Majorana Zero Modes Induced by the Meissner Effect at Small Magnetic Field.

One key difficulty in realizing Majorana zero modes (MZMs) is the required high magnetic field, which causes serious issues, e.g., shrinks the superconducting gap, reduces topological region, and weakens their robustness against disorders. In this Letter, we propose that the Meissner effect can bring the topological superconducting phase to a superconductor/topological-insulator/superconductor (SC/TI/SC) hybrid system. Remarkably, the required magnetic field strength (<10 mT) to support MZMs has been reduced by several orders of magnitude compared to that (>0.5 T) in the previous schemes. Tuning the phase difference between the top and bottom superconductors can control the number and position of the MZMs. In addition, we account for the electrostatic potential in the superconductor/topological-insulator (SC/TI) interface through the self-consistent Schrödinger-Poisson calculation, which shows the experimental accessibility of our proposal. Our proposal only needs a small magnetic field of less than 10 mT and is robust against the chemical potential fluctuation, which makes the SC/TI/SC hybrid an ideal Majorana platform.

Chiral Topological Superconductivity in Superconductor-Obstructed Atomic Insulator-Ferromagnetic Insulator Heterostructures.

Implementing topological superconductivity (TSC) and Majorana states (MSs) is one of the most significant and challenging tasks in both fundamental physics and topological quantum computations. In this work, taking the obstructed atomic insulator (OAI) Nb_{3}Br_{8}, s-wave superconductor (SC) NbSe_{2}, and ferromagnetic insulator (FMI) CrI_{3} as an example, we propose a new setup to realize the 2D chiral TSC and MSs in the SC/OAI/FMI heterostructure, which could avoid the subband problem effectively and has the advantage of huge Rashba spin-orbit coupling. As a result, the TSC phase can be stabilized in a wide region of chemical potential and Zeeman splitting, and four distinct TSC phases with superconducting Chern number N=-1,-2,-3, 3 can be achieved. Moreover, a 2D Bogoliubov-de Gennes Hamiltonian based on the triangular lattice of obstructed Wannier charge centers, combined with the s-wave superconductivity paring and Zeeman splitting, is constructed to understand the whole topological phase diagram analytically. These results expand the application of OAIs and pave a new way to realize the TSC and MSs with unique advantages.

Oxygen therapy accelerates apoptosis induced by selenium compounds via regulating Nrf2/MAPK signaling pathway in hepatocellular carcinoma.

Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na2SeO3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50 %. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1 % O2), while inhibited autophagy and accelerated apoptosis under hyperoxia (60 % O2). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment.

Successful virologic outcomes over time among HAART-treated HIV-infected patients.

Few large studies evaluated the effects of time trends on virologic suppression in people living with HIV/AIDS (PLWHA) in China. To address this, An retrospective observational longitudinal study was conducted. We examined annual trends in the rate of virologic suppression, the viral load at the time of virologic suppression, and other determinants of virologic suppression in Zhejiang Province, China in PLWHA between January 2013 and July 2018. Patients who received a treatment regimen for at least 24 weeks were included. Virologic suppression was defined as VL ≤50 copies/mL. Generalized estimating equation logistic regression models were used to adjust for covariates. We included 16,265 patients with 45023 tests. The proportion of patients who experienced an unsuccessful virologic outcome decreased continuously throughout the observation period (18.14% to 6.64%). Time was significantly negatively associated with detectable VL (all ORs <1). Other factors were positively associated with detectable VL, including patients <30 years of age, single, non-adherent to treatment, and with a follow-up CD4 count <200 cells/µL. Patients infected through homosexual transmission and those with a longer ART duration were more likely to reach virologic suppression. We demonstrated outstanding time trend improvements in the virological outcomes of PLWHA in China.

Mesoporous Silica Nanoparticles Induce Intracellular Peroxidation Damage of Phytophthora infestans: A New Type of Green Fungicide for Late Blight Control.

Nanopesticides are considered to be a promising alternative strategy for enhancing bioactivity and delaying the development of pathogen resistance to pesticides. Here, a new type of nanosilica fungicide was proposed and demonstrated to control late blight by inducing intracellular peroxidation damage to Phytophthora infestans, the pathogen associated with potato late blight. Results indicated that the structural features of different silica nanoparticles were largely responsible for their antimicrobial activities. Mesoporous silica nanoparticles (MSNs) exhibited the highest antimicrobial activity with a 98.02% inhibition rate of P. infestans, causing oxidative stress responses and cell structure damage in P. infestans. For the first time, MSNs were found to selectively induce spontaneous excess production of intracellular reactive oxygen species in pathogenic cells, including hydroxyl radicals (•OH), superoxide radicals (•O2-), and singlet oxygen (1O2), leading to peroxidation damage in P. infestans. The effectiveness of MSNs was further tested in the pot experiments as well as leaf and tuber infection, and successful control of potato late blight was achieved with high plant compatibility and safety. This work provides new insights into the antimicrobial mechanism of nanosilica and highlights the use of nanoparticles for controlling late blight with green and highly efficient nanofungicides.

CXCR7 Agonist TC14012 Improves Angiogenic Function of Endothelial Progenitor Cells via Activating Akt/eNOS Pathway and Promotes Ischemic Angiogenesis in Diabetic Limb Ischemia.

PURPOSE: Endothelial progenitor cells (EPCs) play a critical role in repairing damaged vessels and triggering ischemic angiogenesis, but their number is reduced and function is impaired under diabetic conditions. Improving EPC function has been considered a promising strategy to ameliorate diabetic vascular complications. In the present study, we aim to investigate whether and how CXCR7 agonist TC14012 promotes the angiogenic function of diabetic EPCs. METHODS: High glucose (HG) treatment was used to mimic the hyperglycemia in diabetes. Tube formation, cell scratch recovery and transwell assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and cleaved-caspase3 expression were used to evaluate the angiogenic capability, cell migration, and apoptosis of EPCs, respectively. Hind limb ischemia (HLI) model was used to appraise the ability of TC14012 in promoting diabetic ischemic angiogenesis in vivo. RESULTS: HG treatment impaired EPC tube formation and migration, and induced EPC apoptosis and oxidative damage, while TC14012 rescued tube formation and migration, and prevented HG-induced apoptosis and oxidative damage of EPCs. Furthermore, these beneficial effects of TC14012 on EPCs were attenuated by specific siRNAs against CXCR7, validating that CXCR7 is a functional target of TC14012 in EPCs. Mechanistic studies demonstrated that HG treatment reduced CXCR7 expression in EPCs, and impaired Akt and endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production; similarly, these signal impairments in HG-exposed EPCs could be rescued by TC14012. However, the protective effects of TC14012 on tube formation and migration, Akt and eNOS phosphorylation, and NO production in HG-treated EPCs were almost completely abolished by siRNAs against CXCR7 or Akt specific inhibitor wortmannin. More importantly, in vivo study showed that TC14012 administration enhanced blood perfusion recovery and angiogenesis in the ischemic hind limb and increased the EPC number in peripheral circulation of db/db mice, demonstrating the capability of TC14012 in promoting EPC mobilization and ischemia angiogenic function. CONCLUSION: TC14012 can prevent EPCs from HG-induced dysfunction and apoptosis, improve eNOS activity and NO production via CXCR7/Akt signal pathway, and promote EPC mobilization and diabetic ischemia angiogenesis.

A case of subclinical immune checkpoint inhibitor-associated myocarditis in non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of cancer. Moreover, immune-related adverse events (irAEs) have become a new clinical challenge. ICI-associated myocarditis is a rare but fatal condition among diverse organ injuries, and early recognition and effective interventions are critical for patients. CASE PRESENTATION: In this report, we present the case of a healthy 60-year-old male who was diagnosed with lung squamous cell carcinomas following chemotherapy and received ICIs. The patient presented with asymptomatic cardiac biomarker elevation followed by immune-related myocarditis. Fortunately, the patient achieved a good clinical result after receiving high-dose steroids. The treatment with ICIs was discontinued because of recurrent increases in troponin T. CONCLUSION: ICI-mediated associated myocarditis is an uncommon but potentially life-threatening adverse event. The current data suggest that clinicians need to be cautious about reinitiation in low-grade patients; however, further study of the diagnosis and treatment is necessary.

Design, Synthesis and Antifungal Activities of Novel Pyrazole Analogues Containing the Aryl Trifluoromethoxy Group.

On the basis of the three-component synthetic methodology developed by us, a total of twenty-six pyrazole compounds bearing aryl OCF3 were designed and synthesized. Their chemical structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry. These compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi by the mycelium growth rate method. Most of the compounds showed some activity against each of the fungi at 100 µg/mL. Compounds 1t and 1v exhibited higher activity against all the tested fungi, and 1v displayed the highest activity against F. graminearum with an EC50 value of 0.0530 µM, which was comparable with commercial pyraclostrobin. Structure-activity relationship analysis showed that, with respect to the R1 substituent, the straight chain or cycloalkyl ring moiety was a key structural moiety for the activity, and the R2 substituent on the pyrazole ring could have significant effects on the activity. Simple and readily available pyrazoles with potent antifungal activity were obtained, which are ready for further elaboration to serve as a pharmacophore in new potential antifungal agents.

Hyperammonemia in a septic patient with Ureaplasma parvum arthritis: a case report.

BACKGROUND: Septic arthritis requires prompt diagnosis and treatments. Rare pathogens should be considered when patients respond poorly to the initial antibiotic treatments. Ureaplasma parvum is an opportunistic pathogen that commonly resides in the human urogenital tract. Its infection commonly causes hyperammonemia. Hyperammonemia from Ureaplasma parvum septic arthritis has never been reported previously. CASE PRESENTATION: A 65-year-old male presented with fever and left lower leg pain and swelling for more than ten days. Septic arthritis and sepsis were considered after laboratory tests and arthrocentesis. However, he responded poorly to the antibiotic treatments, including cefoperazone-sulbactam, imipenem-cilastatin, and linezolid. His mental status deteriorated rapidly with elevated blood ammonia levels with unremarkable liver function test and sonogram examination results. Despite the treatments with lactulose, L-ornithine L-aspartate, mannitol, and hemodialysis therapy to lower his ammonia level, his blood ammonia level remained persistently high. Finally, metagenomic sequencing of the left knee synovial fluid reported Ureaplasma parvum, which was considered to contribute to his hyperammonemia. CONCLUSION: Ureaplasma parvum could cause septic arthritis with hyperammonemia. Genetic tests, such as polymerase chain reaction and next-generation sequencing techniques, could provide a sensitive and fast diagnosis of Ureaplasma parvum.

Concurrent severe pulmonary tuberculosis with Evans syndrome: a case report with literature review.

BACKGROUND: Tuberculosis is a bacterial infection involving multiple organs and systems. Its hematological presentation mainly includes anemia and leukocytosis. Evans syndrome is a rare autoimmune disease characterized by autoimmune hemolytic anemia, immune thrombocytopenia, and neutropenia, with positive results for the direct Coombs test and platelet antibodies. The cooccurrence of tuberculosis and Evans syndrome is rarely reported. CASE PRESENTATION: A 69-year-old female presented with a fever and shortness of breath. Her chest computerized tomography scan showed extensive miliary nodules in the bilateral lung fields. She rapidly developed respiratory failure that required endotracheal intubation and mechanical ventilation. The acid-fast bacilli sputum smear results indicated a grade of 3+. Later on, blood testing revealed hemolytic anemia, a positive direct Coombs test result, and the presence of the platelet antibody IgG. This patient was diagnosed as having disseminated pulmonary tuberculosis and Evans syndrome. She successfully recovered after treatment with antituberculosis drugs and glucocorticoids. CONCLUSIONS: Tuberculosis can occur together with Evans syndrome. Affected patients should receive both antituberculosis and immunosuppressive drugs.

The Correlation between 25-Hydroxyvitamin D3 and the Severity and Short-Term Prognosis of Pulmonary Tuberculosis.

BACKGROUND: Pulmonary tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis in the lungs. The present study aims to investigate the correlation between serum 25-hydroxyvitamin D3 (25-VD3) and the severity and short-term prognosis of tuberculosis. METHODS: The clinical data of 261 pulmonary tuberculosis patients, who were admitted to the Tuberculosis Diagnosis and Treatment Center of our hospital from January 1, 2017 to December 31, 2020, was retrospectively collected. Taking the median of 25-VD3 at admission (11.40 ng/mL) as the cutoff value, these patients were divided into two groups: high 25-VD3 group (> 11.40 ng/mL, n = 131) and low 25-VD3 group (≤ 11.40 ng/mL, n = 130). Then, Pearson's correlation analysis was performed using SPSS to determine the correlation between the 25-VD3 level and the length of hospitalization and Acute Physiology and Chronic Health Evaluation II (APACHE II) score of pulmonary tuberculosis patients. According to the clinical outcome after 28 days of treatment, these patients were divided again into two groups: improvement group (n = 170) and death group (n = 91). Then, Pearson's correlation analysis through SPSS was performed to determine the relationship between the 25-VD3 level and short-term prognosis of pulmonary tuberculosis patients. RESULTS: Compared to the low 25-VD3 group, pulmonary tuberculosis patients in the high 25-VD3 group were younger, had a higher percentage of improvement after 28 days of treatment, and had a lower APACHE II score (p < 0.05). However, the 25-VD3 level was not significantly correlated to the length of hospital stay of pulmonary tuberculosis patients (correlation coefficient r = 0.020, p = 0.746) and was significantly negatively correlated to the APACHE II score (correlation coefficient r = -0.211, p = 0.001). In addition, the age and APACHE II score of patients were lower in the improvement group, when compared to the death group, while the 25-VD3 level was higher and the length of hospital stay was longer, when compared to the death group (p < 0.01). The logistic regression analysis revealed that the length of hospital stay, APACHE II score, and 25-VD3 level are independent risk factors that affect the prognosis of pulmonary tuberculosis patients (p < 0.05). CONCLUSIONS: In summary, 25-VD3 is closely correlated to the severity of tuberculosis, and this can be used to evaluate and predict the prognosis of patients.

A novel behavioral three-way decision model with application to the treatment of mild symptoms of COVID-19.

The Coronavirus Disease 2019 (COVID-19) has popularized since late December 2019. In present, it is still highly transmissible and has severe impact on the public health and global economy. Due to the lack of specific drug and the appearance of different variants, the selection of the antiviral therapy to treat the patients with mild symptom is of vital importance. Hence, in this paper, we propose a novel behavioral Three-Way Decision (3WD) model and apply it to the medicine selection decision. First, a new relative utility function is constructed by considering the risk-aversion behavior and regret-aversion behavior of human beings. Second, based on the relative utility function, some new rules are defined to calculate the thresholds and conditional probabilities in 3WD and some corresponding theorems are explored and proved. Next, a new information fusion mechanism in the framework of evidential reasoning algorithm is developed. Then, the decision results are obtained based on the Bayesian decision procedure and the principle of maximum utility. Finally, an example with large-scale data set and an example about medicine selection for COVID-19 are provided to show the implementation process and effectiveness of the proposed method. Comparative analysis and sensitivity analysis are also performed to illustrate the superiority and the robustness of the current proposal.

FGF21 promotes ischaemic angiogenesis and endothelial progenitor cells function under diabetic conditions in an AMPK/NAD+-dependent manner.

Diabetic vascular complications are closely associated with long-term vascular dysfunction and poor neovascularization. Endothelial progenitor cells (EPCs) play pivotal roles in maintaining vascular homeostasis and triggering angiogenesis, and EPC dysfunction contributes to defective angiogenesis and resultant diabetic vascular complications. Fibroblast growth factor 21 (FGF21) has received substantial attention as a potential therapeutic agent for diabetes via regulating glucose and lipid metabolism. However, the effects of FGF21 on diabetic vascular complications remain unclear. In the present study, the in vivo results showed that FGF21 efficiently improved blood perfusion and ischaemic angiogenesis in both type 1 and type 2 diabetic mice, and these effects were accompanied by enhanced EPC mobilization and infiltration into ischaemic muscle tissues and increases in plasma stromal cell-derived factor-1 concentration. The in vitro results revealed that FGF21 directly prevented EPC damage induced by high glucose, and the mechanistic studies demonstrated that nicotinamide adenine dinucleotide (NAD+ ) was dramatically decreased in EPCs challenged with high glucose, whereas FGF21 treatment significantly increased NAD+ content in an AMPK-dependent manner, resulting in improved angiogenic capability of EPCs. These results indicate that FGF21 promotes ischaemic angiogenesis and the angiogenic ability of EPCs under diabetic conditions by activating the AMPK/NAD+ pathway.

Phylogenetic evidence of HIV-1 transmission linkage between two men who have sex with men.

BACKGROUND: In China, an HIV-infected man (complainant; P2) alleged that another man (defendant; P1) had unlawfully infected him with HIV through unprotected homosexual contact in 2018. METHODS: We employed epidemiological, serological and phylogenetic analyses to investigate the transmission linkage between two men who have sex with men (MSM). Partial segments of three HIV-1 gene regions (gag, pol, and env) were amplified and sequenced by cloning. Maximum-likelihood (ML) and Bayesian methods were used to determine the direction and estimate the timing of transmission. Local control sequences and database control sequences were also used in the phylogenetic analysis. RESULTS: It indicated that P2 underwent HIV seroconversion after P1 was diagnosed as HIV positive. The time to the most recent common ancestor (tMRCA) estimates consistently showed that P1 most likely became HIV-1 infected at an earlier date than P2. P1 and P2 were infected with the same HIV-1 CRF01_AE subtype according to segments of all three gene regions (gag, pol, and env). All three genetic regions of P1 have been subject to more potential selective forces than those of P2, indicating a longer evolutionary history. Bayesian and ML trees showed similar paraphyletic-monophyletic topologies of gag and env, with the virus from P1 located at the root, which supported a P1-to-P2 transmission direction. CONCLUSIONS: Phylogenetic investigations can elucidate HIV transmission linkage and might empower its use in the opposition of the intentional transmission of HIV-1 as a forensic tool.

A spatial analysis of the epidemiology of HIV-infected students in Zhejiang province, China.

BACKGROUND: The upsurge in HIV infections among students is a matter of particular concern. However, few studies have explored the epidemiological characteristics including the risky sexual networking of HIV-infected students in Zhejiang province, China. METHODS: Using the provincial surveillance data of HIV-infected students, we conducted a retrospective epidemiology study to describe the epidemiological characteristics of 628 newly diagnosed cases from 2011 to 2016 and detailed information of 124 cases from 2015 to 2016. Spatial analyses were conducted using ArcGIS software, and statistical analyses were performed using SPSS software. RESULTS: A total of 628 cases of HIV/AIDS were diagnosed among students in Zhejiang Province, China between 2011 and 2016. The cases showed an overall increasing trend over time, while the proportions of students with HIV disease status, cases diagnosed by HIV voluntary counseling and testing (VCT), and cases of homosexual transmission remained stable over time. Significant spatial heterogeneity in the cases was seen at the county level. Detailed data on 124 HIV-positive individuals collected from the local Center for Disease Control and Prevention (CDC) from 2015 and 2016, showed that the majority of them (85.5%,) engaged in homosexual behavior, and 93.4% had sex with casual partners. These partners included not only social members, but also other students. Online dating applications represented the most common means of seeking and communicating with homosexual partners. The level of awareness regarding the risk of HIV infection, and the amount coverage of face-to-face education towards students were both low. CONCLUSIONS: HIV infections among students were characterized by increasing trend and spatial clustering in Zhejiang Province between 2011 and 2016, with homosexual sexual activity being the main mode of infection. Interventions are urgently required to prevent HIV infection in this population by increasing awareness of the disease. HIV testing programs and information regarding disease prevention specifically through online dating applications are needed.

Misdiagnosed tuberculosis being corrected as Nocardia farcinica infection by metagenomic sequencing: a case report.

BACKGROUND: Disseminated nocardiosis is liable to be misdiagnosed owing to the non-specific clinical manifestations and laboratory/imaging findings. Metagenomic next-generation sequencing (mNGS) is a culture-independent and rapid method for direct identification of all microorganisms in clinical specimens. CASE PRESENTATION: A 72-year-old man was admitted to our hospital on February 20, 2019 with a history of recurrent cough, expectoration, fever, and diarrhea since 1 month, and unconsciousness since 1 week. Contrast-enhanced magnetic resonance imaging of head showed multiple lesions in the bilateral cerebral hemispheres, brainstem, and cerebellar hemispheres. The presumptive diagnosis was disseminated tuberculosis, although all tests for mycobacterium were negative. However, the patient did not benefit from antituberculosis treatment. Repeat MRI showed multiple abnormal signals in the brain and progression of meningeal thickening. Cerebrospinal fluid and bronchoalveolar lavage fluid specimens were subsequently sent for PMSeq metagenomics sequencing; the results indicated Nocardia. farcinica as the predominant pathogen. The anti-TB treatment was stopped and the patient was prescribed sulphamethoxazole in combination with linezolid and meropenem for nocardiosis. He showed gradual neurological improvement and was transferred to Huashan Hospital. He was discharged from the hospital on April 19, 2019, but died of persistent diarrhea on May 26, 2019. CONCLUSIONS: Patients with suspected nocardiosis do not always respond to conventional treatment; therefore, mNGS can facilitate diagnosis and timely treatment decision-making.

Construction of Function-Oriented Core-Shell Nanostructures in Hydrogen-Bonded Organic Frameworks for Near-Infrared-Responsive Bacterial Inhibition.

Exploration of effective ways to integrate various functional species into hydrogen-bonded organic frameworks (HOFs) is critically important for their applications but highly challenging. In this study, according to the "bottle-around-ship" strategy, core-shell heterostructure of upconversion nanoparticles (UCNPs) and HOFs was fabricated for the first time via a ligand-grafting stepwise method. The UCNPs "core" can effectively upconvert near-infrared (NIR) irradiation (980 nm) into visible light (540 nm and 653 nm), which further excites the perylenediimide-based HOF "shell" through resonance energy transfer. In this way, the nanocomposite inherits the high porosity, excellent photothermal and photodynamic efficiency, NIR photoresponse from two parent materials, achieving intriguing NIR-responsive bacterial inhibition toward Escherichia coli. This study may shed light on the design of functional HOF-based composite materials, not only enriching the HOF library but also broadening the horizon of their potential applications.

Identification and partial purification of thuricin 4AJ1 produced by Bacillus thuringiensis.

Thuricin 4AJ1, produced by Bacillus thuringiensis strain 4AJ1, showed inhibition activity against Bacillus cereus 0938 and ATCC 10987. It began to appear in the stationary phase and reached its maximum activity level of 209.958 U at 18 h against B. cereus 0938 and 285.689 U at 24 h against B. cereus ATCC 10987. Tricine-SDS-PAGE results showed that the partly purified thuricin 4AJ1 was about 6.5 kDa. The molecular weights of the known B. thuringiensis bacteriocins and the ones obtained by the two mainstream websites for predicting bacteriocins were inconsistent with the size of the thuricin 4AJ1, indicating that the bacteriocin obtained in this study may have a novel structure. Based on the biochemical properties, the thuricin 4AJ1 activities increased after treatment with proteinase K and lipase II, and were not affected by a-amylase, catalase, α-chymotrypsin VII and α-chymotrypsin II. It was heat tolerant, being active up to 90º C. In the pH 3-10 range, it maintained most of its activity. Finally, the sensitivity of the strain 4AJ1 to commonly used antibiotics was tested. In view of its stability and antibacterial activity, thuricin 4AJ1 may be applied as a food biopreservative.

Utility of circulating tumor cells and DNA in the management of advanced colorectal cancer.

Aim: Clinical management of colorectal cancer is challenging. Circulating tumor cells (CTCs) and DNA (ctDNA) are investigated to detect key KRAS mutation and for prognosis for risk stratifications. Materials & methods: 200 advance-stage patients with metastatic disease were selected and followed-up. Serial blood draws were used to quantify CTCs and ctDNA. Results: Both CTCs and ctDNA are strongly associated with colorectal cancer patients. The positive predictive values were 96.5 and 96.3% among CTCs and ctDNA, respectively, for all 200 patients using KRAS mutation. Specificity for healthy controls was 100%. As a prognosis indicator, results demonstrated that patients who had positive CTCs and plasma DNA had worse outcomes. Conclusion: Blood-based assessment of colorectal cancer shows promising results in early-risk stratifications.

Effects of a spiroketal compound Peniciketal A and its molecular mechanisms on growth inhibition in human leukemia.

Peniciketal A (Pe-A), a spiroketal compound, is isolated from the saline soil-derived fungus Penicillium raistrickii. However, the underlying molecular mechanistic basis for the effects of Pe-A on leukemia is poorly understood. Here, we investigated that Pe-A reduced cell proliferation in three leukemia cell lines (THP-1, K562 and HL60). Importantly, Pe-A showed little cytotoxicity in primary mouse embryonic fibroblast (MEF) cells in a long-duration treatment. For the mechanistic research, we identified 3449 differentially expressed Pe-A-induced proteins through liquid chromatography-tandem mass spectrometry (LC-MS/MS) with TMT label in THP-1 cells. Results showed that many identified proteins were involved in apoptosis and/or autophagy. Then, we confirmed that Pe-A induced not only apoptosis via the mitochondrial pathway but also cytoprotective autophagy by activating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway indeed. In addition, Pe-A also arrested the cell cycle at the G0-G1 phase by regulating the expressions of checkpoint protein. Collectively, these results provide new insights into the mechanisms that Pe-A may target autophagy-related or apoptosis-related pathways to suppress the development of human leukemia.