A New Index of Energy Dissipation Considering Time Factor under the Impact Loads.

Rock failure phenomena are accompanied by abundant energy variation, and the energy dissipation can explain the dynamic mechanical characteristics of the rock. In this study, a series of granite specimens (a total of 60) with different aspect ratios were dynamically loaded by a split Hopkinson pressure bar (SHPB) to explain the energy dissipation and the rock-crushing degree under dynamic load. A new index, namely energy time density (wtd), is proposed to evaluate the energy dissipation considering the time factor. The relationships between strain rate, energy time density, and specific energy absorption are analyzed. A metric (Ku) is defined to describe the degree of rock fragmentation quantitatively. The correlations of fractal dimension and Ku with different impact pressures are compared. It was concluded that there is a noticeable peak point in the energy time density curve. The energy time density of the stress equilibrium point is three times that of the peak point. The energy time density declines after the peak point, then the energy consumption density tends to be stable. The linear relationship between strain rate and peak point energy time density is stronger. The new index can describe energy dissipation well under dynamic loading. In addition, the experimental results indicate that the degree of crush Ku can describe the degree of crush, and the effect of fractal dimension to quantify the fracture characteristics of the rocks is less good in this test. The crushing degree of rocks increases with the increase of strain rate. Furthermore, the prediction effect of energy time density is better than that of strain rate about Ku.

Synthesis of L-asparagine Catalyzed by a Novel Asparagine Synthase Coupled With an ATP Regeneration System.

Compared with low-yield extraction from plants and environmentally unfriendly chemical synthesis, biocatalysis by asparagine synthetase (AS) for preparation of L-asparagine (L-Asn) has become a potential synthetic method. However, low enzyme activity of AS and high cost of ATP in this reaction restricts the large-scale preparation of L-Asn by biocatalysis. In this study, gene mining strategy was used to search for novel AS with high enzyme activity by expressing them in Escherichia coli BL21 (DE3) or Bacillus subtilis WB600. The obtained LsaAS-A was determined for its enzymatic properties and used for subsequent preparation of L-Asn. In order to reduce the use of ATP, a class III polyphosphate kinase 2 from Deinococcus ficus (DfiPPK2-Ⅲ) was cloned and expressed in E. coli BL21 (DE3), Rosetta (DE3) or RosettagamiB (DE3) for ATP regeneration. A coupling reaction system including whole cells expressing LsaAS-A and DfiPPK2-Ⅲ was constructed to prepare L-Asn from L-aspartic acid (L-Asp). Batch catalytic experiments showed that sodium hexametaphosphate (>60 mmol L-1) and L-Asp (>100 mmol L-1) could inhibit the synthesis of L-Asn. Under fed-batch mode, L-Asn yield reached 90.15% with twice feeding of sodium hexametaphosphate. A final concentration of 218.26 mmol L-1 L-Asn with a yield of 64.19% was obtained when L-Asp and sodium hexametaphosphate were fed simultaneously.

[Effect of positive end expiratory pressure level selection in prone position ventilation on lung recruitment and inflammatory factors in patients with severe acute respiratory distress syndrome].

OBJECTIVE: To investigate the effect of positive end expiratory pressure (PEEP) level selection on prone position ventilation and inflammatory factors in patients with severe acute respiratory distress syndrome (ARDS). METHODS: A prospective randomized controlled study was conducted. The 100 patients with severe ARDS admitted to Union Jiangbei Hospital, Huazhong University of Science and Technology from March 2016 to March 2019 were enrolled. Patients were divided into two groups according to the random number table method, with 50 cases in each group. All patients were given lung protective ventilation strategy and prone position ventilation treatment on the basis of treatment of primary disease. The lower level of PEEP [8-12 cmH2O (1 cmH2O = 0.098 kPa)] was the control group, and the higher level of PEEP (13-17 cmH2O) was the observation group. Patients' vital signs were continuously monitored during mechanical ventilation. The indexes of pulmonary recruitment were recorded, including the dynamic lung compliance (Cdyn), pulmonary drive pressure (DP), heart rate and lactate (Lac) levels before and 48 hours after the treatment. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high sensitivity C-reaction protein (hs-CRP) in serum were detected by enzyme linked immunosorbent assay (ELISA). Arterial blood gas was detected, including arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), and arterial partial pressure of carbon dioxide (PaCO2). The occurrence of pleural effusion and heart, liver and kidney dysfunction were recorded. RESULTS: In the control group, the PEEP level was (10.9±1.2) cmH2O, and the observation group PEEP level was (15.6±1.5) cmH2O. There was no significant difference in the index of lung recruitment, the levels of inflammatory factors and the arterial blood gas analysis index between the two groups before treatment. After prone ventilation, the index of lung recruitment and the arterial blood gas analysis index were much better in both groups. The effect of lung recruitment and oxygenation in the observation group with higher PEEP level were significantly superior to the control group with lower PEEP level [Cdyn (mL/cmH2O): 37.61±5.09 vs. 32.51±4.97, DP (cmH2O): 10.36±1.51 vs. 12.55±1.35, heart rate (bpm): 93.13±10.56 vs. 108.56±12.49, Lac (mmol/L): 2.34±0.41 vs. 3.41±0.57, PaO2 (mmHg, 1 mmHg = 0.133 kPa): 95.13±3.33 vs. 91.81±2.75, PaO2/FiO2 (mmHg): 180.12±7.25 vs. 150.29±8.52, PaCO2 (mmHg): 38.31±2.13 vs. 45.22±2.61, all P < 0.05]. The levels of inflammatory factors after treatment were higher than before treatment in both groups. Higher PEEP level will cause increased inflammatory factor level than the control group [IL-6 (ng/L): 526.24±125.18 vs. 465.18±130.52, TNF-α (ng/L): 42.47±2.20 vs. 34.12±1.89, hs-CRP (mg/L): 101.24±23.26 vs. 83.56±25.51, all P < 0.05]. Furthermore, the occurrence of pleural effusion and heart, liver, kidney dysfunction in the observation group were lower than that of the control group (4.0% vs. 8.0%, 10.0% vs. 16.0%, 2.0% vs. 10.0%, 2.0% vs. 6.0%, respectively, all P < 0.05). CONCLUSIONS: The higher PEEP level combined with prone position ventilation is beneficial to the severe ARDS patients with better lung recruitment effect and arterial blood gas improvement, thus promote the patients' recovery. But the higher initial PEEP will induce the release of inflammatory factors to a certain extent.

Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study.

BACKGROUND: A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. METHODS: A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. RESULTS: A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57-70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5-17) days, and the duration from onset of symptoms to the study date was 31 (24-36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2-8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. CONCLUSIONS: Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4.

A natural small molecule, catechol, induces c-Myc degradation by directly targeting ERK2 in lung cancer.

Various carcinogens induce EGFR/RAS/MAPK signaling, which is critical in the development of lung cancer. In particular, constitutive activation of extracellular signal-regulated kinase 2 (ERK2) is observed in many lung cancer patients, and therefore developing compounds capable of targeting ERK2 in lung carcinogenesis could be beneficial. We examined the therapeutic effect of catechol in lung cancer treatment. Catechol suppressed anchorage-independent growth of murine KP2 and human H460 lung cancer cell lines in a dose-dependent manner. Catechol inhibited ERK2 kinase activity in vitro, and its direct binding to the ERK2 active site was confirmed by X-ray crystallography. Phosphorylation of c-Myc, a substrate of ERK2, was decreased in catechol-treated lung cancer cells and resulted in reduced protein stability and subsequent down-regulation of total c-Myc. Treatment with catechol induced G1 phase arrest in lung cancer cells and decreased protein expression related to G1-S progression. In addition, we showed that catechol inhibited the growth of both allograft and xenograft lung cancer tumors in vivo. In summary, catechol exerted inhibitory effects on the ERK2/c-Myc signaling axis to reduce lung cancer tumor growth in vitro and in vivo, including a preclinical patient-derived xenograft (PDX) model. These findings suggest that catechol, a natural small molecule, possesses potential as a novel therapeutic agent against lung carcinogenesis in future clinical approaches.

A method for establishing a patient-derived xenograft model to explore new therapeutic strategies for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal carcinoma in China. The overall 5-year survival rate of ESCC patients is in the low range of 15-25%. One important reason for the poor prognosis is that the underlying molecular mechanisms are unclear. Furthermore, the development of effective therapeutic strategies to improve patient outcome is needed. Animal models can be beneficial to analyze the molecular mechanisms as well as specific clinical therapeutic strategies for esophageal cancer. In recent years, patient-derived xenografts (PDXs) have been widely used in numerous types of cancers to investigate the basic mechanisms and to conduct preclinical research. Accumulating evidence indicates that the PDX model is an important tool for basic and clinical research. Herein, we successfully established 14 ESCC PDXs. These PDX models preserved the patient pathological characteristics and effectively reflected the patient biological heterogeneity. Cancers exhibit diverse growth rates and tumor texture, even more, they have different signaling pathways. The PDX model is a superior strategy for understanding the underlying molecular mechanisms of ESCC and for screening new therapeutic strategies for ESCC patients.