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The opportunistic human pathogen Pseudomonas aeruginosa (P. aeruginosa) poses a significant threat to human health, causing sepsis, inflammation, and pneumonia, so it is crucial to devise an expeditious detection platform for the P. aeruginosa. In this work, bis (2- (3, 5- dimethylphenyl) quinoline- C2, N') (acetylacetonato) iridium (III) Ir (dmpq) 2 (acac) with excellent electrochemiluminescence (ECL) and fluorescence (FL) and magnetic nanoparticles were encapsulated in silica spheres. The luminescent units exhibited equal ECL and FL properties compared with single iridium complexes, and enabled rapid separation, which was of vital significance for the establishment of biosensors with effective detection. In addition, the luminescent units were further reacted with the DNA with quenching units to obtain the signal units, and the ECL/FL dual-mode biosensor was employed with the CRISPR/Cas12a system to further improve its specific recognition ability. The ECL detection linear range of as-proposed biosensor in this work was 100 fM-10 nM with the detection limit of 73 fM (S/N = 3), and FL detection linear range was 1 pM-10 nM with the detection limit of 0.126 pM (S/N = 3). Importantly, the proposed dual-mode biosensor exhibited excellent repeatability and stability in the detection of P. aeruginosa in real samples, underscoring its potential as an alternative strategy for infection prevention and safeguarding public health and safety in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The high volatility and hydrophobicity of cinnamon essential oils (CiEO) limited their practical application. To enhance their stability and antibacterial activity, nanoemulsions encapsulating CiEO were prepared using hydroxypropyl-β-cyclodextrin/lauroyl arginate (HPCD/LAE) inclusion complexes through high-pressure microfluidization (HPM). Effects of HPM parameters on the stability and antibacterial properties of nanoemulsion were investigated. Results revealed that increased processing pressure and cycle numbers were associated with reduced droplet size and greater homogeneity in CiEO distribution. Storage and thermal stability were optimized at 100 MPa and seven cycles. Moreover, the nanoemulsions showed strong synergistic antibacterial against E. coli (19.79 mm) and S. aureus (23.61 mm) compared with LAE (11.52 mm and 12.82 mm, respectively) and CiEO alone (13.26 mm and 17.68 mm, respectively). This study provided new information for constructing CiEO nanoemulsion, which is suitable for use in the food industry., Competing Interests: Declaration of competing interest The authors have no competing financial or personal interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Herein, we have described a novel organocatalytic approach to access biologically important dihydropyridin-2-ones in a one-pot way with generally high yields (up to 99%) and excellent enantioselectivities (up to 99% ee). This reaction proceeded via a new dual activation mode, including in situ-generated α,β-unsaturated acylazoliums and 4-dimethylaminopyridinium salts that underwent a Michael addition/1,4-H migration/lactamization sequence. The base-triggered 4-dimethylaminopyridinium ylide formation pathway over the competing substitution reaction pathway of vicinal haloamines is noteworthy.

In nature, basic terpene skeletons are produced and subsequently undergo enzymatic or nonenzymatic oxidative transformations, leading to diverse structural variations. To date, thousands of natural products featuring a variety of oxidation patterns have been isolated solely from the labdane family. This work describes a strategy for the comprehensive introduction of oxidation states into the labdane core by employing a combination of enzyme library screening, directed evolution, and sequential chemical oxidation processes. Furthermore, we showcase the functional viability of our chemoenzymatic approach by accomplishing a formal synthesis of nimbolide, highlighting its potential for streamlining the synthesis of complex natural products.

Community-acquired pneumonia (CAP) is a major cause of death in children under 5 years old globally. With Streptococcus pneumoniae ( S. pneumoniae ) and Mycoplasma pneumoniae ( M. pneumoniae ) being the main pathogens linked to CAP that requires hospitalization, there is an urgent need for a straightforward, cost-efficient, and highly accurate diagnostic method for immediate and early detection of CAP. In this work, benzo[1,2- c ;4,5- c ']bis([1,2,5]thiadiazole) (BBT) as π-bridge spacer with the donor unit of poly(9,9-dioctylfluorene) (PF) and the acceptor unit of dithienylbenzoselenadiazole (DBS) has been successfully copolymerized to unprecedentedly prepare novel D-π-A selenium-based polymer dots with efficient NIR electrochemiluminescence (named as Se-Pdots in this work). Se-Pdots exclusively generated excellent anodic ECL in the two-component coreaction system comprising TPrA and K 2 S 2 O 8 . Moreover, a potential-resolved ECL biosensor to simultaneously detect S. pneumoniae and M. pneumoniae has also been successfully constructed based on this novel Se-based NIR Pdots as an anodic emitter with CdS QDs as a cathodic emitter. Under optimal conditions, the biosensor has a wide linear range for S. pneumoniae (10 -15 to 10 -9 M) and M. pneumoniae (10 -15 to 10 -9 M), with low detection limits for S. pneumoniae (0.56 fM) and M. pneumoniae (0.96 fM). The proposed ECL biosensor provides a simple, sensitive, and reliable method for the simultaneous detection of CAP pathogens in clinical applications.

Mutations in the C-terminal of KIF1A (Kinesin family member 1A) may lead to amyotrophic lateral sclerosis (ALS) through unknown mechanisms that are not yet understood. Using iPSC reprogramming technology and motor neuron differentiation techniques, we generated iPSCs from a healthy donor and two ALS patients with KIF1A mutations (R1457Q and P1688L) and differentiated them into spinal motor neurons (iPSC-MN) to investigate KIF1A -related ALS pathology. Our in vitro iPSC-iMN model faithfully recapitulated specific aspects of the disease, such as neurite fragmentation. Through this model, we observed that these mutations led to KIF1A aggregation at the proximal axon of motor neurons and abnormal accumulation of its transport cargo, LAMP1, resulting in autophagy dysfunction and cell death. RNAseq analysis also indicated that the functions of the extracellular matrix, structure, and cell adhesion were significantly disturbed. Notably, using rapamycin during motor neuron differentiation can effectively prevent motor neuron death.

Age-related hearing loss is a complex disease caused by a combination of genetic and environmental factors, and a study have conducted animal experiments to explore the association between BCL11B heterozygosity and age-related hearing loss. The present study used established genetic models to examine the association between BCL11B gene polymorphisms and age-related hearing loss. A total of 410 older adults from two communities in Qingdao, China, participated in this study. The case group comprised individuals aged ≥ 60 years with age-related hearing loss, and the control group comprised individuals without age-related hearing loss from the same communities. The groups were matched 1:1 for age and sex. The individual characteristics of the participants were analyzed descriptively using the Mann-Whitney U test and the chi-square test. To explore the association between BCL11B gene polymorphisms and age-related hearing loss, conditional logistic regression was performed to construct genetic models for two single-nucleotide-polymorphisms (SNPs) of BCL11B, and haplotype analysis was conducted to construct their haplotype domains. Two SNP sites of the BCL11B gene, four genetic models of rs1152781 (additive, dominant, recessive, and codominant), and five genetic models of rs1152783 (additive, dominant, recessive, codominant, and over dominant) were significantly associated with age-related hearing loss in the models both unadjusted and adjusted for all covariates (P < 0.05). Additionally, a linkage disequilibrium between rs1152781 and rs1152783 was revealed through haplotype analysis. Our study revealed that BCL11B gene polymorphisms were significantly associated with age-related hearing loss., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Human herpesvirus type 6A (HHV-6A) can cause a series of immune and neurological diseases, and the establishment of a sensitive biosensor for the rapid detection of HHV-6A is of great significance for public health and safety. Herein, a bis-tridentate iridium complex (BisL T -Ir-NHC) comprising the N-heterocyclic carbene (NHC) ligand as a novel kind of efficient ECL luminophore has been unprecedently reported. Based on its excellent ECL properties, a new sensitive ECL-based sandwich immunosensor to detect the HHV-6A virus was successfully constructed by encapsulating BisL T -Ir-NHC into silica nanoparticles and embellishing ECL sensing interface with MXene@Au-CS. Notably, the immunosensor illustrated in this work not only had a wide linear range of 10 2 to 10 7 cps/μL but also showed outstanding recoveries (98.33-105.11%) in real human serum with an RSD of 0.85-3.56%. Undoubtedly, these results demonstrated the significant potential of the bis-tridentate iridium(III) complex containing an NHC ligand in developing ECL-based sensitive analytical methods for virus detection and exploring novel kinds of efficient iridium-based ECL luminophores in the future.

Based on the monitoring data of 137 Cs and 90 Sr in Tian Bay in 2005-2023, the impacts of the operation of Tianwan Nuclear Power Plant on the marine ecosystem were assessed. The 137 Cs and 90 Sr activity concentrations in the seawater and sediment varied within the background ranges. The radiation dose rates derived from 137 Cs and 90 Sr for the marine organisms ranged from 2.4 × 10 -5 to 2.2 × 10 -4 nGy/h, it was far below the most conservative screening dose rate (10 μGy/h). The committed effective dose for humans was 0.070-0.094 μSv, 1/1500th of the world's mean annual effective dose (0.12 mSv) from ingesting food containing uranium and thorium series nuclides. Radiation risk assessment showed no radiation risk for the long-term discharge of nuclear wastes in the future. Overall, the long-term normal operation of TNPPs has almost no radiation impact on the adjacent marine ecosystem., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study established specialized radiation dose models to evaluate the internal radiation doses derived from 137 Cs and 134 Cs in fishes in the port of the Fukushima Daiichi Nuclear Power Plant from 2012 to 2023. By August 2018, the activities of 134 Cs and 137 Cs in fishes decreased at the T 1/2 of 176 d and 191 d, respectively. The corresponding mass concentrations were far lower than 1 mg/kg and the chemical toxicity can be negligible. Regarding radiotoxicity, 18,000 Bq/kg fresh weight of 134 Cs and 137 Cs in grouper Sebastes schlegelii produced 276 μGy/h of radiation dose, which was below the no-effect-dose-rate benchmarks (400 μGy/h). 740,000 Bq/kg fresh weight of 134 Cs and 137 Cs in greenling Hexagrammos otakii produced 12,600 μGy/h of radiation dose, which was much higher than 400 μGy/h, indicating the possibility of radiation effects. If a person eats these two reported fishes, the resulting committed effective doses for humans are 7.7 μSv and 6.31 mSv, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Ethnopharmacological Relevance: Qingda granule (QDG) is effective for treating hypertension and neuronal damage after cerebral ischemia/reperfusion. However, the anti-neuroinflammatory effect of QDG on injury due to cerebral ischemia/reperfusion is unclear., Aim of the Study: The objective was to evaluate the effectiveness and action of QDG in treating neuroinflammation resulting from cerebral ischemia/reperfusion-induced injury., Materials and Methods: Network pharmacology was used to predict targets and pathways of QDG. An in vivo rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) as well as an in vitro model of LPS-stimulated BV-2 cells were established. Magnetic resonance imaging (MRI) was used to quantify the area of cerebral infarction, with morphological changes in the brain being assessed by histology. Immunohistochemistry (IHC) was used to assess levels of the microglial marker IBA-1 in brain tissue. Bioplex analysis was used to measure TNF-α, IL-1β, IL-6, and MCP-1 in sera and in BV-2 cell culture supernatants. Simultaneously, mRNA levels of these factors were examined using RT-qPCR analysis. Proteins of the TLR4/NF-κB/NLRP3 axis were examined using IHC in vivo and Western blot in vitro, respectively. While NF-κB translocation was assessed using immunofluorescence., Results: The core targets of QDG included TNF, NF-κB1, MAPK1, MAPK3, JUN, and TLR4. QDG suppressed inflammation via modulation of TLR4/NF-κB signaling. In addition, our in vivo experiments using MCAO/R rats demonstrated the therapeutic effect of QDG in reducing brain tissue infarction, improving neurological function, and ameliorating cerebral histopathological damage. Furthermore, QDG reduced the levels of TNF-α, IL-1β, IL-6, and MCP-1 in both sera from MCAO/R rats and supernatants from LPS-induced BV-2 cells, along with a reduction in the expression of the microglia biomarker IBA-1, as well as that of TLR4, MyD88, p-IKK, p-IκBα, p-P65, and NLRP3 in MCAO/R rats. In LPS-treated BV-2 cells, QDG downregulated the expression of proinflammatory factors and TLR4/NF-κB/NLRP3 signaling-related proteins. Additionally, QDG reduced translocation of NF-κB to the nucleus in both brains of MCAO/R rats and LPS-induced BV-2 cells. Moreover, the combined treatment of the TLR4 inhibitor TAK242 and QDG significantly reduced the levels of p-P65, NLRP3, and IL-6., Conclusions: QDG significantly suppressed neuroinflammation by inhibiting the TLR4/NF-κB/NLRP3 axis in microglia. This suggests potential for QDG in treating ischemia stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Cinnamon essential oil (CEO) was emulsified by hydroxypropyl-β-cyclodextrin/ ethyl lauroyl arginate (HPCD/LAE) complex to make nanoemulsions, which were then incorporated into maltodextrin (MD) to prepare HPCD/LAE/CEO/MD microcapsules by spray drying. The starch/polybutylene adipate terephthalate (starch/PBAT, SP) based extrusion-blowing films containing above microcapsules were developed and used as packaging materials for strawberry preservation. The morphology, encapsulation efficiency, thermal and antibacterial properties of microcapsules with different formulations were investigated. The effects of microcapsules on the physicochemical and antimicrobial properties of SP films were evaluated. When the formula was 4 % HPCD/LAE-3% CEO-10% MD (HL-3C-MD), the microcapsule had the smallest particle size (3.3 μm), the highest encapsulation efficiency (84.51 %) of CEO and the best antibacterial effect. The mechanical and antimicrobial properties of the SP film were enhanced while the water vapor transmittance and oxygen permeability decreased with the incorporation of HL-3C-MD microcapsules. The films effectively reduced the weight loss rate (49.03 %), decay rate (40.59 %) and the total number of colonies (2.474 log CFU/g) and molds (2.936 log CFU/g), thus extending the shelf life of strawberries. This study revealed that the developed SP films containing HPCD/LAE/CEO microcapsules had potential applications in degradable bioactive food packaging materials., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2024. Published by Elsevier B.V.)

The establishment of rapid target identification and analysis methods for antibiotic resistance genes (ARGs) is urgently needed. In this study, we unprecedently designed a target-catalyzed hairpin assembly (CHA) electrochemiluminescent (ECL) biosensor for the ultrasensitive detection of ampicillin resistance genes (ARG AMP ) based on a novel, efficient near-infrared ruthenium carbene complex/TPrA/PEI ternary ECL system with low oxidation potential. The ternary NIR-ECL system illustrated in this work displayed double ECL intensity in comparison with their corresponding traditional binary ECL system. The as-prepared ECL biosensor illustrated in this work demonstrates highly selective and sensitive determination of ARG AMP from 1 fM to 1 nM and a low detection limit of 0.23 fM. Importantly, it also exhibits good accuracy and stabilities to identify ARG AMP in plasmid and bacterial genome DNA, which demonstrates its excellent reliability and great potential in detecting ARG AMP in real environmental samples.

Inflammation plays a critical role in vertebral fractures. However, there is a lack of sufficient evidence regarding the prognostic significance of the systemic immuno-inflammatory index (SII), a novel marker of systemic inflammation, in patients with vertebral fractures. In this study, we aimed to assess the predictive value of SII in critically ill patients with vertebral fractures. The data were from the Medical Information Mart for Intensive Care III (MIMIC-III) version 1.4 and Wenzhou Hospital of Traditional Chinese Medicine. The cutoff values for SII were determined using the receiver operating characteristic curve, and the subjects were grouped accordingly. The clinical outcome measured was mortality within 30 days, 90 days, or 1 year. The following formula was used to calculate the SII: SII = (platelet count) × (neutrophil count)/ (lymphocyte count). Cox proportional-hazard models were employed to assess the relationship between SII and survival. Additionally, propensity score matching analysis and COX models were utilized to examine the association between SII and survival outcomes. The Pearson correlation test confirmed the correlation between SII and vertebral T-values measured by bone mineral density and pain indicator. A total of 354 patients were finally included from MIMIC-III in the univariate analysis, for the 30-day mortality, SII ≥ 3164 group, the hazard ratio (HR) (95% confidence interval) was 1.71 (1.01, 2.94). After adjusting for age, gender, race, anion gap, creatinine, systolic blood pressure (SBP), DBP MBP, SOFA, acute physiologic score III, chronic kidney disease, and SAPS II, SII ≥ 3164 was found to be an independent significant risk factor for death in patients (HR = 1.85, 95% CI: 1.06-3.24, P = .0315). A similar trend was observed for 90-day mortality and 1-year mortality. Propensity scores matching analysis further confirmed the association of SII and the prognosis of patients. Our validation results were consistent with it. Besides, the Pearson correlation test confirmed a significant correlation between SII and vertebral T-values measured by bone mineral density and pain indicator. The study findings revealed that SII is an independent predictor of mortality in patients with vertebral fractures. This indicates that SII can serve as a reliable and easily accessible prognostic indicator for newly diagnosed critically ill patients with vertebral fractures., Competing Interests: The authors declared no conflicts of interest in this work., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ethnopharmacological Relevance: Liensinine(Lien, C 37 H 42 N 2 O 6 ) is an alkaloid compound from plumula nelumbinis that demonstrates an antihypertensive effect. The protective effects of Lien on target organs during hypertension are still unclear., Aim of the Study: This study aimed to understand the mechanism of Lien during the treatment of hypertension, with emphasis on vascular protection., Materials and Methods: Lien was extracted and isolated from plumula nelumbinis for further study. In vivo model of Ang II-induced hypertension, non-invasive sphygmomanometer was used to detect the blood pressure in and out of the context of Lien intervention. Ultrasound was used to detect the abdominal aorta pulse wave and media thickness of hypertensive mice, and RNA sequencing was used to detect the differential genes and pathways of blood vessels. The intersection of Lien and MAPK protein molecules was detected by molecular interconnecting technique. The pathological conditions of abdominal aorta vessels of mice were observed by HE staining. The expression of PCNA, α-SMA, Collagen Type Ⅰ and Collagen Type Ⅲ proteins were detected by IHC. The collagen expression in the abdominal aorta was detected by Sirius red staining. The MAPK/TGF-β1/Smad2/3 signaling and the protein expression of PCNA and α-SMA was detected by Western blot. In vitro, MAPK/TGF-β1/Smad2/3 signaling and the protein expression of PCNA and α-SMA were detected by Western blot, and the expression of α-SMA was detected by immunofluorescence; ELISA was used to detect the effect of ERK/MAPK inhibitor PD98059 on Ang Ⅱ-induced TGF-β1secrete; and the detection TGF-β1and α-SMA protein expression by Western blot; Western blot was used to detect the effect of ERK/MAPK stimulant12-O-tetradecanoyl phorbol-13-acetate (TPA) on the protein expression of TGF-β1 and α-SMA., Results: Lien displayed an antihypertensive effect on Ang Ⅱ-induced hypertension, reducing the pulse wave conduction velocity of the abdominal aorta and the thickness of the abdominal aorta vessel wall, ultimately improving the pathological state of blood vessels. RNA sequencing further indicated that the differential pathways expressed in the abdominal aorta of hypertensive mice were enriched in proliferation-related markers compared with the Control group. The profile of differentially expressed pathways was ultimately reversed by Lien. Particularly, MAPK protein demonstrated good binding with the Lien molecule. In vivo, Lien inhibited Ang Ⅱ-induced abdominal aorta wall thickening, reduced collagen deposition in the ventral aortic vessel, and prevented the occurrence of vascular remodeling by inhibiting MAPK/TGF-β1/Smad2/3 signaling activation. In addition, Lien inhibited the activation of Ang II-induced MAPK and TGF-β1/Smad2/3 signaling, attenuating the expression of PCNA and inhibiting the reduction of α-SMA, collectively playing a role in the inhibition of Ang Ⅱ-induced hypertensive vascular remodeling. PD98059 alone could inhibit Ang Ⅱ-induced elevation of TGF-β1 and the decrease of α-SMA expression. Further, PD98059 combined with Lien had no discrepancy with the inhibitors alone. Simultaneously TPA alone could significantly increase the expression of TGF-β1 and decrease the expression of α-SMA. Further, Lien could inhibit the effect of TPA., Conclusion: This study helped clarify the protective mechanism of Lien during hypertension, elucidating its role as an inhibitor of vascular remodeling and providing an experimental basis for the research and development of novel antihypertensive therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Histone lysine acylation, including acetylation and crotonylation, plays a pivotal role in gene transcription in health and diseases. However, our understanding of histone lysine acylation has been limited to gene transcriptional activation. Here, we report that histone H3 lysine 27 crotonylation (H3K27cr) directs gene transcriptional repression rather than activation. Specifically, H3K27cr in chromatin is selectively recognized by the YEATS domain of GAS41 in complex with SIN3A-HDAC1 co-repressors. Proto-oncogenic transcription factor MYC recruits GAS41/SIN3A-HDAC1 complex to repress genes in chromatin, including cell-cycle inhibitor p21. GAS41 knockout or H3K27cr-binding depletion results in p21 de-repression, cell-cycle arrest, and tumor growth inhibition in mice, explaining a causal relationship between GAS41 and MYC gene amplification and p21 downregulation in colorectal cancer. Our study suggests that H3K27 crotonylation signifies a previously unrecognized, distinct chromatin state for gene transcriptional repression in contrast to H3K27 trimethylation for transcriptional silencing and H3K27 acetylation for transcriptional activation., Competing Interests: Declaration of interests M.-M.Z. is a scientific founder, director, and shareholder of Parkside Scientific Inc., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study aims to explore the impact of Orem-based nursing intervention on the pain levels, self-care abilities, psychological statuses, and quality of life in bone cancer patients., Methods: A total of 91 patients with primary bone cancer admitted to our hospital from January 2019 to January 2020 were randomly placed into one of two groups. The patients in the control group (n=43) underwent routine nursing care, and the patients in the experimental group (n=48) underwent Orem-based nursing care during the perioperative period. The two groups were compared in terms of their postoperative recovery times and treatment effects, and their adverse emotion scores, pain levels, self-care abilities, and quality of life before and after intervention., Results: The treatment efficacy in the two groups was similar, but the postoperative recovery times in the experimental group were shorter than they were in the control group (P < 0.05). Compared with before the intervention, the SDS, SAS, and VAS scores were significantly decreased in both groups (P < 0.05), and their self-care abilities and quality of life were significantly higher (P < 0.05) after intervention., Conclusion: Orem-based nursing combined with perioperative care can mobilize patients' initiative, significantly improve patients' adverse emotions and pain levels, shorten their postoperative recovery times, and help improve their self-care abilities and quality of life., Competing Interests: None., (AJTR Copyright © 2023.)

Objective: This study examines the effects of the 3S2E nursing management mode on patients with severe pneumonia in the intensive care unit's respiratory function, psychological status, and quality of life (ICU)., Methods: According to a random number table, 82 ICU patients with severe pneumonia who were admitted between March 2021 and March 2022 were enrolled and assigned to the control and observation class ( n  = 41, respectively) in a 1 : 1 ratio. The observation class added 3S2E manner in addition to ordinary breastfeeding, whereas the control class received treatment in the usual nursing mode. The two groups' preintervention and postintervention times for mechanical ventilation, white blood cell count (WBC) recovery, duration of hospital stay, problems, respiratory function, psychological state, and living quality were compared., Results: Fever time abatement, mechanical ventilation time, WBC recovery time, and length of hospital stay in the observation category were found to be shorter in comparison with the control class ( P < 0.05). In contrast to the other group, the observation group had fewer issues ( P < 0.05). Both teams' oxygenation indices and SaO 2 were higher after the intervention ( P < 0.05), with the observation team's index being higher than the control group's index. The total SAS and SDS scores of the two groups were less in the postintervention period than in the preintervention period, with the observational class having lower postintervention SAS and SDS ratings than the comparison group ( P < 0.05). The postintervention ratings in the observation class were higher than those in the control, and the World Health Organization Quality of Life (WHOQOL) scale scores in the 2 categories were greater after the intervention than they were before ( P < 0.05)., Conclusion: 3S2E nursing management model improves respiratory function, alleviates negative emotions, and improves living quality in ICU patients with severe pneumonia., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yaoyao Xu et al.)

Objective: To explore the genetic basis for a patient with factor VIII deficiency., Methods: All exons of the F13A1 and F13B genes were amplified by PCR and sequenced directly. The sequencing was performed with a reverse primer if a variant was found. Conservation of variant site was analyzed by the ClustalX software. Four online bioinformatic software including Mutation Taster, PolyPhen-2, PROVEAN and SIFT were used to predict the function of the mutation site. The Swiss-PdbViewer software was applied to analyze the changes in the protein model and intermolecular force., Results: The proband was found to harbor a novel c.515G>C (p.Arg171Pro) variant of the F13A1 gene. The corresponding amino acid Arg171 is conserved among homologous species. Bioinformatic analysis indicated that Arg171Pro variant may affect the protein function. Protein model analysis showed that in the wild-type, there is one hydrogen bond between Arg171 and Pro27; one hydrogen bond between Arg171 and Thr28; two hydrogen bonds between Arg171 and Glu102. When Arg171 was mutated to Pro171, the three hydrogen bonds between Arg171 and Pro27, Glu102 are all disappeared and formed a new benzene ring which might affect the stability of the protein structure. No variant was found in the F13B gene., Conclusion: The Arg171Pro variant may account for the decreased FVIII level. Above finding has enriched the spectrum of F13A1 gene variants.

Aim: Inducible nitric oxide synthase (iNOS) is a validated target for anti-inflammatory treatment. Based on the authors' previous work, novel aza-ursolic acid derivatives were designed and synthesized and their inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) release from RAW264.7 cells was evaluated. Materials & results: 16 novel derivatives were screened for their in vitro inhibitory activity against NO release using Griess assays and the cytotoxicity was evaluated using MTT assays. The presence of furoxan joined to the A-ring of ursolic acid and N -methylpiperazine groups in the lead compound was identified for anti-inflammatory activity, and compound  21b showed 94.96% inhibition of NO release at 100 μM with an IC 50 value of 8.58 μM. Conclusion: Compound 21b has potential anti-inflammatory activity with low cytotoxicity that warrants further preclinical study and evaluation.

To improve the antimicrobial properties of chitosan films, cinnamon essential oil (CEO) nanoemulsion (1% and 3% v/v CEO) stabilized by ethyl-N α -lauroyl-l-arginate hydrochloride (LAE) alone or co-stabilized by LAE and hydroxypropyl-β-cyclodextrin (HPCD) were incorporated into chitosan matrix. The micromorphology, physical and antimicrobial properties of the composite films were compared. The dense structure of the CEO nanoemulsion co-stabilized by LAE and HPCD reduced the water vapor permeability and water content. The incorporation of the CEO nanoemulsion co-stabilized by LAE and HPCD, reduced the adverse effects of CEO on the mechanical properties and microstructure of the film, and even slightly increased the tensile strength. In addition, the antimicrobial properties of chitosan films were enhanced due to the encapsulation and emulsification effect of HPCD and LAE on CEO. This work indicated that the prepared chitosan based edible films had the potential to be used in the field of food packaging to improve food safety., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Physalis angulata L. is commonly used in many countries as popular medicine for the treatment of a variety of diseases such as malaria, hepatitis, dermatitis and rheumatism. But the anti-inflammatory active constituents of this medicinal plant and their molecular mechanism are still not elucidated clearly., Aim of the Study: The aim of the study is to isolate and identify a series of compounds from the ethanolic extract of Physalis angulata L., and to investigate the anti-inflammatory activities in vitro and the molecular mechanism of physagulin A, physagulin C, and physagulin H., Materials and Methods: In order to further understand the anti-inflammatory mechanism of the three compounds, their potential anti-inflammatory activities were investigated in vitro in LPS-activated RAW 264.7 macrophage cells by Griess assay, ELISA, Western blot and immunofluorescence methods in the present study., Results: Physagulin A, physagulin C, and physagulin H could not only inhibit the release of NO, PGE 2 , IL-6 and TNF-α, but also could down-regulate the expression of iNOS and COX-2 proteins. Furthermore, physagulin A, physagulin C, and physagulin H could remarkably block the degradation of IκB-α and the nuclear translocation of NF-κB/p65 in LPS-activated RAW 264.7 cells. However, none of them could inhibit the phosphorylation of MAPKs family proteins ERK, JNK and p38. Thus, the anti-inflammatory actions of physagulin A, physagulin C, and physagulin H were mainly due to the significant inhibition of NF-κB signaling pathway rather than MAPKs signaling pathway., Conclusions: All the results clearly showed that physagulin A, physagulin C, and physagulin H demonstrated potent anti-inflammatory activity and can be used as novel NF-κB inhibitors. They are potential to be developed as an alternative or complementary agents for inflammatory diseases., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mitogen-activated protein kinase kinases are an important part of evolutionary conserved signaling modules that are involved in a variety of cellular processes in response to environmental stimuli. Among them, mitogen-activated protein kinase kinase 2 (MEK2) is the most crucial upstream signaling pathway of ERK1/2 cascade as a therapeutic target for overcoming Ras-driven cancers. However, the mechanisms of MEK2 regulation during tumor progression remain not fully elucidated. Herein, we identified that MEK2 was post-translationally regulated by O-GlcNAcylation. We found that MEK2 associated with OGT and was modified by O-GlcNAc. Mass spectrometry analysis further verified that O-GlcNAcylation of MEK2 occurred at Thr13, which was in the docking domain for specifically identifying its target proteins. While total O-GlcNAcylation stimulated the protein stability and phosphorylation of MEK2, Thr13 O-GlcNAcylation of MEK2 specifically enhanced its Thr394 phosphorylation as well as downstream ERK1/2 activation. Genetic ablation of MEK2 O-GlcNAcylation at Thr13 abrogated its ability to promote the proliferation and migration of breast cancer cells. Together, our data demonstrate that O-GlcNAcylation of MEK2 might be a key regulatory mechanism during tumorigenesis and is a potential therapeutic target for tumor treatment., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Elevation is important for determining the nutrient biogeochemical cycle in forest ecosystems. Changes in the ecological stoichiometry of nutrients along an elevation gradient can be used to predict how an element cycle responds in the midst of global climate change. We investigated changes in concentrations of and relationships between nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) in the leaves and roots of the dominant tree species, Castanopsis fargesii, along an elevation gradient (from 500 to 1,000 m above mean sea level) in a subtropical natural forest in China. We analyzed correlations between C. fargesii 's above-ground biomass and stoichiometry with environmental factors. We also analyzed the soil and plant stoichiometry of this C. fargesii population. Our results showed that leaf N decreased while leaf K and Ca increased at higher elevations. Meanwhile, leaf P showed no relationship with elevation. The leaf N:P indicated that C. fargesii was limited by N. Elevation gradients contributed 46.40% of the total variance of ecological stoichiometry when assessing environmental factors. Our research may provide a theoretical basis for the biogeochemical cycle along with better forest management and fertilization for this C. fargesii population., Competing Interests: The authors declare there are no competing interests., (©2021 Liu et al.)

S-Nitrosylation is an important post-translational modification that occurs on cysteine amino acid and regulates signal transduction in diverse cell processes. Dysregulation of protein nitrosylation has shown close association with cardiovascular and neurological diseases, thus demanding further precise and in-depth understanding. Mass spectrometry-based proteomics has been the method of choice for analyzing S-nitrosylated (SNO-) proteins. However, due to their extremely low expression level and rapid turnover rate, quantitative analysis of the S-nitrosylation at the proteomic level remains challenging. Herein, we developed a novel approach termed FluoroTRAQ, which combined the fluorous solid-phase extraction of SNO-peptides and iTRAQ labeling for the quantitative analysis of the SNO-proteome with high sensitivity and specificity. This new analytical strategy was subsequently applied to examine the dynamic SNO-proteome changes of human umbilical vein endothelial cells upon in vitro S-nitrosoglutathione induction. Our data identified a number of novel SNO-proteins and revealed their temporal modulation as validated by biotin switch assay. Our study offered a practical approach for quantitative analysis of protein S-nitrosylation.

Surgical simulators and injury-prediction human models require a combination of representative tissue geometry and accurate tissue material properties to predict realistic tool-tissue interaction forces and injury mechanisms, respectively. While biological tissues have been individually characterized, the transition regions between tissues have received limited research attention, potentially resulting in inaccuracies within simulations. In this work, an approach to characterize the transition regions in transversely isotropic (TI) soft tissues using functionally graded material (FGM) modeling is presented. The effect of nonlinearities and multi-regime nature of the TI model on the functional grading process is discussed. The proposed approach has been implemented to characterize the transition regions in the leaflet (LL), chordae tendinae (CT) and the papillary muscle (PM) of porcine tricuspid valve (TV) and mitral valve (MV). The FGM model is informed using high resolution morphological measurements of the collagen fiber orientation and tissue composition in the transition regions, and deformation characteristics predicted by the FGM model are numerically validated to experimental data using X-ray diffraction imaging. The results indicate feasibility of using the FGM approach in modeling soft-tissue transitions and has implications in improving physical representation of tissue deformation throughout the body using a scalable version of the proposed approach.

A tungsten-catalyzed allylic allylation of sodium sulfinate as the heteroatom nucleophile was developed. The reaction utilizes inexpensive and readily available (CH 3 CN) 3 W(CO) 3 as a precatalyst and proceeds at 60 °C temperature in the presence of 2,2'-bipyridine and its derivatives as ligand. The synthetic utility of allylic sulfones as electrophile was further demonstrated through Suzuki-Miyaura cross-coupling as showcased by the formal synthesis of (±)-hinokiresinol.

Clove essential oil (CLO) Pickering emulsions were prepared with zein colloid particles as stabilizer, and the effects of CLO Pickering emulsion incorporation on the structure, mechanical, barrier and antimicrobial properties of chitosan-based edible films were explored. CLO Pickering emulsions with 3% w/v zein and 50% v/v CLO had smaller particle size and more even distribution. Incorporation of CLO Pickering emulsion in the films decreased the water vapor permeability and tensile strength, but the elongation at break firstly increased then decreased with the maximum value of 19.2% when the content of emulsion was 0.4%. Scanning electron microscopy revealed the formation of microstructure-sized holes in the films by the addition of CLO Pickering emulsion. The emulsified oil droplets were uniformly distributed, due to the good compatibility between oil phase and chitosan matrix. The antimicrobial properties of the films were strengthened by CLO Pickering emulsion incorporation and mainly depended on its concentration., Competing Interests: Declaration of competing interest The authors declare that no conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The first molybdenum-catalyzed allylic sulfonylation of tertiary allylic electrophiles is described. The method employs a readily accessible catalyst (Mo(CO) 6 /2,2'-bipyridine, both are commercially available) and represents the first example of the use of a group 6 transition metal-catalyst for allylic sulfonylation of substituted tertiary allylic electrophiles to form carbon-sulfur bonds. This atom economic and operationally simple methodology is characterized by its relatively mild conditions, wide substrate scope, and excellent regioselectivity profile, thus unlocking a new platform to forge sulfone moieties, even in the context of late-stage functionalization and providing ample opportunities for further derivatization through traditional Suzuki cross-coupling reactions., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

An atom interferometer based on Doppler-insensitive Raman transition is proposed, which has sharply peaked interference fringes for multi-wave interference. We show that two sets of counter-propagating Doppler-insensitive Raman beam pairs can be used to construct a new type of multi-wave beam splitter, which can be used to construct an atom interferometer. Although the spacing between adjacent diffraction orders of the interferometer is small, they can be distinguished by the internal state of the atom. Our analysis shows that the width of the fringes of this atom interferometer is inversely proportional to the width (duration) of the beam splitter and the Rabi frequency of the Raman beams, that is, the interferometer can achieve high resolution at high light intensity and long pulse width.

Auricularia auricula-judae is an important culinary-medicinal mushroom. The A. auricula-judae polysaccharides (AAPs) were prepared from A. auricula-judae in the early stage through alkali extraction and deproteination with the Sevag method, and optimal acid hydrolysis conditions were established by Box-Behnken to prepare the degraded polysaccharides (AAPs-F) from AAPs. In this study, a nonenzymatic glycosylation reaction system was used for the evaluation of the inhibitory effects on the formation of advanced glycation end products (AGEs). In addition, high glucose resistance was assessed by glucose consumption of HepG2 cells and the lifespan of Caenorhabditis elegans under high sugar stress. It was found that both 0.5 mg·mL-1 AAPs and 0.2 mg·mL-1 AAPs-F could significantly inhibit AGE formation in short- and long-term glycosylation (P < .05) in a dose-dependent manner, determined by ultraviolet and fluorospectrophotometry. It indicated activity against AGE formation for different concentrations of AAPs and AAPs-F. AAPs-F at 0.5 mg·mL-1 significantly enhanced the glucose absorption of HepG2 cells by 24.4% (P < .05) in a dose-dependent manner at 24 h, and markedly extended the lifespan of C. elegans by 32.9% (P < 0.05) under high sugar stress conditions. This study demonstrated that the derived hydrolysates produced by the hydrolysis of acid had a prominent effect on the inhibition of AGE formation and relieved the stress state caused by high sugar levels.

Time is an inevitable quantity involved in absolute gravity measurements, and 10 MHz frequency standards are usually utilized as time base. Here we investigate the influence of time base bias on atom-interferometry-based gravity measurements and present an onsite calibration of the time base bias relying on an atom gravimeter itself. With a microwave source referenced to the time base, the time base bias leads to a magnified frequency shift of the microwave source output. The shift is then detected by Ramsey spectroscopy with the clock transition of 87 Rb atoms as a frequency discriminator. Taking advantage of available free-fall cold atoms and developed techniques of measuring the atom energy level shift in atom gravimeters, the calibration achieves an accuracy of 0.6 mHz for the time base. And the corresponding error for gravity measurements is constrained to 0.1 μ Gal, meeting the requirement of state-of-the-art gravimeters. The presented evaluation is important for the applications of atom gravimeters.

The importance of BET protein BRD4 in gene transcription is well recognized through the study of chemical modulation of its characteristic tandem bromodomain (BrD) binding to lysine-acetylated histones and transcription factors. However, while monovalent inhibition of BRD4 by BET BrD inhibitors such as JQ1 blocks growth of hematopoietic cancers, it is much less effective generally in solid tumors. Here, we report a thienodiazepine-based bivalent BrD inhibitor, MS645, that affords spatially constrained tandem BrD inhibition and consequently sustained repression of BRD4 transcriptional activity in blocking proliferation of solid-tumor cells including a panel of triple-negative breast cancer (TNBC) cells. MS645 blocks BRD4 binding to transcription enhancer/mediator proteins MED1 and YY1 with potency superior to monovalent BET inhibitors, resulting in down-regulation of proinflammatory cytokines and genes for cell-cycle control and DNA damage repair that are largely unaffected by monovalent BrD inhibition. Our study suggests a therapeutic strategy to maximally control BRD4 activity for rapid growth of solid-tumor TNBC cells., Competing Interests: The authors declare no conflict of interest.

Background: Auricularia auricular polysaccharides (AAPs) derived from the dried fruit body of A. auricular are valuable compounds with many bioactivities. This research aimed to investigate the antioxidant and anti- diabetic activities of these polysaccharides and their artificial gastrointestinal fluid hydrolysates (AAPHs)., Methods: Artificially simulated gastrointestinal fluid was used to obtain polysaccharide-de- rived fragments, and a rat model of type 2 diabetes mellitus (T2DM) using a high-fat diet and low-dose streptozotocin (STZ) was established to assess their antioxidant and anti-diabetic effects., Results: It was found that AAPs and AAPHs were both heteropolysaccharides and were comprised of arab- inose, xylose, mannose, 2-deoxy-glucose, glucose and glucosamine, but at different mole ratios. AAPHs was purified by Sephadex G-100 chromatography to produce three fractions, namely, AAPHs1, AAPHs2, and AAPHs3. The molecular weights of these three fractions were 320, 169, and 62 kDa respectively. Both AAPs and AAPHs exhibited the evident ability to enhance the activities of antioxidant enzymes and the level of GSH, while increasing the content of liver glycogen and plasma C-peptide compared with the diabetic model group (p < 0.05). Furthermore, AAPHs could cause a marked improvement in glucose-stimulated GLP-1 secretion from 0 min to 30 min (p < 0.05)., Conclusions: The possible mechanism was that AAPHs could partly restore the STZ-induced impairment of GLP-1 secretion, and inhibit the oxidative stress pathway, and thereby alleviate the progression of diabetes. This data demonstrated that the molecular mole ratio and molecular weight had a definite effect on antioxi- dant and anti-diabetic activities.

An efficient acid-hydrolysis method was developed and optimized for the hydrolyses of polysaccharide from Auricularia auricula with the ABTS· scavenging ability as the detective marker. Based on the single factor experimental results, Box-Behnken design (BBD) were applied for the optimization of acid-hydrolysis conditions. The possible antioxidant mechanism of the hydrolyses (AAPs-F) in vivo was performed using the C. elegans model. The acid-hydrolysis conditions were found to be the optimal hydrolyzing time 2.78h (166.8min), hydrolyzing temperature 95.04°C and the acid concentration 14.03mol/L, respectively. Under the optimal acid-hydrolysis conditions, the ABTS· scavenging ability of AAPs-H was 97.94±0.87%, which was well matched with the predicted value (99.77%) of the BBD model. AAPs-F was the main fraction of AAPs-H separated through Sephadex G-10 as the stationary phase. AAPs-F was a kind of heteropolysaccharide and comprised of glucose, galactose and fucose with the molar ratio of 50:1:2. The molecular weight of AAPs-F was 143.15kDa. AAPs-F showed a remarkable protective effect to the injury induced by hydrogen peroxide or paraquat (p<0.01), and it could up-regulate stress-resistance related enzymes including superoxide dismutase (SOD) by 109.74% and CAT by 106.84% at concentration of 0.2mg/mL in C. elegans., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Dye-sensitized solar cells (DSSCs) have shown significant potential for indoor and building-integrated photovoltaic applications. Herein we present three new D-A-π-A organic sensitizers, XY1, XY2, and XY3, that exhibit high molar extinction coefficients and a broad absorption range. Molecular modifications of these dyes, featuring a benzothiadiazole (BTZ) auxiliary acceptor, were achieved by introducing a thiophene heterocycle as well as by shifting the position of BTZ on the conjugated bridge. The ensuing high molar absorption coefficients enabled the fabrication of highly efficient thin-film solid-state DSSCs with only 1.3 μm mesoporous TiO2 layer. XY2 with a molar extinction coefficient of 6.66 × 10(4) M(-1) cm(-1) at 578 nm led to the best photovoltaic performance of 7.51%.

To facilitate comparative treatment selection when there is substantial heterogeneity of treatment effectiveness, it is important to identify subgroups that exhibit differential treatment effects. Existing approaches model outcomes directly and then define subgroups according to interactions between treatment and covariates. Because outcomes are affected by both the covariate-treatment interactions and covariate main effects, direct modeling outcomes can be hard due to model misspecification, especially in presence of many covariates. Alternatively one can directly work with differential treatment effect estimation. We propose such a method that approximates a target function whose value directly reflects correct treatment assignment for patients. The function uses patient outcomes as weights rather than modeling targets. Consequently, our method can deal with binary, continuous, time-to-event, and possibly contaminated outcomes in the same fashion. We first focus on identifying only directional estimates from linear rules that characterize important subgroups. We further consider estimation of comparative treatment effects for identified subgroups. We demonstrate the advantages of our method in simulation studies and in analyses of two real data sets., (© 2015, The International Biometric Society.)