[Research progress in Astragali Radix and its active ingredients in treatment of lung cancer].

Lung cancer is the leading cause of cancer death, and its effective treatment is a difficult medical problem. Lung cancer belongs to the traditional Chinese medicine(TCM) disease categories of lung accumulation, lung amassment, and overstrain cough. Rich theoretical basis and practical experience have been accumulated in the TCM treatment of lung cancer. Astragali Radix is one of the representatives of Qi-tonifying drugs. It mainly treat the lung cancer with the syndrome of Qi deficiency and pathogen stagnation, following the principle of reinforcing healthy Qi and eliminating patgogenic Qi. Astragali Radix exerts a variety of pharmacological activities in the treatment of lung cancer, including inhibiting tumor cell proliferation and promoting tumor cell apoptosis, inhibiting tumor invasion and migration, regulating the tumor microenvironment, suppressing tumor angiogenesis, modulating autophagy, inducing macrophage polarization, enhancing immunity, inhibiting immune escape, and reversing cisplatin resistance. The active ingredients of Astragali Radix in treating lung cancer include polysaccharides, saponins, and flavonoids. This study reviewed the pharmacological activities and active ingredients of Astragali Radix in the treatment of lung cancer, providing a basis for the development and utilization of Astragali Radix resources and active ingredients and the research and development of anti-tumor drugs.

Liposomal gel loaded with pro-xylane intermediate promotes chronic wound healing.

Chronic wounds are a common and difficult problem in clinics. It is of great significance to develop effective and economical methods to treat chronic wounds. The present study aimed to investigate the effects of liposomal gel loaded with Pro-xylane intermediate on chronic wounds. Rat models of chronic wounds were created and verified. The pro-xylane intermediate (C-ß-D-xylopyranoside-n-propan-2-one, PXYI) were encapsulated with liposomes and the liposomes containing PXYI were mixed with Pluronic F-127 gel to obtain PXYI liposomal gel (PXYI-LG). PXYI-LG has been applied to the rat's chronic wounds. The therapeutic effects were evaluated by wound healing rate and wound healing time. Additionally, Alamar Blue was used to detect the effect of PXYI on the proliferation of human skin fibroblasts (HF) and human immortalized epidermal cells (HaCaT). It was not found that PXYI alone could promote the proliferation of HF and HaCaT. From the 12th to the 32nd day, the wound healing rate of PXYI-LG group were significantly higher than that of the normal saline (NS) group (P <0.05). The number of days when the wound healing rate reached 90% was significantly shorter in the PXYI-LG group (21.8 ±1.8) than in the NS group (28.4 ±1.6) (P < 0.01). In summary, the results demonstrate that the PXYI-LG can promote chronic wound healing.

Hyperbaric oxygen therapy may be effective to improve hypoxemia in patients with severe COVID-2019 pneumonia: two case reports.

Objectives: To determine whether hyperbaric oxygen (HBO2) therapy be effective to improve hypoxemia for severe COVID-19 pneumonia patients. Methods: Two male patients ages 57 and 64 years old were treated. Each met at least one of the following criteria: shortness of breath; respiratory rate (RR) ≥30 breaths/minute; finger pulse oxygen saturation (SpO2) ≤93% at rest; and oxygen index (P/F ratio: PaO2/FiO2 ≤300 mmHg). Each case excluded any combination with pneumothorax, pulmonary bullae or other absolute contraindications to HBO2. Patients were treated with 1.5 atmospheres absolute HBO2 with an oxygen concentration of more than 95% for 60 minutes per treatment, once a day for one week. Patients' self-reported symptoms, daily mean SpO2 (SO2), arterial blood gas analysis, D-dimer, lymphocyte, cholinesterase (che) and chest CT were conducted and measured. Results: For both patients, dyspnea and shortness of breath were immediately alleviated after the first HBO2 treatment and remarkably relieved after seven days of HBO2 therapy. The RR also decreased daily. Neither patient became critically ill. The decreasing trend of SO2 and P/F ratio was immediately reversed and increased day by day. The lymphocyte count and ratio corresponding to immune function gradually recovered. D-dimer corresponding to peripheral circulation disorders and serum cholinesterase, reflecting liver function had improved. Follow-up chest CT showed that the pulmonary inflammation had clearly subsided. Conclusion: Our preliminary uncontrolled case reports suggest that HBO2 therapy may promptly improve the progressive hypoxemia of patients with COVID-2019 pneumonia. However, the limited sample size and study design preclude a definitive statement about the potential effectiveness of HBO2 therapy to COVID-2019 pneumonia. It requires evaluation in randomized clinical trials in future.

Methionine-Capped Gold Nanoclusters as a Fluorescence-Enhanced Probe for Cadmium(II) Sensing.

Gold nanoclusters (Au NCs) have been considered as novel heavy metal ions sensors due to their ultrafine size, photo-stability and excellent fluorescent properties. In this study, a green and facile method was developed for the preparation of fluorescent water-soluble gold nanoclusters with methionine as a stabilizer. The nanoclusters emit orange fluorescence with excitation/emission peaks at 420/565 nm and a quantum yield of about 1.46%. The fluorescence of the Au NCs is selectively and sensitively enhanced by addition of Cd(II) ions attributed to the Cd(II) ion-induced aggregation of nanoclusters. This finding was further used to design a fluorometric method for the determination of Cd(II) ions, which had a linear response in the concentration range from 50 nM to 35 µM and a detection limit of 12.25 nM. The practicality of the nanoprobe was validated in various environmental water samples and milk powder samples, with a fairly satisfactory recovery percent.

MicroRNA-224 targets ERG2 and contributes to malignant progressions of meningioma.

MicroRNA-224 is overexpressed in various malignant tumors with poor prognosis, which plays a critical role in biological processes including cell proliferation, apoptosis and several developmental and physiological progressions. However, the potential association between miR-224 and clinical outcome in patients with meningiomas remains unknown. Here, we investigate miR-224 expression and biological functions in meningiomas. MiR-224 expression was measured by Northern blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in meningioma and normal brain tissues. Kaplan-Meier analysis and Cox regression analysis were used to exam its correlation with clinicopathological features and prognostic value. The biological effects of miR-224 on the cell proliferation and apoptosis in meningioma cells were examined by MTT assay and apoptosis assay. We found the expression levels of miR-224 were significantly higher in meningioma tissues than that in normal brain, positively correlated with advanced pathological grade. Kaplan-Meier analysis indicated that meningioma patients with low miR-224 expression exhibited significantly prolonged overall and recurrence-free survival. Furthermore, we demonstrated that ERG2 was an identical candidate target gene of MiR-224 in vitro. Our results indicated that downregulation of miR-224 suppressed cell growth and resulted in the enhancement of cell apoptosis through activation of the ERG2-BAK-induced apoptosis pathway. Our findings imply the miR-224 expression could predict the overall survival and recurrence-free survival of patients with meningioma and it might be a promising therapeutic target for treating malignant meningiomas.

Effect of placental mesenchymal stem cells on promoting the healing of chronic burn wounds.

The treatment of chronic burn wounds is difficult in clinical practice. The ideal therapy is required to be continuously explored. Mesenchymal stem cells revolutionize the treatment of many diseases. The placental mesenchymal stem cells (PMSCs) have the characteristics of easy access, strong proliferation ability and multi-directional differentiation potential. The aim of this study was to investigate the potential of PMSCs in chronic burn wound healing. In this study, species of bacteria of 317 patients with chronic burn wounds have been analyzed. Samples of chronic burn wound fluid were collected from representative patients and then co-cultured with cells. In vitro studies showed that chronic burn wound fluid inhibited the proliferation of human keratinocytes and fibroblasts, while PMSCs can counteract the effects of burn wound fluid on inhibiting the proliferation and migration of human keratinocytes and fibroblasts. In addition, in vivo studies showed that a rat chronic burn wound model was successfully created. The expression of MMP-2, MMP-9, MDA, IL-6 and TNF-α in chronic burn wounds was significantly higher than that in acute burn wounds. Finally, the rat chronic burn wound model was used to verify that placental mesenchymal stem cell transplantation increased the wound healing rate, decreased the wound healing time, and promoted wound healing by increasing the thickness of epidermis and promoting the expression of P63 and CK10. The findings provide support for the hypothesis that PMSCs promote the repair of chronic burn wounds and key scientific data for the application of PMSCs as a new method for treating chronic burn wounds.

Network pharmacology and experimental verification reveal the mechanism of Hedysari Radix and Curcumae Rhizoma with the optimal compatibility ratio against colitis-associated colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The herb pair Astragali Radix (AR) and Curcumae Rhizoma (vinegar-processed, VPCR), derived from the traditional Chinese medicine (TCM) text 'Yixuezhongzhongcanxilu', have long been used to treat gastrointestinal diseases, notably colitis-associated colorectal cancer (CAC). Hedysari Radix (HR), belonging to the same Leguminosae family as AR but from a different genus, is traditionally used as a substitute for AR when paired with VPCR in the treatment of CAC. However, the optimal compatibility ratio for HR-VPCR against CAC and the underlying mechanisms remain unclear. AIM OF THE STUDY: To investigate the optimal compatibility ratio and underlying mechanisms of HR-VPCR against CAC using a combination of comparative pharmacodynamics, network pharmacology, and experimental verification. MATERIALS AND METHODS: The efficacy of different compatibility ratios of HR-VPCR against CAC was evaluated using various indicators, including the body weight, colon length, tumor count, survival rate, disease activity index (DAI) score, Haemotoxylin and Eosin (H&E) pathological sections, inflammation cytokines (IL-1ß, IL-6, IL-10, TNF-α), tumor markers (K-Ras, p53), and intestinal permeability proteins (claudin-1, E-cadherin, mucin-2). Then, the optimal compatibility ratio of HR-VPCR against CAC was determined based on the fuzzy matter-element analysis by integrating the above indicators. After high-performance liquid chromatography (HPLC) analysis for the optimal compatibility ratio of HR-VPCR, potential active components of HR-VPCR were identified by TCMSP and the previous bibliographies. Swiss Targets and GeneCards were adopted to predict the targets of the active components and the targets of CAC, respectively. Then, the common targets of HR-VPCR against CAC were obtained by Venn analysis. PPI networks were constructed in STRING. GO and KEGG enrichments were visualized by the David database. Finally, the predicted pathway was experimentally validated via Western blot. RESULTS: Various compatibility ratios of HR-VPCR demonstrated notable therapeutic effects to some extent, evidenced by improvements in body weight, colon length, tumor count, pathological symptoms (DAI score), colon and organ indexes, survival rate, and modulation of inflammation factors (IL-1ß, IL-6, IL-10, TNF-α), as well as tumor markers (K-Ras, p53), and down-regulation of intestinal permeability proteins (claudin-1, E-cadherin, mucin-2) in CAC mice. Among these ratios, the ratio 4:1 represents the optimal compatibility ratio by the fuzzy matter-element analysis. Thirty active components of HR-VPCR were carefully selected, targeting 553 specific genes. Simultaneously, 2022 targets associated with CAC were identified. 88 common targets were identified after generating a Venn plot. Following PPI network analysis, 29 core targets were established, with AKT1 ranking highest among them. Further analysis via GO and KEGG enrichment identified the PI3K-AKT signaling pathway as a potential mechanism. Experimental validation confirmed that HR-VPCR intervention effectively reversed the activated PI3K-AKT signaling pathway. CONCLUSIONS: The optimal compatibility ratio for the HR-VPCR herb pair in alleviating CAC is 4:1. HR-VPCR exerts its effects by alleviating intestinal inflammation, improving intestinal permeability, and regulating the PI3K-AKT signaling pathway.

Shikonin promotes hypertrophic scar repair by autophagy of hypertrophic scar-derived fibroblasts.

PURPOSE: To investigate the Shikonin (SHI) induce autophagy of hypertrophic scar-derived fibroblasts (HSFs) and the mechanism of which in repairing hypertrophic scar. METHODS: This study showed that SHI induced autophagy from HSFs and repaired skin scars through the AMPK/mTOR pathway. Alamar Blue and Sirius red were used to identify cell activity and collagen. Electron microscopy, label-free quantitative proteomic analysis, fluorescence and other methods were used to identify autophagy. The differences in the expression of autophagy and AMPK/mTOR pathway-related proteins after SHI treatment were quantitatively analyzed by Western blots. A quantitative real-time polymerase chain reaction assay was used to detect the expression of LC3, AMPK and ULK after adding chloroquine (CQ) autophagy inhibitor. RESULTS: After treatment with SHI for 24 hours, it was found that the viability of HSFs was significantly reduced, the protein expression of LC3-II/LC3-I and Beclin1 increased, while the protein expression of P62 decreased. The expression of phosphorylated AMPK increased and expression of phosphorylated mTOR decreased. After the use of CQ, the cell autophagy caused by SHI was blocked. The key genes LC3 and P62 were then reexamined by immunohistochemistry using a porcine full-thickness burn hypertrophic scar model, and the results verified that SHI could induce autophagy in vivo. CONCLUSIONS: These findings suggested that SHI promoted autophagy of HSFs cells, and the potential mechanism may be related to the AMPK/mTOR signal pathway, which provided new insights for the treatment of hypertrophic scars.

Identifications of metabolic differences between Hedysari Radix Praeparata Cum Melle and Astragali Radix Praeparata Cum Melle for spleen-qi deficiency rats: A comparative study.

Hedysari Radix Praeparata Cum Melle (HRPCM) and Astragali Radix Praeparata Cum Melle (ARPCM) are capable of improving spleen-qi deficiency (SQD) syndrome especially in the gastrointestinal dysfunction and decreased immunity in traditional Chinese medicine clinically. This study aims to compare and reveal the metabolic differences between HRPCM and ARPCM for SQD rats. Firstly, HRPCM (12.6 g/kg) and ARPCM (12.6 g/kg) were used to intervene SQD rats to further evaluate the effect. The results showed that HRPCM and ARPCM were able to improve the spleen pathology, increase the body weight, the rectal temperature, the spleen index, the thymus index, the levels of GAS and D-xylose in serum, and decrease the levels of IL-2, IL-6 and TNF-α in serum for SQD rats. Then, the studies of metabolic differences in serum and spleen were carried out using UPLC-Q-TOF-MS. The findings emphasized that HRPCM and ARPCM not only regulated metabolic profiling of serum and spleen in SQD rats, but also existed differences. HRPCM and ARPCM regulated metabolic pathways mainly including lipid metabolism, energy metabolism, amino acid metabolism, nucleotide metabolism, sugar metabolism and other types of metabolism for SQD rats. However, the metabolite profiles in SQD rats changed significantly, mainly involving abnormal glycine synthesis occurred in SQD rats. The expression trends of metabolites in HRPCM and ARPCM intervention for SQD rats were partly the same. Interestingly, there are similarities and differences in metabolic profiling between HRPCM and ARPCM for SQD rats. The differences were mainly in the synthesis of L-glutamine in amino acid metabolism.

Research Progress of Soil Microorganisms in Response to Heavy Metals in Rice.

Soil heavy-metal pollution leads to excessive heavy metals in rice and other food crops, which has caused serious impacts on the ecological environment and on human health. In recent years, environmental friendly treatment methods that reduce the bioavailability of heavy metals in soil by soil microorganisms improving the tolerance of heavy metals in rice and reducing the transfer of heavy metals from the roots to the above-ground parts of rice have attracted much attention. This paper reviews the role and mechanism of soil microorganisms in alleviating heavy-metal stress in rice at home and abroad in recent years. At present, microorganisms tolerant to heavy metals mainly include bacteria and fungi, and their mechanisms include the adsorption of heavy metals by microorganisms, the secretion of growth-promoting substances (growth hormone, ACC deaminase, IAA), changing the physical and chemical properties of the soil and the composition of the microbial community, changing the transport mode of heavy metals in soil, the improvement of the antioxidant capacity of rice, etc. Hence, soil microorganisms have good application value and prospects in rice and other crops. However, the vast majority of current research focuses on a single strain, the screening principles of strains are limited, the pathogenicities of the strains have not been evaluated, and there are still few field experiments under natural conditions. In the future, we should strengthen the action of soil microorganisms on rice in response to the above problems in heavy metals, to better promote the microbial remediation technology.

Risk factors associated with the progression of COVID-19 in elderly diabetes patients.

AIM: To describe the clinical characteristics and risk factors associated with the progression of COVID-19 in elderly diabetes patients. METHODS: This was a retrospective cohort study, including elderly COVID-19 patients admitted to Wuhan Huoshenshan Hospital between February 10 and 13, 2020. Demographic data, medical history, signs and symptoms, and laboratory parameters were collected and analysed. RESULTS: We included 131 elderly COVID-19 patients (50 patients with diabetes). COVID-19 diabetes patients experienced more severe pneumonia and abnormal organ functions than non-diabetes patients (P < 0.05 or P < 0.01). Most function indicators were significantly different between the mild to moderate and severely ill groups in diabetes patients (P < 0.05 or P < 0.01). Python analysis confirmed diabetes was the independent risk factor of COVID-19 progression in elderly patients. All blood glucose (BG) indices went into the risk factor equation. The cut-off values of COVID-19 progression were BG value on admission > 8.0 mmol/L or maximum BG value > 12.0 mmol/L in all elderly patients, and BG value on admission > 5.1 mmol/L or maximum BG value > 5.4 mmol/L in non-diabetes patients. CONCLUSIONS: Diabetes is an independent important risk factor, and glucose levels associate closely with COVID-19 progression in elderly patients.

One case of coronavirus disease 2019 (COVID-19) in a patient co-infected by HIV with a low CD4+ T-cell count.

The ongoing outbreak of COVID-19 that began in Wuhan, China, become an emergency of international concern when thousands of people were infected around the world. This study reports a case simultaneously infected by SARS-Cov-2 and HIV, which showed a longer disease course and slower generation of specific antibodies. This case highlights that a co-infection of SARS-Cov-2 and HIV may severely impair the immune system.

The Diagnostic Trap Occurred in Two COVID-19 Cases Combined Pneumocystis Pneumonia in Patient with AIDS.

Background: The limited knowledge on the diagnosis of Coronavirus disease 2019 (COVID-19) at the early stage of the pandemic may lead to misdiagnoses, especially when the nucleic acid inspection cannot meet the mass requirement. This condition is even actual for people who are living with HIV/AIDS (PLWHA), for the latter is vulnerable to variable infections. Case Presentation: In this short communication, we introduced two HIV infected individuals who had PCP but was misdiagnosed as COVID-19 initially, and finally infected with SARS-CoV-2 in hospital in Wuhan, China. Eventually, both patients improved soon after they were switched to the treatment of SMZ/TMP. Conclusions: We suggested that the hospitalized COVID-19 cases should be screened with HIV and other pathogens, to prevent that PLWHA who have PCP from being misdiagnosed as COVID-19.

Coronavirus disease 2019 associated with aggressive neurological and mental abnormalities confirmed based on cerebrospinal fluid antibodies: A case report.

INTRODUCTION: Coronavirus disease (COVID-19) is spreading worldwide. The reported possible neurological symptoms are varied and range from subtle neurologic deficits to unconsciousness. Knowledge regarding the detection, diagnosis, treatment, and follow-up of COVID-19-associated neurological damage is still limited. We report a case of serious neurological damage and mental abnormalities in a patient who was finally confirmed to have COVID-19 based on IgM and IgG antibodies in the cerebrospinal fluid (CSF). PATIENT CONCERNS: A 68-year-old man had slight flu-like symptoms and transient loss of consciousness in early February. Exaggerated unconsciousness and deteriorating mental abnormalities occurred over the next month without severe respiratory symptoms. Craniocerebral computed tomography showed normal results, but antibodies against severe acute respiratory syndrome coronavirus 2 were 100 times higher in the CSF than in the serum; tests for viral ribonucleic acid showed negative results with both a nasopharyngeal swab and CSF sample. DIAGNOSIS: COVID-19 pneumonia was diagnosed based on symptoms and positive results for IgM and IgG in the CSF. INTERVENTIONS: Antiviral, fluid, and nutritional support were administered for 30 days before admission without obvious improvement. A further 18 days of routine antiviral therapy, immunoglobulin therapy (10 g per day for 5 days), and antipsychotic drug treatment were administered. OUTCOMES: The patient's neurological and mental abnormalities were greatly ameliorated. He was discharged with mild irritability, slight shaking of the hands, and walking fatigue. These symptoms have persisted up to our last follow-up (May 4, 2020). CONCLUSION: We believe this is the first case involving neural system injury in a patient who confirmed COVID-19 based on CSF antibody test results. Negative ribonucleic acid test results, strong positivity for antibodies, and high protein levels in the CSF suggest the possibility of autoimmune encephalitis secondary to COVID-19. This case highlights additional novel symptoms of COVID-19, and these data are important for the assessment and follow-up of COVID-19 patients.

Slow slip source characterized by lithological and geometric heterogeneity.

Slow slip events (SSEs) accommodate a significant proportion of tectonic plate motion at subduction zones, yet little is known about the faults that actually host them. The shallow depth (<2 km) of well-documented SSEs at the Hikurangi subduction zone offshore New Zealand offers a unique opportunity to link geophysical imaging of the subduction zone with direct access to incoming material that represents the megathrust fault rocks hosting slow slip. Two recent International Ocean Discovery Program Expeditions sampled this incoming material before it is entrained immediately down-dip along the shallow plate interface. Drilling results, tied to regional seismic reflection images, reveal heterogeneous lithologies with highly variable physical properties entering the SSE source region. These observations suggest that SSEs and associated slow earthquake phenomena are promoted by lithological, mechanical, and frictional heterogeneity within the fault zone, enhanced by geometric complexity associated with subduction of rough crust.

Micromechanism of Cold Deformation of Two-Phase Polycrystalline Ti⁻Al Alloy with Void.

Cold deformation behavior of polycrystalline metallic material is affected by intrinsic defects such as dislocations, voids, inclusions etc. Existing studies on α 2 ( Ti 3 Al ) + γ ( TiAl ) two-phase Ti⁻Al alloy cover about deformation behavior mainly on macro scale. This paper focuses on the cold deformation mechanism of two-phase Ti⁻Al alloy at micro scale, and the role of voids in deformation process. Molecular dynamics simulations were performed to study the evolution of micro structure of material under uniaxial tension. Interaction between spherical nano voids with different size and position was also examined in the simulation. The results show that (1) In elastic stage, deformation of the two-phase is coordinated, but Ti 3 Al is more deformable; (2) In plastic stage, γ phase is the major dislocation source in two-phase alloy; (3) voids detracts the strength of the two-phase alloy, while the position of void affect the degree of this subtraction, voids located at the boundary of α 2 / γ phase have significant detraction to strength.

Donor-Acceptor Supramolecular Organic Nanofibers as Visible-Light Photoelectrocatalysts for Hydrogen Production.

Perylene tetracarboxylic diimide (PTCDI) derivatives have been extensively studied for one-dimensional (1D) self-assembled systems and for applications in photocatalysis. Herein, we constructed a PTCDI-based donor-acceptor (D-A) supramolecular system via in situ self-assembly on an indium tin oxide conductive glass surface. The self-assembled PTCDI nanostructures exhibit well-defined nanofibril morphologies and strong photocurrents. Interestingly, a strong and reversible electrochromic color change was observed during cyclic voltammetry. The color of the nanofibers changed from red to blue and then to violet as the reduction progressed to the radical anion and then to the dianion. This series of one-electron reductions was confirmed by UV absorption, electron paramagnetic resonance spectroscopy, and hydrazine reduction. Most importantly, these PTCDI nanofibers exhibit efficient photoelectrocatalytic hydrogen production with remarkable stability under xenon lamp illumination (λ ≥ 420 nm). Among the three nanofibers prepared, the fibers assembled from PTCDI molecule 2 were found to be the most effective catalyst with 30% Faradaic efficiency. In addition, the nanofibers produced hydrogen at a steady-state for more than 8 h and produced repeatable results in 3 consecutive testing cycles, giving them great potential for practical industrial applications. Under an applied bias voltage, the 1D intermolecular stacking along the long axis of the nanofibers affords efficient separation and migration of photogenerated charge carriers, which play a crucial role in the photoelectrocatalytic process. As a proof-of-concept, the D-A-structured PTCDI nanofibers presented herein may guide future research on photoelectrocatalysis based on self-assembled supramolecular systems by providing more options for material design of the catalysts to achieve greater efficiencies.

Shikonin promotes hypertrophic scar repair by autophagy of hypertrophic scar-derived fibroblasts

Purpose: To investigate the Shikonin (SHI) induce autophagy of hypertrophic scar-derived fibroblasts (HSFs) and the mechanism of which in repairing hypertrophic scar. Methods: This study showed that SHI induced autophagy from HSFs and repaired skin scars through the AMPK/mTOR pathway. Alamar Blue and Sirius red were used to identify cell activity and collagen. Electron microscopy, label-free quantitative proteomic analysis, fluorescence and other methods were used to identify autophagy. The differences in the expression of autophagy and AMPK/mTOR pathway-related proteins after SHI treatment were quantitatively analyzed by Western blots. A quantitative real-time polymerase chain reaction assay was used to detect the expression of LC3, AMPK and ULK after adding chloroquine (CQ) autophagy inhibitor. Results: After treatment with SHI for 24 hours, it was found that the viability of HSFs was significantly reduced, the protein expression of LC3-II/LC3-I and Beclin1 increased, while the protein expression of P62 decreased. The expression of phosphorylated AMPK increased and expression of phosphorylated mTOR decreased. After the use of CQ, the cell autophagy caused by SHI was blocked. The key genes LC3 and P62 were then reexamined by immunohistochemistry using a porcine full-thickness burn hypertrophic scar model, and the results verified that SHI could induce autophagy in vivo. Conclusions: These findings suggested that SHI promoted autophagy of HSFs cells, and the potential mechanism may be related to the AMPK/mTOR signal pathway, which provided new insights for the treatment of hypertrophic scars.

Paleoseismic study of the Kamishiro Fault on the northern segment of the Itoigawa-Shizuoka Tectonic Line, Japan.

The Mw 6.2 (Mj 6.8) Nagano (Japan) earthquake of 22 November 2014 produced a 9.3-km long surface rupture zone with a thrust-dominated displacement of up to 1.5 m, which duplicated the pre-existing Kamishiro Fault along the Itoigawa-Shizuoka Tectonic Line (ISTL), the plate-boundary between the Eurasian and North American plates, northern Nagano Prefecture, central Japan. To characterize the activity of the seismogenic fault zone, we conducted a paleoseismic study of the Kamishiro Fault. Field investigations and trench excavations revealed that seven morphogenic paleohistorical earthquakes (E2-E8) prior to the 2014 Mw 6.2 Nagano earthquake (E1) have occurred on the Kamishiro Fault during the last ca. 6000 years. Three of these events (E2-E4) are well constrained and correspond to historical earthquakes occurring in the last ca. 1200 years. This suggests an average recurrence interval of ca. 300-400 years on the seismogenic fault of the 2014 Kamishiro earthquake in the past 1200 years. The most recent event prior to the 2014 earthquakes (E1) is E2 and the penultimate and antepenultimate faulting events are E3 and E4, respectively. The penultimate faulting event (E3) occurred during the period of AD 1800-1400 and is associated with the 1791 Mw 6.8 earthquake. The antepenultimate faulting event (E4) is inferred to have occurred during the period of ca. AD 1000-700, likely corresponding to the AD 841 Mw 6.5 earthquake. The oldest faulting event (E8) in the study area is thought to have occurred during the period of ca. 5600-6000 years. The throw rate during the early Holocene is estimated to be 1.2-3.3 mm/a (average, 2.2 mm/a) with an average amount of characteristic offset of 0.7-1.1 m produced by individual event. When compared with active intraplate faults on Honshu Island, Japan, these slip rates and recurrence interval estimated for morphogenic earthquakes on the Kamishiro Fault along the ISTL appear high and short, respectively. This indicates that present activity on this fault is closely related to seismic faulting along the plate boundary between the Eurasian and North American plates.

An integrated 3D-printed platform for the automated isolation of N-glycans.

The development of techniques for the rapid analysis of N-glycans is a key step in enabling the roles of glycoproteins in biological processes to be studied. Analysis is usually performed through the liberation of the carbohydrate moieties from proteins, followed by fluorescent labeling and identification using either standardized HPLC or mass spectrometry techniques. A simple and robust automated process for the release and isolation of N-glycans would greatly improve analytical throughput and reproducibility, and is thus highly desirable. Inspired by the increasing number of reported projects involving open source labware, which allows the design and construction of otherwise inaccessible laboratory equipment using low-cost 3D printers, we used this technique to fabricate a platform for the automated isolation of N-glycans. As a proof of concept, we demonstrated the successful recovery of glycan samples from the glycoprotein model fetuin using our self-made 3D-printed equipment.