Cortical parenchyma wall width regulates root metabolic cost and maize performance under suboptimal water availability.

We describe how increased root cortical parenchyma wall width (CPW) can improve tolerance to drought stress in maize by reducing the metabolic costs of soil exploration. Significant variation (1.0 to 5.0 µm) for CPW was observed in maize germplasm. The functional-structural model RootSlice predicts that increasing CPW from 2 to 4 µm is associated with ca. 15% reduction in root cortical cytoplasmic volume, respiration rate, and nitrogen content. Analysis of genotypes with contrasting CPW grown with and without water stress in the field confirms that increased CPW is correlated with ca. 32 to 42% decrease in root respiration. Under water stress in the field, increased CPW is correlated with 125% increased stomatal conductance, 325% increased leaf CO2 assimilation rate, 73 to 78% increased shoot biomass, and 92 to 108% increased yield. CPW was correlated with leaf mesophyll midrib parenchyma wall width, indicating pleiotropy. GWAS analysis identified candidate genes underlying CPW. OpenSimRoot modeling predicts that a reduction in root respiration due to increased CPW would also benefit maize growth under suboptimal nitrogen, which requires empirical testing. We propose CPW as a new phene that has utility under edaphic stress meriting further investigation.

THAP3 recruits SMYD3 to OXPHOS genes and epigenetically promotes mitochondrial respiration in hepatocellular carcinoma.

Mitochondria harbor the oxidative phosphorylation (OXPHOS) system to sustain cellular respiration. However, the transcriptional regulation of OXPHOS remains largely unexplored. Through the cancer genome atlas (TCGA) transcriptome analysis, transcription factor THAP domain-containing 3 (THAP3) was found to be strongly associated with OXPHOS gene expression. Mechanistically, THAP3 recruited the histone methyltransferase SET and MYND domain-containing protein 3 (SMYD3) to upregulate H3K4me3 and promote OXPHOS gene expression. The levels of THAP3 and SMYD3 were altered by metabolic cues. They collaboratively supported liver cancer cell proliferation and colony formation. In clinical human liver cancer, both of them were overexpressed. THAP3 positively correlated with OXPHOS gene expression. Together, THAP3 cooperates with SMYD3 to epigenetically upregulate cellular respiration and liver cancer cell proliferation.

PYCR3 modulates mtDNA copy number to drive proliferation and doxorubicin resistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) poses significant challenges in treatment due to its aggressive nature and limited therapeutic targets. Understanding the underlying molecular mechanisms driving TNBC progression and chemotherapy resistance is imperative for developing effective therapeutic strategies. Thus, in this study, we aimed to elucidate the role of pyrroline-5-carboxylate reductase 3 (PYCR3) in TNBC pathogenesis and therapeutic response. We observed that PYCR3 is significantly upregulated in TNBC specimens compared to normal breast tissues, correlating with a poorer prognosis in TNBC patients. Knockdown of PYCR3 not only suppresses TNBC cell proliferation but also reverses acquired resistance of TNBC cells to doxorubicin, a commonly used chemotherapeutic agent. Mechanistically, we identified the mitochondrial localization of PYCR3 in TNBC cells and demonstrated its impact on TNBC cell proliferation and sensitivity to doxorubicin through the regulation of mtDNA copy number and mitochondrial respiration. Importantly, Selective reduction of mtDNA copy number using the mtDNA replication inhibitor 2', 3'-dideoxycytidine effectively recapitulates the phenotypic effects observed in PYCR3 knockout, resulting in decreased TNBC cell proliferation and the reversal of doxorubicin resistance through apoptosis induction. Thus, our study underscores the clinical relevance of PYCR3 and highlight its potential as a therapeutic target in TNBC management. By elucidating the functional significance of PYCR3 in TNBC, our findings contribute to a deeper understanding of TNBC biology and provide a foundation for developing novel therapeutic strategies aimed at improving patient outcomes.

Dimorphic effect of TFE3 in determining mitochondrial and lysosomal content in muscle following denervation.

BACKGROUND: Muscle atrophy is a common consequence of the loss of innervation and is accompanied by mitochondrial dysfunction. Mitophagy is the adaptive process through which damaged mitochondria are removed via the lysosomes, which are regulated in part by the transcription factor TFE3. The role of lysosomes and TFE3 are poorly understood in muscle atrophy, and the effect of biological sex is widely underreported. METHODS: Wild-type (WT) mice, along with mice lacking TFE3 (KO), a transcriptional regulator of lysosomal and autophagy-related genes, were subjected to unilateral sciatic nerve denervation for up to 7 days, while the contralateral limb was sham-operated and served as an internal control. A subset of animals was treated with colchicine to capture mitophagy flux. RESULTS: WT females exhibited elevated oxygen consumption rates during active respiratory states compared to males, however this was blunted in the absence of TFE3. Females exhibited higher mitophagy flux rates and greater lysosomal content basally compared to males that was independent of TFE3 expression. Following denervation, female mice exhibited less muscle atrophy compared to male counterparts. Intriguingly, this sex-dependent muscle sparing was lost in the absence of TFE3. Denervation resulted in 45% and 27% losses of mitochondrial content in WT and KO males respectively, however females were completely protected against this decline. Decreases in mitochondrial function were more severe in WT females compared to males following denervation, as ROS emission was 2.4-fold higher. In response to denervation, LC3-II mitophagy flux was reduced by 44% in females, likely contributing to the maintenance of mitochondrial content and elevated ROS emission, however this response was dysregulated in the absence of TFE3. While both males and females exhibited increased lysosomal content following denervation, this response was augmented in females in a TFE3-dependent manner. CONCLUSIONS: Females have higher lysosomal content and mitophagy flux basally compared to males, likely contributing to the improved mitochondrial phenotype. Denervation-induced mitochondrial adaptations were sexually dimorphic, as females preferentially preserve content at the expense of function, while males display a tendency to maintain mitochondrial function. Our data illustrate that TFE3 is vital for the sex-dependent differences in mitochondrial function, and in determining the denervation-induced atrophy phenotype.

Modulation of mitochondrial function by extracellular acidosis in tumor cells and normal fibroblasts: Role of signaling pathways.

In many tumors pronounced extracellular acidosis resulting from glycolytic metabolism is found. Since several environmental stress factors affect the mitochondrial activity the aim of the study was to analyze the impact of acidosis on cellular oxygen consumption and which signaling pathways may be involved in the regulation. In two tumor cell lines and normal fibroblasts cellular oxygen consumption rate (OCR) and mitochondrial function were measured after 3 h at pH 6.6. Besides the activation of ERK1/2, p38 and PI3K signaling in the cytosolic and mitochondrial compartment, the mitochondrial structure and proteins related to mitochondria fission were analyzed. The acidic extracellular environment increased OCR in tumor cells but not in fibroblasts. In parallel, the mitochondrial membrane potential increased at low pH. In both tumor lines (but not in fibroblasts), the phosphorylation of ERK1/2 and PI3K/Akt was significantly increased, and both cascades were involved in OCR modulation. The activation of signaling pathways was located predominantly in the mitochondrial compartment of the cells. At low pH, the mitochondrial structure in tumor cells showed structural changes related to elongation whereas mitochondria fragmentation was reduced indicating mitochondria fusion. However, these morphological changes were not related to ERK1/2 or PI3K signaling. Acidic stress seems to induce an increased oxygen consumption, which might further aggravate tumor hypoxia. Low pH also induces mitochondria fusion that is not mediated by ERK1/2 or PI3K signaling. The mechanism by which these signaling cascades modulate the respiratory activity of tumor cells needs further investigation.

Cardiorespiratory DB: Collection of cardiorespiratory data acquired during normal breathing, deep breathing and breath holding.

The database is constituted by 50 datasets containing cardiorespiratory signals acquired from 50 healthy volunteer subjects (one dataset for each subject; 23 males and 27 females; age: 23±5 years) while performing normal breathing, deep breathing, and breath holding, and two spreadsheet files, namely the "SubjectsInfo.xlsx" and "DBInfo.xlsx" containing the metadata of subjects (including demographic data) and of acquired signals, respectively. Cardiorespiratory signals consisted in simultaneously recorded 12-lead electrocardiograms acquired by the clinical M12 Global InstrumentationⓇ digital Holter ECG recorder, and single-lead electrocardiograms and respiration signals acquired by the wearable chest strap BioHarness 3.0 by Zephyr. The database may be useful to: (1) validate the use of wearable sensors in the acquisition of cardiorespiratory data during different respiration kinds, including apnea; (2) investigate the physiological association between cardiovascular and respiratory systems; (3) validate algorithms able to indirectly extract the respiration signal from the electrocardiogram; (4) study the fatigue level induced by a series of controlled respiration patterns; and (5) investigate the effect of COVID-19 infection on the cardiorespiratory system.

Diagnostic utility of capnography in emergency department triage for screening acidemia: a pilot study.

BACKGROUND: Capnography is a quantitative and reliable method of determining the ventilatory status of patients. We describe the test characteristics of capnography obtained during Emergency Department triage for screening acidemia. RESULTS: We performed an observational, pilot study of adult patients presenting to Emergency Department (ED) triage. The primary outcome was acidemia, as determined by the basic metabolic panel and/or blood gas during the ED visit. Secondary outcomes include comparison of estimated and measured respiratory rates (RR), relationships between end-tidal CO2 (EtCO2) and venous partial pressure of CO2, admission disposition, in-hospital mortality during admission, and capnogram waveform analysis. A total of 100 adult ED encounters were included in the study and acidemia ([Formula: see text] or [Formula: see text]) was identified in 28 patients. The measured respiratory rate (20.3 ± 6.4 breaths/min) was significantly different from the estimated rate (18.4 ± 1.6 breaths/min), and its area under the receiver operating curve (c-statistic) to predict acidemia was only 0.60 (95% CI 0.51-0.75, p = 0.03). A low end-tidal CO2 (EtCO2 < 32 mmHg) had positive (LR+) and negative (LR-) likelihood ratios of 4.68 (95% CI 2.59-8.45) and 0.34 (95% CI 0.19-0.61) for acidemia, respectively-corresponding to sensitivity 71.4% (95% CI 51.3-86.8) and specificity 84.7% (95% CI 74.3-92.1). The c-statistic for EtCO2 was 0.849 (95% CI 0.76-0.94, p = 0.00). Waveform analysis further revealed characteristically abnormal capnograms that were associated with underlying pathophysiology. CONCLUSIONS: Capnography is a quantitative method of screening acidemia in patients and can be implemented feasibly in Emergency Department triage as an adjunct to vital signs. While it was shown to have only modest ability to predict acidemia, triage capnography has wide generalizability to screen other life-threatening disease processes such as sepsis or can serve as an early indicator of clinical deterioration.

Feasibility and Acceptability of Pediatric Smartphone Lung Auscultation by Parents: Cross-Sectional Study.

Background: The use of a smartphone built-in microphone for auscultation is a feasible alternative to the use of a stethoscope, when applied by physicians. Objective: This cross-sectional study aims to assess the feasibility of this technology when used by parents-the real intended end users. Methods: Physicians recruited 46 children (male: n=33, 72%; age: mean 11.3, SD 3.1 y; children with asthma: n=24, 52%) during medical visits in a pediatric department of a tertiary hospital. Smartphone auscultation using an app was performed at 4 locations (trachea, right anterior chest, and right and left lung bases), first by a physician (recordings: n=297) and later by a parent (recordings: n=344). All recordings (N=641) were classified by 3 annotators for quality and the presence of adventitious sounds. Parents completed a questionnaire to provide feedback on the app, using a Likert scale ranging from 1 ("totally disagree") to 5 ("totally agree"). Results: Most recordings had quality (physicians' recordings: 253/297, 85.2%; parents' recordings: 266/346, 76.9%). The proportions of physicians' recordings (34/253, 13.4%) and parents' recordings (31/266, 11.7%) with adventitious sounds were similar. Parents found the app easy to use (questionnaire: median 5, IQR 5-5) and were willing to use it (questionnaire: median 5, IQR 5-5). Conclusions: Our results show that smartphone auscultation is feasible when performed by parents in the clinical context, but further investigation is needed to test its feasibility in real life.

Scan-associated anxiety (scanxiety): the enigma of emotional breathing oscillations at 0.32 Hz (19 bpm).

MRI-related anxiety in healthy participants is often characterized by a dominant breathing frequency at around 0.32 Hz (19 breaths per minute, bpm) at the beginning but in a few cases also at the end of scanning. Breathing waves at 19 bpm are also observed in patients with anxiety independently of the scanned body part. In patients with medically intractable epilepsy and intracranial electroencephalography (iEEG), spontaneous breathing through the nose varied between 0.24 and 0.37 Hz (~19 bpm). Remarkable is the similarity of the observed breathing rates at around 0.32 Hz during different types of anxiety states (e.g., epilepsy, cancer, claustrophobia) with the preferred breathing frequency of 0.32 Hz (19 bpm), which is predicted by the binary hierarchy model of Klimesch. This elevated breathing frequency most likely reflects an emotional processing state, in which energy demands are minimized due to a harmonic coupling ratio with other brain-body oscillations.

Bioenergetics of iron snow fueling life on Europa.

The main sources of redox gradients supporting high-productivity life in the Europan and other icy ocean world oceans were proposed to be photolytically derived oxidants, such as reactive oxygen species (ROS) from the icy shell, and reductants (Fe(II), S(-II), CH4, H2) from bottom waters reacting with a (ultra)mafic seafloor. Important roadblocks to maintaining life, however, are that the degree of ocean mixing to combine redox species is unknown, and ROS damage biomolecules. Here, we envisage a unique solution using an acid mine drainage (AMD)-filled pit lakes analog system for the Europan ocean, which previous models predicted to be acidic. We hypothesize that surface-generated ROS oxidize dissolved Fe(II) resulting in Fe(III) (hydr)oxide precipitates, that settle to the seafloor as "iron snow." The iron snow provides a respiratory substrate for anaerobic microorganisms ("breathing iron"), and limits harmful ROS exposure since they are now neutralized at the ice-water interface. Based on this scenario, we calculated Gibbs energies and maximal biomass productivities of various anaerobic metabolisms for a range of pH, temperatures, and H2 fluxes. Productivity by iron reducers was greater for most environmental conditions considered, whereas sulfate reducers and methanogens were more favored at high pH. Participation of Fe in the metabolic redox processes is largely neglected in most models of Europan biogeochemistry. Our model overcomes important conceptual roadblocks to life in icy ocean worlds and broadens the potential metabolic diversity, thus increasing total primary productivity, the diversity and volume of habitable environmental niches and, ultimately, the probability of biosignature detection.

A Redox-Regulated, Heterodimeric NADH:cinnamate Reductase in Vibrio ruber.

Genes of putative reductases of α,ß-unsaturated carboxylic acids are abundant among anaerobic and facultatively anaerobic microorganisms, yet substrate specificity has been experimentally verified for few encoded proteins. Here, we co-produced in Escherichia coli a heterodimeric protein of the facultatively anaerobic marine bacterium Vibrio ruber (GenBank SJN56019 and SJN56021; annotated as NADPH azoreductase and urocanate reductase, respectively) with Vibrio cholerae flavin transferase. The isolated protein (named Crd) consists of the sjn56021-encoded subunit CrdB (NADH:flavin, FAD binding 2, and FMN bind domains) and an additional subunit CrdA (SJN56019, a single NADH:flavin domain) that interact via their NADH:flavin domains (Alphafold2 prediction). Each domain contains a flavin group (three FMNs and one FAD in total), one of the FMN groups being linked covalently by the flavin transferase. Crd readily reduces cinnamate, p-coumarate, caffeate, and ferulate under anaerobic conditions with NADH or methyl viologen as the electron donor, is moderately active against acrylate and practically inactive against urocanate and fumarate. Cinnamates induced Crd synthesis in V. ruber cells grown aerobically or anaerobically. The Crd-catalyzed reduction started by NADH demonstrated a time lag of several minutes, suggesting a redox regulation of the enzyme activity. The oxidized enzyme is inactive, which apparently prevents production of reactive oxygen species under aerobic conditions. Our findings identify Crd as a regulated NADH-dependent cinnamate reductase, apparently protecting V. ruber from (hydroxy)cinnamate poisoning.

A Tracheostomy Support Device to Reduce Tracheostomy-Related Pressure Injury.

BACKGROUND: Tracheostomies provide many advantages for the care of patients who are critically ill but may also result in complications, including tracheostomy-related pressure injuries. Research efforts into the prevention of these pressure injuries has resulted in specialized clinical care teams and pathways. These solutions are expensive and labor intensive, and fail to target the root cause of these injuries; namely, pressure at the device-skin interface. Here we measure that pressure directly and introduce a novel medical device, the tracheostomy support system, to reduce it. METHODS: This was a cross-sectional study of 21 subjects in the ICU, each with a tracheostomy tube connected to a ventilator. A force-sensing resistor was used to measure baseline pressures at the device-skin interface along the inferior flange. This pressure was then measured again with the use of the tracheostomy support system in the inactive and active states. Resultant pressures and demographics were compared. RESULTS: Fifteen male and 6 female subjects, with an average age of 47 ± 14 (mean ± SD) years, were included in this study. Average pressures at the tracheostomy-skin interface at baseline in these 21 ICU subjects were 273 ± 115 (mean ± SD) mm Hg. Average pressures were reduced by 59% (median 62%, maximum 98%) with the active tracheostomy support system to 115 ± 83 mm Hg (P < .001). All the subjects tolerated the tracheostomy support system without issue. CONCLUSIONS: Despite best clinical practice, pressure at the tracheostomy-skin interface can remain quite high. Here we provide measures of this pressure directly and show that a tracheostomy support system can be highly effective at minimizing that pressure. There is room for improvement in tracheostomy care, and such improvement does not have to come at a great expense.

Ecotoxicological impact of butisanstar and clopyralid herbicides on soil microbial respiration and the enzymatic activities.

The application of herbicides in soil has been noted for its detrimental effect on the soil microbial community, crucial for various biochemical processes. This study provides a comprehensive assessment of the impact of butisanstar and clopyralid herbicides, both individually and in combination at different dosage (recommended field dose (RFD), ½, 2 and 5-times RFD). The assessment focuses on soil basal respiration (SBR), cumulative microbial respiration (CMR), and the activities dehydrogenase (DH), catalase (CAT), urease, acid and alkaline phosphatases (Ac-P and Alk-P) enzymes, along with their variations on days 10, 30, 60, and 90 post-herbicide application. Results indicate that, although herbicides, even at lower doses of RFD, demonstrate inhibitory effects on DH, CAT, and microbial respiration, they paradoxically lead to a significant enhancement in urease and phosphatase activities, even at higher doses. The inhibitory/enhancing intensity varies based on herbicide type, incubation period, and dosage. Co-application of herbicides manifests synergistic effects compared to individual applications. The most notable inhibitory effects on DH, CAT, and SBR are observed on the 30th day, coinciding with the highest activities of urease and phosphatases on the same day. The persistent inability to restore respiration and enzyme activities to initial soil (control) levels emphasizes the lasting adverse and inhibitory effects of herbicides, especially clopyralid, over the long term. It becomes apparent that soil microorganisms require an extended duration to decompose and acclimate to the presence of herbicides. Consequently, these agrochemical compounds pose a potential risk to crucial biochemical processes, such as nutrient cycling, ultimately impacting crop production.

Changes in soil oxidase activity induced by microbial life history strategies mediate the soil heterotrophic respiration response to drought and nitrogen enrichment.

Drought and nitrogen deposition are two major climate challenges, which can change the soil microbial community composition and ecological strategy and affect soil heterotrophic respiration (Rh). However, the combined effects of microbial community composition, microbial life strategies, and extracellular enzymes on the dynamics of Rh under drought and nitrogen deposition conditions remain unclear. Here, we experimented with an alpine swamp meadow to simulate drought (50% reduction in precipitation) and multilevel addition of nitrogen to determine the interactive effects of microbial community composition, microbial life strategy, and extracellular enzymes on Rh. The results showed that drought significantly reduced the seasonal mean Rh by 40.07%, and increased the Rh to soil respiration ratio by 22.04%. Drought significantly altered microbial community composition. The ratio of K- to r-selected bacteria (BK:r) and fungi (FK:r) increased by 20 and 91.43%, respectively. Drought increased hydrolase activities but decreased oxidase activities. However, adding N had no significant effect on microbial community composition, BK:r, FK:r, extracellular enzymes, or Rh. A structural equation model showed that the effects of drought and adding nitrogen via microbial community composition, microbial life strategy, and extracellular enzymes explained 84% of the variation in Rh. Oxidase activities decreased with BK:r, but increased with FK:r. Our findings show that drought decreased Rh primarily by inhibiting oxidase activities, which is induced by bacterial shifts from the r-strategy to the K-strategy. Our results highlight that the indirect regulation of drought on the carbon cycle through the dynamic of bacterial and fungal life history strategy should be considered for a better understanding of how terrestrial ecosystems respond to future climate change.

The responses of CO2 emission to nitrogen application and earthworm addition in the soybean cropland.

The effects of nitrogen application or earthworms on soil respiration in the Huang-Huai-Hai Plain of China have received increasing attention. However, the response of soil carbon dioxide (CO2) emission to nitrogen application and earthworm addition is still unclear. A field experiment with nitrogen application frequency and earthworm addition was conducted in the Huang-Huai-Hai Plain. Results showed nitrogen application frequency had a significant effect on soil respiration, but neither earthworms nor their interaction with nitrogen application frequency were significant. Low-frequency nitrogen application (NL) significantly increased soil respiration by 25%, while high-frequency nitrogen application (NH), earthworm addition (E), earthworm and high-frequency nitrogen application (E*NH), and earthworm and low-frequency nitrogen application (E*NL) also increased soil respiration by 21%, 21%, 12%, and 11%, respectively. The main reason for the rise in soil respiration was alterations in the bacterial richness and keystone taxa (Myxococcales). The NH resulted in higher soil nitrogen levels compared to NL, but NL had the highest bacterial richness. The abundance of Corynebacteriales and Gammaproteobacteria were positively connected with the CO2 emissions, while Myxococcales, Thermoleophilia, and Verrucomicrobia were negatively correlated. Our findings indicate the ecological importance of bacterial communities in regulating the carbon cycle in the Huang-Huai-Hai Plain.

Long-range electron proton coupling in respiratory complex I - insights from molecular simulations of the quinone chamber and antiporter-like subunits.

Respiratory complex I is a redox-driven proton pump. Several high-resolution structures of complex I have been determined providing important information about the putative proton transfer paths and conformational transitions that may occur during catalysis. However, how redox energy is coupled to the pumping of protons remains unclear. In this article, we review biochemical, structural and molecular simulation data on complex I and discuss several coupling models, including the key unresolved mechanistic questions. Focusing both on the quinone-reductase domain as well as the proton-pumping membrane-bound domain of complex I, we discuss a molecular mechanism of proton pumping that satisfies most experimental and theoretical constraints. We suggest that protonation reactions play an important role not only in catalysis, but also in the physiologically-relevant active/deactive transition of complex I.

A numerical analysis of ventilation motion after chest surgery with a RESPIRholter device.

This case report presents a numerical evaluation of respiration in terms of biomechanical parameters of chest motion. This experimental evaluation is performed with RESPIRholter, a wearable device specifically developed to monitor the movement in the ribcage through the motion of the sixth rib whose characteristic motion is considered as representative of the motion of the thorax. Here we present test results acquired with a RESPIRholter device in a 6-h acquisition. These results characterize respiration biomechanics for diagnostic purposes in a chest surgery patient, highlighting the diagnostic utility of RESPIRholter in the identification of post-operation respiratory problem.

Scrutinizing a Lactococcus lactis mutant with enhanced capacity for extracellular electron transfer reveals a unique role for a novel type-II NADH dehydrogenase.

Lactococcus lactis, a lactic acid bacterium used in food fermentations and commonly found in the human gut, is known to possess a fermentative metabolism. L. lactis, however, has been demonstrated to transfer metabolically generated electrons to external electron acceptors, a process termed extracellular electron transfer (EET). Here, we investigated an L. lactis mutant with an unusually high capacity for EET that was obtained in an adaptive laboratory evolution (ALE) experiment. First, we investigated how global gene expression had changed, and found that amino acid metabolism and nucleotide metabolism had been affected significantly. One of the most significantly upregulated genes encoded the NADH dehydrogenase NoxB. We found that this upregulation was due to a mutation in the promoter region of NoxB, which abolished carbon catabolite repression. A unique role of NoxB in EET could be attributed and it was directly verified, for the first time, that NoxB could support respiration in L. lactis. NoxB, was shown to be a novel type-II NADH dehydrogenase that is widely distributed among gut microorganisms. This work expands our understanding of EET in Gram-positive electroactive microorganisms and the special significance of a novel type-II NADH dehydrogenase in EET.IMPORTANCEElectroactive microorganisms with extracellular electron transfer (EET) ability play important roles in biotechnology and ecosystems. To date, there have been many investigations aiming at elucidating the mechanisms behind EET, and determining the relevance of EET for microorganisms in different niches. However, how EET can be enhanced and harnessed for biotechnological applications has been less explored. Here, we compare the transcriptomes of an EET-enhanced L. lactis mutant with its parent and elucidate the underlying reason for its superior performance. We find that one of the most significantly upregulated genes is the gene encoding the NADH dehydrogenase NoxB, and that upregulation is due to a mutation in the catabolite-responsive element that abolishes carbon catabolite repression. We demonstrate that NoxB has a special role in EET, and furthermore show that it supports respiration to oxygen, which has never been done previously. In addition, a search reveals that this novel NoxB-type NADH dehydrogenase is widely distributed among gut microorganisms.

Effects of extracorporeal diaphragm pacing combined with inspiratory muscle training on respiratory function in people with stroke: a randomized controlled trial.

OBJECTIVES: To evaluate the effect of external diaphragmatic pacing (EDP) combined with inspiratory muscle training on respiratory function in post-stroke patients. METHODS: Patients with stroke were enrolled from the First Affiliated Hospital of Soochow University in China between 2021 and 2022. The patients were randomized into an EDP treatment group (control group) or an EDP treatment plus inspiratory muscle training group (experimental group). Each therapy was administered once a day for 6 days per week. The peak inspiratory flow (PIF), maximal inspiratory pressure (MIP), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC% ratio, and diaphragm thickness and mobility were measured and compared between the two groups after 4 weeks. RESULTS: After 4 weeks of intervention, respiratory muscle function indicators including PIF (95% CI: 0.21-1.28, p = 0.008) and MIP (95% CI: 6.92-25.44, p = 0.001) significantly improved in the experimental group. Diaphragmatic thickness also significantly increased in the experimental group (p < 0.05), while diaphragmatic excursion showed no significant difference between the two groups. Additionally, FVC (95% CI: 0.14-1.14, p = 0.013) and FEV1 (95% CI: 0.20-1.06, p = 0.005) demonstrated a significant increase in the experimental group, whereas FEV1/FVC% (95% CI: -0.84 to 9.36, p = 0.099) exhibited no significant group difference. CONCLUSION: EDP combined with inspiratory muscle training in individuals with stroke provides greater benefits than EDP alone in terms of respiratory function recovery, except for the parameters of diaphragmatic excursion and FEV1/FVC%.