Heterologous expression of pediocin PA-1 in Pichia pastoris: cloning, expression, characterization, and application in pork bologna preservation.

OBJECTIVE: Pediocin PA-1, an antimicrobial peptide derived from Pediococcus acidilactici PAC1.0, has a potential application as a food preservative thanks to its strong inhibitory activity against the foodborne pathogen L. monocytogenes. This study aimed to produce Pediocin PA-1 from the yeast P. pastoris and evaluate its characteristics. METHODS: Gene encoding Pediocin PA-1 was integrated into P. pastoris X33 genome to establish the strain X33::ped, which could produce and secrete this peptide into culture medium. The antimicrobial activity of Pediocin PA-1 was examined using agar diffusion assay. The stability of pediocin PA-1 was determined based on its remaining antibacterial activity after exposure to proteases and extreme pH and temperatures. The potential use of this bacteriocin in food preservation was demonstrated using the L. monocytogenes infected pork bologna. The anticancer activity of Pediocin PA-1 was also investigated on some cancer cells using MTT assay. RESULTS: We established the yeast P. pastoris X33::ped capable of producing pediocin PA-1 with antimicrobial activity against L. monocytogenes and some other harmful bacteria. Pediocin PA-1 was stable at 100˚C and resistant against pH 1-12 for 1 h, but susceptible to trypsin, α-chymotrypsin, and proteinase K. This peptide could reduce the number of L. monocytogenes in pork bologna by 3.59 log CFU/g after 7 days of storage at 4˚C. Finally, Pediocin PA-1 (25 µg/ml) inhibited the proliferation of A549 and Hela cancer cells. CONCLUSION: We succeeded in producing active Pediocin PA-1 from P. pastoris and demonstrated its potential use in food preservation and pharmaceutical industry.

Optogenetically engineered calcium oscillations promote autophagy-mediated cell death via AMPK activation.

Autophagy is a double-edged sword for cells; it can lead to both cell survival and death. Calcium (Ca2+) signalling plays a crucial role in regulating various cellular behaviours, including cell migration, proliferation and death. In this study, we investigated the effects of modulating cytosolic Ca2+ levels on autophagy using chemical and optogenetic methods. Our findings revealed that ionomycin and thapsigargin induce Ca2+ influx to promote autophagy, whereas the Ca2+ chelator BAPTA-AM induces Ca2+ depletion and inhibits autophagy. Furthermore, the optogenetic platform allows the manipulation of illumination parameters, including density, frequency, duty cycle and duration, to create different patterns of Ca2+ oscillations. We used the optogenetic tool Ca2+-translocating channelrhodopsin, which is activated and opened by 470 nm blue light to induce Ca2+ influx. These results demonstrated that high-frequency Ca2+ oscillations induce autophagy. In addition, autophagy induction may involve Ca2+-activated adenosine monophosphate (AMP)-activated protein kinases. In conclusion, high-frequency optogenetic Ca2+ oscillations led to cell death mediated by AMP-activated protein kinase-induced autophagy.

Miliutine C methyl ester, a new drimane sesquiterpene and bioactive alkaloids from the stems of Miliusa velutina.

Previous results from the our research group have isolated numerous compounds, including novel ones, but the anticancer activity of Miliusa velutina has not been demonstrated. In this study, from the most active ethyl acetate extract of the stems of Miliusa velutina, seven compounds were isolated and determined structures, including a new drimane sesquiterpenoid compound named miliutine C methyl ester (1) and three bioactive alkaloids (5-7). These three alkaloids (5-7) exhibited strong anticancer activities against various cancer cell lines such as MCF-7, HepG2, HeLa, NCI H460 and normal fibroblasts. Especially, on MCF-7 and normal fibroblasts with values of IC50 (µM) in order for compounds 5 (3.38, 31.15), 6 (21.96, 102.00), 7 (7.90, greater than 300), to compare with positive control camptothecin (0.020, 4.51); which is highly noteworthy. These results contribute to elucidating and confirming the value of Miliusa velutina, similar to other published and folkloric findings.

Prevalence of common autosomal recessive mutation carriers in women in the Southern Vietnam following the application of expanded carrier screening.

The common autosomal recessive (AR) mutation carrier is still unknown in Vietnam. This study aims to identify the most common AR gene mutation carriers in women of reproductive age to build a Vietnamese-specific carrier screening panel for AR and X-linked disorders in the preconception and prenatal healthcare program. A cross-sectional study was conducted at University Medical Center-Branch 2 in Ho Chi Minh City from December 1st, 2020, to June 30th, 2023. 338 women have consented to take a 5 mL blood test to identify 540 recessive genes. The carrier screening panel was designed based on the American College of Medical Genetics and Genomics (ACMG)-recommended genes and suggestions from 104 clinical experts in Vietnam. Obstetricians and genetic experts counseled all positive testing results to discuss the possibility of recessive diseases in their offspring. The most common recessive disorders were defined at a prevalence of 1 in 60 or greater, and those were added to a Vietnamese-specific carrier screening panel. 338 non-pregnant and pregnant women underwent the expanded carrier screening (ECS). The carrier frequency was 63.6%, in which 215 women carried at least one AR gene mutation. GJB2 hearing impairment was identified as the most common chronic condition (1 in 5). The second most common AR disorder was beta-thalassemia (1 in 16), followed by cystic fibrosis (1 in 23), G6PD deficiency (1 in 28), Wilson's disease (1 in 31), Usher's syndrome (1 in 31), and glycogen storage disease (1 in 56). Seven common recessive genes were added in ethnic-based carrier screening. Women in the South of Vietnam have been carried for many recessive conditions at high frequency, such as hearing impairment, genetic anemia, and cystic fibrosis. It is necessary to implement a preconception and prenatal screening program by using seven widely popular AR genes in a Vietnamese-specific carrier screening panel to reduce the burden related to AR and X-linked disorders.

Helicobacter pylori-Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma in a Girl.

Introduction: Extranodal marginal zone lymphoma (MZL) arises in a number of epithelial tissues, including the stomach, salivary gland, lung, small bowel, thyroid, ocular adnexa, skin, and elsewhere. It has also been called low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). MALT lymphoma predominantly occurs in adults and is rare in children. Case Presentation: We report a case of MALT lymphoma involving the stomach, which is the most common subtype, in a 12-year-old girl. Initially, the patient relapsed after antibiotic therapy but achieved successful treatment subsequently through irradiation. Conclusion: Helicobacter pylori eradication therapy should be given to all patients with gastric MZL, irrespective of stage. In patients who do not respond to antibiotic therapy, treatment options such as irradiation and systemic cancer therapies should be considered, depending on the disease stage.

Store-operated calcium entry inhibits primary ciliogenesis via the activation of Aurora A.

The primary cilium is an antenna-like organelle protruding from the cell surface that can detect physical and chemical stimuli in the extracellular space to activate specific signaling pathways and downstream gene expressions. Calcium ion (Ca2+ ) signaling regulates a wide spectrum of cellular processes, including fertilization, proliferation, differentiation, muscle contraction, migration, and death. This study investigated the effects of the regulation of cytosolic Ca2+ levels on ciliogenesis using chemical, genetic, and optogenetic approaches. We found that ionomycin-induced Ca2+ influx inhibited ciliogenesis and Ca2+ chelator BATPA-AM-induced Ca2+ depletion promoted ciliogenesis. In addition, store-operated Ca2+ entry and the endoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1) negatively regulated ciliogenesis. Moreover, an optogenetic platform was used to create different Ca2+ oscillation patterns by manipulating lighting parameters, including density, frequency, exposure time, and duration. Light-activated Ca2+ -translocating channelrhodopsin (CatCh) is activated by 470-nm blue light to induce Ca2+ influx. Our results show that high-frequency Ca2+ oscillations decrease ciliogenesis. Furthermore, the inhibition of cilia formation induced by Ca2+ may occur via the activation of Aurora kinase A. Cilia not only induce Ca2+ signaling but also regulate cilia formation by Ca2+ signaling.

Deep-Ultraviolet Transparent Electrode Design for High-Performance and Self-Powered Perovskite Photodetector.

In this study, a highly crystalline and transparent indium-tin-oxide (ITO) thin film was prepared on a quartz substrate via RF sputtering to fabricate an efficient bottom-to-top illuminated electrode for an ultraviolet C (UVC) photodetector. Accordingly, the 26.6 nm thick ITO thin film, which was deposited using the sputtering method followed by post-annealing treatment, exhibited good transparency to deep-UV spectra (67% at a wavelength of 254 nm), along with high electrical conductivity (11.3 S/cm). Under 254 nm UVC illumination, the lead-halide-perovskite-based photodetector developed on the prepared ITO electrode in a vertical structure exhibited an excellent on/off ratio of 1.05 × 104, a superb responsivity of 250.98 mA/W, and a high specific detectivity of 4.71 × 1012 Jones without external energy consumption. This study indicates that post-annealed ITO ultrathin films can be used as electrodes that satisfy both the electrical conductivity and deep-UV transparency requirements for high-performance bottom-illuminated optoelectronic devices, particularly for use in UVC photodetectors.

Microplastic accumulation in bivalves collected from different coastal areas of Vietnam and an assessment of potential risks.

Microplastic (MP) pollution is an emerging problem in many areas around the world and in coastal areas of Vietnam, requiring more studies dedicated to the accumulation of this pollutant in the food chain as well as its potential risk to human health. This study investigated MP levels in tissues of five common bivalve species collected from aquaculture areas along the coast of Vietnam. MPs were found in all bivalve samples, with average values of 10.84 ± 2.61 items/individual or 2.40 ± 1.34 items/g wet weight. Impacts of feeding habits of bivalves showed influences on MP abundance in the samples. Fibers were the dominant shape of MPs recorded, most of which accumulated in the gills and digestive glands of all bivalve samples, with the majority falling within the size range of 300-2000 µm. MPs found in all studied species had relatively similar chemical compositions, mainly composed of polypropylene (PP) and polyethylene (PE). In this study, a diverse diet consisting of different bivalve species and detailed data on the consumption rate of these species were used to assess the human health risk of MPs dedicated to the coastal communities of Vietnam. The results suggested a significant part of MP uptake by human could be via bivalve consumption, in which removing viscera and proper depuration should be applied prior to eating, thereby reducing the risk.

A case of primary gastrointestinal stromal tumor of the liver.

A gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. The tumor originates from Cajal cells, which generated peristaltic motion. Primary gastrointestinal stromal tumor of the liver is rare and should be considered in imaging diagnosis. We report a case of an 82-year-old female patient who represented with upper abdominal pain and poor appetite. Magnetic resonance imaging detected a large left lobe cystic lesion (10 × 15 cm). The tumor was resected. The histopathological and immunohistochemical results were of a primary gastrointestinal stromal tumor in the liver with cystic changes. On imaging, it is difficult to differentiate from other cystic lesions.

Toward Industrial Production of a High-Performance Self-Powered Ultraviolet Photodetector Using Nanoporous Al-Doped ZnO Thin Films.

Al-doped ZnO (AZO) thin films are effective n-type semiconductors for ultraviolet (UV) detection because of their low cost, high electron mobility, and high sensitivity to UV light, especially in the UVA spectrum. However, a reasonable compromise between performance (such as sensitivity, detectivity, and response time) and fabrication ease remains an obstacle to the practicability of AZO-based UV photodetectors. To address this issue, we propose an efficient strategy to achieve a large AZO photoactive area for outstanding performance, along with a facile sol-gel method. Consequently, the device exhibits a superb on/off ratio of >104, a high detectivity of 1.85 × 1012 Jones, and a fast response speed under 365 nm UVA illumination without external energy consumption. Hence, this study suggests a self-powered and high-performance nanoporous AZO-based UVA detector with an environmentally friendly scalable process that satisfies industrial production requirements for numerous practical UV-detection applications.

Quality of Life in Patients With Unstable Angina Before and After Percutaneous Coronary Intervention: A Single-Center Pilot Study Using the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Questionnaire.

Background Unstable angina (UA) has a negative impact on patients' quality of life. Percutaneous coronary intervention (PCI) is a commonly recommended treatment that exhibits positive therapeutic effects and enhances quality of life. This study aimed to compare the alterations in quality of life and related factors before and after PCI in UA patients. Methods A longitudinal follow-up study was conducted on 48 patients with UA before and one month after undergoing PCI. The European Quality of Life (EuroQol) 5-Dimension 5-Level (EQ-5D-5L) scale was utilized to measure the quality of life of patients. Results The study revealed a significant improvement in the quality of life score after one month of coronary artery intervention compared to the pre-intervention stage: the quality of life score before the intervention was 0.73 ± 0.32, whereas it increased to 0.89 ± 0.20 after one month (p<0.001). Sex, occupation, and troponin T were associated with changes in quality of life one month after the coronary artery intervention. Conclusion The pilot study demonstrated a notable enhancement in the quality of life among patients with UA following coronary intervention. Additionally, sex, occupation, and troponin T were identified as factors associated with this improvement.

YAP nuclear translocation induced by HIF-1α prevents DNA damage under hypoxic conditions.

Maladaptive repair of acute kidney injury (AKI) is associated with a high risk of developing chronic kidney disease deemed irremediable even in present days. When AKI arises from ischemia-reperfusion injury, hypoxia usually plays a major role. Although both hypoxia-inducible factor-1α (HIF-1α) and yes-associated protein (YAP) have been proven to promote renal cell survival under hypoxia, there is a lack of research that studies the crosstalk of the two and its effect on kidney repair. In studying the crosstalk, CoCl2 was used to create a mimetic hypoxic environment. Immunoprecipitation and proximity ligation assays were performed to verify protein interactions. The results show that HIF-1α interacts with YAP and promotes nuclear translocation of YAP at a high cell density under hypoxic conditions, suggesting HIF-1α serves as a direct carrier that enables YAP nuclear translocation. This is the first study to identify HIF-1α as a crucial pathway for YAP nuclear translocation under hypoxic conditions. Once translocated into a nucleus, YAP protects cells from DNA damage and apoptosis under hypoxic conditions. Since it is unlikely for YAP to translocate into a nucleus without HIF-1α, any treatment that fosters the crosstalk between the two holds the potential to improve cell recovery from hypoxic insults.

Quality of Life and Related Factors in Patients With Ankylosing Spondylitis: A Cross-Sectional Study Using 36-Item Short Form Survey (SF-36).

BACKGROUND:  Ankylosing spondylitis is a chronic condition that affects the vertebral and sacroiliac joints, causing progressive back pain and stiffness. Patients with this condition experience a lower quality of life compared to the general population, with physical health being more impacted than mental health. In Vietnam, little attention has been given to the quality of life of patients with ankylosing spondylitis, and there are conflicting studies on the factors that affect their quality of life. Therefore, it is essential to assess the quality of life of these patients to provide appropriate recommendations for improving their overall well-being. METHODOLOGY: The descriptive cross-sectional study was conducted on patients with ankylosing spondylitis who visited University Medical Center Ho Chi Minh City from March 2022 to May 2022. Participants were interviewed face-to-face using the 36-item short form survey (SF-36) questionnaire and the visual analogue scale. In addition, some information related to ankylosing spondylitis was also collected through medical records. RESULTS AND CONCLUSION: Seventy-five patients met the inclusion criteria with a median age of 33 (26 - 37); men accounted for 68%. The mean physical and mental health scores on the SF-36 scale were 37.73 ± 9.30 and 47.04 ± 7.11, respectively. Young age, lower pain score and duration of illness, and higher education were associated with a high physical health score with p<0.05. Similarly, the educational level and occupation were positively correlated, and pain scores were inversely correlated with mental health with p< 0.05.

Recent Advances of Doped SnO2 as Electron Transport Layer for High-Performance Perovskite Solar Cells.

Perovskite solar cells (PSCs) have garnered considerable attention over the past decade owing to their low cost and proven high power conversion efficiency of over 25%. In the planar heterojunction PSC structure, tin oxide was utilized as a substitute material for the TiO2 electron transport layer (ETL) owing to its similar physical properties and high mobility, which is suitable for electron mining. Nevertheless, the defects and morphology significantly changed the performance of SnO2 according to the different deposition techniques, resulting in the poor performance of PSCs. In this review, we provide a comprehensive insight into the factors that specifically influence the ETL in PSC. The properties of the SnO2 materials are briefly introduced. In particular, the general operating principles, as well as the suitability level of doping in SnO2, are elucidated along with the details of the obtained results. Subsequently, the potential for doping is evaluated from the obtained results to achieve better results in PSCs. This review aims to provide a systematic and comprehensive understanding of the effects of different types of doping on the performance of ETL SnO2 and potentially instigate further development of PSCs with an extension to SnO2-based PSCs.

Exploring Shigella vaccine priorities and preferences: Results from a mixed-methods study in low- and middle-income settings.

Background: Shigella is the leading bacterial cause of diarrheal mortality in children and can cause long-term effects on growth and development. No licensed Shigella vaccines currently exist but several promising candidates are in development and could be available in the next five years. Despite Shigella being a well-known public health target of the World Health Organization for decades, given current burden estimates and competing preventable disease priorities in low-income settings, whether the availability of an effective Shigella vaccine will lead to its prioritization and widespread introduction among countries at highest risk is unknown. Methods: We conducted a mixed-methods study of national stakeholders and healthcare providers in five countries in Asia and Africa and regional stakeholders in the Pan American Health Organization to identify preferences and priorities for forthcoming Shigella vaccines. Results: In our study of 89 individuals, diarrhea was the most frequently mentioned serious health concern for children under five years. Antimicrobial resistance (AMR) was more often considered very concerning than diarrhea or stunting. Shigella awareness was high but not considered a serious health concern by most stakeholders. Most participants were willing to consider adding a new vaccine to the routine immunization schedule but expressed reservations about a Shigella vaccine because of lower perceived burden relative to other preventable diseases and an already crowded schedule; interest was highest among national stakeholders in countries receiving more financial support for immunization. The priority of a Shigella vaccine rose when participants considered vaccine impacts on reducing stunting and AMR. Participants strongly preferred oral and combination vaccines compared to injectable and a single-antigen presentations, citing greater perceived community acceptability. Conclusions: This study provides a critical opportunity to hear directly from country and regional stakeholders about health priorities and preferences around new vaccines. These findings should inform ongoing Shigella vaccine development efforts and eventual vaccine introduction and implementation planning.

Depletion of intracellular Ca2+ induces FOXM1 SUMOylation and accumulation on the inner nuclear membrane and accelerates G2/M cell cycle transition.

Intracellular calcium (Ca2+) has been reported to regulate transcription factor activity and cancer development, but how it affects the function of Forkhead box protein M1 (FOXM1), a crucial transcription factor and key oncogene participating in tumorigenesis, remains unclear. Here, we investigated the regulatory role of Ca2+ on FOXM1 and found that Ca2+ depletion caused the distribution of FOXM1 to aggregate on the nuclear envelope, which was also observed in many cell lines. Further experiments revealed that sequestrated FOXM1 colocalized with lamin B in the inner nuclear membrane (INM) and was affected by the activity of nuclear export protein exportin 1 (XPO1). To investigate how intracellular Ca2+ affects FOXM1, we found that among the posttranscriptional modifications, only SUMOylation of FOXM1 showed a pronounced increase under reduced Ca2+, and suppressed SUMOylation rescued FOXM1 sequestration. In addition, Ca2+-dependent SUMOylated FOXM1 appeared to enhance the G2/M transition of the cell cycle and decrease cell apoptosis. In conclusion, our findings provide a molecular basis for the relationship between Ca2+ signaling and FOXM1 regulation, and we look to elucidate Ca2+-dependent FOXM1 SUMOylation-related biological functions in the future.

Thiol-Surface-Engineered Cellulose Nanocrystals in Favor of Copper Ion Uptake.

Cellulose, the most abundant natural polymer on earth, has recently gained attention for a large spectrum of applications. At a nanoscale, nanocelluloses (mainly involving cellulose nanocrystals or cellulose nanofibrils) possess many predominant features, such as highly thermal and mechanical stability, renewability, biodegradability and non-toxicity. More importantly, the surface modification of such nanocelluloses can be efficiently obtained based on the native surface hydroxyl groups, acting as metal ions chelators. Taking into account this fact, in the present work, the sequential process involving chemical hydrolysis of cellulose and autocatalytic esterification using thioglycolic acid was performed to obtain thiol-functionalized cellulose nanocrystals. The change in chemical compositions was attributed to thiol-functionalized groups and explored via the degree of substitution using a back titration method, X-ray powder diffraction, Fourier-transform infrared spectroscopy and thermogravimetric analysis. Cellulose nanocrystals were spherical in shape and ca. 50 nm in diameter as observed via transmission electron microscopy. The adsorption behavior of such a nanomaterial toward divalent copper ions from an aqueous solution was also assessed via isotherm and kinetic studies, elucidating a chemisorption mechanism (ion exchange, metal chelation and electrostatic force) and processing its operational parameters. In contrast to an inactive configure of unmodified cellulose, the maximum adsorption capacity of thiol-functionalized cellulose nanocrystals toward divalent copper ions from an aqueous solution was 4.244 mg g-1 at a pH of 5 and at room temperature.

Antioxidant Nanozymes: Mechanisms, Activity Manipulation, and Applications.

Antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase play important roles in the inhibition of oxidative-damage-related pathological diseases. However, natural antioxidant enzymes face some limitations, including low stability, high cost, and less flexibility. Recently, antioxidant nanozymes have emerged as promising materials to replace natural antioxidant enzymes for their stability, cost savings, and flexible design. The present review firstly discusses the mechanisms of antioxidant nanozymes, focusing on catalase-, superoxide dismutase-, and glutathione peroxidase-like activities. Then, we summarize the main strategies for the manipulation of antioxidant nanozymes based on their size, morphology, composition, surface modification, and modification with a metal-organic framework. Furthermore, the applications of antioxidant nanozymes in medicine and healthcare are also discussed as potential biological applications. In brief, this review provides useful information for the further development of antioxidant nanozymes, offering opportunities to improve current limitations and expand the application of antioxidant nanozymes.

Optogenetically engineered Ca2+ oscillation-mediated DRP1 activation promotes mitochondrial fission and cell death.

Mitochondrial dynamics regulate the quality and morphology of mitochondria. Calcium (Ca2+) plays an important role in regulating mitochondrial function. Here, we investigated the effects of optogenetically engineered Ca2+ signaling on mitochondrial dynamics. More specifically, customized illumination conditions could trigger unique Ca2+ oscillation waves to trigger specific signaling pathways. In this study, we found that modulating Ca2+ oscillations by increasing the light frequency, intensity and exposure time could drive mitochondria toward the fission state, mitochondrial dysfunction, autophagy and cell death. Moreover, illumination triggered phosphorylation at the Ser616 residue but not the Ser637 residue of the mitochondrial fission protein, dynamin-related protein 1 (DRP1, encoded by DNM1L), via the activation of Ca2+-dependent kinases CaMKII, ERK and CDK1. However, optogenetically engineered Ca2+ signaling did not activate calcineurin phosphatase to dephosphorylate DRP1 at Ser637. In addition, light illumination had no effect on the expression levels of the mitochondrial fusion proteins mitofusin 1 (MFN1) and 2 (MFN2). Overall, this study provides an effective and innovative approach to altering Ca2+ signaling for controlling mitochondrial fission with a more precise resolution than pharmacological approaches in the temporal dimension.

Phylogenetic and genotypic characteristics of the foot-and-mouth disease virus from outbreaks in southern Vietnam, 2019.

In 2019, multiple FMD outbreaks occurred in swine farms vaccinated against FMDV in southern Vietnam. This study investigated the genotypic characteristics of FMDV strains from these outbreaks. Seven samples were collected from pigs exhibiting FMD clinical signs. All FMDV-positive samples were amplified and sequenced for the gene encoding the VP1. Results were analyzed and compared with sequences of reference strains and vaccine strains on GenBank. Phylogenetic analysis showed that all seven field isolates belonged to serotype O, topotype SEA/Mya-98. These strains shared high homology with strains from Vietnam (2018), Korea, and China, but low homology with vaccine strains. Moreover, 21 amino acid substitutions were found in the VP1 protein of the FMDV field strains, many of which were crucial antigenic determinants involved in the neutralization of FMDV. These findings suggest that the current vaccine may not be effective against the emerging FMDV strains in southern Vietnam.