Temporal changes in biomarkers of neutrophil extracellular traps and NET-promoting autoantibodies following adenovirus-vectored, mRNA, and recombinant protein COVID-19 vaccination.

Neutrophil extracellular traps (NETs) play a role in innate pathogen defense and also trigger B-cell response by providing antigens. NETs have been linked to vaccine-induced thrombotic thrombocytopenia. We postulated a potential link between NET biomarkers, NET-promoting autoantibodies, and adverse events (AEs) after COVID-19 vaccine boosters. Healthy donors (HDs) who received ChAdOx1-S (A), mRNA-1273 (M), or recombinant protein (MVC-COV1901) vaccines at the National Taiwan University Hospital between 2021 and 2022 were recruited. We measured serial NET-associated biomarkers, citrullinated-histone3 (citH3), and myeloperoxidase (MPO)-DNA. Serum citH3 and MPO-DNA were significantly or numerically higher in HDs who reported AEs (n = 100, booster Day 0/Day 30, p = 0.01/p = 0.03 and p = 0.30/p = 0.35, respectively). We also observed a positive correlation between rash occurrence in online diaries and elevated citH3. A linear mixed model also revealed significantly higher citH3 levels in mRNA-1273/ChAdOx1-S recipients than MVC-COV1901 recipients. Significant positive correlations were observed between the ratios of anti-heparin platelet factor 4 and citH3 levels on Booster Day 0 and naïve and between the ratios of anti-NET IgM and citH3 on Booster Day 30/Day 0 in the AA-M and MM-M group, respectively. The increased levels of citH3/MPO-DNA accompanied by NET-promoting autoantibodies suggest a potential connection between mRNA-1273/ChAdOx1-S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines.

Risk factors of recurrent secondary hyperparathyroidism after adequate primary surgical treatment.

Background: Secondary hyperparathyroidism (SHPT) is a common condition in patients with end-stage renal disease (ESRD) who are on dialysis. Parathyroidectomy is a treatment for patients when medical therapy has failed. Recurrence may occur and is indicated for further surgery in the era of improved quality of care for ESRD patients. Methods: We identified, 1060 patients undergoing parathyroidectomy from January, 2011 to June, 2020. After excluding patients without regular check-up at our institute, primary hyperparathyroidism, or malignancy, 504 patients were enrolled. Sixty-two patients (12.3%, 62/504) were then excluded due to persistent SHPT even after the first parathyroidectomy. We aimed to identify risk factors for recurrent SHPT after the first surgery. Results: During the study period, 20% of patients who underwent parathyroidectomy at our institute (in, 2019) was due to recurrence after a previous parathyroidectomy. There were 442 patients eligible for analysis of recurrence after excluding patients with the persistent disease (n = 62). While 44 patients (9.95%) had recurrence, 398 patients did not. Significant risk factors for recurrent SHPT within 5 years after the first parathyroidectomy, including dialysis start time to first operation time < 3 years (p = 0.046), postoperative PTH >106.5 pg/mL (p < 0.001), and postoperative phosphorus> 5.9 mg/dL (p = 0.016), were identified by multivariate analysis. Conclusions: The starting time of dialysis to first operation time < 3 years in the patients with dialysis, postoperative PTH> 106.5 pg/mL, and postoperative phosphorus> 5.9 mg/dL tended to have a higher risk for recurrent SHPT within 5 years after primary treatment.

Lactiplantibacillus plantarum PS128 Alleviates Exaggerated Cortical Beta Oscillations and Motor Deficits in the 6-Hydroxydopamine Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by midbrain dopaminergic neuronal loss and subsequent physical impairments. Levodopa manages symptoms best, while deep brain stimulation (DBS) is effective for advanced PD patients; however, side effects occur with the diminishing therapeutic window. Recently, Lactiplantibacillus plantarum PS128 (PS128) was found to elevate dopamine levels in rodent brains, suggesting its potential to prevent PD. Here, the therapeutic efficacy of PS128 was examined in the 6-hydroxydopamine rat PD model. Suppression of the power spectral density of beta oscillations (beta PSD) in the primary motor cortex (M1) was recorded as the indicator of disease progression. We found that 6 weeks of daily PS128 supplementation suppressed M1 beta PSD as well as did levodopa and DBS. Long-term normalization of M1 beta PSD was found in PS128-fed rats, whereas levodopa and DBS showed only temporal effects. PS128 + levodopa and PS128 + DBS exhibited better therapeutic effects than did levodopa + DBS or either alone. Significantly improved motor functions in PS128-fed rats were correlated with normalization of M1 beta PSD. Brain tissue analyses further demonstrated the role of PS128 in dopaminergic neuroprotection and the enhanced availability of neurotransmitters. These findings suggest that psychobiotic PS128 might be used alongside conventional therapies to treat PD patients.

Lactobacillus paragasseri BBM171 Ameliorates Allergic Airway Inflammation Induced by Ovalbumin in Mice via Modulating the Th1/Th2 Balance

Supplementation with specific probiotics has been shown to improve allergic airway symptoms. This study aimed to investigate immunomodulatory effects of a potential probiotic strain isolated from breast milk, Lactobacillus paragasseri BBM171 (BBM171), in an ovalbumin (OVA)-induced allergic mouse model. OVA-sensitized and OVA-challenged BALB/c mice were orally administered live or heat-inactivated BBM171 for 48 consecutive days. After the last allergen challenge, serum immunoglobulin (Ig) levels, inflammatory cell levels in the lungs, and cytokine levels in bronchoalveolar lavage fluid (BALF) were assessed. The results showed that oral administration of live or heat-inactivated BBM171 decreased serum levels of total IgE, OVA-specific IgE, and OVA-specific IgG1, while increasing OVA-specific IgG2a and reducing the extent of airway inflammation in OVA-induced allergic mice. In addition, both live and heat-inactivated BBM171 modulated the cytokine profile in BALF to a type 1 T helper (Th1) response. Furthermore, ex vivo experiments using OVA-induced allergic mouse splenocytes showed that both live and heat-inactivated BBM171 could regulate the Th1/Th2 balance, decrease the proinflammatory cytokine interleukin (IL)-17 level, and increase the anti-inflammatory cytokine IL-10 level. Taken together, these results suggest that oral administration of live or heat-inactivated BBM171 improved allergen-induced airway inflammation symptoms by modulating the host immune response toward Th1 dominance.

Psychobiotic supplementation of HK-PS23 improves anxiety in highly stressed clinical nurses: a double-blind randomized placebo-controlled study.

Nurses often experience adverse health effects associated with increasing levels of work-related stress. Stress may induce systemic effects through the HPA axis, glucocorticoid responses, and inflammatory cascades. Psychobiotics may help alleviate stress through associations of the microbiota, anti-inflammation factors, and the gut-brain axis. We aimed to investigate whether interventions with a psychobiotic, heat-killed (HK)-PS23 cells, may help improve perceived stress, anxiety, and related biological markers among highly stressed clinical nurses. This double-blind, randomized, placebo-controlled study included seventy clinical nurses from a medical center in Northern Taiwan who scored 27 or higher on the 10-item version of the Perceived Stress Scale (PSS), and participants were randomized into either taking HK-PS23 or a placebo for 8 weeks. Baseline and endpoint results of the PSS, Job Stress Scale, State and Trait Anxiety Index (STAI), emotional questionnaires, gastrointestinal severity questionnaires, Trails Marking Tests, blood biological markers, and sleep data were analyzed. While both groups demonstrated improvements in most measures over time, only the blood cortisol measure demonstrated significant group differences after the 8-week trial. Further analyses of the subgroup with higher anxiety (nurses with STAI ≥ 103) revealed that anxiety states had improved significantly in the HK-PS23 group but not in the placebo group. In summary, this placebo-controlled trial found significant reduction in the level of blood cortisol after 8 weeks of HK-PS23 use. The distinctive anxiolytic effects of HK-PS23 may be beneficial in improving perceived anxiety and stress hormone levels in female nurses under pressure. Clinical trial registration: https://clinicaltrials.gov/, identifier: NCT04452253-sub-project 1.

Streptococcus mutans PrsA mediates AtlA secretion contributing to extracellular DNA release and biofilm formation in the pathogenesis of infective endocarditis.

The role of secretion chaperone-regulated virulence proteins in the pathogenesis of infective endocarditis (IE) induced by viridans streptococci such as Streptococcus mutans is unclear. In this study, we investigated the contribution of the foldase protein PrsA, a putative parvulin-type peptidyl-prolyl isomerase, to the pathogenesis of S. mutans-induced IE. We found that a prsA-deficient strain had reduced virulence in terms of formation of vegetation on damaged heart valves, as well as reduced autolysis activity, eDNA release and biofilm formation capacity. The secretion and surface exposure of AtlA in vitro was reduced in the prsA-deficient mutant strain, and complementation of recombinant AtlA in the culture medium restored a wild type biofilm phenotype of the prsA-deficient mutant strain. This result suggests that secretion and surface localization of AtlA is regulated by PrsA during biofilm formation. Together, these results demonstrate that S. mutans PrsA could regulate AtlA-mediated eDNA release to contribute to biofilm formation in the pathogenesis of IE.

Biomarker of neutrophil extracellular traps is associated with deep-seated infections and predicts mortality and cardiovascular morbidity in commensal streptococcal bacteremia.

BACKGROUND: Neutrophil extracellular traps (NETs) play important roles in sepsis and deep-seated infections, but whether NET formation correlates with clinical outcomes of patients with streptococcal bloodstream infections (BSIs) is unclear. METHODS: We analyzed serum levels of complexes of myeloperoxidase and DNA (MPO-DNA) in patients with streptococcal-BSIs. In vitro assay of NET induction by serum from BSI patients was performed. RESULTS: MPO-DNA values for the Streptococci-BSI group (n = 59) were significantly higher than those for healthy controls (p < 0.00001) and matched control groups (n = 59, p = 0.004). The rate of higher MPO-DNA levels (>1.87 µg/mL) were higher in abscess-prone streptococcal groups (streptococcus milleri group) (72.2% vs. 52.5%, p = 0.02). For patients with BSIs due to highly infective endocarditis (IE)-prone pathogens, the values of serum MPO-DNA were also higher in patients diagnosed of IE compared to their counterparts (p = 0.009). Notably, serum from patients with leukopenia could induce higher amounts of in vitro NET formation, despite having low MPO-DNA levels, suggesting that NET formation could be influenced by WBC counts. Therefore, we combined WBC counts with MPO-DNA to predict all-cause 30-day mortality in patients with commensal streptococcal-BSIs. The mortality risk was lowest among patients who had neither high MPO-DNA levels nor abnormal WBC counts (p = 0.058). Furthermore, this group of patients also had a favorable composite outcome consisting of major adverse cardiovascular events (MACE) and all-cause mortality (p = 0.026). CONCLUSION: Together, these study data suggested that serum MPO-DNA can be a biomarker for predicting a composite outcome consisting of MACE and all-cause mortality in patients with commensal streptococcal-BSIs.

Transient Bacteremia Promotes Catheter-Related Central Venous Thrombosis through Neutrophil Extracellular Traps.

Formation of intravenous catheter-related thrombosis leads to central venous stenosis in patients requiring renal replacement therapy or chemotherapy infusion, yet the triggers or mechanisms remain unclear, especially in patients without symptoms of infection. In this study, we found that neutrophil extracellular traps (NETs) could be detected in the fibrin sheaths from dialysis patients without clinical manifestations of infection. Confocal microscopy revealed bacteria imbedded in NETs in the fibrin sheaths. Thirty-nine of 50 (78%) fibrin sheath specimens contained bacteria detectable by 16S ribosomal RNA genome typing with a predominance of Staphylococcus aureus (69%). In rat models, transient bacteremia of S. aureus induced NETs in enlarged fibrin sheaths, and treatment with DNase I alone significantly reduced both NET and fibrin sheath formation surrounding the catheter. Therefore, transient bacteremia could be a silent trigger that induces NET-related immunothrombosis enhancing catheter-related central venous stenosis.

Optimal Perioperative Nutrition Therapy for Patients Undergoing Pancreaticoduodenectomy: A Systematic Review with a Component Network Meta-Analysis.

Numerous strategies for perioperative nutrition therapy for patients undergoing pancreaticoduodenectomy (PD) have been proposed. This systematic review aimed to summarize the current relevant published randomized controlled trials (RCTs) evaluating different nutritional interventions via a traditional network meta-analysis (NMA) and component network meta-analysis (cNMA). EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov were searched to identify the RCTs. The evaluated nutritional interventions comprised standard postoperative enteral nutrition by feeding tube (Postop-SEN), preoperative enteral feeding (Preop-EN), postoperative immunonutrients (Postop-IM), preoperative oral immunonutrient supplement (Preop-IM), and postoperative total parenteral nutrition (TPN). The primary outcomes were general, infectious, and noninfectious complications; postoperative pancreatic fistula (POPF); and delayed gastric emptying (DGE). The secondary outcomes were mortality and length of hospital stay (LOS). The NMA and cNMA were conducted with a frequentist approach. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Two primary outcomes, infectious complications and POPF, were positively influenced by nutritional interventions. Preop-EN plus Postop-SEN (OR 0.11; 95% CI 0.02~0.72), Preop-IM (OR 0.22; 95% CI 0.08~0.62), and Preop-IM plus Postop-IM (OR 0.11; 95% CI 0.03~0.37) were all demonstrated to be associated with a decrease in infectious complications. Postop-TPN (OR 0.37; 95% CI 0.19~0.71) and Preop-IM plus Postop-IM (OR 0.21; 95% CI 0.06~0.77) were clinically beneficial for the prevention of POPF. While enteral feeding and TPN may decrease infectious complications and POPF, respectively, Preop-IM plus Postop-IM may provide the best clinical benefit for patients undergoing PD, as this approach decreases the incidence of both the aforementioned adverse effects.

Lactobacillus plantarum PS128 prevents cognitive dysfunction in Alzheimer's disease mice by modulating propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis.

BACKGROUND: According to recent evidence, psychobiotics exert beneficial effects on central nervous system-related diseases, such as mental disorders. Lactobacillus plantarum PS128 (PS128), a novel psychobiotic strain, improves motor function, depression, and anxiety behaviors. However, the psychobiotic effects and mechanisms of PS128 in Alzheimer's disease (AD) remain to be explored. OBJECTIVES: The goal of the current study was to evaluate the beneficial effects of PS128 and to further elucidate its mechanism in AD mice. METHODS: PS128 (1010 colony-forming unit (CFU)/ml) was administered via oral gavage (o.g.) to 6-month-old male wild-type B6 and 3 × Tg-AD mice (harboring the PS1M146V, APPswe and TauP30IL transgenes) that received an intracerebroventricular injection of streptozotocin (icv-STZ, 3 mg/kg) or vehicle (saline) for 33 days. After serial behavioral tests, fecal short-chain fatty acid levels and AD-related pathology were assessed in these mice. RESULTS: Our findings show that intracerebroventricular injection of streptozotocin accelerated cognitive dysfunction associated with increasing levels of glycogen synthase kinase 3 beta (GSK3ß) activity, tau protein phosphorylation at the T231 site (pT231), amyloid-ß (Aß) deposition, amyloid-ß protein precursor (AßPP), ß-site AßPP-cleaving enzyme (BACE1), gliosis, fecal propionic acid (PPA) levels and cognition-related neuronal loss and decreasing postsynaptic density protein 95 (PSD95) levels in 3 × Tg-AD mice. PS128 supplementation effectively prevented the damage induced by intracerebroventricular injection of streptozotocin in 3 × Tg-AD mice. CONCLUSIONS: Based on the experimental results, intracerebroventricular injection of streptozotocin accelerates the progression of AD in the 3 × Tg-AD mice, primarily by increasing the levels of gliosis, which were mediated by the propionic acid and glycogen synthase kinase 3 beta pathways. PS128 supplementation prevents damage induced by intracerebroventricular injection of streptozotocin by regulating the propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis in 3 × Tg-AD mice. Therefore, we suggest that PS128 supplementation is a potential strategy to prevent and/or delay the progression of AD.

Oxygen Concentration Effect on Conductive Bridge Random Access Memory of InWZnO Thin Film.

In this study, the influence of oxygen concentration in InWZnO (IWZO), which was used as the switching layer of conductive bridge random access memory, (CBRAM) is investigated. With different oxygen flow during the sputtering process, the IWZO film can be fabricated with different oxygen concentrations and different oxygen vacancy distribution. In addition, the electrical characteristics of CBRAM device with different oxygen concentration are compared and further analyzed with an atomic force microscope and X-ray photoelectron spectrum. Furthermore, a stacking structure with different bilayer switching is also systematically discussed. Compared with an interchange stacking layer and other single layer memory, the CBRAM with specific stacking sequence of bilayer oxygen-poor/-rich IWZO (IWZOx/IWZOy, x < y) exhibits more stable distribution of a resistance state and also better endurance (more than 3 × 104 cycles). Meanwhile, the memory window of IWZOx/IWZOy can even be maintained over 104 s at 85 °C. Those improvements can be attributed to the oxygen vacancy distribution in switching layers, which may create a suitable environment for the conductive filament formation or rupture. Therefore, it is believed that the specific stacking bilayer IWZO CBRAM might further pave the way for emerging memory applications.

Metabolism of Proteins and Amino Acids in Critical Illness: From Physiological Alterations to Relevant Clinical Practice.

The clinical impact of nutrition therapy in critically ill patients has been known for years, and relevant guidelines regarding nutrition therapy have emphasized the importance of proteins. During critical illness, such as sepsis or the state following major surgery, major trauma, or major burn injury, patients suffer from a high degree of stress/inflammation, and during this time, metabolism deviates from homeostasis. The increased degradation of endogenous proteins in response to stress hormones is among the most important events in the acute phase of critical illness. Currently published evidence suggests that adequate protein supplementation might improve the clinical outcomes of critically ill patients. The role of sufficient protein supplementation may even surpass that of caloric supplementation. In this review, we focus on relevant physiological alterations in critical illness, the effects of critical illness on protein metabolism, nutrition therapy in clinical practice, and the function of specific amino acids.

Psychobiotic Supplementation of PS128TM Improves Stress, Anxiety, and Insomnia in Highly Stressed Information Technology Specialists: A Pilot Study.

Background: Information technology (IT) is an industry related to the production of computers, information processing, and telecommunications. Such industries heavily rely on the knowledge and solutions provided by IT specialists. Previous reports found that the subjective stress scores were higher in IT specialists who developed diabetes, hypertension, and depression. Specific probiotics, known as psychobiotics, may alleviate stress and mood symptoms. This study aimed to examine whether an 8-week intervention of a novel psychobiotic, Lactobacillus plantarum PS128TM (PS128TM), improved self-perceived stress and mood symptoms among high-stress IT specialists. Methods: This open-label, single-arm, baseline-controlled study included IT specialists from a large IT company in Northern Taiwan. Participants with a Perceived Stress Scale (PSS) 10-item version score of 27 or higher were included. Participants were asked to take two capsules containing PS128TM powder, equivalent to 20 billion colony-forming units, daily. Self-report measures, such as the Job Stress Scale, Visual Analog Scale of Stress, the Insomnia Severity Index, the State and Trait Anxiety Index, the Questionnaire for Emotional Trait and State, the Patient Health Questionnaire, the Quality of Life Enjoyment and Satisfaction Questionnaire, and Gastrointestinal Severity Index were compared at baseline and at the end of the trial period. The primary outcome was a 20% reduction in the PSS score at endpoint. Objective measures included salivary levels of stress biomarkers, including cortisol, α-amylase, immunoglobulin A, lactoferrin, and lysozymes, as well as results of the Test of Attentional Performance. Results: Of the 90 eligible IT specialists, 36 met the inclusion criteria. After the 8-week trial period, significant improvements in self-perceived stress, overall job stress, job burden, cortisol level, general or psychological health, anxiety, depression, sleep disturbances, quality of life, and both positive and negative emotions were found. Conclusion: Our results suggest that PS128TM has the distinct advantage of providing stress relief and can improve mental health for people with a high-stress job. Future placebo-controlled studies are warranted to explore the effect and underlying mechanisms of action of PS128TM. Clinical Trial Registration: https://clinicaltrials.gov/ (identifier: NCT04452253-sub-project 2).

Identification of potential therapeutic antimicrobial peptides against Acinetobacter baumannii in a mouse model of pneumonia.

Acinetobacter baumannii-induced nosocomial pneumonia has become a serious clinical problem because of high antibiotic resistance rates. Antimicrobial peptides (AMP) are an ideal alternative strategy due to their broad-spectrum of antimicrobial activity and low incidence of bacterial resistance. However, their application is limited by toxicity and stability in vivo. The present study used a mouse model to directly identify potential AMPs effective for treatment of A. baumannii-induced pneumonia. Fifty-eight AMPs were screened and two identified (SMAP-29 and TP4) to have prophylactic effects which prevented the death of mice with pneumonia. Furthermore, two TP4 derivatives (dN4 and dC4) were found to have therapeutic activity in pneumonia mouse models by peritoneal or intravenous administration. Both dN4 and dC4 also inhibited and/or eliminated A. baumannii biofilms at higher doses. Taken together, these data suggest the AMP derivatives dN4 and dC4 represent a potential treatment strategy for A. baumannii-induced pneumonia.

PspC domain-containing protein (PCP) determines Streptococcus mutans biofilm formation through bacterial extracellular DNA release and platelet adhesion in experimental endocarditis.

Bacterial extracellular DNA (eDNA) and activated platelets have been found to contribute to biofilm formation by Streptococcus mutans on injured heart valves to induce infective endocarditis (IE), yet the bacterial component directly responsible for biofilm formation or platelet adhesion remains unclear. Using in vivo survival assays coupled with microarray analysis, the present study identified a LiaR-regulated PspC domain-containing protein (PCP) in S. mutans that mediates bacterial biofilm formation in vivo. Reverse transcriptase- and chromatin immunoprecipitation-polymerase chain reaction assays confirmed the regulation of pcp by LiaR, while PCP is well-preserved among streptococcal pathogens. Deficiency of pcp reduced in vitro and in vivo biofilm formation and released the eDNA inside bacteria floe along with reduced bacterial platelet adhesion capacity in a fibrinogen-dependent manner. Therefore, LiaR-regulated PCP alone could determine release of bacterial eDNA and binding to platelets, thus contributing to biofilm formation in S. mutans-induced IE.

Alternative application of percutaneous cholecystostomy in patients with biliary obstruction.

PURPOSE: Percutaneous cholecystostomy (PC) is an important modality for acute cholecystitis and has been applied for other clinical scenarios as well. In the present study, we aimed to investigate an alternative use of PC for obstructive jaundice. METHODS: From January 2012 to December 2018, eligible subjects were selected from patients undergoing PC in our institute. The characteristics, spectrum of underlying disease, indication for PC performance, details of the procedure, and treatment effect were all investigated. RESULTS: During the study period, 1364 patients underwent PC. Seventy patients fulfilled the defined inclusion criteria. While 47 patients were diagnosed with malignant biliary obstruction with or without cholangitis, 23 patients were diagnosed with nonmalignant biliary obstruction and acute cholangitis. There were 63 patients (90%) diagnosed with acute cholangitis. Pancreatic cancer (n = 24, 51%) and advanced malignancy (n = 28, 59%) were noted mostly in the group with malignant biliary obstruction. Treatment effects were proven by laboratory data, including the white blood cell count, C-reactive protein level, and hepatic function. CONCLUSION: PC can temporize definitive therapies and serve as an alternative treatment for patients with nonmalignant conditions. For patients with advanced malignancy, PC can serve as a palliative procedure that has a high success rate and low complication rate and effectively relieves biliary obstruction.

Candida tropicalis RON1 is required for hyphal formation, biofilm development, and virulence but is dispensable for N-acetylglucosamine catabolism.

NDT80-like family genes are highly conserved across a large group of fungi, but the functions of each Ndt80 protein are diverse and have evolved differently among yeasts and pathogens. The unique NDT80 gene in budding yeast is required for sexual reproduction, whereas three NDT80-like genes, namely, NDT80, REP1, and RON1, found in Candida albicans exhibit distinct functions. Notably, it was suggested that REP1, rather than RON1, is required for N-acetylglucosamine (GlcNAc) catabolism. Although Candida tropicalis, a widely dispersed fungal pathogen in tropical and subtropical areas, is closely related to Candida albicans, its phenotypic, pathogenic and environmental adaptation characteristics are remarkably divergent. In this study, we focused on the Ron1 transcription factor in C. tropicalis. Protein alignment showed that C. tropicalis Ron1 (CtRon1) shares 39.7% identity with C. albicans Ron1 (CaRon1). Compared to the wild-type strain, the C. tropicalis ron1Δ strains exhibited normal growth in different carbon sources and had similar expression levels of several GlcNAc catabolic genes during GlcNAc treatment. In contrast, C. tropicalis REP1 is responsible for GlcNAc catabolism and is involved in GlcNAc catabolic gene expressions, similar to C. albicans Rep1. However, REP1 deletion strains in C. tropicalis promote hyphal development in GlcNAc with low glucose content. Interestingly, CtRON1, but not CaRON1, deletion mutants exhibited significantly impaired hyphal growth and biofilm formation. As expected, CtRON1 was required for full virulence. Together, the results of this study showed divergent functions of CtRon1 compared to CaRon1; CtRon1 plays a key role in yeast-hyphal dimorphism, biofilm formation and virulence. LAY ABSTRACT: In this study, we identified the role of RON1, an NDT80-like gene, in Candida tropicalis. Unlike the gene in Candida albicans, our studies showed that RON1 is a key regulator of hyphal formation, biofilm development and virulence but is dispensable for N-acetylglucosamine catabolism in C. tropicalis.

Effect of tungsten doping on the variability of InZnO conductive-bridging random access memory.

The characteristics of conductive-bridging random access memory (CBRAM) with amorphous indium-tungsten-zinc-oxide (a-InWZnO) switching layer and copper (Cu) ion-supply layer were prepared by sputtering. It was found that the doping ratio of tungsten has a significant effect on the memory characteristics of the CBRAM, and the doping of tungsten acts as a suppressor of oxygen vacancies in the InWZnO film. The O 1s binding energy associated with the oxygen-deficient regions in the α-InWZnO thin film decreases with increasing tungsten doping ratio, which can be demonstrated by x-ray photoelectron spectroscopy. When the tungsten doping ratio is 15%, the a-InWZnO CBRAM can achieve the excellent memory characteristics, such as high switching endurance (up to 9.7 × 103 cycling endurance), low operating voltage, and good retention capability. Moreover, the electrical uniformity and switching behavior of InWZnO device are evidently improved as the doping ratio of tungsten in the switching layer increases. These results suggest that CBRAM based on novel material InWZnO have great potential to be used in high-performance memory devices.

Lactobacillus plantarum PS128 alleviates neurodegenerative progression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse models of Parkinson's disease.

Evidence suggests that the Parkinson's disease (PD) pathogenesis is strongly associated with bidirectional pathways in the microbiota-gut-brain axis (MGBA), and psychobiotics may inhibit PD progression. We previously reported that the novel psychobiotic strain, Lactobacillus plantarum PS128 (PS128), ameliorated abnormal behaviors and modulated neurotransmissions in dopaminergic pathways in rodent models. Here, we report that orally administering PS128 for 4 weeks significantly alleviated the motor deficits, elevation in corticosterone, nigrostriatal dopaminergic neuronal death, and striatal dopamine reduction in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mouse models. PS128 ingestion suppressed glial cell hyperactivation and increased norepinephrine and neurotrophic factors in the striatum of the PD-model mice. PS128 administration also attenuated MPTP-induced oxidative stress and neuroinflammation in the nigrostriatal pathway. Fecal analysis showed that PS128 modulated the gut microbiota. L. plantarum abundance was significantly increased along with methionine biosynthesis-related microbial modules. PS128 also suppressed the increased family Enterobacteriaceae and lipopolysaccharide and peptidoglycan biosynthesis-related microbial modules caused by MPTP. In conclude, PS128 ingestion alleviated MPTP-induced motor deficits and neurotoxicity.PS128 supplementation inhibited neurodegenerative processes in PD-model mice and may help prevent PD.