Search

Abstract: In this paper, the advanced preparation methods of nanocellulose are reviewed and their advantages and disadvantages are compared, especially the application of using a eutectic solvent to prepare nanocellulose instead of strong acid and strong base solvent is listed. In this paper, the wide application of nanocellulose in medicine, sewage treatment, electrochemistry, gas absorption and other fields is summarized, such as drug transport as a drug carrier and the construction of biological tissue scaffolds for the medical field. Further research is needed, and the expectation of more green and efficient preparation of nanocellulose and its application prospect in more fields is expressed.

3,3-Disubstituted oxetanes have been utilized as bioisosteres for gem-dimethyl and cyclobutane functionalities. We report the discovery of a novel class of oxetane indole-amine 2,3-dioxygenase (IDO1) inhibitors suitable for Q3W (once every 3 weeks) oral and parenteral dosing. A diamide class of IDO inhibitors was discovered through an automated ligand identification system (ALIS). Installation of an oxetane and fluorophenyl dramatically improved the potency. Identification of a biaryl moiety as an unconventional amide isostere addressed the metabolic liability of amide hydrolysis. Metabolism identification (Met-ID)-guided target design and the introduction of polarity resulted in the discovery of potent IDO inhibitors with excellent pharmacokinetic (PK) profiles in multiple species. To enable rapid synthesis of the key oxetane intermediate, a novel oxetane ring cyclization was also developed, as well as optimization of a literature route on kg scale. These IDO inhibitors may enable unambiguous proof-of-concept testing for the IDO1 inhibition mechanism for oncology.

Lung ischemia-reperfusion injury (LIRI) is a common complication after lung transplantation, embolism, and trauma. N6-methyladenosine (m6A) methylation modification has been found to be implicated in the pathogenesis of ischemia/reperfusion injury. However, there are no or few reports of m6A-related regulators in LIRI till now. In this text, differentially expressed genes in lung tissues of LIRI rats versus the sham group were identified by RNA sequencing (RNA-seq). RNA-seq outcomes revealed that only YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) were differentially expressed in the LIRI versus sham group among 20 m6A-related regulators. Next, the functions and molecular mechanisms of YTHDF3 and IGF2BP2 in LIRI were investigated in a hypoxia/reoxygenation-induced BEAS-2B cell injury model in vitro. Loss-of-function experiments demonstrated that YTHDF3 or IGF2BP2 knockdown attenuated hypoxia/reoxygenation-mediated inhibitory effects on cell survival and cell cycle progression and inhibited hypoxia/reoxygenation-induced cell apoptosis and pro-inflammatory cytokine secretion in BEAS-2B cells. Genes that could be directly regulated by YTHDF3 or IGF2BP2 were identified based on prior experimental data and bioinformatics analysis. Moreover, multiple potential downstream pathways of YTHDF3 and IGF2BP2 were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis of the above-mentioned genes. Among these potential pathways, we demonstrated that YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-κB pathways in BEAS-2B cells. In conclusion, YTHDF3 or IGF2BP2 knockdown weakened hypoxia/reoxygenation-induced human lung bronchial epithelial cell injury by inactivating p38, AKT, ERK1/2, and NF-κB pathways.

Circular RNA (circRNA)-associated competing endogenous RNA (ceRNA) mechanism have emerged as critical mechanism in cancer initiation and progression. However, the roles of the circRNA-microRNA (miRNA)-messenger RNA ceRNA network in osteosarcoma are still not fully characterized. In this study, therefore, circ_0078767-related ceRNA mechanism in osteosarcoma was studied. Bioinformatics tools primarily identified differentially expressed circRNAs and their downstream miRNAs in osteosarcoma, implying the potential interaction between circ_0078767, miR-330-3p, and cyclin-dependent kinase 14 (CDK14) in this malignancy, which were further verified by means of RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter gene assays. Aberrant abundance of circ_0078767 was found in both osteosarcoma tissues and cells, relating to dismal prognosis in patients with osteosarcoma. Functionally, circ0078767 strengthened the proliferation, invasiveness, and migration of osteosarcoma cells, which could be neutralized by miR-330-3p. Additionally, miR-330-3p targeted and decreased CDK14 expression whereby motivating the malignant phenotypes of osteosarcoma cells. Through in vivo experiments, we further confirmed that circ_0078767 targeted miR-330-3p to upregulate CDK14, whereby strengthening the in vivo tumorigenic and metastatic ability of osteosarcoma cells. Circ_0078767 promotes the occurrence and development of osteosarcoma by upregulating CDK14 in a miR-330-3p-dependent manner.

Background The activation and assembly of the NLRP3 inflammasome is dependent on the interaction between NLRP3 and the intermediate filament protein vimentin in an acute respiratory distress syndrome (ARDS) model. We investigated the role of vimentin in this process using human fetal lung (HFL-1) fibroblasts with vimentin transfer genes or gene knockdown and lipopolysaccharide (LPS) intervention. Methods HFL-1 cells [con-vector + LPS, vimentin-pCMV3 (VIM-pCMV3), con-siRNA, and vimentin siRNA (VIM-siRNA)] were treated with LPS. An oxidative stress damage assessment, apoptosis analysis, and quantification of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 by enzyme linked immunosorbent assay (ELISA) were performed. Immunoblotting was used to reveal the autophagy pathway. Results We demonstrated that in response to LPS vimentin expression was lower in the HFL-1 cells with the vimentin gene knocked down. Specifically, an increase in oxidative stress, a decrease in mitochondrial membrane potential, or an increase in calcium ion permeability resulted in an increase in the fibroblast apoptosis rate. In addition, the inflammatory response after vimentin gene knockout was upregulated, as indicated by higher levels of TNF-a, IL-1β, IL-6, and IL-10. Importantly, the mechanism of suppression of vimentin in the lung fibroblasts was caused by a decrease in autophagy, an increase in mitochondrial membrane protein, and a decrease in mitochondrial function, which may contribute to the augmented cellular injury generated during the response to LPS. Conclusions This study provides insights into whether vimentin may interfere with the inflammatory cascade by activating the autophagy pathway of mitochondrial lung fibroblasts in the early stage of acute lung injury (ALI).

Angiotensin-converting enzyme 2 (ACE2) is an aminopeptidase that functions as a part of the renin-angiotensin system (RAS). The RAS pathway plays a crucial role in regulating the local blood flow within a tissue. As a consequence, the role of ACE2 in regulating vasculature properties has been widely appreciated. Additionally, ACE2 has also been reported to show anti-tumorigenic activity. However, the mechanistic basis of this function has remained largely unexplored. In the current study, using a lentivirus-based expression system in lung cancer cells (A549), we show that ACE2 overexpression reduces the viability and migratory potential of cancer cells, highlighting the robust anti-tumorigenic effects of ACE2 function. Moreover, a quantitative proteome-level comparison between ACE2 overexpressed (OE) and empty vector-controlled (NC) cells reveals a large number (227) of differentially expressed proteins (DEPs) that may have contributed to this phenomenon. Functional enrichment of these DEPs has uncovered that most of them perform binding activities and enzymatic reactions associated with metabolic pathways and various post-transcriptional gene expression regulatory mechanisms. Besides, cellular component analysis reveals that the DEPs function across a range of compartments within a cell with a relatively heterogeneous distribution. Our study, therefore, supports the previously established anti-tumorigenic effects of ACE2 overexpression in lung cancer cells. An analysis based on comprehensive, unbiased, and quantitative proteomics, we have provided a rigorous mechanistic explanation for its functions.

Objective. To prospectively investigate early prognostic assessments of patients with Multiple Organ Dysfunction Syndrome in the Elderly (MODSE) who were receiving invasive mechanical ventilation (IMV). Methods. The clinical data of 351 patients were enrolled prospectively between January 2013 and January 2018. The Acute Physiology and Chronic Health Evaluation II (APACHE II), APACHE III, Simplified Acute Physiology Score (SAPS II), and Multiple Organ Dysfunction Score (MODS) were calculated. According to the outcome of 28-day, the patients were divided into survivors and nonsurvivors. Additionally, based on whether weaning could be implemented, all patients were divided into a successful-weaning group and a failure-to-wean group. Results. According to the prognosis, the areas under the receiver operating characteristic curve of the APACHE II, APACHE III, SAPS II, and MODS scoring systems were 0.837, 0.833, 0.784, and 0.860, respectively. MODS exhibited the highest sensitivity, whereas APACHE II showed the highest specificity, and successful weaning was conducive to ameliorating patients’ prognosis. Multivariate logistic regression analyses revealed that underlying lung disease, plasma albumin, serum creatinine level, number of failing organs, and IMV duration were related to prognosis of weaning, with odds ratios (ORs) of 1.447, 0.820, 1.603, 2.374, and 3.105, respectively. Conclusions. The APACHE II, APACHE III, SAPS II, and MODS systems could perform excellent prognostic assessment for patients with Multiple Organ Dysfunction Syndrome in the elderly. Underlying lung disease, plasma albumin, serum creatinine, number of failing organs, and IMV duration were independent prognostic factors of weaning in MODSE patients with invasive mechanical ventilation.

BACKGROUND: To analyze the clinical value of microbiological rapid on-site evaluation (M-ROSE) in the respiratory intensive care unit (RICU) and its impact on the prognosis of critically ill patients. METHODS: We retrospectively included patients who underwent bedside bronchoalveolar lavage in the RICU of Chinese People’s Liberation Army (PLA) General Hospital between January 2017 and December 2020. The patients were divided into M-ROSE and control groups according to whether bedside M-ROSE was performed with to guide the treatment, and for control group, routine treatments were administrated based on all the clinical information. The basic information, treatment methods, test indicators, and prognostic evaluation of the patients were collected and analyzed. RESULTS: A total of 242 patients were enrolled, including 130 patients in the M-ROSE group and 112 patients in the control group. The inflammatory indicators of the patients in the M-ROSE group decreased significantly faster after admission than those of patients in the control group, and the patients in the M-ROSE group used significantly more types of antibiotics [5 (3.0, 5.0)] than those in the control group [3 (2.0, 4.0)] (P

Background The cytological analysis of bronchoalveolar lavage fluid (BALF) plays an essential role in the differential diagnosis of respiratory diseases. In recent years, deep learning has demonstrated excellent performance in image processing and object recognition. Objectives We aim to apply deep learning to the automated interpretation and analysis of BALF. Method Visual images were acquired using an automated biological microscopy platform. We propose a three-step algorithm to automatically interpret BALF cytology based on a convolutional neural network (CNN). The clinical value was evaluated at the patient level. Results Our model successfully detected most cells in BALF specimens and achieved a sensitivity, precision, and F1 score of over 0.9 for most cell types. In two tests in the clinical context, the algorithm outperformed experienced practitioners. Conclusion The program can automatically provide the cytological background of BALF and augment clinical decision-making for clinicians.

A practical synthesis and detailed development process of 2H-1,3-benzoxazine derivatives catalyzed by aldimine and trifluoromethanesulfonic acid is described. A broad range of substrates with diverse steric and electronic properties were explored. Aliphatic/aromatic/heteroaromatic substrates all proceed well under conditions which have been optimized into a robust, scalable process.

To investigate the therapeutic effect of different doses of methylprednisolone (MP) in smoke inhalation-induced acute lung injury (SI-ALI).Adult male Sprague-Dawley (SD) rats were divided into control group (group A, n = 6), smoke inhalation group (group B, smoke inhalation 30 minutes, n = 30) and smoke + MP 40, 4, 0.4 mg/kg intervention group (groups C, D, E; intraperitoneal injection of MP at 1 hour before smoke inhalation, n = 30) according to random number table method. The survival status of rats in each group was observed at 24 hours, and murine smoke inhalation induced trauma score (MSITS) according to the symptoms and signs of rats at 3 hours after smoke inhalation were scored. The blood of abdominal aorta of rats was collected. Then the rats were sacrificed to harvest bronchoalveolar lavage fluid (BALF) and lung tissue. The levels of interleukin (IL-6, IL-17a) in plasma and BALF were detected by enzyme linked immunosorbent assay (ELISA); the total number of white blood cells and the proportion of leukocytes or macrophages in BALF were calculated; the histopathological changes of lung were observed and the lung injury score was given; the expression of myeloperoxidase (MPO) and high mobility group protein B1 (HMGB1) in lung tissue were detected by Western Blot.The 24-hour survival rate of group B rats was 33.67%. The survival rate of groups C, D and E (65.73%, 85.17%, 60.07%) were significantly higher than that of group B (all P0.05), and the survival rate of group D was significantly higher than that of groups C and E. Diffuse inflammatory cell infiltration, intra-alveolar hemorrhage and a large amount of edema fluid were seen in the lung tissue of group B; and the lung injury score was significantly higher than that of group A. Compared with group B, the lung injury in different doses of MP group were decreased to different degrees, while the lung injury scores in groups C and D were significantly decreased (3.31±1.37, 2.62±0.98 vs. 5.52±0.97, both P0.01); correlation analysis showed that MSITS score was significantly and positively correlated with lung injury score (r = 0.862, P0.001). The levels of plasma inflammatory factors and BALF protein, inflammatory cells and inflammatory factors, and the expression of MPO, HMGB1 in group B were significantly higher than those in group A. Compared with group B, the levels of inflammatory factors in plasma, and protein content, inflammatory cells and inflammatory factors in BALF in different doses of MP group were decreased to different degrees, with significant differences in groups C and D [plasma: IL-17a (pg/L): 49.28±27.12, 36.57±16.52 vs. 191.79±88.21; IL-6 (ng/L): 206.47±109.96, 197.52±113.86 vs. 669.00±299.60; BALF: protein content (mg/L): 892.0±164.5, 566.1±120.9 vs. 1 838.0±145.8; white blood cell count (×10MP can significantly improve the survival rate of SI-ALI rats and reduce the acute pulmonary and systemic inflammatory response. The MP effect of 4 mg/kg was better than 40 mg/kg and 0.4 mg/kg.

This article describes recent developments in chemical study on a series of butterfly-shaped μ-CO-containing Fe/E (E = S, Se, Te) cluster salts. These salts include eleven novel cluster anions, which are the single butterfly one μ-CO-containing [(μ-RE)(μ-CO)Fe2(CO)6]− (A), the double butterfly two μ-CO-containing {[(μ-CO)Fe2(CO)6]2(μ-EZE-μ)}2− (B, E = S; C, E = Se), the triple butterfly three μ-CO-containing {[(μ-CO)Fe2(CO)6]3[(μ-SCH2CH2)3N]}3− (D), {[(μ-CO)Fe2(CO)6]3[1,3,5-(μ-SCH2)3C6H3]}3− (E), {[(μ-CO)Fe2(CO)6]3[(μ-SCH2)3CMe]}3− (F), the double butterfly one μ-CO-containing {[(μ-CO)Fe2(CO)6] [Fe2(CO)6][(μ-SCH2)3CMe]}− (G) derived in situ from F, the quadruple butterfly four μ-CO-containing {[(μ-CO)Fe2(CO)6]4[1,2,4,5-(μ-SCH2)4C6H2]}4− (H), the triple butterfly two μ-CO-containing {[(μ-CO)Fe2(CO)6]2 [Fe2(CO)6][1,2,4,5-(μ-SCH2)4C6H2]}2− (I) derived in situ from H, the quadruple butterfly four μ-CO-containing {[(μ-CO)Fe2(CO)6]4[(μ-SCH2)4C]}4− (J), and the triple butterfly two μ-CO-containing {[(μ-CO)Fe2 (CO)6]2[Fe2(CO)6][(μ-SCH2)4C]}2− (K) derived in situ from J. This article describes not only the synthetic methods for formation of such anionic cluster (A-K) salts, but also their novel reactions leading to various new types of butterfly Fe/E cluster complexes. All these findings described in this article are important both theoretically and practically.

We have studied the nonlinear refractive properties of the organometalic fullerene-C 60 derivatives fac- and mer- [bis (1,2-diphenylphosphino) ethane] (tricarbonyl)(η 2 -fullerene-C 60 ) chromium and molybdenum using the Z-scan method. These compounds change from being self-defocusing to self-focusing as the input light intensity increases. The experimental results have been interpreted using rate-equation theory. Critical conditions for the occurrence of this kind of transition have been elucidated for the steady-state situation.

The nonlinear refraction property of excited-state nonlinear optical materials was studied based on rate-equation theory. The effects of the ratios of excited-state absorption cross section and refrangibility to those of ground state upon their nonlinear refraction properties were analyzed. The nonlinear optical properties of ( m -MeC 6 H 4 ) 5 C 60 H-toluene solution were investigated by using Z -scan method with 8 ns 532 nm laser pulses. The solution was proved to possess strong nonlinear absorption and weak nonlinear refraction.

Singlet excited-state absorption properties and optical limiting behaviors of organochromium and organomolybdenum C60 derivatives (C89H24CrO3P2 and C89H24MoO3P2) were studied by using a double frequency ns/ps Nd:YAG pulse laser system at wavelength of 532 nm and pulse width 21 ps. The experimental results demonstrated that the optical limiting behavior of organochromium C60 derivative is better than both organomolybdenum C60 derivative and fullerene–C60 itself. The experimental results agree well with the singlet excited-state absorption theory.