Autophagy and machine learning: Unanswered questions.

Autophagy is a critical conserved cellular process in maintaining cellular homeostasis by clearing and recycling damaged organelles and intracellular components in lysosomes and vacuoles. Autophagy plays a vital role in cell survival, bioenergetic homeostasis, organism development, and cell death regulation. Malfunctions in autophagy are associated with various human diseases and health disorders, such as cancers and neurodegenerative diseases. Significant effort has been devoted to autophagy-related research in the context of genes, proteins, diagnosis, etc. In recent years, there has been a surge of studies utilizing state of the art machine learning (ML) tools to analyze and understand the roles of autophagy in various biological processes. We taxonomize ML techniques that are applicable in an autophagy context, comprehensively review existing efforts being taken in this direction, and outline principles to consider in a biomedical context. In recognition of recent groundbreaking advances in the deep-learning community, we discuss new opportunities in interdisciplinary collaborations and seek to engage autophagy and computer science researchers to promote autophagy research with joint efforts.

Potential source and health risks of black carbon based on MERRA-2 reanalysis data in a typical industrial city of North China Plain.

Black carbon (BC) significantly affects climate, environmental quality, and human health. This study utilised Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2), which can compensate for the shortcomings of ground BC monitoring in spatial-temporal distribution to study the pollution characteristics of BC and potential pollution sources in a typical industrial city (Xinxiang) with serious air pollution in northern China. The results showed that average daily ground observation and MERRA-2 concentration of BC of 7.33 µg m-3 and 9.52 µg m-3. The mean BC concentration derived from MERRA-2 reanalysis data was higher than ground measurement due to resolution limitations and pollution from the northern regions. The reliability of the MERRA-2 data was confirmed through correlation analysis. Consideration of the spatial distribution of BC from MERRA-2 and incorporating the potential source contribution function (PSCF), concentration-weighted trajectory (CWT), and emission inventory, other possible source areas and primary sources of BC in Xinxiang were investigated. The results indicated that implementing transportation and residential emission control measures in Henan Province and its surrounding provinces, such as Hebei Province, will effectively decrease the BC level in Xinxiang City. A passively smoked cigarettes model was used to evaluate the risk of BC exposure. The percentage of lung function decrement (PLFD) was the highest in school-age children, while the impact on lung cancer (LC) health risk was comparatively lower. Notably, the BC health risk in Xinxiang was lower than in most cities across Asia.

Potential benefits of Rehmanniae Radix after ancient rice-steaming process in promotion of antioxidant activity in rats' health.

Rice steam processed product of Rehmanniae Radix (RSRR), one of the processed products of Rehmanniae Radix (RR), is popular as an herbal medicine and food. However, the health-promoting effects and mechanisms of RSRR are still unclear. In this study, 10-week-old Sprague-Dawley female rats were treated with different processed products of RR. No organ coefficient differences were observed between RSRR and the control group, indicating that RSRR did not cause damage to the rats. Compared with other RR products, superoxide dismutase, glutathione, and catalase levels were significantly higher and malondialdehyde levels were significantly lower in the RSRR group, indicating that RSRR exerted a better antioxidant effect. Gene expression analysis showed that hemoglobin genes (Hba-a1, Hba-a2, Hbb-bs, Hbb, Hbq1b, Hbb-b1, and LOC103694857) may be potential biomarkers to evaluate the antioxidant effect of RSRR. Antioxidation-related signaling pathways in GO annotation, including cellular oxidant detoxification, hydrogen peroxide metabolic process, hemoglobin complex, and oxygen binding signaling pathways were significantly enriched, indicating these pathways may represent the antioxidant mechanism of RSRR. To explore the main active compounds primarily responsible for the antioxidant activity of RSRR, UPLC-Q-TOF-MS was used and six components (catalpol, rehmannioside A, rehmannioside D, melittoside, ajugol, and verbascoside) were identified in rat serum. Catalpol and rehmannioside A were predicted to be the major active components by network pharmacology. These results suggested that RSRR exhibits antioxidant activity and has health-promoting properties. This study provides a scientific basis for the antioxidant mechanism and clinical use of RSRR.

Retraction: Structural characterization and anticancer potency of centipede oligopeptides in human chondrosarcoma cancer: inducing apoptosis.

[This retracts the article DOI: 10.1039/D0RA04811A.].

Complications after endoscopic submucosal dissection for early colorectal cancer (Review).

Colorectal cancer (CRC) is a gastrointestinal malignancy that seriously threatens human life and health, resulting in a heavy disease burden. Endoscopic submucosal dissection (ESD) is widely used in clinical practice and is an effective treatment for early CRC (ECC). Colorectal ESD is a challenging operation, and the incidence of postoperative complications is relatively high because of the thin intestinal wall and limited space for endoscopic operations. Systematic reports on the postoperative complications of colorectal ESD, such as fever, bleeding and perforation, from both China and elsewhere are lacking. In the present review, progress in research on postoperative complications after ESD for ECC is summarized.

PredDSMC: A predictor for driver synonymous mutations in human cancers.

Introduction: Driver mutations play a critical role in the occurrence and development of human cancers. Most studies have focused on missense mutations that function as drivers in cancer. However, accumulating experimental evidence indicates that synonymous mutations can also act as driver mutations. Methods: Here, we proposed a computational method called PredDSMC to accurately predict driver synonymous mutations in human cancers. We first systematically explored four categories of multimodal features, including sequence features, splicing features, conservation scores, and functional scores. Further feature selection was carried out to remove redundant features and improve the model performance. Finally, we utilized the random forest classifier to build PredDSMC. Results: The results of two independent test sets indicated that PredDSMC outperformed the state-of-the-art methods in differentiating driver synonymous mutations from passenger mutations. Discussion: In conclusion, we expect that PredDSMC, as a driver synonymous mutation prediction method, will be a valuable method for gaining a deeper understanding of synonymous mutations in human cancers.

Electrotaxis of alveolar epithelial cells in direct-current electric fields.

PURPOSE: This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury. METHODS: AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis. RESULTS: The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11. CONCLUSION: EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.

Improved Performance of g-C3N4 for Optoelectronic Detection of NO2 Gas by Coupling Metal-Organic Framework Nanosheets with Coordinatively Unsaturated Ni(II) Sites.

Sensitive and selective optoelectronic detection of NO2 with g-C3N4 (CN) is critical, but it remains challenging to achieve ultralow concentration (ppb-level) detection. Herein, Ni metal-organic frameworks/CN nanosheet heterojunctions were successfully fabricated by the electrostatic induced assembly strategy and then treated by a post-alkali etching process for creating coordinatively unsaturated Ni(II) sites. The optimized heterojunction exhibits a record detection limitation of 1 ppb for NO2, well below that observed on pristine CN, and an outstanding selectivity over other gases, along with long-time stability (120 days) at room temperature. The resulting superior detection performance benefits from the enhanced charge transfer and separation of the closely contacted heterojunction interface and the favorable adsorption of NO2 by unsaturated Ni(II) as selective adsorption sites mainly by means of the time-resolved photoluminescence spectra and in situ X-ray photoelectron spectra. Moreover, the in situ Fourier transform infrared spectra and temperature-programmed desorption disclose that the promotion adsorption of NO2 depends on the strengthened interaction between NO2 and Ni(II) node sites at the aid of OH groups from unsaturated coordination. This work offers a versatile solution to develop promising CN-based optoelectronic sensors at room temperature.

A New Method for Programmable RNA Editing Using CRISPR Effector Cas13X.1.

Type VI CRISPR-Cas13 is the only CRISPR system that can bind and cleave RNA without DNase activity. We used the newly discovered, smaller Cas13X.1 protein to construct an editing system in mammalian cells, aiming to break the delivery restrictions of CRISPR-Cas13 system in vivo and promote the application of Cas13X system in clinical therapy. We employed exogenous fluorescence reporter gene mCherry and endogenous gene transketolase (TKT) closely related to cancer cell metabolism as target genes to evaluate the Cas13X.1 system. The recombinant plasmids targeting exogenous gene mCherry and endogenous gene TKT were constructed based on Cas13X.1 backbone plasmid. The editing efficiency, protein expression level, downstream gene transcript level and safety of Cas13X.1 system were evaluated. Both TKT transcripts of endogenous genes and mCherry transcripts of exogenous genes were significantly degraded by Cas13X.1 system with a knockdown efficiency up to 50%. At the same time, Cas13X.1 down-regulated the expression of the corresponding protein level in the editing of transcripts. In addition, the transcripts of key metabolic enzymes related to TKT were also down-regulated synchronously, suggesting that the degradation of TKT transcripts by Cas13X.1 system affected the main metabolic pathways related to TKT. The morphology, RNA integrity and apoptosis of cells loaded with Cas13X.1 system were not affected. The Cas13X.1 system we constructed had strong RNA knockdown ability in mammalian cells with low cellular toxicity. Compared with other CRISPR-Cas13 systems, Cas13X.1 system with smaller molecular weight has more advantages in vivo delivery. The Cas13X.1 system targeting TKT transcripts also provides an alternative method for the study of anti-cancer therapy.

Survival benefit of surgical resection for stage IV gastric cancer: A SEER-based propensity score-matched analysis.

Background: Gastric cancer (GC) is a major malignancy worldwide, and its incidence and mortality rate are increasing year by year. Clinical guidelines mainly use palliative drug combination therapy for stage IV gastric cancer. In accordance with some small sample studies, surgery can prolong survival. There is no uniform treatment plan for stage IV gastric cancer. This study focused on collecting evidence of the survival benefit of cancer-directed surgery (CDS) for patients with stage IV gastric cancer by analyzing data from a large sample. Methods: Data on patients with stage IV gastric cancer diagnosed between 2010 and 2015 was extracted and divided into CDS and no-CDS groups using the large dataset in the Surveillance, Epidemiology, and End Results (SEER) database. With bias between the two groups minimized by propensity score matching (PSM), the prognostic role of CDS was studied by the Cox proportional risk model and Kaplan-Meier. Results: A total of 6,284 patients with stage IV gastric cancer were included, including 514 patients with CDS who were matched with no-CDS patients according to propensity score (1:1), resulting in the inclusion of 432 patients each in the CDS and no-CDS groups. The results showed that CDS appeared to prolong the median survival time for stage IV gastric cancer (from 6 months to 10 months). Multifactorial analysis showed that poorly differentiated tumors (grades III-IV) significantly affected patient survival, and chemotherapy was a protective prognostic factor. Conclusion: The findings support that CDS can provide a survival benefit for stage IV gastric cancer. However, a combination of age, underlying physical status, tumor histology, and metastatic status should be considered when making decisions about CDS, which will aid in clinical decision-making.

[Effect of modified Danggui Shaoyao Powder on SOCS3/TLR4 signaling pathway in rats with chronic atrophic gastritis].

This study aims to investigate the effect of modified Danggui Shaoyao Powder on the suppressor of cytokine signaling 3(SOCS3)/Toll-like receptor 4(TLR4) signaling pathway in gastric tissue of rats with chronic atrophic gastritis(CAG).Sixty SPF-grade SD rats were randomly assigned into the normal group, model group, Moluo Pills group, and high-, medium-, and low-dose groups of modified Danggui Shaoyao Powder.The rats in other groups except the normal group were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) to establish the CAG model.After 12 weeks of modeling, the rats in each group were administrated with corresponding drugs by gavage for 8 weeks.After the last administration, the histopathological changes of rat gastric mucosa were observed via hematoxylin-eosin(HE) staining.The serum levels of IL-6, TNF-α, and CRP were determined by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of SOCS3 and TLR4 were determined by real-time PCR.The protein levels of SOCS3, TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 in rat gastric tissue were measured by Western blot.Immunohistochemical method was employed to determine the protein levels of NF-κB, MyD88, NLRP3, Bcl-2, Bax, and Bad in rat gastric tissue.The results showed that modified Danggui Shaoyao Powder alleviated gastric mucosal atrophy of rats, significantly lowered the levels of IL-6, TNF-α, and CRP in rat serum, up-regulated the mRNA level of SOCS3, and down-regulated the mRNA level of TLR4 in rat gastric tissue.Furthermore, modified Danggui Shaoyao Powder up-regulated the protein level of SOCS3, down-regulated the protein levels of TLR4, p-JAK2, p-STAT3, NF-κB, MyD88, NLRP3, Bax, and Bad, and promoted the expression of Bcl-2 protein.Therefore, modified Danggui Shaoyao Powder may mitigate the gastric mucosal atrophy of rats by regulating the SOCS3/TLR4 signaling pathway.

PDGFR kinase inhibitor protects against septic death via regulation of BTLA.

Sepsis, defined as life-threatening organ failure caused by a dysregulated host response to severe infection, is a major cause of death among intensive care unit patients. Therapies targeting on immunomodulatory is a new research field in sepsis treatment. B- and T-lymphocyte attenuator (BTLA) is an inhibitory costimulatory factor molecule of B and T lymphocytes. Studies have shown that elevated expression of BTLA in lymphocytes can reduce mortality in sepsis, but its regulatory compounds and the underlying mechanism remains to be elucidated. Here, we show that treatment with CP-673451 significantly decreases mortality of septic mouse. CP-673451 is a PDGFR kinase inhibitor which can promote the expression of BTLA, inhibit the release of chemokines such as CXCL13, and reduce first the chemotaxis of B cells to the peripheral blood and vital organs. CP-673451 also inhibits both the release of cytokines and chemokines such as IL-1ß, IL-6, IL-10, TNF-α, CCL1, CCL2 and CCL7 and reduces both the chemotactic ability of T cells. This suggests that CP-673451 may prevent septic death by inhibiting lymphocyte chemotaxis and alleviating "cytokine storm". In conclusion, our study provides a new therapeutic target and an effective compound for sepsis treatment.

Exogenous growth hormone functionally alleviates glucocorticoid-induced longitudinal bone growth retardation in male rats by activating the Ihh/PTHrP signaling pathway.

Glucocorticoid (GC)-induced longitudinal bone growth retardation is a common and severe adverse effect in pediatric patients receiving GC immunosuppressive therapy. Molecular mechanisms underlying GC-induced growth inhibition are unclear. GC withdrawal following short-term high-dose use is common, including in the immediate post-transplant period. However, whether skeleton growth recovery is sufficient or whether growth-promoting therapy is required following GC withdrawal is unknown. The aim of this study was to investigate the effect of exogenous growth hormone (GH) on growth plate impairment in GC-induced longitudinal bone growth retardation. Here, apoptotic chondrocytes in the hypertrophic layer of growth plates increased whereas Indian Hedgehog (Ihh) and Parathyroid Hormone Related Peptide (PTHrP) protein levels in the growth plate decreased following GC exposure. The hypertrophic zone of the growth plate expanded following GC withdrawal. Subcutaneously injected GH penetrated the growth plate and modified its organization in rats following GC withdrawal. Ihh and PTHrP expression in GC-induced apoptotic chondrocytes decreased in vitro. GH promoted chondrocyte proliferation by activating Ihh/PTHrP signaling. Downregulating Ihh using specific siRNAs increased chondrocyte apoptosis and inhibited PTHrP, Sox9, and type II collagen (Col2a1) protein expression. GH inhibited apoptosis of Ihh-deficient growth plate chondrocytes by upregulating PTHrP, Sox9, and Col2a1 expression. Thus, reversal of the effect of GC on growth plate impairment following its withdrawal is insufficient, and exogenous GH provides growth plate chondral protection and improved longitudinal growth following GC withdrawal by acting on the Ihh/PTHrP pathway.

Iron-carbon microelectrolysis for wastewater remediation: Preparation, performance and interaction mechanisms.

Rapid industrialization and urbanization have produced a lot of hazardous substances in water and wastewater, which has turned into a crucial issue to the environment and the public health. Recently, iron carbon microelectrolysis (IC-ME) has attracted extensive attention in environmental remediation due to its low costs and excellent performance. Nevertheless, there is still a lack of a more systematic review on IC-ME preparation methods, their performance, and the interaction mechanisms of IC-ME in the remediation of wastewater. Herein, this work summarizes the synthetic methods, application of IC-ME materials, and the mechanism of pollutant removal by IC-ME. A variety approaches have been applied to prepare IC-ME materials, and the preparation methods and conditions have a certain influence on the properties of IC-ME materials, thus affecting the performance of pollutant removal. The mechanisms of IC-ME for contaminants removal are very complex, including adsorption, coprecipitation, reduction, surface complexation, and oxidation. Moreover, research vacant fields and problems that existed in the application of IC-ME are proposed. At last, the problems to be addressed to adapt IC to future applications are introduced. This paper reviews and prospects IC-ME wastewater remediation technology, which provides a reference for further scientific research and engineering applications.

Simultaneous removal of nitrate and hexavalent chromium in groundwater using indigenous microorganisms enhanced by emulsified vegetable oil: Interactions and remediation threshold values.

Combined pollution in groundwater has become increasingly serious. Adding emulsified vegetable oil to an aquifer is an effective method to remediate multiple pollutants. However, the efficiency and threshold values for the remediation of groundwater contaminated by both nitrate and hexavalent chromium (Cr(VI)) stimulated by emulsified vegetable oil remain unclear. In this study, emulsified vegetable oil was used for the first time to simultaneously remediate nitrate and Cr(VI) in groundwater. The results suggested that the addition of emulsified vegetable oil could effectively remediate nitrate and Cr(VI), and there were interplay effects between nitrate and Cr(VI). Nitrate promoted Cr(VI) removal, while Cr(VI) inhibited nitrate reduction. The remediation thresholds for nitrate and Cr(VI) alone were 1600 mg/L and 10 mg/L, respectively (emulsified vegetable oil = 7 g/L). For combined pollution, the remediation threshold values were 868.10 mg/L for nitrate and 12.43 mg/L for Cr(VI) (emulsified vegetable oil = 7 g/L). The dose of emulsified vegetable oil played an important role in the threshold value. When the concentration of emulsified vegetable oil was 10.8 g/L, the maximum threshold values were 1379.79 mg/L for nitrate and 12.67 mg/L for Cr(VI). When the pollutant concentration was below the threshold value, the contaminant could be completely removed.

Efficacy of Yiqigubiao pill on chronic obstructive pulmonary disease in rats with the disease induced by lipopolysaccharide and cigarette-smoke fumigation.

OBJECTIVE: To investigate the efficacy of Yiqigubiao pill (YQGB) on chronic obstructive pulmonary disease (COPD) in rats with the COPD induced by lipopolysaccharide (LPS) and cigarette- smoke fumigation. METHODS: In this study, six groups of rats were set up, including control group, model group, positive control group (aminophylline) and YQGB (high, medium and low doses) groups. Tracheal injection of lipopolysaccharide (LPS) and cigarette-smoke fumigation induced COPD in rats. The general condition, incubation period and coughing times, lung function, level of inflammatory factors, leukocyte condition and pathological changes of bronchus and lung tissue were observed in rats of each group. RESULTS: In the COPD rats, the latent period of coughing was shortened and the cough frequency was increased significantly; the pulmonary function was significantly decreased, which was manifested by the increased lung tissue resistance and respiratory system resistance, and the decreasing percentage of forced expiratory volume and forced expiratory volume in the 0.3 s (FEV0.3/FVC); the contents of tumor necrosis factor-alpha (TNF-α) and interleukin-4 in serum were obviously increased, and the NEUT% in bronchoalveolar lavage fluid was significantly increase. YQGB could obviously prolong the latent period of cough, and reduce the cough frequency and the content of TNF-α in serum. YQGB can also significantly reduce respiratory resistance and increase FEV0.3/FVC value. The results of histopathology showed that YQGB significantly reduced the pathological changes of tracheal mucosa and lung caused by COPD. YQGB obviously increased level of AQP1, which was down-regulated in the COPD rats. CONCLUSION: YQGB could significantly improve the pulmonary function, reduce inflammation and alleviate lung and bronchial diseases in the COPD rats.

Optimal H2O2 preconditioning to improve bone marrow mesenchymal stem cells' engraftment in wound healing.

BACKGROUND: The transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising therapeutic strategy for wound healing. However, the poor migration capacity and low survival rate of transplanted BMSCs in wounds weaken their potential application. OBJECTIVE: To identify the optimal protocol for BMSCs preconditioned with H2O2 and improve the therapeutic efficacy using H2O2-preconditioned BMSCs in wound healing. METHODS: Mouse BMSCs were exposed to various concentrations of H2O2, and the key cellular functional properties were assessed to determine the optimal precondition with H2O2. The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds to evaluate their healing capacity and tissue engraftment. RESULTS: Treatment BMSCs with 50 µM H2O2 for 12 h could significantly enhance their proliferation, migration, and survival by maximizing the upregulation of cyclin D1, SDF-1, and its receptors CXCR4/7 expressions, and activating the PI3K/Akt/mTOR pathway, but inhibiting the expression of p16 and GSK-3ß. Meanwhile, oxidative stress-induced BMSC apoptosis was also significantly attenuated by the same protocol pretreatment with a decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. Moreover, after the identification of the optimal protocol of H2O2 precondition in vitro, the migration and tissue engraftment of transfused BMSCs with H2O2 preconditioning were dramatically increased into the wound site as compared to the un-preconditioned BMSCs. The increased microvessel density and the speedy closure of the wounds were observed after the transfusion of H2O2-preconditioned BMSCs. CONCLUSIONS: The findings suggested that 50 µM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSCs, which gives a considerable insight that this protocol may be served as a promising candidate for improving the therapeutic potential of BMSCs for wound healing.

Value of lung ultrasound score for evaluation of blast lung injury in goats.

PURPOSE: To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury. METHODS: Twenty female healthy goats were randomly divided into three groups by different driving pressures: 4.0 MPa group (n = 4), 4.5 MPa group (n = 12) and 5.0 MPa group (n = 4). The severe blast lung injury model of goats was established using a BST-I bio-shock tube. Vital signs (respiration, heart rate and blood pressure), lung ultrasound score (LUS), PO2/FiO2 and extravascular lung water (EVLW) were measured before injury (0 h) and at 0.5 h, 3 h, 6 h, 9 h, 12 h after injury. Computed tomography scan was performed before injury (0 h) and at 12 h after injury for dynamic monitoring of blast lung injury and measurement of lung volume. The correlation of LUS with PaO2/FiO2, EVLW, and lung injury ratio (lesion volume/total lung volume*100%) was analyzed. All animals were sacrificed at 12 h after injury for gross observation of lung injury and histopathological examination. Statistical analysis was performed by the SPSS 22.0 software. The measurement data were expressed as mean ± standard deviation. The means of two samples were compared using independent-sample t-test. Pearson correlation analysis was conducted. RESULTS: (1) At 12 h after injury, the mortality of goats was 0, 41.67% and 100% in the 4.0 Mpa, 4.5 MPa and 5.0 MPa groups, respectively; the area of pulmonary hemorrhage was 20.00% ± 13.14% in the 4.0 Mpa group and 42.14% ± 15.33% in the 4.5 MPa group. A severe lung shock injury model was established under the driving pressure of 4.5 MPa. (2) The respiratory rate, heart rate, LUS and EVLW were significantly increased, while PaO2/FiO2 was significantly reduced immediately after injury, and then they gradually recovered and became stabilized at 3 h after injury. (3) LUS was positively correlated with EVLW (3 h: r = 0.597, 6 h: r = 0.698, 9 h: r = 0.729; p < 0.05) and lung injury ratio (12 h: r = 0.884, p < 0.05), negatively correlated with PaO2/FiO2 (3 h: r = -0.871, 6 h: r = -0.637, 9 h: r = -0.658; p < 0.05). CONCLUSION: We established a severe blast lung injury model of goats using the BST-I bio-shock tube under the driving pressure of 4.5 MPa and confirmed that ultrasound can be used for quick evaluation and dynamic monitoring of blast lung injury.

Structural characterization and anticancer potency of centipede oligopeptides in human chondrosarcoma cancer: inducing apoptosis.

Anticancer oligopeptides are rarely studied because they are often present in very low concentrations in a complex matrix. In the current study, twelve oligopeptides were isolated and the amino acid sequence identified from the centipede. MTT results indicated that Trp-Gly-His-Glu (CO-10) showed excellent anti-proliferative potency against chondrosarcoma cells in vitro. Further study showed that CO-10 induced SW1353 cells apoptosis and blocked cell cycle in the G0/G1 phase. Further, results demonstrate that the apoptotic and cytotoxic effects of CO-10 are mediated by the intrinsic mitochondria-mediated apoptotic pathway, which in turn causes the release of cytochrome c and the activation of caspases. This study will be important for the development of pharmaceutical anticancer peptides from natural products as anticancer agents against chondrosarcoma.

SLC1A3 contributes to L-asparaginase resistance in solid tumors.

L-asparaginase (ASNase) serves as an effective drug for adolescent acute lymphoblastic leukemia. However, many clinical trials indicated severe ASNase toxicity in patients with solid tumors, with resistant mechanisms not well understood. Here, we took a functional genetic approach and identified SLC1A3 as a novel contributor to ASNase resistance in cancer cells. In combination with ASNase, SLC1A3 inhibition caused cell cycle arrest or apoptosis, and myriads of metabolic vulnerabilities in tricarboxylic acid (TCA) cycle, urea cycle, nucleotides biosynthesis, energy production, redox homeostasis, and lipid biosynthesis. SLC1A3 is an aspartate and glutamate transporter, mainly expressed in brain tissues, but high expression levels were also observed in some tumor types. Here, we demonstrate that ASNase stimulates aspartate and glutamate consumptions, and their refilling through SLC1A3 promotes cancer cell proliferation. Lastly, in vivo experiments indicated that SLC1A3 expression promoted tumor development and metastasis while negating the suppressive effects of ASNase by fueling aspartate, glutamate, and glutamine metabolisms despite of asparagine shortage. Altogether, our findings identify a novel role for SLC1A3 in ASNase resistance and suggest that restrictive aspartate and glutamate uptake might improve ASNase efficacy with solid tumors.