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Abstract Background Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency. Results In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO2) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7. Conclusions This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Summary: Ventricular tachycardia (VT) and ventricular fibrillation are most causes of early death in patients with acute myocardial infarction (AMI). Conditional cardiac-specific low-density lipoprotein receptor-related protein 6 (LRP6)-knockout mice with connexin 43 (Cx43) reduction triggered the lethal ventricular arrhythmias. Thus, it is necessary for exploring whether LRP6 and its upstream genes circRNA1615 mediate the phosphorylation of Cx43 in VT of AMI. Here, we showed that circRNA1615 regulated the expression of LRP6 mRNA through sponge adsorption of miR-152-3p. Importantly, LRP6 interference fragments aggravated hypoxia injury of Cx43, while overexpression of LRP6 improved the phosphorylation of Cx43. Subsequently, interference with G-protein alpha subunit (Gαs) downstream of LRP6 further inhibited the phosphorylation of Cx43, along with increasing VT. Our results demonstrated that LRP6 upstream genes circRNA1615 controlled the damage effect and VT in AMI, and LRP6 mediated the phosphorylation of Cx43 via Gαs which played a role in VT of AMI.

Abstract Background Germinal vesicle (GV) chromatin configurations of oocytes are proposed to be related to oocyte competence and may reflect the quality of oocyte. Currently, a limited number of published studies investigated the GV chromatin configurations of guinea pig oocytes. Objective In this study on the in vitro maturation (IVM) of guinea pig oocytes, we examined the changes in their GV chromatin configurations during meiotic progression. Methods Based on the degree of chromatin compaction, the GV chromatin configurations of guinea pig oocytes could be divided into three categories depending on whether the nucleolus‐like body (NLB) was surrounded or partly surrounded by compacted chromatin, namely the uncondensed (NSN), the intermediate type (SN‐1) and the compacted type (SN‐2). Results The percentage of cells displaying the SN‐2 configuration increased with the growth of guinea pig oocytes, suggesting that this configuration presents the potential for maturation in oocytes. Oocytes derived from larger follicle exhibited increased meiotic potential. Serum starvation affected the GV chromatin configurations of guinea pig oocytes. Conclusions Collectively, these results suggest that the SN‐2 type might be a more mature form of configuration in guinea pig oocyte, whose proportion was associated with the follicle size and susceptible to the environment (e.g. serum concentration).

This paper describes the genetic etiology of sporadic amyotrophic lateral sclerosis in a single population. Polymerase chain reaction-restriction fragment length polymorphism and DNA sample sequencing of 3 common HFE gene variants (C282Y and H63D and S65C) were performed on 10 randomly selected samples of H63D gene variant (124 patients with sporadic amyotrophic lateral sclerosis) and 10 wild types of H63D samples (210 controls). The C282Y and S65C gene variant were absent. There were 24 cases (7.18%) with H63D heterozygous variants, including 16 cases (13%) in the sporadic amyotrophic lateral sclerosis group and 8 cases (4%) in the healthy control group. The polymorphism frequency of the H63D gene variant in the sporadic amyotrophic lateral sclerosis group was significantly different than that in the control group (p < 0.05), and the difference at allele level, which is still more significant (p < 0.05). H63D gene variant could be a risk factor for sporadic amyotrophic lateral sclerosis in a single population. The results showed HFE gene variants play a role in the occurrence of sporadic amyotrophic lateral sclerosis, but its effect should be carefully estimated.

Abstract TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.

Underwater wireless optical communication (UWOC) is a promising solution for Gb/s rate and long-distance underwater communication. However, random changes in the local temperature and salinity of seawater have caused different refractive indices of ocean water. This study investigated the UWOC system in different saline water while simultaneously changing the temperature and water flow. A maximum bit error rate (BER) of 4.851 × 10−6 was measured at −7.41 dBm in 3 m of 45.56 g/L saline water. By changing the temperature to 30 °C, the bit error rate (BER) value reached 5.12 × 10−6 in the saline water. On the other hand, water flow was generated in various types of water salinity to compare simultaneous environmental effects in the UWOC system. In 45.56 g/L of saline water with water flow, the UWOC system was still capable of reaching a BER value of 4 × 10−4.

The microstructure, fracture morphology and mechanical properties of Al-10Si alloy modifi ed with Al-5Ti were analyzed and tested by optical microscopy, scanning electron microscopy, and universal electronic testing machine. Compared with unmodifi ed Al-10Si alloy, the area fraction of α-Al phase in Al-10Si alloy modifi ed at 740 °C increased fi rst and then decreased with the increase of added amounts of Al-5Ti, and reached the maximum when the added amount of Al-5Ti was 0.5wt.%. When the modifi cation temperature increased from 700 to 740 °C with Al-5Ti being fi xed at 0.5wt.%, α-Al dendrites were refi ned obviously and the area fraction remarkably increased. Compared with unmodifi ed Al-10Si alloy, the ultimate tensile strength and elongation of the alloy modifi ed at 740 °C with 0.5wt.% Al-5Ti increased by 9% and 49%, respectively. The fracture surface of modifi ed alloy predominantly exhibited ductile fracture.

Background: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. Methods: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. Results: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0–8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5–6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. Conclusions: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. Trial Registration: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.

In the title compound, C10H10N2O6·H2O, the carboxylic acid group and the nitro group are essentially coplanar with the benzene ring [maximum deviation = 0.0264 (9) Å], while the amide group is oriented at a dihedral angle of 9.22 (5)° with respect to the benzene ring. In the crystal, classical O—H...O and N—H...O hydrogen bonds and weak C—H...O interactions link the organic molecules and water molecules of crystallization into a three-dimensional supramolecular architecture.

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs, miRs) play important roles in carcinogenesis. MiR-126 has been shown to be down-regulated in CRC. In this study, we identified the potential effects of miR-126 on some important biological properties of CRC cells and clarified the regulation of insulin receptor substrate 1 (IRS-1) and its possible signaling pathway by miR-126.The effect of miR-126 on IRS-1, AKT, and ERK1/2 expression was assessed in the CRC cell lines HT-29 and HCT-116 with a miR-126 mimic or inhibitor to increase or decrease miR-126 expression. Furthermore, the roles of miR-126 in regulation of the biological properties of CRC cells were analyzed with miR-126 mimic or inhibitor-transfected cells. The 3'-untranslated region (3'-UTR) of IRS-1 regulated by miR-126 was analyzed by using a dual-luciferase reporter assay.We found that IRS-1 is the functional downstream target of miR-126 by directly targeting the 3'-UTR of IRS-1. Endogenous miR-126 and exogenous miR-126 mimic inhibited IRS-1 expression. Furthermore, gain-of-function or loss-of-function studies showed that over-expression of miR-126 down-regulated IRS-1, suppressed AKT and ERK1/2 activation, CRC cells proliferation, migration, invasion, and caused cell cycle arrest, but had no effect on cell apoptosis. Knockdown of miR-126 promoted these processes in HCT-116 cells and promoted AKT and ERK1/2 activation by up-regulating the expression of the IRS-1 protein.MiR-126 may play roles in regulation of the biological behavior of CRC cells, at least in part, by targeting IRS-1 via AKT and ERK1/2 signaling pathways.

In the title compound, C9H7ClN2O6, the nitro groups and the ester group make dihedral angles of 44.0 (1), 89.6 (1) and 164.1 (1)°, respectively, with the benzene ring. In the crystal, molecules are linked through weak C—H...O hydrogen-bonding interactions. Molecules are stacked via π–π interactions about inversion centers, with a centroid–centroid distance of 3.671 (2) Å.

In the molecule of the title compound, C10H11NO4, the nitro group is approximately coplanar with the benzene ring [dihedral angle = 4.57 (10)°], while the carboxylate group is slightly twisted, making an angle of 12.16 (8)°. In the crystal, weak intermolecular C—H...O hydrogen bonding and π–π stacking interactions [centroid–centroid distances = 3.670 (2) and 3.665 (2) Å] are observed.

The title compound, C9H8ClNO4, crystallizes with two molecules in the asymmetric unit. In each molecule, the carboxylate group is nearly coplanar with the benzene ring, forming dihedral angles of 2.4 (1) and 4.9 (1)°. In the crystal, molecules are linked through weak C—H...O and C—H...Cl hydrogen bonds. A short O...N contact of 2.7660 (19) Å occurs between the nitro groups of adjacent molecules.

The title compound, C10H8I3NO4, crystallizes with two molecules in the asymmetric unit. The I atoms and the benzene ring plane in the two molecules are approximately coplanar, the I atoms deviating by −0.1631 (1), 0.0704 (1) and −0.0507 (1) Å from the mean plane of the benzene ring in one molecule and by 0.1500 (1), −0.0034 (1) and −0.1213 (1) Å in the other. The planes of the ester groups are almost orthogonal to those of the benzene rings in both molecules, forming dihedral angles of 83.5 (3), 76.4 (3), 97.3 (1) and 75.7 (1)°. The mean planes of the benzene rings in two molecules are inclined at 69.8 (3)° with respect to each other. In the crystal, intermolecular I...O interactions link the molecules into infinite chains. In addition, N—H...O and non-classical C—H...O hydrogen bonds are observed.

The molecule of the title compound, C9H12O2, is approximately planar (mean atomic deviation = 0.0346 Å) and disposed about a crystallographic centre of symmetry. The H atom of the benzene ring is disordered over four orientations, with occupancies of 0.100 (3) and 0.401 (3) at the C atoms in the 2- and 3-positions and the same at their symmetric location. The H atoms of methyl group at the 2-position are disordered over two positions of equal occupancy. In the crystal structure, adjacent molecules are linked through O—H...O hydrogen bonds, forming a two-dimensional network.

In the molecule of the title compound, C8H5ClN2O6, the two nitro groups and the ester group make dihedral angles of 29.6 (1)°, 82.3 (1)° and 13.7 (1)°, respectively, with the benzene ring. In the crystal structure weak C—H...O interactions are present.

In the title compound, C26H14Cl6N2, the phenanthroline ring system is essentially planar, with an r.m.s. deviation of 0.048 (6) Å, and makes dihedral angles of 64.8 (14) and 66.6 (6)° with the two terminal phenyl rings. One of the trichloromethyl groups is disordered over two positions, with occupancies of 0.42 (2) and 0.58 (2).

The title compound, C12H12I3NO4, crystallizes with two molecules in an asymmetric unit. In one of the molecules, the conformation of the O—C—O—C in one ester group is cis and trans in the other. The corresponding conformations for both the ester groups in the other molecule are trans. The I atoms and the benzene rings in the two molecules are approximately coplanar, the I atoms deviating by 0.219 (14), 0.056 (15) and −0.143 (14) Å from the mean plane of the benzene ring in one molecule and 0.189 (14), −0.162 (15) and −0.068 (14) Å in the other. The planes of the ester groups are almost orthogonal to those of the benzene rings in both molecules, forming dihedral angles of 88.1 (4), 72.2 (4), 73.0 (4) and 86.6 (4)°. The mean planes of the benzene rings in the two molecules are inclined at 74.6 (4)° with respect to each other. In the crystal, intermolecular I...O interactions [3.138 (7) and 3.144 (7) Å] link the molecules into infinite chains along the a axis. In addition, non-classical C—H...O hydrogen bonds are observed.

In the molecule of the title compound, C11H12O2, the cyclohexane ring adopts a half-chair conformation. In the crystal structure, molecules are linked into centrosymmetric dimers by pairs of O—H...O hydrogen bonds, and the dimers are linked together by π–π interactions [centroid–centroid distance = 3.8310 (13) Å] and C—H...O bonds.

In the molecule of the title compound, C8H7NO4, the nitro group is approximately coplanar with the benzene ring [dihedral angle = 0.6 (1)°], while the dihedral angle between the methoxycarbonyl group and the benzene ring is 8.8 (1)°. In the crystal structure, weak intermolecular aromatic C—H...Ocarboxyl and C—H...Onitro hydrogen-bonding interactions are present.

In the title compound, C14H11NO2, the tricyclic aromatic ring system is essentially planar [maximum deviation = 0.025 (2) Å]. The dihedral angle between the two benzene rings is 2.8 (5)°, while the carboxyl group forms a dihedral angle of 88.5 (1)° with the pyrrole ring. Intermolecular O—H...O hydrogen bonds may contribute to the overall stabilization of the crystal structure.

The carbonyl chloride group in the title compound, C7H3ClN2O5, is disordered over two orientations with occupancies of 0.505 (5) and 0.495 (5). The molecule is approximately planar, the dihedral angle between the carbonyl chloride plane and benzene ring being 9.6 (4)° in the major disorder component and 7.1 (4)° in the minor component. The nitro group at the 5-position is twisted, forming a dihedral angle of 6.7 (4)°. The crystal packing is stabilized by C—H...O hydrogen bonds.

The molecule of the title compound, C16H28O4, is centrosymmetric. The cyclohexane ring and both six-membered dioxane rings adopt chair conformations. In the crystal, the molecules lie in layers in the (100) planes and the shortest intermolecular contacts are H...H (2.30 Å).

The title compound, C15H13NO2, was synthesized by N-alkylation of methyl bromoacetate with 9H-carbazole. The carbazole ring system is essentially planar (mean atomic deviation = 0.0346 Å) and makes a dihedral angle of 86.5 (7)° with the methyl acetate group. Weak intermolecular C—H...O hydrogen bonding is present in the crystal structure.

In the title compound, C10H9NO6, the carboxy, ethoxycarbonyl and nitro groups form dihedral angles of 3.8 (1), 4.5 (1) and 164.8 (1)°, respectively, with the mean plane of the benzene ring. In the crystal structure, molecules lying about inversion centers are linked through O—H...O hydrogen bonds. C—H...O interactions are also present.

In the structure of the title compound, C11H12N2O6, the molecules are stacked along the b axis without any π–π interactions. The stacked columns are linked together by non-classical intermolecular C—H...O interactions,. In the molecule, the nitro groups make dihedral angles of 9.4 (5) and 10.3 (5)° with the benzene ring.

The structure of the title compound, C9H7NO6, is essentially planar [maximum deviation 0.284 (2)Å] except for the methyl H atoms. The crystal structure is stabilized by asymmetric O—H...O hydrogen bonds linking the hydrogen carboxylates into pairs around the inversion centres. There is also π–π stacking of the benzene rings [centroid–centroid distance 3.6912 (12) Å].

In the molecule of the title compound, C10H9NO6, the two ester groups and the nitro group are inclined at 9.2 (2), 123.3 (6) and 135.2 (5)°, respectively to the mean plane of the benzene ring. In the crystal structure, molecules are stacked along the a axis, without any π–π interactions. The stacked columns are linked together by non-classical intermolecular interactions of the type C—H...O

The nitro group in the title compound, C10H9NO6, is rotated by 10.9 (5)° out of the plane of the benzene ring.

Objective: To analyze the epidemiological and clinical characteristics of foreign-imported patients infected with SARS-CoV-2 in Chengdu City. Methods: A total of 290 foreignimported patients infected with SARS-CoV-2 and discharged from Public Health Clinical Center of Chengdu were included in our study, they were divided into asymptomatic infection group (131 cases) and confirmed cases group (159 cases) in order to compare the epidemiology, clinical characteristics and laboratory tests between two groups. Multifactor logistic regression analysis was used to investigate the influence factors of becoming a dominant infection after infected with SARS-CoV-2. Results: Among the 290 cases aged from 2 months to 68 years old, 83.4% were males, 62.1% came from Asia, and 43.8% were complicated with fatty liver disease, the age group of 14-49 years old had the largest number (247 cases). 80.5% confirmed case group cases were general type, there was only 1 severe patient. Hospital stays in asymptomatic infection group was shorter than that in confirmed cases group, lymphocyte count, CD4+T count, CD8+T count, CD4+T/CD8+T creatine kinase in two groups half a month after discharge were relatively lower than those on admission, and alanine aminotransferase, aspartate aminotransferase, albumin, lactate dehydrogenase, creatine kinase isoenzyme were relatively higher than those on admission (P < 0.05). Logistic regression analysis showed that increased age, decreased lymphocyte count on admission and increased lactate dehydrogenase on admission were associated with dominant infection. Chest CT of 13 general type cases indicated an increase in lesions compared with that at discharge and 3 of them had re-detectable positive RNA test. Conclusion: The majority of foreign-imported cases in Chengdu are mainly from Asia, fewer of them are severe patients. In the early stage of recovery, some SARS-CoV-2 infected patients still have intermittent viral replication. Early isolation and early treatment of imported patients is not only conducive to epidemic prevention and control, but also may change the natural course of the disease [ABSTRACT FROM AUTHOR]