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Abstract Bacterial genotoxins damage host cells by targeting their chromosomal DNA. In the present study, we demonstrate that a genotoxin of Salmonella Typhi, typhoid toxin, triggers the senescence-associated secretory phenotype (SASP) by damaging mitochondrial DNA. The actions of typhoid toxin disrupt mitochondrial DNA integrity, leading to mitochondrial dysfunction and disturbance of redox homeostasis. Consequently, it facilitates the release of damaged mitochondrial DNA into the cytosol, activating type I interferon via the cGAS-STING pathway. We also reveal that the GCN2-mediated integrated stress response plays a role in the upregulation of inflammatory components depending on the STING signaling axis. These SASP factors can propagate the senescence effect on T cells, leading to senescence in these cells. These findings provide insights into how a bacterial genotoxin targets mitochondria to trigger a proinflammatory SASP, highlighting a potential therapeutic target for an anti-toxin intervention.

Abstract This study entailed a comprehensive GC‒MS analysis conducted on 121 patient samples to generate a clinical breathomics dataset. Breath molecules, indicative of diverse conditions such as psychological and pathological states and the microbiome, were of particular interest due to their non-invasive nature. The highlighted noninvasive approach for detecting these breath molecules significantly enhances diagnostic and monitoring capacities. This dataset cataloged volatile organic compounds (VOCs) from the breath of individuals with asthma, bronchiectasis, and chronic obstructive pulmonary disease. Uniform and consistent sample collection protocols were strictly adhered to during the accumulation of this extensive dataset, ensuring its reliability. It encapsulates extensive human clinical breath molecule data pertinent to three specific diseases. This consequential clinical breathomics dataset is a crucial resource for researchers and clinicians in identifying and exploring important compounds within the patient’s breath, thereby augmenting future diagnostic and therapeutic initiatives.

IntroductionThere are differences in the gut microbiome and metabolome when the host undergoes different physical or pathological conditions. However, the inter-relationship of microbiome and metabolome biomarkers to potentially promote the health of dairy cows needs to be studied. Further, the development of next-generation probiotics for dairy cattle health promotion has not been demonstrated.ObjectiveIn the present study, we identified the microbiome and metabolome biomarkers associated with healthy cows.MethodsWe analyzed the relationships of the ruminal microorganism profile and metabolites between healthy and mastitis lactating dairy cows. The roles of bacterial biomarker were further verified by in vitro fermentation and cow-to-mouse fecal microbiota transplantation (FMT).ResultsTwo species, Ruminococcus flavefaciens and Bifidobacterium longum subsp. longum, and six rumen metabolites were positively correlated with healthy cows by Spearman’s correlation analysis. Through in vitro ruminal fermentation, inoculating R. flavefaciens and B. longum subsp. longum showed the upregulation of the levels of putrescine, xanthurenic acid, and pyridoxal in the mastitis ruminal fluid, which confirmed the inter-relationships between these microbiota and metabolites associated with healthy cows. Further, we verified the role of R. flavefaciens and B. longum subsp. longum in promoting health by FMT. The administration of R. flavefaciens and B. longum subsp. longum reduced the death rate and recovered the bodyweight loss of germ-free mice caused by FMT mastitis feces.DiscussionWe provided evidence that the bacterial biomarkers alter downstream metabolites. This could indirectly indicate that the two bacterial biomarkers have the potential to be used as next-generation probiotics for dairy cattle, although it needs more evidence to support our hypothesis. Two species, R. flavefaciens and B. longum subsp. longum, with three metabolites, putrescine, xanthurenic acid, and pyridoxal, identified in the ruminal fluid, may point to a new health-promoting and disease-preventing approach for dairy cattle.

Environmental issues related to global warming and urbanization are becoming more serious. Many studies have shown that urban vertical planting can effectively reduce ambient temperature. However, the impact of different vertical planting combinations on urban microclimate has rarely been studied in Taiwan. Thus, in this study, the impact of different proportions of green walls and green roofs on the environment is explored. Referring to 6 times 6 high-rise buildings of 90 m in the ideal city. FLUENT was used to simulate the average climatic conditions of the Taipei Station in the past ten years’ summer. Since the actual building has openings that cannot reach 100% vertical plant coverage, the coverage is calculated based on the proportion of the green coverage area to the area of bare walls and roof decks. We had four options, including case 1 without greening, case 2 (green wall 25% + green roof 75%), case 3 (50% green wall + 50% green roof), and case 4 (75% green wall + 25% green roof). The research results show that at the height of the pedestrian layer (1.5 m), the wind speed of urban streets is reduced due to the obstruction of surrounding buildings. The installation of wall greening slows down the wind speed and reduces the ambient temperature, which is better than roof greening. In the urban canopy (90.5 m), as the Z-axis height increases, the higher the green roof ratio, the higher the wind speed. To improve the overall urban wind below 100% of the total greening balance of walls and roofs, it is recommended that wall greening be 50–75% and roof greening be 25–50%.

A 75-year-old previously healthy female became severely ill, functionally dependent, and required long-term home oxygen therapy, after recovery from coronavirus disease 2019 (COVID-19) with acute respiratory failure and extensive pulmonary fibrosis. After two months of respiratory muscle training and a comprehensive cardiopulmonary rehabilitation program, her dyspnea, physical performance, pulmonary function parameters, and activities of daily living rapidly improved. This Case highlights the importance of a timely active rehabilitation program for COVID-19 survivors experiencing the long-term effects of coronavirus (long COVID).

Abstract Background Pectus excavatum (PE) negatively impacts psychological function, but its effect on autonomic nervous system (ANS) function has not been investigated. We evaluated ANS function following postural changes in patients with PE. Methods The participants were 14 healthy men (control group) and 20 men with PE (study group). Psychological function was assessed using the visual analog scale for pain, Brief Symptom Rating Scale-5, and Beck Depression Inventory-II. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). ANS regulation in response to postural change was measured in the supine position and immediately after sitting. All measurements were compared between the control and study groups at baseline and between the study groups before and after Nuss surgery. Results At baseline, upon postural change, symptomatic activity increased in the control group (50.3–67.4%, p = 0.035) but not in the study group (55.0–54.9%, p = 0.654); parasympathetic activity decreased in the control group (49.7–32.6%, p = 0.035) but not in the study group (45.1–45.1%, p = 0.654); and overall ANS regulation increased in the control group (1.02–2.08, p = 0.030) but not in the study group (1.22–1.22, p = 0.322). In response to postural change after Nuss surgery in the study group, sympathetic activity increased (48.7–70.2%, p = 0.005), parasympathetic activity decreased (51.3–29.8%, p = 0.005), and overall ANS regulation increased (0.95–2.36, p = 0.012). Conclusion ANS function in response to postural change is dysregulated in patients with PE, which improved after Nuss surgery. Trial registration ClinicalTrials.gov, ID: NCT03346876, November 15, 2017, retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007KGI&selectaction=Edit&uid=U0003JZU&ts=2&cx=cstxeg

The chiral iridium rotors Ir(ppy)2(pyX)Cl (X = C≡C-SiR3, R = alkyl) remarkably contain two distinct rotational conformers in the ground (S0) and excited (T1) states that can be detected by NMR and emission measurements respectively at variable temperatures. The observed phosphorescent emissions, vibronic (involving L = ppy) and broad (L = pyX), arise from different triplet ligand to metal charge transfers from the two rotational conformers at distinct ³MLCT excited states. Both conformers exist in these Ir(ppy)2(pyX)Cl rotors due to the electron-withdrawing, conjugated substituent X. [ABSTRACT FROM AUTHOR]

This study estimates the association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with type 2 diabetes mellitus (T2DM). Participants were recruited from a primary care clinic in Kaohsiung City. According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged 50–80 years) were divided into three groups: non-sarcopenia (n = 38), possible sarcopenia (n = 31), and sarcopenia (n = 41). Blood samples were collected, and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and a Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, reduced serum 25-hydroxyvitamin D [25(OH)D] levels and daily energy intake were significantly associated with possible sarcopenia. Age, lower BMI, reduced serum 25(OH)D, and reduced dietary protein and vitamin D intake were significantly associated with sarcopenia. These findings may serve as the basis for intervention trials to reduce the prevalence of sarcopenia.

Severe acute respiratory syndrome-associated coronavirus 2 is a major global health issue and is driving the need for new therapeutics. The surface spike protein, which plays a central role in virus infection, is currently the target for vaccines and neutralizing treatments. The emergence of novel variants with multiple mutations in the spike protein may reduce the effectiveness of neutralizing antibodies by altering the binding activity of the protein with angiotensin-converting enzyme 2 (ACE2). To understand the impact of spike protein mutations on the binding interactions required for virus infection and the effectiveness of neutralizing monoclonal antibody (mAb) therapies, the binding activities of the original spike protein receptor binding domain (RBD) sequence and the reported spike protein variants were investigated using surface plasmon resonance. In addition, the interactions of the ACE2 receptor, an anti-spike mAb (mAb1), a neutralizing mAb (mAb2), the original spike RBD sequence, and mutants D614G, N501Y, N439K, Y453F, and E484K were assessed. Compared to the original RBD, the Y453F and N501Y mutants displayed a significant increase in ACE2 binding affinity, whereas D614G had a substantial reduction in binding affinity. All mAb-RBD mutant proteins displayed a reduction in binding affinities relative to the original RBD, except for the E484K-mAb1 interaction. The potential neutralizing capability of mAb1 and mAb2 was investigated. Accordingly, mAb1 failed to inhibit the ACE2-RBD interaction while mAb2 inhibited the ACE2-RBD interactions for all RBD mutants, except mutant E484K, which only displayed partial blocking.

Typhoid toxin is an essential virulence factor for Salmonella Typhi, the cause of typhoid fever in humans. This toxin has an unusual biology in that it is produced by Salmonella Typhi only when located within host cells. Once synthesized, the toxin is secreted to the lumen of the Salmonella-containing vacuole from where it is transported to the extracellular space by vesicle carrier intermediates. Here, we report the identification of the typhoid toxin sorting receptor and components of the cellular machinery that packages the toxin into vesicle carriers, and exports it to the extracellular space. We found that the cation-independent mannose-6-phosphate receptor serves as typhoid toxin sorting receptor and that the coat protein COPII and the GTPase Sar1 mediate its packaging into vesicle carriers. Formation of the typhoid toxin carriers requires the specific environment of the Salmonella Typhi-containing vacuole, which is determined by the activities of specific effectors of its type III protein secretion systems. We also found that Rab11B and its interacting protein Rip11 control the intracellular transport of the typhoid toxin carriers, and the SNARE proteins VAMP7, SNAP23, and Syntaxin 4 their fusion to the plasma membrane. Typhoid toxin’s cooption of specific cellular machinery for its transport to the extracellular space illustrates the remarkable adaptation of an exotoxin to exert its function in the context of an intracellular pathogen.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complicated inflammatory disease, and the underlying mechanism remains unclear. While some reactive oxygen/nitrogen species-related gene products are reported to participate in CRSwNP, a systemic and full analysis of oxidative-stress-associated genes in CRSwNP has not been extensively studied. Therefore, this study sought to catalog the gene-expression patterns related to oxidative stress and antioxidant defense in control and CRSwNP patients. In total, 25 control and 25 CRSwNP patients were recruited. The distribution and expression of 4-hydroxynonenal and 3-nitrotyrosine as markers of oxidative stress—which is represented by lipid peroxidation and the protein nitration of tyrosine residues in CRSwNP nasal polyps (NPs)—were more apparently increased than those found in the control nasal mucosae, as determined by immunohistochemistry (IHC). The expression of 84 oxidative-stress-related genes in nasal mucosae and NP tissues was analyzed via real-time PCR, which showed that 19 genes and 4 genes were significantly up- and downregulated, respectively; among them, inducible nitric oxide synthase (iNOS) and heme oxygenase 1 (HO-1) were notably upregulated, whereas lactoperoxidase (LPO), myeloperoxidase (MPO), and superoxide dismutase 3 (SOD3) were highly downregulated. Changes in the mRNA and protein levels of these redox proteins were confirmed with a customized, real-time PCR array and RT-PCR analysis, as well as Western blotting and IHC assays. A receiver operating characteristic curve analysis further suggested that LPO, MPO, SOD3, HO-1, and iNOS are possible endotype predictors of CRSwNP development. Collectively, we present an oxidative-stress-related gene profile of CRSwNP NP tissues, providing evidence that the systemic changes in oxidative stress and the antioxidative defense system, including novel iNOS, heme peroxidases, and other genes, are closely linked to CRSwNP pathology, development, and progression.

Facing the rapidly growing popularity of bike-sharing systems worldwide, this study explores the trip characteristics of using public bikes at the level of zonal Origin-Destination (O-D) pairs, particularly with respect to the effect of pricing scheme change. Based on the transaction records of Youbike, a bike-sharing system in Taipei, Taiwan, which contain data before and after an increase of the rental fee (as the cancellation of a free-usage period for the first 30-minute), the associated demand-side responses are studied in the context of multivariate analysis. Two regression models are developed thereupon to investigate the effect of the change on the O-D demand associated various land-use patterns. A multiple linear regression model is developed for direct before-after analysis on the variation of zonal O-D demand. A finite mixture model is further constructed, which identifies three usage groups with different levels of sensitivity toward the price change. Both models suggest that the pricing scheme change have greater impact on short-distance trips and O-D pairs where alternative transit services are provided; these affected trips can be generally related to frequent users. Such research findings enable better understanding of the usage pattern of bike-sharing systems, which can benefit the associated planning and operation. They also imply the trade-off between the perspective of encouraging greener mobility and other managerial principles regarding public transportation and government subsidy. Keywords: Bike sharing system, Pricing scheme, Land use pattern, User-pays principle, Before-after analysis

Abstract Background Enterobius vermicularis (pinworm) is one of the most common human parasitic helminths, and children are the most susceptible group. Some behavioral and environmental factors may facilitate pinworm infection. In the Republic of the Marshall Islands (RMI), the status of pinworm infections among children remains unknown. Methods In Majuro City, there are 14 kindergartens with a total of 635 preschool children (PSC) whose age range of 5~6 years. The present investigation attempted to determine the pinworm prevalence and associated risk factors as well as investigate whether eggs contaminated the clothes of PSC or the ground and tables in classrooms of 14 kindergartens. Informed consent form and a self-administered questionnaire were given to parents prior to pinworm screening. Perianal specimens were collected by an adhesive scotch tape method, and clothing of belly and hip sites and the ground and tables of the classrooms were inspected using a cellophane tape method to detect any eggs contamination. Results In total, 392 PSC (5.28 ± 0.56 yrs. old) participated in this project. The overall prevalence of pinworm infection was 22.4% (88/392). Boys (24.5%) had higher prevalence than girls (20.31%) (p = 0.32). PSC aged > 5 years (32.77%) showed a significantly higher prevalence than those aged ≤5 years (17.95%) (p = 0.01). A univariate analysis indicated that PSC who lived in urban areas (22.95%) had a higher prevalence than those who lived in rural areas (20.69%) (p = 0.69). The employment status of the parents showed no association with the pinworm infection rate (p > 0.05). A logistic regression analysis indicated that “having an older sister” produced a higher risk of acquiring pinworm infection for PSC compared to those who did not have an older sister (OR = 2.02; 95%CI = 1.05~3.88; p = 0.04). No significant association between various other risk factors and pinworm infection was found (p > 0.05). Also, no eggs contamination was found on the clothes of the belly and hip sites or on the ground and tables in the 14 kindergartens. Conclusions Mass screening and treatment of infected PSC are important measures in pinworm control in the RMI.

Being one of the renal replacement therapies, peritoneal dialysis (PD) maintains around 15% of end-stage kidney disease patients’ lives; however, complications such as peritoneal fibrosis and ultrafiltration failure during long-term PD compromise its application. Previously, we established a sodium hypochlorite (NaClO)-induced peritoneal fibrosis porcine model, which helped to bridge the rodent model toward pre-clinical human peritoneal fibrosis research. In this study, the peritoneal equilibration test (PET) was established to evaluate instant functional changes in the peritoneum in the pig model. Similar to observations from long-term PD patients, increasing small solutes transport and loss of sodium sieving were observed. Mechanistic investigation from both in vivo and in vitro data suggested that disruption of cytoskeleton induced by excessive reactive oxygen species defected intracellular transport of aquaporin 1, this likely resulted in the disappearance of sodium sieving upon PET. Functional interference of aquaporin 1 on free water transport would result in PD failure in patients.

Longans, which are produced in tropical countries, are rich in nutrients and high in commercial value. To extend their shelf life, fresh longans are roasted to dry them out. For the convenience of cooking applications, the dried longan pulp is peeled and seeded beforehand. Presently, this is done manually; thus, this research aims to automate this process. A cutting tool with a serrated bending angle is used to cut the dried longan pulp, and then the longan is fixed by a lifting mechanism. The pulp is breached with a cutting tool and this breach is pushed up against a 6 mm hole in the silicone soft plate of the lifting mechanism to separate out the seed by squeezing. Commercially available dried longans are used in this experiment. The cutting surface width of the cutter designed in this study is 20 mm, and the serration bending angle is 30°. This cutter operates at a speed of 29 cm/s on dried longan pulp, attaining a success rate of 85%. The lifting mechanism also presented in this study fixes the dried longan and uses a squeezing motion to separate the flesh from the seed with a silicone soft plate. Here, a lifting speed of 28 mm/s achieves the highest rate of success at peeling, and the success rate of pulp-and-seed separation can reach 86.7%.

本研究旨在觀察國小師資生修習「自然科教材教法、教育實習」課程，是否能獲得探究式教學法的專業成長，並探討其發展歷程。本研究利用詮釋性研究法以某國立教育大學自然科學教育學系的13 位師資生為研究對象，利用5Why 鷹架式提問教學和POE 教學等教學理論配合案例教學影片介紹，探討師資生在教案設計、實際教學活動與班級經營的改變歷程。師資生先學習理論課程，接著觀摩教學案例，然後設計教案、微型教學及到國小實地試教，研究者蒐集學習歷程檔案、教案、教學回饋單、上課錄影及晤談資料，進行分析形成主張。研究結果顯示：1. 師資生上完理論課程能初步了解5Why 鷹架式提問教學和POE 教學，而案例教學影片幫助師資 生更清楚的將這些教學法實施於教學活動中。2. 師資生所設計之教案，融入生活事件引起學習動機，以學童為中心，給予學童更多的參與，自行建構屬於自己的知識。3. 師資生在經過兩種探究式教學法的教學活動後，普遍認為自己的提問技巧有待加強，且能找出自己的缺失，尋求改進之道。4. 所有師資生都認為案例教學影片有助於他們在教案設計及實際教學活動的專業成長。根據研究結果建議：案例教學影片應該上網，讓師資生自由取用，師資生可多利用機會至國小現場見習國小教師教學，學習班級經營技巧。 The purpose of this study is to observe whether pre-service teachers can successfully develop inquiry-based teaching knowledge and skills through the “methods course and educational practicum for teaching natural science” curriculum. Based on the curriculum, to explore the processes of their professional development. The subjects of this study were thirteen pre-service teachers majoring in Nature Science Education in a University of Education. Based on instructional theories, and with the use of case teaching videos, the authors attempted to observe and understand pre-service teachers’ changes in their designs of teaching plans, classroom teaching activities, and classroom management. Throughout the course, the pre-service teachers studied at first theoretical foundations of inquiry-based teaching, followed by watching case teaching videos, designing lesson plans, micro-teaching, and finally practice teaching in elementary schools. Meanwhile, the researchers collected data from a range of sources, including pre-service teachers learning portfolios, lesson plans, feedback sheets, videos of their classroom teaching, and interviews. These data were then analyzed, leading to the following assertions. First, pre-service teachers gained basic understanding of 5Why scaffolding guided questioning teaching and POE teaching method after studying the theoretical part in this course. They understand more about teaching after watching videos of examples on how to use inquiry-based teaching method during class. Second, pre-service teachers were able to design lesson plans, which were student-centered and relevant to students’ real life. Such inquiry-based teaching invoked students’ motivation and participation, enabling them to construct knowledge by themselves. Third, most of pre-service teachers considered their skills in asking good questions still lacking, even after they went through the teaching activities on inquiry science teaching methods. However, they were able to identify their shortcomings and to explore ways for further improvement.Fourth, all of the participating pre-service teachers agreed that studying inquiry-based teaching through watching videos of teaching examples could help them on the design of lesson plans and on science teaching practice. According to the results obtained, it is suggested that the video clips of teaching examples should be uploaded on the internet, making them easily accessible for pre-service teachers to use. In addition, pre-service teachers are encouraged to visit elementary schools to observe classroom teachers’ teaching, in order to improve their own classroom management skills.

Diodes with an erbium and nitrogen codoped magnesium zinc oxide (MgZnO:Er,N) active layer were fabricated by spray pyrolysis on Si substrate with aqueous solutions including magnesium nitrate, zinc acetate, erbium acetate, ammonium acetate, and indium nitrate precursors. Diodes with different nitrogen content in their precursor were prepared and their properties were investigated. With scanning electron microscopy, film surface with mixed hexagonal flakes and tiny blocks was characterized for all samples. Certain morphologies varied for samples with different N contents. In the photoluminescence analyses, the intensity of the oxygen-related defects peak increased with the increasing of nitrogen content. The diodes were fabricated with an Au and In deposition on the top and backside. The diode current−voltage as well as capacitance−voltage characteristics were examined. An ununiformed n-type concentration distribution with high concentration near the interface in the MgZnO:Er,N layer was characterized for all samples. Diodes with high nitrogen content exhibit reduced breakdown voltage and higher interface concentration characteristics. Under reversed bias conditions with an injection current of 50 mA, a light spectrum with two distinct green emissions around wavelengths 532 and 553 nm was observed. A small spectrum variation was characterized for diodes prepared from different nitrogen content. The diode luminescence characteristics were examined and the diode prepared from N/Zn=1 in the precursor showed an optimal injection current-to-luminescence property. The current and luminescence properties of the diode were characterized and discussed.

We detected a significant elevation of serum HSP90α levels in pancreatitis patients and even more in pancreatic ductal adenocarcinoma (PDAC) patients. However, there was no significant difference in the serum HSP90α levels between patients with early-stage and late-stage PDAC. To study whether elevation of serum HSP90α levels occurred early during PDAC development, we used LSL-KrasG12D/Pdx1-Cre transgenic mice as a studying model. Elevated serum HSP90α levels were detected before PDAC formation and an extracellular HSP90α (eHSP90α) inhibitor effectively prevented PDAC development. Both serum HSP90α level and pancreatic lesion were suppressed when the mice were administered a CD11b-antagonizing antibody, suggesting that CD11b+-myeloid cells were associated with eHSP90α levels and pancreatic carcinogenesis. Consistently, in CD11b-DTR-EGFP transgenic mouse model with CD11b+-myeloid cells depletion, serum HSP90α levels were suppressed and Panc-02 cell grafts failed to develop tumors. Macrophages and granulocytes are two common tissue-infiltrating CD11b+-myeloid cells. Duplex in situ hybridization assays suggested that macrophages were predominant HSP90α-expressing CD11b+-myeloid cells during PDAC development. Immunohistochemical and immunohistofluorescent staining results revealed that HSP90α-expressing cells included not only macrophages but also pancreatic ductal epithelial (PDE) cells. Cell culture studies also indicated that eHSP90α could be produced by macrophages and macrophage-stimulated PDE cells. Macrophages not only secreted significant amount of HSP90α, but also secreted interleukin-6 and interleukin-8 to induce a JAK2−STAT3 signaling axis in PDE cells, stimulating them to express and secrete HSP90α. eHSP90α further promoted cellular epithelial-mesenchymal transition, migration, and invasion in PDE cells. Besides myeloid cells, eHSP90α can be potentially taken as a target to suppress PDAC pathogenesis.

Aminopeptidase P, a metalloprotease, targets Xaa-Proline peptides for cleavage [1-4]. There are two forms of human AMPP, a membrane-bound form (hmAMPP) and a soluble cytosolic form (hcAMPP)[5]. Similar to the angiotensin-I-converting enzyme, AMPP plays an important role in the catabolism of inflammatory and vasoactive peptides, known as kinins. The plasma kinin, bradykinin, was used as the substrate to conduct enzymatic activity analyses and to determine the Michaelis constant (Km) of 174 μM and the catalytic rate constant (kcat) of 10.8 s-1 for hcAMPP. Significant differences were observed in the activities of Y527F and R535A hcAMPP mutants, which displayed a 6-fold and 13.5-fold for decrease in turnover rate, respectively. Guanidine hydrochloride restored the activity of R535A hcAMPP, increasing the kcat/Km 20-fold, yet it had no impact on the activities of the wild-type or Y527F mutant hcAMPPs. Activity restoration by guanidine derivatives followed the order guanidine hydrochloride >> methyl-guanidine > amino-guanidine > N-ethyl-guanidine. Overall, the results indicate the participation of R535 in the hydrogen bond network that forms a proton relay system. The quaternary structure of hcAMPP was determined by using analytical ultracentrifugation (AUC). The results show that alanine replacement of Arg535 destabilizes the hcAMPP dimer and that guanidine hydrochloride restores the native monomer-dimer equilibrium. It is proposed that Arg535 plays an important role in hcAMMP catalysis and in stabilization of the catalytically active dimeric state.

Cisplatin is a potent anti-cancer drug, however, its accompanied organ-toxicity hampers its clinical applications. Cisplatin-associated kidney injury is known to result from its accumulation in the renal tubule with excessive generation of reactive oxygen species. In this study, we encapsulated honokiol, a natural lipophilic polyphenol constituent extracted from Magnolia officinalis into nano-sized liposomes (nanosome honokiol) and examined the in vivo countering effects on cisplatin-induced renal injury. We observed that 5 mg/kg body weight. nanosome honokiol was the lowest effective dosage to efficiently restore renal functions of cisplatin-treated animals. The improvement is likely due the maintenance of cellular localization of cytochrome c and thus preserves mitochondria integrity and their redox activity, which as a consequence, reduced cellular oxidative stress and caspase 3-associated apoptosis. These improvements at the cellular level are later reflected on the observed reduction of kidney inflammation and fibrosis. In agreement with our earlier in vitro study showing protective effects of honokiol on kidney cell lines, we demonstrated further in the current study, that nanosuspension-formulated honokiol provides protective effects against cisplatin-induced chronic kidney damages in vivo. Our findings not only benefit cisplatin-receiving patients with reduced renal side effects, but also provide potential alternative and synergic solutions to improve clinical safety and efficacy of cisplatin treatment on cancer patients.

Erbium-doped magnesium zinc oxides were prepared through spray pyrolysis deposition at 450 °C with an aqueous solution containing magnesium nitrate, zinc acetate, erbium acetate, and indium nitrate precursors. Diodes with different erbium-doped magnesium zinc oxide thicknesses were fabricated. The effect of erbium-doped magnesium zinc oxide was investigated. The crystalline structure and surface morphology were analyzed using X-ray diffraction and scanning electron microscopy. The films exhibited a zinc oxide structure, with (002), (101), and (102) planes and tiny rods in a mixed hexagonal flakes surface morphology. With the photoluminescence analyses, defect states were identified. The diodes were fabricated via a metallization process in which the top contact was Au and the bottom contact was In. The current⁻voltage characteristics of these diodes were characterized. The structure resistance increased with the increase in erbium-doped magnesium zinc oxide thickness. With a reverse bias in excess of 8 V, the light spectrum, with two distinct green light emissions at wavelengths of 532 nm and 553 nm, was observed. The light intensity that resulted when using a different operation current of the diodes was investigated. The diode with an erbium-doped magnesium zinc oxide thickness of 230 nm shows high light intensity with an operational current of 80 mA. The emission spectrum with different injection currents for the diodes was characterized and the mechanism is discussed.