Oxidation behavior and atomic structural transition of size-selected coalescence-resistant tantalum nanoclusters.

Herein a series of size-selected TaN(N = 147, 309, 561, 923, 1415, 2057, 6525, 10 000, 20 000) clusters are generated using a gas-phase condensation cluster beam source equipped with a lateral time-of-flight mass-selector. Aberration-corrected scanning transmission electron microscopy (AC-STEM) imaging reveals good thermal stability of TaNclusters in this study. The oxidation-induced amorphization is observed from AC-STEM imaging and further demonstrated through x-ray photoelectron spectroscopy and energy-dispersive spectroscopy. The oxidized Ta predominantly exists in the +5 oxidation state and the maximum spontaneous oxidation depth of the Ta cluster is observed to be 5 nm under prolonged atmosphere exposure. Furthermore, the size-dependent sintering and crystallization processes of oxidized TaNclusters are observed with anin situheating technique, and eventually, ordered structures are restored. As the temperature reaches 1300 °C, a fraction of oxidized Ta309clusters exhibit decahedral and icosahedral structures. However, the five-fold symmetry structures are absent in larger clusters, instead, these clusters exhibit ordered structures resembling those of the crystalline Ta2O5films. Notably, the sintering and crystallization process occurs at temperatures significantly lower than the melting point of Ta and Ta2O5, and the ordered structures resulting from annealing remain well-preserved after six months of exposure to ambient conditions.

Epigallocatechin gallate suppresses mitotic clonal expansion and adipogenic differentiation of preadipocytes through impeding JAK2/STAT3-mediated transcriptional cascades.

BACKGROUND: Mitotic clonal expansion (MCE) is a prerequisite for preadipocyte differentiation and adipogenesis. Epigallocatechin gallate (EGCG) has been shown to inhibit preadipocyte differentiation. However, the exact molecular mechanisms are still elusive. PURPOSE: This study investigated whether EGCG could inhibit adipogenesis and lipid accumulation by regulating the cell cycle in the MCE phase of adipogenesis and its underlying molecular mechanisms. METHOD: 3T3-L1 preadipocytes were induced to differentiate by a differentiation cocktail (DMI) and were treated with EGCG (25-100 µM) for 9, 18, and 24 h to examine the effect on MCE, or eight days to examine the effect on terminal differentiation. C57BL/6 mice were fed a high-fat diet (HFD) for three months to induce obesity and were given EGCG (50 or 100 mg/kg) daily by gavage. RESULTS: We showed that EGCG significantly inhibited terminal adipogenesis and lipid accumulation in 3T3-L1 cells and decreased expressions of PPARγ, C/EBPα, and FASN. Notably, at the MCE phase, EGCG regulated the cell cycle in sequential order, induced G0/G1 arrest at 18 h, and inhibited the G2/M phase at 24 h upon DMI treatment. Meanwhile, EGCG regulated the expressions of cell cycle regulators (cyclin D1, cyclin E1, CDK4, CDK6, cyclin B1, cyclin B2, p16, and p27), and decreased C/EBPß, PPARγ, and C/EBPα expressions at MCE. Mechanistic studies using STAT3 agonist Colivelin and antagonist C188-9 revealed that EGCG-induced cell cycle arrest in the MCE phase and terminal adipocyte differentiation was mediated by the inhibition of JAK2/STAT3 signaling cascades and STAT3 (Tyr705) nuclear translocation. Furthermore, EGCG significantly protected mice from HFD-induced obesity, reduced body weight and lipid accumulations in adipose tissues, reduced hyperlipidemia and leptin levels, and improved glucose intolerance and insulin sensitivity. Moreover, RNA sequencing (RNA-seq) analysis showed that the cell cycle changes in epididymal white adipose tissue (eWAT) were significantly enriched upon EGCG treatment. We further verified that EGCG treatment significantly reduced expressions of adipogenic factors, cell cycle regulators, and p-STAT3 in eWAT. CONCLUSION: EGCG inhibits MCE, resulting in the inhibition of early and terminal adipocyte differentiation and lipid accumulation, which were mediated by inhibiting p-STAT3 nucleus translocation and activation.

Application of glutamate weighted CEST in brain imaging of nicotine dependent participants in vivo at 7T.

INTRODUCTION: With nicotine dependence being a significant healthcare issue worldwide there is a growing interest in developing novel therapies and diagnostic aids to assist in treating nicotine addiction. Glutamate (Glu) plays an important role in cognitive function regulation in a wide range of conditions including traumatic brain injury, aging, and addiction. Chemical exchange saturation transfer (CEST) imaging via ultra-high field MRI can image the exchange of certain saturated labile protons with the surrounding bulk water pool, making the technique a novel tool to investigate glutamate in the context of addiction. The aim of this work was to apply glutamate weighted CEST (GluCEST) imaging to study the dorsal anterior cingulate cortex (dACC) in a small population of smokers and non-smokers to determine its effectiveness as a biomarker of nicotine use. METHODS: 2D GluCEST images were acquired on 20 healthy participants: 10 smokers (ages 29-50) and 10 non-smokers (ages 25-69), using a 7T MRI system. T1-weighted images were used to segment the GluCEST images into white and gray matter tissue and further into seven gray matter regions. Wilcoxon rank-sum tests were performed, comparing mean GluCEST contrast between smokers and non-smokers across brain regions. RESULTS: GluCEST levels were similar between smokers and non-smokers; however, there was a moderate negative age dependence (R2 = 0.531) in smokers within the cingulate gyrus. CONCLUSION: Feasibility of GluCEST imaging was demonstrated for in vivo investigation of smokers and non-smokers to assess glutamate contrast differences as a potential biomarker with a moderate negative age correlation in the cingulate gyrus suggesting reward network involvement.

Genetic analysis of two children with Coffin-Siris syndrome due to variants of ARID1B gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of two children with unexplained psychomotor developmental delay and facial dysmorphisms suggestive of Coffin-Siris syndrome (CSS).@*METHODS@#A boy and a girl suspected for CSS at the 980th Hospital of the People's Liberation Army Joint Service Support Force respectively in July 2019 and January 2021, and seven members from their families, were selected as the study subjects. Clinical data and family history of the children were collected, and detailed physical examination was carried out, in addition with laboratory and related auxiliary examinations. Potential variants and copy number variations (CNVs) were detected by whole exome sequencing (WES) and copy number variation sequencing (CNV-seq).@*RESULTS@#Child 1, an 8-month-old female, had featured microcephaly, atrial septal defect, curving of fifth finger/toe, and low limb muscle tone. Child 2 was a 2.5-year-old male with language delay, social impairment, dense hair but no curving of the fifth fingers. Genetic testing revealed that child 1 had loss of heterozygosity for exons 8 to 21 of the ARID1B gene, which was unreported previously. Family verification showed that both of her parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and American Society of Molecular Pathology (AMP), the variant was rated as pathogenic (PVS1+PS2+PM2-supporting). Child 2 was found to harbor a heterozygous c.4263-6 (IVS17) T>G variant of the ARID1B gene. Transcriptome sequencing confirmed that the variant can affect the normal splicing, resulting in retention of a 5 bp sequence in intron 17. Family verification showed that both of his parents were of the wild type. Based on the guidelines from the ACMG, the variant was rated as pathogenic (PS2+PM2-supporting+PP3+PS3).@*CONCLUSION@#WES and RNA-seq have confirmed the diagnosis of CSS in both children. Discovery of the novel variants has expanded the spectrum of pathogenic mutations underlying CSS, and provided a basis for the genetic counseling.

Factors associated with thermal injury of abdominal skin in focused ultrasound ablation of uterine fibroids.

OBJECTIVE: To investigate the factors which may cause thermal injury of abdominal skin in patients with uterine fibroids (UFs) who underwent ultrasound-guided focused ultrasound ablation surgery (FUAS). METHOD: A total of 123 patients were enrolled in the injury group. In contrast, 246 patients without thermal injury were assigned to the non-injury group. The relationship between patient and treatment parameters and injury were explored using univariate analysis and multiple logistic regression analyses. In addition, the factors influencing the degree of thermal injury were analyzed using Kruskal-Wallis H. RESULTS: (1) Abdominal scars (p = .007, OR = 2.187, 95% CI: 1.242-3.849), abdominal wall thickness (p < .001, OR = 1.042, 95% CI: 1.019-1.067), fundus fibroids (p = .038, OR = 1.790, 95% CI: 1.033-3.100), UFs with hyperintense/mixed T2-weighted imaging (T2WI) signals (p = .022, OR = 1.843, 95% CI: 1.091-3.115), average sonication power (AP) (p = .025, OR = 1.021, 95% CI: 1.003-1.039), and treatment time (TT) (p < .001, OR = 1.017, 95% CI: 1.011-1.023) were independent risk factors for thermal injury, while treatment volume (TV) (p = .002, OR = 0.775, 95% CI: 0.661-0.909) was a protective factor for injury. (2) Four groups were subdivided according to the degree of thermal injury(Group A: without skin injury. Group B: with changed T2WI signal in the abdominal wall, Group C: mild skin injury, Group D: severe skin injury), comparison of each with every other showed that the abdominal wall in Groups A and D was thinner than Groups B and C, with statistically significant differences (PAB<0.05, PAC<0.01, PDC<0.05, PDB<0.05); Group A was slightly thicker than D, however, without statistical difference. The ratio of sonication time (ST) to TV in Group A was the lowest of all (PAB, PAC, PAD all < 0.05). And as the level of thermal injury rose, the ratio gradually increased, however, without statistical difference. CONCLUSIONS: Based on our limited results, the following conclusion was made. (1) Abdominal scars, abdominal wall thickness, fundus fibroids, UFs with T2WI hyperintense/mixed signals, AP and TT were independent risk factor. (2) Neither too thick nor too thin abdominal walls would be recommended, as both might increase the risk of skin injury. (3) Noticeably, the risk of skin injury might increase considerably when the ST was longer and the sonication area was more fixed.

Valorization of fruit and vegetable byproducts for the beta-glucan production from Euglena gracilis.

Five fruit and vegetable byproducts were evaluated as carbon sources and media for beta-glucan production from Euglena gracilis. Orange peel showed the highest beta-glucan concentration (6.5 g/L) and productivity (1.9 g/L/day) when used as a medium. However, when employed as carbon sources, apple pomace showed the highest beta-glucan concentration (10.6 g/L) and productivity (3.5 g/L/day). The appropriate chemical oxygen demand/nitrogen ratio (71.1) and favorable carbon sources of apple contributed to beta-glucan production. Increasing sugar concentrations in apple pomace and orange peel from 10 to 30 g/L raised the beta-glucan concentration to 11.6 g/L. Using apple pomace and orange peel individually proved more effective than mixing them for beta-glucan production. Therefore, apple as a carbon source is the most effective fruit and vegetables byproduct for beta-glucan production. This is expected to reduce the cost of E. gracilis cultivation on a large-scale and contribute to the circular economy.

Diallyl disulfide augments sensitivity of DJ-1 overexpressed human gastric cells to 5-FU / 中国药理学通报

Aim To investigate whether diallyl disul-fide (DADS) augments the sensitivity of DJ-1 (protein/ nucleic acid deglycase) overexpressed human gastric SGC7901 cells to 5-FU (5-fluorouracil). Methods The experimental groups include control group, DADS group, VCR (vincristine) group, VCR + DADS group, DJ-1 group, DJ-1 + DADS group. MTT was used to analyze the effect of DADS on 5 -FU (5 -fluorou- racil) induced proliferation inhibition. Flow cytometry was performed to examine the effect of DADS on cell apoptosis. RT-PCR, Western blot, and immunofluo-rescence were used for determine the effect of DADS on the drug resistance associated gene expression. Results DADS enhanced the proliferation inhibitory effect of 5-FU on DJ-1 overexpressed cells and VCR resistant cells. DADS could induce apoptosis in VCR-resistant cells. DADS downregulated the expression of DJ-1 while inducing apoptosis in DJ-1 overexpressed cells. DJ-1 overexpression upregulated the expression of P-gp (P-glycoprotein), Bcl-2, and XIAP (X-linked inhibitor of apoptosis protein), downregulated the expression of caspase-3. DADS decreased the expression of P-gp, Bcl-2, and XIAP, while increased the expression of caspase-3 in DJ-1 overexpressed cells and VCR-resistant cells. Conclusions DADS can augment the sensitivity of DJ-1 overexpressed cells to 5-FU, which is related to its antagonism against DJ-1 mediated upregula- tion of P-gp, Bcl-2, XIAP, and downregulation of caspase-3.

Effects of different storage and transportation devices on the temperatures of “internet plus drug delivery”in hospital under high-temperature conditions in summer / 中国药房

OBJECTIVE To explore suitable storage and transportation conditions for “internet plus drug delivery” under high- temperature conditions. METHODS A survey on high-temperature conditions in summer in Beijing was conducted； a retrospective analysis was conducted on “internet plus drug delivery” orders in our hospital from July 2021 to June 2022， summarizing the proportion and delivery range of drugs under different storage and transportation conditions. Additionally， simulation and validation experiments were performed to investigate optimal drug storage and transportation devices for “internet plus drug delivery” in Beijing under high-temperature conditions in summer. RESULTS The monthly average temperature in Beijing from June to August consistently exceeded 25.0 ℃ between 1991 and 2022. From July 2021 to June 2022， a total of 104 drugs were required to be stored below 25.0 ℃， accounting for 31.23% of the 333 drugs listed in our hospital’s “internet plus drug delivery” catalog in Beijing. These drugs were delivered 1 058 times， accounting for 19.63% of the total deliveries. Simulation and validation experiments demonstrated that the average maximum temperature during the next-day delivery process of “carton + foam box + composite aluminum film pearl cotton + 500 g ice bag×2 + gas column bag” was 9.6 ℃， the average minimum temperature was 2.7 ℃， and all the temperatures remained below 15.0 ℃， which could effectively ensure the quality of drugs. CONCLUSIONS Under the high-temperature conditions in summer in Beijing， the storage and transportation device of “carton + foam box + composite aluminum film pearl cotton + 500 g ice bag×2 + gas column bag” can meet the temperature requirements specified in the drug storage instructions for Beijing intra-city drug delivery.

Effects of lead contamination on histology, antioxidant and intestinal microbiota responses in freshwater crayfish, Procambarus clarkii.

The red swamp crayfish (Procambarus clarkii) is an important farming species in China and there is a high degree of overlap between the main crayfish production areas and areas contaminated with the heavy metal lead (Pb), thus putting crayfish farming at potential risk of Pb contamination. To assess the toxic effects of Pb on crayfish, in this study they were exposed to different concentrations of Pb (0, 0.1, 1, 10, 50 mg/L) for 72 h, and 0.1 mg/L represents the level of Pb in the contaminated water. Histomorphology and activities of antioxidant or immune-related enzymes suggest that the damage of Pb to the hepatopancreas and intestine was dose- and time-dependent, with the intestine being more sensitive to Pb than the hepatopancreas. Notably, after a short period (24 h) of stress at low concentrations (0.1 mg/L) of Pb, the malondialdehyde (MDA) content and antioxidant enzymes such as catalase (CAT) and glutathione peroxidase (GSH-Px) in the intestine of crayfish showed significant changes, indicating that low concentrations of Pb were also highly detrimental to crayfish. High-throughput sequencing of the intestinal microbial community indicated that Pb exposure led to a disturbance in the relative abundance of intestinal bacteria, increasing the abundance of pathogenic bacteria (Bosea, Cloacibacterium, Legionella spp.) and decreasing the abundance of potentially beneficial bacteria (Chitinibacter, Chitinilyticum, Paracoccus, Microbacterium, Demequina, and Acinetobacter spp.). In conclusion, Pb damages the hepatopancreas and intestinal barrier of crayfish, leading to the destruction of their anti-stress ability and immune response, and at the same time disrupts the homeostasis of intestinal microbes, resulting in adverse effects on the gut. This study contributed to the assessment of the ecotoxicity of the heavy metal Pb to the crustacean aquatic animals.

Biomarkers for distinguishing tuberculous pleural effusion from non-tuberculosis effusion: a retrospective study.

BACKGROUND: Pleural effusion (PE) is a common clinical feature that presents a diagnostic challenge for clinicians. In this retrospective study, we aimed to assess the biomarkers, ratios, and multiple indicators in serum and Pleural effusion for the differential diagnosis of tuberculous pleural effusion (TPE) from non-tuberculosis effusion (non-TPE). METHODS: The participants, who were divided into two groups: TPE and non-TPE (MPE and PPE), from Ningbo First Hospital, were incorporated in this study. The clinical and laboratory features were collected and analyzed using logistic regression analysis. Twelve biomarkers and their ratios in serum and PE were investigated for TPE versus non-TPE. Additionally, the value of multiple indicators for joint diagnosis was estimated. RESULTS: Biomarkers and ratios showed good diagnostic performance. The five variables including Serum ADA, IGRA, Effusion ADA, Effusion ADA/Serum ADA and Effusion LDH/Effusion ADA were identified as valuable parameters for differential diagnosis of TPE from non-TPE. The combined diagnosis of the five indexes yielded the highest diagnostic accuracy for TPE with an AUC (0.919), sensitivity (90.30%), and specificity (94.50%). CONCLUSIONS: The biomarkers and ratios demonstrated strong diagnostic performance, and the utilization of multiple indicators for joint diagnosis can improve the diagnostic efficacy of tuberculous pleurisy.

Investigating the role and mechanisms of tricin in ischemia-reperfusion-induced myocardial injury in LDLr -/- MICE.

The objective of this study was to investigate the function and biological mechanisms of tricin in in-vivo damage to the myocardium produced by ischemia-reperfusion in LDLr -/- mice. The hypercholesterolemia animal model employed was male LDLr -/- mice. Coronary artery occlusion in mice resulted in the detection of oxidative stress and inflammatory pathology. In mice with coronary artery blockage, tricin reduced oxidative burden in the cardiac tissue and inflammatory mediators. Additionally, the ST segment of the animals receiving tricin was resumed. Tricine could dramatically lessen myocardial damage, according to pathological examination and triphenyltetrazolium chloride (TTC) staining. As a result of the research described above, the protective effects of tricin on myocardial injury have been explored, and the influence of inflammation and oxidative assaults in the ischemia-reperfusion injury (I/R) model of the heart has been demonstrated.

HnRNPK is involved in stress-induced depression-like behavior via ERK-BDNF pathway in mice.

As a ubiquitous RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK) interacts with numerous nucleic acids and proteins and is involved in various cellular functions. Available literature indicates that it can regulate dendritic spine density through the extracellular signal-regulating kinase (ERK) - brain-derived neurotrophic factor (BDNF) pathway, which is crucial to retain the synaptic plasticity in patients with major depressive disorder (MDD) and mouse depression models. However, ERK upstream regulatory kinase has not been fully elucidated. Furthermore, it remains unexplored whether hnRNPK may impact the depressive condition via the ERK pathway. The present study addressed this issue by integrating approaches of genetics, molecular biology, behavioral testing. We found that hnRNPK in the brain was mainly distributed in the hippocampal neurons; that it was significantly downregulated in mice that displayed stress-induced depression-like behaviors; and that the level of hnRNPK markedly decreased in MDD patients from the GEO database. Further in vivo and in vitro analyses revealed that the changes in the expressions of BDNF and PSD95 and in the phosphorylation of ERK (Thr202/Tyr204) paralleled the variation of hnRNPK levels in the ventral hippocampal neurons in mice with depression-like behaviors. Finally, esketamine treatment significantly increased the level of hnRNPK in mice. These findings evidence that hnRNPK involved in the pathogenesis of depression via the ERK-BDNF pathway, pinpointing hnRNPK as a potential therapeutic target in treating MDD patients.

Ultra-robust, Highly Stretchable, and Conductive Nanocomposites with Self-healable Asymmetric Structures Prepared by a Simple Green Method.

Flexible conductive polymer nanocomposites based on silver nanowires (AgNWs) have been extensively studied to develop the next generation of flexible electronic devices. Fiber materials with high strength and large stretching are an important part of high-performance wearable electronics. However, manufacturing conductive composites with both high mechanical strength and good stability remains challenging. In addition, the process of effectively dispersing conductive fillers into substrates is relatively complex, which greatly hampers its widespread application. Here, a simple green self-assembly preparation method in water is reported. The AgNW is evenly dispersed in aqueous, i.e., water-borne polyurethane (WPU) with water as the solvent, and a AgNW/WPU conductive nanocomposite film with an asymmetric structure is formed by self-assembly in one step. The film has high strength (≈49.2 MPa) and high strain (≈910%), low initial resistance (99.9 mΩ/sq), high conductivity (9968.1 S/cm), and excellent self-healing (93%) and adhesion. With good self-healing performance, fibers with a conductive filler spiral structure are formed. At the same time, the application of the conductive composite material with an asymmetric structure in intelligent wearability is demonstrated.

Identification of salt stress-tolerant candidate genes in the BC2F2 population at the seedling stages of G. hirsutum and G. darwinii using NGS-based bulked segregant analysis.

Salinity is a major threat to the yield and productivity of cotton seedlings. In the present study, we developed a BC2F2 population of cotton plants from Gossypium darwinii (5-7) and Gossypium hirsutum (CCRI 12-4) salt-susceptible parents to identify salt-resistant candidate genes. The Illumina HiSeq™ strategy was used with bulked segregant analysis. Salt-resistant and salt-susceptible DNA bulks were pooled by using 30 plants from a BC2F2 population. Next-generation sequencing (NGS) technology was used for the sequencing of parents and both bulks. Four significant genomic regions were identified: the first genomic region was located on chromosome 18 (1.86 Mb), the second and third genomic regions were on chromosome 25 (1.06 Mb and 1.94 Mb, respectively), and the fourth was on chromosome 8 (1.41 Mb). The reads of bulk1 and bulk2 were aligned to the G. darwinii and G. hirsutum genomes, respectively, leading to the identification of 20,664,007 single-nucleotide polymorphisms (SNPs) and insertions/deletions (indels). After the screening, 6,573 polymorphic markers were obtained after filtration of the candidate regions. The SNP indices in resistant and susceptible bulks and Δ(SNP-index) values of resistant and susceptible bulks were measured. Based on the higher Δ(SNP-index) value, six effective polymorphic SNPs were selected in a different chromosome. Six effective SNPs were linked to five candidate genes in four genomic regions. Further validation of these five candidate genes was carried out using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), resulting in an expression profile that showed two highly upregulated genes in the salt-tolerant species G. darwinii, i.e., Gohir.D05G367800 and Gohir.D12G239100; however, the opposite was shown in G. hirsutum, for which all genes, except one, showed partial expression. The results indicated that Gohir.D05G367800 and Gohir.D12G239100 may be salt-tolerant genes. We are confident that this study could be helpful for the cloning, transformation, and development of salt-resistant cotton varieties.

Antioxidation, immunity and hepatopancreatic histology of red swamp crayfish (Procambarus clarkii) subjected to low-temperature aerial exposure stress and re-immersion.

Desiccation is a stressful situation that decapods often experience during live transportation. This study investigated the effects of low-temperature aerial exposures (LTAEs) (dry exposure (DL) and moist exposure (ML) at 6 °C) and re-immersion on the antioxidative and immune responses and hepatopancreatic histopathology in P. clarkii. Compared to the control group (normally feeding at 24.0 °C water temperature), the crayfish under LTAEs showed overall severe hepatopancreatic oxidative damage, with significantly increased malondialdehyde (MDA) contents and significantly reduced total antioxidant capacity (T-AOC), and oxidant damage was not fully recovered even after 12 h of re-immersion; the expression of hsp70 was significantly increased within 24-48 h of stress and re-immersion. The activity of hemolymphatic acid phosphatase (ACP) was significantly increased during 24-48 h of the stress and at 12 h of re-immersion; the activity of aspartic aminotransferase (AST) and alanine aminotransferase (ALT) was significantly increased throughout the experiment; and the gene expression of proPO or TLR was significantly increased during 12-48 h of the stress. Severe histopathological changes (lumen dilatation, vacuolation of epithelial cells and reduced cell numbers) were observed in hepatopancreas at 48 h of stress and 12 h of re-immersion. These results indicated that 48 h of low-temperature aerial exposure stress stimulated the non-specific immunity but adversely affected the antioxidation and hepatopancreatic histomorphology of P. clarkii, whereas 12 h of re-immersion was not sufficient to restore crayfish from stress to a normal state.

Development and validation of dynamic nomogram of frailty risk for older patients hospitalized with heart failure.

Objective: This study aimed to establish and validate a dynamic online nomograph for predicting the risk of frailty in older patients hospitalized with heart failure in China. Methods: A total of 451 older adults with heart failure hospitalized were selected between December 2021 and November 2022 at the Department of Cardiovascular Medicine in a Class A tertiary hospital in Shandong, China. The data of patients were obtained by using Barthel Index, instrumental activity of daily living scale, mini nutrition assessment-short form, Pittsburgh sleep quality index scale, Morse fall risk assessment scale and general information scale. The brain natriuretic peptide and echocardiographic indexes of patients were collected by electronic medical records. All participants were randomly divided into the training set (n = 319) and the validation set (n = 132) at the ratio of 7:3. The training set is used for model construction, and the validation set is used for internal validation. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression method to filter modeling variables, while the multivariable logistic regression was used to establish the nomogram based on the screened optimal variables. The performance of the model was evaluated by the area under the curve (AUC) of the receiver operator characteristic (ROC) curve, Hosmer-Lemeshow test, calibration plot, and decision curve analysis (DCA). Results: The prevalence of frailty in 451 patients was 50.6%, 51.4%, and 48.5% in the training and validation sets, respectively. Drinking, grip strength, New York Heart Association (NYHA) class, multimorbidity, hospitalization history of heart failure, Barthel Index, the instrumental activities of daily living, nutritional status, sleep, fall, and left atrial end-diastolic diameter were used for LASSO regression analysis as the significant predictors of frailty. According to internal validation, the AUC of the ROC curve for the nomogram was 0.920, with a sensitivity of 86.8% and specificity of 84.4%. Moreover, in the validation set, the P-values of the H-L test were 0.742, and the calibration curve had good concordance between the estimated frailty risk and actual observation, indicating the model was well-calibrated. The DCA results confirmed that the nomogram had a well-performance in clinical suitability. Conclusions: An online dynamic nomogram predicting frailty for older patients hospitalized for heart failure in China was well-established and identified in this study. This model benefits medical professionals in identifying high-risk frailty in older hospitalized patients with heart failure, which could reduce the medical and disease burden of heart failure to a certain extent. However, further verification is needed in the future.

Enhancing Mechanical Properties of 3D Printing Metallic Lattice Structure Inspired by Bambusa Emeiensis.

Metallic additive manufacturing process parameters, such as inclination angle and minimum radius, impose constraints on the printable lattice cell configurations in complex components. As a result, their mechanical properties are usually lower than their design values. Meanwhile, due to unavoidable process constraints (e.g., additional support structure), engineering structures filled with various lattice cells usually fail to be printed or cannot achieve the designed mechanical performances. Optimizing the cell configuration and printing process are effective ways to solve these problems, but this is becoming more and more difficult and costly with the increasing demand for properties. Therefore, it is very important to redesign the existing printable lattice structures to improve their mechanical properties. In this paper, inspired by the macro- and meso-structures of bamboo, a bionic lattice structure was partitioned, and the cell rod had a radius gradient, similar to the macro-scale bamboo joint and meso-scale bamboo tube, respectively. Experimental and simulated results showed that this design can significantly enhance the mechanical properties without adding mass and changing the printable cell configuration. Finally, the compression and shear properties of the Bambusa-lattice structure were analyzed. Compared with the original scheme, the bamboo lattice structure design can improve the strength by 1.51 times (ß=1.5). This proposed strategy offers an effective pathway to manipulate the mechanical properties of lattice structures simultaneously, which is useful for practical applications.

Molecular dynamics simulations on interactions of five antibiotics with luciferase of Vibrio Qinghaiensis sp.-Q67.

A large number of antibiotics have been used in the medical industry, agriculture, and animal husbandry industry in recent years. It may cause pollution to the aquatic environment and ultimately threaten to human health due to their prolonged exposure to the environment. We aim to study the toxicity mechanism of enrofloxacin (ENR), chlortetracycline hydrochloride (CTC), trimethoprim (TMP), chloramphenicol (CMP), and erythromycin (ETM) to luciferase of Vibrio Qinghaiensis sp.-Q67 (Q67) by using toxicity testing combined with molecular docking, molecular dynamics, and binding free energy analysis. The curve categories for ENR were different from the other four antibiotics, with ENR being J-type and the rest being S-type, and the toxicity of these five antibiotics (pEC50) followed the order of ENR (7.281) > ETM (6.814) > CMP (6.672) > CTC (6.400) > TMP (6.123), the order of toxicity value is consistent with the the magnitude of the binding free energy (ENR (-47.759 kcal/mol), ETM (-46.821 kcal/mol), CMP (-42.905 kcal/mol), CTC (-40.946 kcal/mol), TMP (-28.251 kcal/mol)). The van der Waals force provided the most important contribution to the binding free energy of the five antibiotics in the binding system with Q67 luciferase. Therefore, the dominant factor for the binding of antibiotics to luciferase was shape compensation. The face-to-face π-π stacking interaction between the diazohexane structure outside the active pocket region and the indoles structure of Phe194 and Phe250 in the molecular structure was the main reason for the highest toxicity value of antibiotic ENR. The hormesis effect of ENR has a competitive binding relationship with the α and ß subunits of luciferase. Homology modeling, molecular docking, molecular dynamics simulations and binding free energy calculations were used to derive the toxicity magnitude of different antibiotics against Q67, and insights at the molecular level. The conclusion of toxicological experiments verified the correctness of the simulation results. This study contributes to the understanding of toxicity mechanisms of five antibiotics and facilitates risk assessment of antibiotic contaminants in the aquatic environment.

Efficacy and safety of vapocoolant spray for vascular puncture in children and adults: A systematic review and meta-analysis.

OBJECTIVE: The aim was to evaluate the effectiveness and safety of the vapocoolants for vascular puncture in children and adults. METHOD: The search was carried out in PubMed, Web of Science, Embase and The Cochrane Library, from inception to March 2022. Randomized controlled trials comparing vapocoolants to control conditions for participants received intravenous cannulation or arterial puncture were included. Two reviewers independently performed selection of studies, data extraction, and assessment of risk of bias. The analysis was performed using fixed or random-effects model with mean differences or standardized mean difference and risk ratios. RESULTS: A total of 25 studies involving 3143 participants were included. Compared with control conditions, vapocoolants may not decrease the pain of patients with arterial puncture (SMD = -0.36, 95% CI = -0.92 to -0.19, P = 0.20), but may more effectively relieve pain for adults received vein puncture (SMD = -0.65, 95% CI = -0.85 to -0.45, P < 0.00001). The application of vapocoolant increased the procedural difficulty of medical personnel (RR = 2.49, 95% CI = 1.62 to 3.84, P<0.000 1) and participants were more willing to use the spray in the future (RR = 1.88, 95% CI = 1.34 to 2.64, P = 0.0002). There was no significant difference for the first attempt success rate of the procedure and the occurrence of adverse events. CONCLUSIONS: Vapocoolant spray may relieve pain in adults received vein puncture and cannot cause severe side effects, but is ineffective in children. It also had no effect on patients with arterial puncture. In addition, the application of spray increases procedural difficulties for medical professionals, but does not decrease first attempt success rate, and many patients would like to use the spray again for pain relief in the future. Thus, more rigorous and large-scale studies are needed to determine its effectiveness in vascular access.

Synaptotagmin-like protein 1 is a potential diagnostic and prognostic biomarker in endometrial cancer based on bioinformatics and experiments.

Endometrial cancer (EC) is one of the most common gynecologic malignancies. Identification of potential EC biomarkers is essential to improve the prognosis and development of therapies against EC. Synaptotagmin-like protein 1 (SYTL1), as a small GTPase Rab27 effector, mainly plays a role in vesicle trafficking and cytotoxic granule exocytosis in lymphocytes. However the role of SYTL1 in EC remains uncertain. We performed a comprehensive assessment of the relationship between SYTL1 and patient diagnosis and prognosis by analysis of EC patients' data from TCGA. We employed the LinkedOmics and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to analyze the biological function of SYTL1 in EC. In addition, the correlation between SYTL1 expression and its DNA methylation was performed by using cBioportal, UALCAN, TCGA Wanderer and MethSurv databases. We further assessed the link between SYTL1 and tumor-infiltrating immune cells by using gene set variation analysis (GSVA).Results We found that SYTL1 was highly expressed in EC patients and cell lines. And increased expression of SYTL1 was associated with age, clinical stage, histological type, histological grade and good overall survival (OS).SYTL1 DNA methylation is negatively associated with SYTL1 expression and UCEC patients' OS. SYTL1 expression is closely correlated with immune infiltration. Furthermore, we carried out in vitro experiments to verify the results of bioinformatic analysis.Conclusion Our results demonstrated that the elevation of SYTL1 expression is associated with good OS and SYTL1 might be a potential diagnostic and prognostic marker in EC.