0.958; 95% CI: 0.92, 0.997) measurements with SSF = 4 were significantly and independently associated with PFS, while tumor size and tumor SD (HR, 0.928; 95% CI: 0.882, 0.976) measurements with SSF = 3 were significantly and independently associated with OS. None of the post-therapy texture parameters or Δ value had a significant association with OS or PFS in multivariate Cox regression models. Medium SD (SSF = 3) of more than 38.38 and coarse SD (SSF = 4) of more than 40.67 were associated with longer PFS after chemotherapy (for SSF = 3, median PFS was 10.0 vs 6.0 months [P = 0.024], and for SSF = 4, median PFS was 12.0 vs 6.0 months [P = 0.003]). SD of 38.38 or greater (SSF = 3) as a dichotomized variable was a significant positive prognostic factor for OS (median OS, 20.0 vs 9.0 months [P = 0.04]). Survival models that included a combination of pretreatment SD (SSF = 3) with tumor size, had the potential to perform better than SD alone, while having no statistical significance in this study (area under the ROC curve, 0.756 vs 0.715 [P = 0.066]). Conclusions Pretreatment CT quantitative imaging biomarkers from texture analysis are associated with PFS and OS in patients with unresectable PDAC who were treated with chemotherapy, and the combination of pretreatment texture parameters and tumor size have the potential to perform better in survival models than imaging biomarker alone.

Background Chronic granulomatous disease (CGD) is a rare disease in China, and very little large‐scale studies have been conducted to date. We aimed to investigate the clinical and genetic features of CGD in Chinese pediatric patients. Methods Pediatric patients with CGD from Beijing Children's Hospital, Capital Medical University, China, were enrolled from January 2006 to December 2016. Results A total of 159 pediatric patients with CGD were enrolled. The median age of clinical onset was 1.4 months, and 73% (116/159) had clinical onset symptoms before the 1 year of age. The most common site of invasion was the lungs. The lymph nodes, liver, and skin were more frequently invaded in X‐linked (XL) CGD patients than in autosomal recessive (AR) CGD patients (P

The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has grown into an emerging threat, labelling and inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. Here, we report a potent covalent scaffold, ebsulfur, for targeting the protein in vitro and in vivo. Enzymatic kinetic study indicated that eighteen ebsulfurs gained except 1a–b and 1f inhibited NDM-1, exhibiting an IC50 value ranging of 0.16–9 μM, and 1g was found to be the best, dose- and time-dependent inhibitor with an IC50 of 0.16 μM. Also, these ebsulfurs effectively restored the antibacterial activity of cefazolin against E. coli expressing NDM-1, and the best effect was observed to be from 1g, 1i and 1n, resulting in an 256-fold reduction in MIC of the antibiotic at a dose of 16 μg/mL. The equilibrium dialysis study implied that the ebsulfur disrupted the coordination of one Zn(II) ion at active site of NDM-1. Labelling of NDM-1 using a constructed fluorescent ebsulfur Ebs-R suggested that the inhibitor covalently bound to the target through SDS-PAGE analysis in vitro. Also, labelling NDM-1 in living E. coli cells with Ebs-R by confocal microscopic imaging showed the real-time distribution change process of intracellular recombinant protein NDM-1. Moreover, the cytotoxicity of these ebsulfurs against L929 mouse fibroblastic cells was tested, and their capability to restore antibacterial activity of antibiotic against clinical strains E. coli EC08 producing NDM-1 was determined. The ebsulfur scaffold proposed here is valuable for development of the covalent irreversible inhibitors of NDM-1, and also for labelling the target in vitro and in vivo.

Nanocrystalline hydroxyapatite (NHA) is a biocompatible, biodegradable, and osteoconductive bone graft material; however, it lacks osteoinductivity. The present study is aimed at investigating the feasibility of nanocrystalline hydroxyapatite (NHA) as an osteoinductive growth factor carrier. Bone morphogenic protein 2 (BMP2), an osteoinductive growth factor, was incorporated into NHA (BMP2-NHA) using a simple adsorption method. The growth factor loading and release kinetics were profiled using fluorescein-isothiocyanate-labeled bovine serum albumin (FITC-BSA) as a mimic of the osteoinductive growth factor BMP2. The effect of BMP2-NHA on the osteogenic differentiation of C2C12 cells and ectopic bone formation in mice were tested. Confocal laser-scanning microscopy showed that FITC-BSA was diffused throughout the porous structure of NHA. FITC-BSA was efficiently loaded in NHA and sustained release was observed up to 35 days in vitro. BMP2-NHA enhanced the expression of osteogenic markers Runx2, Osterix, Alp, and Col1α1 and ALP activity in C2C12 cells compared to NHA. Similarly, μ-CT and histological examinations showed that BMP2-NHA robustly induced ectopic bone formation in mice. This study suggests that NHA could be used as an effective carrier of osteoinductive growth factors, which ensures osteoinductivity of NHA via sustained release of the growth factor.

The Tuchengzi Formation is widely distributed in western Liaoning Province with a clear top and bottom. It is the focal area for the delineation of the terrestrial Jurassic–Cretaceous boundary in China. Based on continuous core samples taken from well YD1, detailed lithostratigraphic sequences and zircon uranium–lead (U-Pb) dating WERE used to investigate the Tuchengzi Formation. The zircon U-Pb ages of the tuff samples taken from the First and Third Members of the Tuchengzi Formation ranged from 153.8 to 137.16 Ma, indicating that they were formed in the late Middle Jurassic–Early Cretaceous. Dating results from the bottom of the Second Member of the Tuchengzi Formation indicate that the sedimentary time of the stratum is no later than 145.7 ± 2.1 Ma. We concluded that the Jurassic–Cretaceous boundary of the Jinyang Basin in western Liaoning province may be located at the interface at a depth of 464 m in well YD1. This conclusion is consistent with the Jurassic–Cretaceous boundary that has been presumed by other researchers based on paleontological assemblage features found in recent years, and can provide useful geological marker beds for the future study of the terrestrial Jurassic–Cretaceous boundary. In addition, the authors also systematically sorted the potential development areas and layers of the terrestrial Jurassic–Cretaceous boundary line, which may also provide useful geological marker beds for the future study of the terrestrial Jurassic–Cretaceous boundary.

This study aimed to investigate the effects of psychological nursing care (PNC) on anxiety relief in perioperative lung cancer (LC) patients.We searched the Cochrane Library, PubMed, Embase, CNKI, CBM, and Wangfang electronic databases from inception to May 1, 2022. Eligible randomized controlled trials (RCTs) investigating the effects and safety of PNC on anxiety relief in perioperative LC patients. Anxiety was the primary outcome measure. The secondary outcomes were depression, length of hospital stay, and the occurrence of adverse events.Six eligible RCTs with 494 patients were included in this study. Compared with routine nursing care, PNC showed better outcomes in terms of anxiety relief (mean difference [MD] = -13.24; random 95% confidence interval (CI), -18.28 to -8.20; P.001), depression decrease (MD = -11.84; random 95% CI, -18.67 to -5.01; P.001), and length of hospital stay (MD = -2.6; fixed 95% CI, -3.13 to -2.07; P.001). No data on adverse events were pooled because only 1 trial reported this outcome.This study showed that PNC may benefit more than routine nursing care for patients with LC in anxiety, depression, and length of hospital stay. High-quality RCTs are needed to validate the current findings in the future.

In this work, we experimentally demonstrate an electrically tunable superconducting composite structure metamaterial capable of modulating terahertz (THz) waves. Compared with other superconducting switching devices, our device is composed of golden structures and niobium nitride (NbN) film junctions together. Its unique structural characteristics allow our device to achieve relatively large amplitude modulation effects with the smallest superconducting films. With a 4 V bias voltage, a modulation depth of 73.8% for this switch can be achieved at 0.308 THz. The experimental results agree well with the simulations. To better illustrate the physical mechanism behind the resonance mode transition, a hybrid coupling model was introduced. Our work provides an alternative tuning method and delivers a promising approach for designing active and miniaturized devices in THz cryogenic systems.