Mutagenesis enhances gellan gum production by a novel Sphingomonas spp: upstream optimization, kinetic modeling, and structural and physico-functional evaluation / La mutagénesis mejora la producción de goma gellan mediante una nueva especie de Sphingomonas: optimización ascendente, modelado cinético y evaluación estructural y físico-funcional

Gellan gum (GG) has gained tremendous attention owing to its diversified applications. However, its high production and hence market cost are still a bottleneck in its widespread utilization. In the present study, high GG producing mutant of Sphingomonas spp. was developed by random mutagenesis using ethyl methylsulphonate (EMS) for industrial fermentation and identified as Sphingomonas trueperi after 16S rRNA and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF–MS) analysis. The fermentation conditions such as pH, temperature, and inoculum ratio were optimized by one factor at a time (OFAT) followed by screening of medium components by the Plackett–Burman statistical design. The most critical nutrients were further optimized by response surface methodology for maximizing GG production. The effect of dissolved oxygen tension in bioreactor on cell growth, substrate consumption, GG production, and batch productivity was elucidated. The highest GG titer (23 ± 2.4 g/L) was attained in optimized medium at 10% inoculum (6.45 ± 0.5 log cfu/mL) under controlled fermentation conditions of pH (7), temperature (30 °C), agitation (300–600 rpm), and aeration (0.5–2.0 SLPM) at 22 ± 2% dissolved oxygen tension in a 10-L bioreactor. Kinetic modeling of optimized batch process revealed that logistic growth model could best explain biomass accumulation, while GG formation and substrate consumption were best explained by Luedeking-Piret and exponential decay model, respectively. Structural and physico-functional features of GG produced by mutant Sphingomonas spp. were characterized by HPLC, FTIR, NMR, DSC, TGA, GPC, SEM, and rheological analysis. The higher productivity (0.51 g/L/h) under optimized fermentation conditions suggests potential consideration of mutant and process for commercial utilization.(AU)

ALDH2 activation attenuates oxygen–glucose deprivation/reoxygenation-induced cell apoptosis, pyroptosis, ferroptosis and autophagy

Purpose It is previously reported that aldehyde dehydrogenase 2 family member (ALDH2) shows neuroprotective effects in cerebral ischemia/reperfusion injury. However, whether the protective effects are through mediating the programmed cell death is yet to be fully elucidated. Methods In vitro oxygen–glucose deprivation/reoxygenation (OGD/R) model was established in HT22 cells and mouse cortical neurons. Subsequently, ALDH2 expression were assessed by qRT-PCR and western blot. The methylation status was examined by methylation-specific PCR (MS-PCR). Then, ALDH2 expression was promoted and suppressed to explore the role of ALDH2 in OGD/R-treated cells. CCK-8 assay was applied to detect cell viability, and flow cytometry was applied to evaluate cell apoptosis. Western blot was applied to detect the apoptosis-related proteins (Caspase 3, Bcl-2 and Bax), necroptosis-related proteins (RIP3 and MLKL), pyroptosis-related proteins (NLRP3 and GSDMD), ferroptosis-related protein (ACSL4 and GPX4), and autophagy-related proteins (LC3B, and p62). IL-1β and IL-18 production was evaluated by ELISA assay. Reactive oxygen species production and Fe2+ content were evaluated by the corresponding detection kit. Results In OGD/R-treated cells, ALDH2 expression was decreased, which was due to the hypermethylation of ALDH2 in the promoter region. ALDH2 overexpression improved cell viability and ALDH2 knockdown suppressed cell viability in OGD/R-treated cells. We also found that ALDH2 overexpression attenuated OGD/R-induced cell apoptosis, pyroptosis, ferroptosis and autophagy, while ALDH2 knockdown facilitated the OGD/R-induced cell apoptosis, pyroptosis, ferroptosis and autophagy. Conclusions Collectively, our results implied that ALDH2 attenuated OGD/R-induced cell apoptosis, pyroptosis, ferroptosis and autophagy to promote cell viability in HT22 cells and mouse cortical neurons (AU)

HIF-1 signaling: an emerging mechanism for mitochondrial dynamics

A growing emphasis has been paid to the function of mitochondria in tumors, neurodegenerative disorders (NDs), and cardiovascular diseases. Mitochondria are oxygen-sensitive organelles whose function depends on their structural basis. Mitochondrial dynamics are critical in regulating the structure. Mitochondrial dynamics include fission, fusion, motility, cristae remodeling, and mitophagy. These processes could alter mitochondrial morphology, number, as well as distribution, to regulate complicated cellular signaling processes like metabolism. Meanwhile, they also could modulate cell proliferation and apoptosis. The initiation and progression of several diseases, such as tumors, NDs, cardiovascular disease, were all interrelated with mitochondrial dynamics. HIF-1 is a nuclear protein presented as heterodimers, and its transcriptional activity is triggered by hypoxia. It plays an important role in numerous physiological processes including the development of cardiovascular system, immune system, and cartilage. Additionally, it could evoke compensatory responses in cells during hypoxia through upstream and downstream signaling networks. Moreover, the alteration of oxygen level is a pivotal factor to promote mitochondrial dynamics and HIF-1 activation. HIF-1α might be a promising target for modulating mitochondrial dynamics to develop therapeutic approaches for NDs, immunological diseases, and other related diseases. Here, we reviewed the research progress of mitochondrial dynamics and the potential regulatory mechanism of HIF-1 in mitochondrial dynamics. (AU)

Hypoxic Burden in Obstructive Sleep Apnea: Present and Future

Conventional measures of obstructive sleep apnea (OSA) severity, such as the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) are commonly used to quantify OSA severity and guide therapeutical decision-making processes. However, it is widely recognized that both AHI and ODI have important limitations and novel physiologically-informed metrics are needed to better capture the severity of OSA and characterize its physiological consequences, particularly the severity of recurrent nocturnal hypoxemia, ensuing the respiratory events. According to recent studies, the sleep apnea-specific “hypoxic burden (HB)”, defined as the sum of individual areas under the oxygen desaturation curve, has shown some promise in identifying high risk individuals with OSA. In addition to the frequency of respiratory events, HB capture the depth and duration of OSA-related hypoxemia that may prove to be important disease characterizing features, not captured by the conventional “frequency-based” metrics, such as AHI and ODI. In this “perspective” paper the methods to quantify the HB, its characteristics, associations with health outcomes, and its limitations will be discussed. (AU)

Antiviral drugs against SARS-CoV-2

The use of antiviral drugs represents an important progress in the therapeutic management of COVID-19, leading to a substantial reduction of SARS-CoV-2-related complications and mortality. In immunocompetent host, peak viral replication occurs around the symptom’s onset, and it prolongs for 5 to 7 days that is the window of opportunity for giving an antiviral. Accordingly, early and rapid diagnostic of the infection in the outpatient clinic is essential as well as the availability of oral agents that can be easily prescribe. Remdesivir has demonstrated its efficacy in hospitalized patients requiring oxygen support and in mild/moderate cases to avoid the hospitalization, however, the intravenous administration limits its use among outpatients. Molnupiravir and nirmatrelvir/ritonavir are potent oral antiviral agents. In the present review we discuss the potential targets against SARS-CoV-2, and an overview of the main characteristics and clinical results with the available antiviral agents for the treatment of SARS-CoV-2. (AU)

Análisis descriptivo de las causas, consecuencias y respuesta de los sistemas de Salud Pública en los ahogamientos pediátricos en Galicia. Un estudio retrospectivo de 17 años / Descriptive analysis of triggers, outcomes and the response of the health systems of child drowning in Galicia (Spain). A 17-year retrospective study

FUNDAMENTOS: El ahogamiento es un importante problema de Salud Pública en la etapa infantil. El objetivo de este trabajofue describir las características, localizaciones, intervenciones y resultados del ahogamiento pediátrico en Galicia durante 17 años.MÉTODOS: Se realizó un estudio retrospectivo del 100% de los datos de ahogamiento de personas entre 0 y 14 años de edad delaño 2004 a 2020, que fueran atendidos por los servicios de emergencias de Galicia 061. Se analizaron las características del incidente,perfil de la víctima, localización, tipo de asistencia sanitaria recibida y supervivencia respecto a muerte mediante el test Chi Cuadradopara comparar frecuencias relativas, yOdds Ratio para estimar el riesgo.RESULTADOS: Se registraron 100 ahogamientos pediátricos. En el 55% la principal causa fue la falta de supervisión. Los niños yniñas de 0-4 años se ahogaban mayoritariamente en piscinas, mientras que los/las adolescentes (10-14 años) en playas. En el 42% delos incidentes el testigo hizo reanimación cardiopulmonar (un 37% incluyó ventilaciones). Los servicios de emergencia tardaron 12minutos de media en llegar. Un 6% fallecióin situ y el resto fueron trasladados al hospital e ingresaron el 47% en UCI, 26% en planta, y 8% cursaron alta en Urgencias (43% con edema pulmonar, 41% con oxígeno suplementario, 13% con VMI/VMNI [ventilación mecánicainvasiva/no invasiva]). La neumonía fue una complicación habitual y la supervivencia al alta fue del 77%.CONCLUSIONES: Los niños/as más pequeños se ahogan habitualmente en instalaciones acuáticas por falta de supervisión mien-tras que los/las adolescentes se suelen ahogar en playas marítimas. El inicio de la reanimación por parte de testigos y la rápidarespuesta de los servicios de emergencias se asocia a una alta tasa de supervivencia. Numerosos datos fueron perdidos durante elproceso por lo que es necesaria una correcta y unificada codificación del ahogamiento.(AU)

BACKGROUND: Drowning is one of major public health problem in childhood. The aim of this paper was to describe the characte-ristics, locations, interventions and outcomes of child drowning in Galicia over 17 years. METHODS: Retrospective study of 100% of data of drowning amongst children aged 0-14 in the 2004–2020 period who were attended by the 061 emergency services in Galicia (Spain) was made. The characteristics of the incident, the victim’s profile, location, type ofmedical care given and whether the victim survived or died were analysed using the Chi Square test to compare relative frequencies,and Odds Ratio to estimate the risk.RESULTS: During the period under study, 100 child drownings were recorded. In 55%, the main cause was lack of supervision.Young children (aged 0-4) primarily drowned in pools, and pre-teens and teenagers (aged 10-14) in the sea. In 42% of the incidents, bystanders performed CPR (37% included ventilation). Emergency services took 12 minutes on average to arrive at the scene. 6% diedin situ and of the rest, were taken to hospital and admitted in 47% PICU, 26% ward, 8% discharged from A&E (43% with pulmonaryoedema, 41% with supplemental oxygen, 13% with IMV/NIMV [invasive mechanical ventilation/non-invasive]). Pneumonia was the most common complication and survival to discharge was 77%.CONCLUSIONS: Small children usually drown in pools and water facilities because of lack of supervision, whereas adolescentsusually drown in the sea. CPR started by bystanders and the fast response of emergency services contributed to a high rate of survi-val. A large amount of data was lost during the process: accurate, standardized coding of drowning is necessary.(AU)

About “Absence of Relevant Clinical Effects of SARS-CoV-2 on the Affinity of Hemoglobin for O2 in Patients with COVID-19”

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Effect of oxygen on the germination and culturability of Bacillus atrophaeus spores / Efecto del oxígeno sobre la germinación y cultivabilidad de las esporas de Bacillus atrophaeus

The effect of oxygen on the germination and culturability of aerobic Bacillus atrophaeus spores was investigated in this study. Under oxic or anoxic conditions, various nutritional and non-nutritional germinants were utilized to induce germination. Tb3+-dipicolinic acid fluorescence assay and phase-contrast microscopy were used to track the germination process. The final germination level, germination half time, and germination speed were used to define germination kinetics. Colony-forming unit enumeration was used to assess the culturability of germinated spores germinated with or without oxygen. The results show that in the absence of oxygen, the final germination level was unaffected, germination half time decreased by up to 35.0%, germination speed increased by up to 27.4%, and culturability decreased by up to 95.1%. It is suggested that oxygen affects some germinant receptor-dependent germination pathways, implying that biomolecules engaged in these pathways may be oxygen-sensitive. Furthermore, spores that have completed the germination process in either anoxic or oxic conditions may have different culturability. This research contributed to a better understanding of the fundamental mechanism of germination.(AU)

Respuesta a «Ausencia de efectos clínicos destacables del SARS-CoV-2 sobre la afinidad de la hemoglobina por el O2 en pacientes con COVID-19» / Reply to «Absence of Relevant Clinical Effects of SARS-CoV-2 on the Affinity of Hemoglobin for O2 in Patients with COVID-19»

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[Translated article] Reply to “Absence of Relevant Clinical Effects of SARS-CoV-2 on the Affinity of Hemoglobin for O2 in Patients With COVID-19” / Respuesta a «Ausencia de efectos clínicos destacables del SARS-CoV-2 sobre la afinidad de la hemoglobina por el O2 en pacientes con COVID-19»

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