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1.
Heart Fail Rev ; 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36184714

RESUMO

Several guidelines have recommended the use of angiotensin receptor neprilysin inhibitors (ARNIs) as replacement for angiotensin-converting enzyme inhibitors in the management of heart failure. Till date, there are no reviews done that comprehensively cover different aspects of efficacy and safety parameters. Hence, we have performed a comprehensive systematic review and meta-analysis on role of ARNIs for the management of heart failure patients. Searches were done in Embase, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, PubMed Central, Cochrane Library, MEDLINE, Google Scholar, ScienceDirect and Clinicaltrials.gov until June 2022. Risk of bias assessment was done with Cochrane's risk of bias tool. Meta-analysis was carried out using random-effects model. Pooled standardized mean difference (SMD)/mean difference (MD) and/or risk ratio (RR) with 95% confidence intervals (CIs) was reported. In total, we analysed 34 studies, with almost all of them had a high risk of bias. Pooled RR was 0.88 (95% CI: 0.82-0.95) for all-cause mortality, 0.84 (95% CI: 0.77-0.92) for cardiovascular mortality and 0.78 (95% CI: 0.70-0.87) for hospitalization. Pooled MD was 3.74 (95% CI: 1.93-5.55) for left ventricular ejection fraction, -2.16 (95% CI: -3.58 to -0.74) for left atrial volume index, -3.80 (95% CI: -6.60 to -1.00) for left ventricular end-diastolic dimension and -1.16 (95% CI: -1.98 to -0.35) for E/E' ratio. Regarding adverse events, pooled RR was 1.55 (95% CI: 1.31-1.85) for symptomatic hypotension, 0.93 (95% CI: 0.78-1.11) for worsening renal function, 1.09 (95% CI: 0.94-1.26) for hyperkalaemia and 1.29 (95% CI: 0.67-2.50) for angioedema. ARNIs had beneficial efficacy and safety profile on the management of heart failure especially patients with reduced ejection fraction.

2.
ISA Trans ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36182612

RESUMO

The bipartite containment control of nonlinear fractional multi-agent systems (FMASs) on fixed and switching signed directed networks is addressed in this article. Delayed control protocols are put forward to provide several simple algebraic criteria by means of using signed graph theory, fractional Razumikhin technique and common Lyapunov function approach. The presented method can well overcome the difficulty resulting from fractional calculus, time delay and switchings. Two numerical examples are presented for further clarifying the theoretical conclusions.

3.
Front Oncol ; 12: 996438, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185253

RESUMO

FLT3 mutations are one of the most common genetic alterations in acute myeloid leukemia (AML) and are identified in approximately one-third of newly diagnosed patients. Aberrant FLT3 receptor signaling has important implications for the biology and clinical management of AML. In recent years, targeting FLT3 has been a part of every course of treatment in FLT3-ITD/TKD-mutated AML and contributes to substantially prolonged survival. At the same time, wide application of next-generation sequencing (NGS) technology has revealed a series of non-canonical FLT3 mutations, including point mutations and small insertions/deletions. Some of these mutations may be able to influence downstream phosphorylation and sensitivity to FLT3 inhibitors, while the correlation with clinical outcomes remains unclear. Exploration of FLT3-targeted therapy has made substantial progress, but resistance to FLT3 inhibitors has become a pressing issue. The mechanisms underlying FLT3 inhibitor tolerance can be roughly divided into primary resistance and secondary resistance. Primary resistance is related to abnormalities in signaling factors, such as FL, CXCL12, and FGF2, and secondary resistance mainly involves on-target mutations and off-target aberrations. To overcome this problem, novel agents such as FF-10101 have shown promising potential. Multitarget strategies directed at FLT3 and anomalous signaling factors simultaneously are in active clinical development and show promising results.

4.
Front Immunol ; 13: 954221, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059536

RESUMO

Neutrophils have been recognized to play an important role in the pathogenesis of tuberculosis in recent years. Interferon-induced blood transcriptional signatures in ATB are predominantly driven by neutrophils. In this study, we performed global RNA-seq on peripheral blood neutrophils from active tuberculosis patients (ATB, n=15); latent tuberculosis infections (LTBI, n=22); and healthy controls (HC, n=21). The results showed that greater perturbations of gene expression patterns happened in neutrophils from ATB individuals than HC or those with LTBI, and a total of 344 differentially expressed genes (DEGs) were observed. Functional enrichment analysis showed that besides the interferon signaling pathway, multiple pattern recognition receptor pathways were significantly activated in ATB, such as NOD-like receptors and Toll-like receptors. Meanwhile, we also observed that the expression of genes related to endocytosis, secretory granules, and neutrophils degranulation were downregulated. Our data also showed that the NF-κB signaling pathway might be inhibited in patients with ATB, which could increase Mycobacterium tuberculosis survival and lead to active tuberculosis status. Furthermore, we validated the accuracy of some differentially expressed genes in an independent cohort using quantitative PCR, and obtained three novel genes (RBM3, CSRNP1, SRSF5) with the ability to discriminate active tuberculosis from LTBI and HC.


Assuntos
Tuberculose Latente , Tuberculose , Biomarcadores , Humanos , Interferons/metabolismo , Tuberculose Latente/genética , Neutrófilos/metabolismo , Proteínas de Ligação a RNA/genética , Tuberculose/microbiologia , Sequenciamento Completo do Exoma
5.
World J Surg Oncol ; 20(1): 282, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36058930

RESUMO

BACKGROUND: The clinical application of robotic-assisted gastrectomy remains controversial, especially as clinical studies of this operation navigated by carbon nanoparticle suspension injection (CNSI) have not been conducted. This study aims to assess the perioperative safety and efficacy of CNSI-guided robotic-assisted gastrectomy in patients with gastric cancer by focusing on short-term outcomes. METHODS: A retrospective analysis of patients who underwent CNSI-guided laparoscopic or robotic-assisted gastrectomy with a pathological diagnosis of gastric cancer was conducted. Data on demographics, surgical management, clinical-pathological results and short-term outcomes were compared among the groups. RESULTS: A total of 126 eligible patients were separated into the robotic-assisted gastrectomy (RAG) group (n = 16) and the laparoscopic gastrectomy (LG) group (n = 110) in total. The operation time of the RAG group is longer than the LG group (p = 0.0000). When it comes to perioperative and short-term complications, there exists no statistical difference between the two groups. CONCLUSION: The time required for CNSI-guided robotic-assisted gastrectomy is longer than that for CNSI-guided laparoscopic gastrectomy. CNSI-guided robotic-assisted gastrectomy is safe and effective.


Assuntos
Laparoscopia , Nanopartículas , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas , Carbono , Gastrectomia/métodos , Humanos , Laparoscopia/métodos , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
6.
J Oncol ; 2022: 5681206, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36065303

RESUMO

Background: Glioma is the most common primary brain tumor, representing approximately 80.8% of malignant tumors. Necroptosis triggers and enhances antitumor immunity and is expected to be a new target for tumor immunotherapy. The effectiveness of necroptosis-related lncRNAs as potential therapeutic targets for glioma has not been elucidated. Methods: We acquired RNA-seq data sets from LGG and GBM samples, and the corresponding clinical characteristic information is from TCGA. Normal brain tissue data is from GTEX. Based on TCGA and GTEx, we used univariate Cox regression to sort out survival-related lncRNAs. Lasso regression models were then built. Then, we performed a separate Kaplan-Meier analysis of the lncRNAs used for modeling. We validated different risk groups via OS, DFS, enrichment analysis, comprehensive immune analysis, and drug sensitivity. Results: We constructed a 12 prognostic lncRNAs model after bioinformatic analysis. Subsequently, the risk score of every glioma patient was calculated based on correlation coefficients and expression levels, and the patients were split into low- and high-risk groups according to the median value of the risk score. A nomogram was established for every glioma patient to predict prognosis. Besides, we found significant differences in OS, DFS, immune infiltration and checkpoints, and immune therapy between different risk subgroups. Conclusion: Predictive models of 12 necroptosis-related lncRNAs can facilitate the assessment of the prognosis and molecular characteristics of glioma patients and improve treatment modalities.

7.
BMC Pulm Med ; 22(1): 354, 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36117164

RESUMO

BACKGROUND: Sporadic lymphangioleiomyomatosis (S-LAM) is a rare neoplasm with heterogeneous clinical features that is conventionally considered to be related to TSC2. This study serves to elucidate the mutation landscape and potential correlation between S-LAM genomic profiles and clinical phenotypes. METHODS: Genomic profiles of 22 S-LAM patients were obtained by sequencing genomic DNA and cell-free DNA from various specimens using an NGS (next-generation sequencing)-based tumor-driver gene panel. Detected mutations were summarized. Symptoms, serum vascular endothelial growth factor D (VEGF-D) values, pulmonary function, and six-minute walk distance (6MWD) were compared among groups with different TSC2 status and genotypes to analyze genotype-phenotype correlations. RESULTS: 67 Variants in 43 genes were detected, with a TSC2 mutation detection rate of 68.2%. The TSC2 detection rate was similar in specimens obtained either through transbronchial lung biopsy (TBLB) or surgical lung biopsy (70.0% vs. 69.2%, p > 0.05). A novel mutation in VEZF1 (c.A659G) was detected in four participants and may represent a mild disease state. TSC2 mutation was significantly related to a shorter 6MWD (p < 0.05), and a higher percentage of VEGF-D over 800 pg/mL (p < 0.05); stop-gain mutation was significantly related to a higher prevalence of pneumothorax. CONCLUSIONS: Tumor-driver mutations in genes other than TSC2 may have a role in S-LAM, and TBLB specimens are practical alternatives for genomic analysis. TSC2 mutation detectability and types are related to the disease severity and phenotypes of S-LAM.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Pulmonares , Linfangioleiomiomatose , Proteínas de Ligação a DNA/genética , Estudos de Associação Genética , Humanos , Neoplasias Pulmonares/genética , Linfangioleiomiomatose/genética , Mutação , Fatores de Transcrição/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Fator D de Crescimento do Endotélio Vascular/genética
8.
RSC Adv ; 12(38): 24769-24777, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36128367

RESUMO

Construction of delicate nanostructures with a facile, mild-condition and economical method is a key issue for building high-performance electrode materials. We demonstrate a facile and novel "reassembling strategy" to hollow MnCoS nanospheres derived from dual-ZIF for supercapacitors. The spherical shell's surface structure, thickness and Mn distribution were controlled by regulating the solvothermal reaction time. The chemical composition, phases, specific surface areas and microstructure were studied and the electrochemical performances were systematically estimated. As the unique low-crystalline and optimized hollow nanosphere structure contributes to increasing active sites, MnCoS nanospheres exhibit excellent electrochemical performance. The test results show that the specific capacitance increases with increasing solvothermal time, and the MCS with a 5 h reaction time exhibits optimal electrochemical properties with a high specific capacity of 957 C g-1 (1 A g-1). Furthermore, an MCS-5//AC asymmetric supercapacitor device delivers a specific energy as high as 36.9 W h kg-1 at a specific power of 750 W kg-1.

9.
Acta Biomater ; 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36115651

RESUMO

Insufficient vascularization is a major challenge in the repair of critical-sized bone defects. Deferoxamine (DFO) has been reported to play a potential role in promoting the formation of H-type blood vessels, a specialized vascular subtype with coupled angiogenesis and osteogenesis. However, whether DFO promotes the expression of H-type vessels in critical femoral defects with complete periosteal damage remains unknown. Moreover, stable drug loading systems need to be designed owing to the short half-life and high-dose toxic effects of DFO. In this study, we developed an injectable DFO-gelatin microspheres (GMs) hydrogel complex as a stable drug loading system for the treatment of critical femoral defects in rats. Our results showed that sustained release of DFO in critical femoral defects stimulated the generation of functional H-type vessels. The DFO-GMs hydrogel complex effectively promoted proliferation, formation, and migration of human umbilical vein endothelial cells in vitro. In vivo, the application of the DFO-GMs hydrogel complex expanded the distribution range and prolonged the expression time of H-type vessels in the defect area and was positively correlated with the number of osterix+ cells and new bone tissue. Topical application of the HIF-1α inhibitor PX-478 partially blocked the stimulation of H-type vessels by DFO, whereas the osteogenic potential of the latter was also weakened. Our results extended the local application of DFO and provided a theoretical basis for targeting H-type vessels to treat large femoral defects. STATEMENT OF SIGNIFICANCE: Abundant functional blood vessels are essential for bone repair. The H-type blood vessel is a functional subtype with angiogenesis and osteogenesis coupling potential. A drug loading system with long-term controlled release was first used to investigate the formation of H-type blood vessels in critical femoral defects and promotion of bone repair. Our results showed that the application of DFO-GMs hydrogel complex expanded the distribution range and expression time of H-type vessels, and was positively correlated with the number of osteoblasts and volume of new bone tissue. These results expanded the local application approach of DFO and provide a theoretical basis for targeting H-type vessels to treat large femoral defects.

10.
Eur J Med Chem ; 243: 114737, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36115209

RESUMO

Blocking the de novo biosynthesis of pyrimidine by inhibiting human dihydroorotate dehydrogenase (hDHODH) is an effective way to suppress the proliferation of cancer cells and activated lymphocytes. Herein, eighteen teriflunomide derivatives and four ASLAN003 derivatives were designed and synthesized as novel hDHODH inhibitors based on a benzophenone scaffold. The optimal compound 7d showed a potent hDHODH inhibitory activity with an IC50 value of 10.9 nM, and displayed promising antiproliferative activities against multiple human cancer cells with IC50 values of 0.1-0.8 µM. Supplementation of exogenous uridine rescued the cell viability of 7d-treated Raji and HCT116 cells. Meanwhile, 7d significantly induced cell cycle S-phase arrest in Raji and HCT116 cells. Furthermore, 7d exhibited favorable safety profiles in mice and displayed effective antitumor activities with tumor growth inhibition (TGI) rates of 58.3% and 42.1% at an oral dosage of 30 mg/kg in Raji and HCT116 cells xenograft models, respectively. Taken together, these findings provide a promising hDHODH inhibitor 7d with potential activities against some tumors.

11.
Nat Mater ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109673

RESUMO

The production of large-area twisted bilayer graphene (TBG) with controllable angles is a prerequisite for proceeding with its massive applications. However, most of the prevailing strategies to fabricate twisted bilayers face great challenges, where the transfer methods are easily stuck by interfacial contamination, and direct growth methods lack the flexibility in twist-angle design. Here we develop an effective strategy to grow centimetre-scale TBG with arbitrary twist angles (accuracy, <1.0°). The success in accurate angle control is realized by an angle replication from two prerotated single-crystal Cu(111) foils to form a Cu/TBG/Cu sandwich structure, from which the TBG can be isolated by a custom-developed equipotential surface etching process. The accuracy and consistency of the twist angles are unambiguously illustrated by comprehensive characterization techniques, namely, optical spectroscopy, electron microscopy, photoemission spectroscopy and photocurrent spectroscopy. Our work opens an accessible avenue for the designed growth of large-scale two-dimensional twisted bilayers and thus lays the material foundation for the future applications of twistronics at the integration level.

12.
Bioresour Technol ; : 127986, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36126851

RESUMO

Lignocellulose, the most prevalent biomass on earth, can be enzymatically converted into carbohydrates for bioethanol production and other uses. Among lignocellulosic enzymes, endoglucanase, xylanase, and laccase are the key enzymes, owing to their ability to disrupt the main structure of lignocellulose. Recently, new discovery methods have been established to obtain key lignocellulosic enzymes with excellent enzymatic properties. Molecular modification of enzymes to modulate their thermostability, catalytic activity, and substrate specificity has been performed with protein engineering technology. In addition, the enzyme expression has been effectively improved through expression element screening and host modification, as well as fermentation optimization. Immobilization of enzymes, use of surfactants, synergistic degradation, and optimization of reaction conditions have addressed the inefficiency of enzymatic saccharification. In this review, recent advances in key lignocellulosic enzymes are summarized, along with future prospects for the development of super-engineered strains and integrative technologies for enzymatic biomass saccharification.

13.
Biomater Res ; 26(1): 47, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138489

RESUMO

BACKGROUND: Mitochondria play an essential role in cellular redox homeostasis maintenance and meanwhile serve as an important target for organelle targeted therapy. Photodynamic therapy (PDT) is a promising strategy for organelle targeted therapy with noninvasive nature and highly spatiotemporal selectivity. However, the efficacy of PDT is not fully achieved due to tumor hypoxia. Moreover, aerobic respiration constantly consumes oxygen and leads to a lower oxygen concentration in mitochondria, which continuously limited the therapeutic effects of PDT. The lack of organelle specific oxygen delivery method remains a main challenge. METHODS: Herein, an Oxygen Tank is developed to achieve the organelle targeted synergistic hypoxia reversal strategy, which not only act as an oxygen storage tank to open sources and reduce expenditure, but also coated with red blood cell membrane like the tank with stealth coating. Within the oxygen tank, a mitochondrion targeted photosensitizer (IR780) and a mitochondria respiration inhibitor (atovaquone, ATO) are co-loaded in the RBC membrane (RBCm) coated perfluorocarbon (PFC) liposome core. RESULTS: Inside these bio-mimic nanoparticles, ATO effectively inhibits mitochondrial respiration and economized endogenous oxygen consumption, while PFC supplied high-capacity exogenous oxygen. These Oxygen modulators reverse the hypoxia status in vitro and in vivo, and exhibited a superior anti-tumor activity by mitochondria targeted PDT via IR780. Ultimately, the anti-tumor effects towards gastric cancer and colon cancer are elicited in vivo. CONCLUSIONS: This oxygen tank both increases exogeneous oxygen supply and decreases endogenous oxygen consumption, may offer a novel solution for organelle targeted therapies.

14.
Enzyme Microb Technol ; 162: 110120, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36088753

RESUMO

Lipoxygenase (LOX) catalyzes the peroxidation of unsaturated fatty acids to produce hydroperoxides, which had been widely used in food, medicine and chemical industries due to its decoloration of food and conversion of renewable oils. Thus, higher catalytic activity and stability is desired for low-cost and expanded industrial applications of LOX. To improve the catalytic activity of LOX, a mutant library of Pseudomonas aeruginosa lipoxygenase (PaLOX) was firstly built via semi-rational design. The kcat/Km of mutant increased by 9.2-fold and the half-life (t1/2) at 50 °C increased by 4.6 min. Molecular dynamics (MD) simulation indicated that mutation reduced steric hindrance to substrate binding and increased the flexibility of the lid domain that covered the bound unsaturated fatty acid substrate. In addition, van der Waals interactions between the substrate and amino acid residues of the binding pocket increased and alkyl and Pi-alkyl interactions decreased, which might improve the flexibility and substrate binding affinity. These findings promoted understanding of the structure-function relationship of LOX and increase its catalytic efficiency and stability for further industrial application.

15.
Front Bioeng Biotechnol ; 10: 996138, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159689

RESUMO

Glutaminase (EC 3.5.1.2) can catalyze the deamidation of glutamine, which has been used to improve umami taste in oriental fermented foods. However, a high salt concentration is still a fundamental challenge for glutaminase application, especially in soy sauce production. To improve the salt tolerance of glutaminase, the self-assembling amphiphilic peptides EAK16 and ELK16 were fused to the N-terminus of a mutant (E3C/E55F/D213T) derived from Bacillus subtilis glutaminase, yielding the fusion enzymes EAK16-E3C/E55F/D213T and ELK16-E3C/E55F/D213T, respectively. As ELK16-E3C/E55F/D213T was expressed as insoluble active inclusion bodies, only the purified EAK16-E3C/E55F/D213T was subjected to further analyses. After the incubation with 18% (w/v) NaCl for 200 min, the residual activities of EAK16-E3C/E55F/D213T in a NaCl-free solution reached 43.6%, while E3C/E55F/D213T was completely inactivated. When the enzyme reaction was conducted in the presence of 20% NaCl, the relative activity of EAK16-E3C/E55F/D213T was 0.47-fold higher than that of E3C/E55F/D213T. As protein surface hydrophobicity and protein particle size analysis suggested, oligomerization may play an important role in the salt-tolerance enhancement of the fusions. Furthermore, EAK16-E3C/E55F/D213T achieved a 0.88-fold increase in the titer of glutamic acid in a model system of soy sauce fermentation compared to E3C/E55F/D213T. Therefore, the fusion with self-assembling amphiphilic peptides is an efficient strategy to improve the salt-tolerance of glutaminase.

16.
Ecotoxicol Environ Saf ; 244: 114026, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36055041

RESUMO

Effective treatment of water pollution is an economic and social requirement globally. Humic acid (HA) is a popular mitigator for such waters. However, the combined effect of HA and restorative plants on cadmium (Cd) remediation is not well understood. Therefore, we experimented on Cd remediation using HA along with vetiver grass and HA-vetiver grass. We observed that vetiver grass effectively removed Cd at 15~30 mg/L. The accumulation capacity of the root was significantly higher than the shoots (P < 0.05), and Cd distribution followed the trend: cell wall > organelle > soluble substance (F1 > F2 > F3). The plant's accumulation capacity against 25 mg/L Cd was higher than for other treatments. The root accumulation capacity was much higher (702.3 mg/L) than those without added HA. However, upon adding 200 and 250 mg/L HA, the phytoremediation of Cd in the root and shoot significantly reduced (P < 0.05). Conversely, HA improved the Cd removal efficiency of the plants, notably at a lower HA concentration (150 mg/L). In addition, HA (especially at 150 mg/L) influences Cd distribution in vetiver cells (P < 0.05) and can significantly increase the proportion of Cd in the root cytoplasm. Consequently, a low HA concentration can significantly improve Cd accumulation in the vetiver, shorten the metal's bioremediation cycle, and improve the biological absorption efficiency.


Assuntos
Vetiveria , Poluentes do Solo , Biodegradação Ambiental , Cádmio/metabolismo , Vetiveria/metabolismo , Substâncias Húmicas , Plantas/metabolismo , Poluentes do Solo/análise , Poluição da Água
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(9): 988-993, 2022.
Artigo em Chinês | MEDLINE | ID: mdl-36111716

RESUMO

OBJECTIVES: To investigate the current status of antibiotic use in very low birth weight/extremely low birth weight infants in Jiangsu Province of China, and to provide a clinical basis for the quality and improvement of antibiotic management in the neonatal intensive care unit (NICU). METHODS: A retrospective analysis was performed on the data on general conditions and antibiotic use in the very low birth weight/extremely low birth weight infants who were admitted to 15 hospitals of Jiangsu Province from January 1, 2019 to December 31, 2020. A questionnaire containing 10 measures to reduce antibiotic use was designed to investigate the implementation of these intervention measures. RESULTS: A total of 1 920 very low birth weight/extremely low birth weight infants were enrolled, among whom 1 846 (96.15%) were treated with antibiotic, and the median antibiotic use rate (AUR) was 50/100 patient-days. The AUR ranged from 24/100 to 100/100 patient-days in the 15 hospitals. After adjustment for the confounding factors including gestational age, birth weight, and neonatal critical score, the Poisson regression analysis showed that there was a significant difference in the adjusted AUR (aAUR) among the hospitals (P<0.01). The investigation results showed that among the 10 measures to reduce antibiotic use, 8 measures were implemented in less than 50% of these hospitals, and the number of intervention measures implemented was negatively correlated with aAUR (rs=-0.564, P=0.029). CONCLUSIONS: There is a high AUR among the very low birth weight/extremely low birth weight infants in the 15 hospitals of Jiangsu Province, with a significant difference among hospitals. The hospitals implementing a relatively few measures to reduce antibiotic use tend to have a high AUR. It is expected to reduce AUR in very low birth weight/extremely low birth weight infants by promoting the quality improvement of antibiotic use management in the NICU.


Assuntos
Antibacterianos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Antibacterianos/uso terapêutico , China , Hospitais , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Inquéritos e Questionários
18.
J Agric Food Chem ; 70(39): 12672-12680, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36154122

RESUMO

Raw starch glucoamylase (RSGA) can degrade the raw starch below the starch gelatinization temperature. In this study, to improve the catalytic activity of raw corn starch, N-glycosylation was introduced into the RSGA from Aspergillus fumigatus through site-directed mutation and the recombinant expression in Komagataella phaffii. Among them, the mutants G101S (N99-L100-S101) and Q113T (N111-S112-T113) increased the specific activity of raw corn starch by 1.19- and 1.21-fold, respectively. The optimal temperature of Q113T decreased from 70 to 60 °C. Notably, the combined mutant G101S/Q113T increased the specific activity toward raw starch by 1.22-fold and reduced the optimal temperature from 70 to 60 °C. Moreover, the mutant Q113M with a 1.5-fold increase in the catalytic activity was obtained via saturation mutation at site 113. Thus, the N-glycosylation site engineering is an efficient method to improve the activity of RSGA toward raw starch.

19.
Sci Rep ; 12(1): 14177, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35986169

RESUMO

The combination of trastuzumab and chemotherapy is recommended as first-line therapy for patients with human epidermal growth factor receptor 2 (HER2) positive advanced gastric cancers (GCs). Successful trastuzumab-induced targeted therapy should be based on the assessment of HER2 overexpression. This study aimed to evaluate the feasibility of multivariate models based on hematological parameters, endoscopic biopsy, and computed tomography (CT) findings for assessing HER2 overexpression in GC. This retrospective study included 183 patients with GC, and they were divided into primary (n = 137) and validation (n = 46) cohorts at a ratio of 3:1. Hematological parameters, endoscopic biopsy, CT morphological characteristics, and CT value-related and texture parameters of all patients were collected and analyzed. The mean corpuscular hemoglobin concentration value, morphological type, 3 CT value-related parameters, and 22 texture parameters in three contrast-enhanced phases differed significantly between the two groups (all p < 0.05). Multivariate models based on the regression analysis and support vector machine algorithm achieved areas under the curve of 0.818 and 0.879 in the primary cohort, respectively. The combination of hematological parameters, CT morphological characteristics, CT value-related and texture parameters could predict HER2 overexpression in GCs with satisfactory diagnostic efficiency. The decision curve analysis confirmed the clinical utility.


Assuntos
Neoplasias Gástricas , Humanos , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Trastuzumab/uso terapêutico
20.
Sci Rep ; 12(1): 14193, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35987758

RESUMO

Under the influence of additive white Gaussian noise, sparse representation cannot effectively remove noise associated with the polynomial phase signal (PPS) via most dictionary learning algorithms whose training data come from the noisy signal, such as K-SVD and RLS-DLA. In this paper, we present a novel dictionary learning algorithm based on secondary exponentially weighted moving average (SEWMA) to denoise PPS. In the proposed algorithm, we first estimate the signal-to-noise (SNR) of the PPS to set the optimal rate of a weighted decline using covariance matrix model. Second we use RLS-DLA to train the dictionary. Thirdly, SEWMA is used to refine atoms in the learned dictionary. In this way, the SNR of the reconstructed signal obtained using the proposed algorithm is clearly higher than that of other algorithms, whereas the mean squared error is lower than that of other algorithms. To obtain the optimal denoising performance, the optimal rate of a weighted decline is set based on the estimated SNR. Simulation results show that the proposed method outperforms the K-SVD, RLS-DLA in mean square error and the SNR.

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