H2S protects rat cerebral ischemia-reperfusion injury by inhibiting expression and activation of hippocampal ROCK2 at the Thr436 and Ser575 sites.

BACKGROUND: H2S is an endogenous gas signal molecule, which protects cerebral ischemia/reperfusion (I/R) injury by phosphorylating rho-associated coiled coil-containing protein kinase 2 (ROCK2) at Tyr722, and inhibiting ROCK2 protein expression and activities. We previously reported that H2S protected rat neurons from hypoxia/reoxygenation injury in vitro through inhibiting phosphorylation of ROCK2 at Thr436 and Ser575, but it is unclear whether these two sites are involved in protection of H2S against cerebral I/R injury. METHOD: Rats transfected with wild-type and mutant eukaryotic plasmids of ROCK2 in hippocampus were used to establish I/R model by ligating bilateral common carotid artery. Rat behavioral deficit was detected by water maze assay, and ROCK2, lactate dehydrogenase (LDH), nerve-specific enolase (NSE) and reactive oxygen species (ROS) were determined by ELISA. ROCK2 expressions was examined by western-blot assay, and bcl-2 and Bax mRNAs were examined by RT-qPCR. RESULTS: NaHS (4.8mg/kg) significantly inhibited the I/R-increased serum LDH, NSE and ROS in the ROCK2wild-pEGFP-N1-transfected rats, but had no obvious effect in the ROCK2T436A-pEGFP-N1- or the ROCK2S575F-pEGFP-N1-transfected rats; inhibitions of NaHS on the I/R-increased escape latency and the I/R-decreased percentage of target quadrant distance to total distance were markedly attenuated or abolished in the ROCK2T436A-pEGFP-N1- or the ROCK2S575F-pEGFP-N1-transfected rats compared with those in the ROCK2wild-pEGFP-N1-transfected rats; NaHS obviously inhibited the I/R-increased hippocampal ROCK2 and GFP-ROCK2 proteins, Bax mRNA, and ROCK2 activity, as well as the I/R-decreased hippocampal bcl-2 mRNA in the hippocampus of the ROCK2wild-pEGFP-N1-transfected rats, but had no significant effect in the ROCK2T436A-pEGFP-N1- or the ROCK2S575F-pEGFP-N1-transfected rats. CONCLUSION: H2S protects cerebral I/R injury in rats by inhibiting expression and activation of hippocampal ROCK2 via the Thr436 and Ser575 sites.

Oxalate-upregulated annexin A6 promotes the formation of calcium oxalate kidney stones by exacerbating calcium release-mediated oxidative stress injury in renal tubular epithelial cells and crystal-cell adhesion.

Kidney stones result from abnormal biomineralization, although the mechanism behind their formation remains unclear. Annexin A6 (AnxA6), a calcium-dependent lipid-binding protein, is associated with several mineralization-related diseases, but its role in kidney stones is unknown. This study aimed to explore the role and mechanism of AnxA6 in calcium oxalate (CaOx) kidney stones. An in vitro model in which renal tubular epithelial cells (RTECs) were treated with 1 mmol/L oxalate was established, and AnxA6 protein and mRNA expression were examined. Genetic engineering, drug intervention, and biochemical assays were used to investigate the role of AnxA6. The results revealed that AnxA6 was significantly overexpressed in the CaOx model. AnxA6 knockdown in RTECs reduced oxalate-induced oxidative stress, ROS accumulation, and mitochondrial damage, whereas AnxA6 overexpression exacerbated these effects. Blocking ryanodine receptor-mediated calcium release reversed AnxA6-induced oxidative damage. Additionally, AnxA6 increased oxalate adhesion to RTECs by binding to oxalate. In conclusion, AnxA6 contributes to CaOx kidney stone formation by promoting both oxidative stress via calcium release and crystal-cell adhesion by binding to oxalate. This study offers new insight into CaOx kidney stone formation.

Visual reading for [18F]Florzolotau Tau PET scans in progressive supranuclear palsy.

PURPOSE: The identification of tau accumulation within living brains holds significant potential in facilitating accurate diagnosis of progressive supranuclear palsy (PSP). While visual assessment is frequently employed, standardized methods for tau positron emission tomography (PET) specifically in PSP are absent. We aimed to develop a visual reading algorithm dedicated to the evaluation of [18F]Florzolotau PET in PSP. METHODS: 148 PSP and 30 healthy volunteers were divided into a development set (for the establishment of the reading rules; n = 89) and a testing set (for the validation of the reading rules; n = 89). For differential diagnosis, 55 α-synucleinopathies were additionally included into the testing set. The visual reading method was established by an experienced assessor (Reader 0) and was then validated by Reader 0 and two additional readers on regional and overall binary manners. A positive binding in both midbrain and globus pallidus/putamen regions was characterized as a PSP-like pattern, whereas any other pattern was classified as non-PSP-like. RESULTS: Reader 1 (94.4%) and Reader 2 (93.8%) showed excellent agreement for the overall binary determination against Reader 0. The regional binary determinations of midbrain and globus pallidus/putamen showed excellent agreement among readers (kappa > 0.80). The overall binary evaluation demonstrated reproducibility of 86.1%, 94.4% and 77.8% for three readers. The visual reading algorithm showed high agreement with regional standardized uptake value ratios and clinical diagnoses. CONCLUSION: Through the application of the suggested visual reading algorithm, [18F]Florzorotau PET imaging demonstrated a robust performance for the imaging diagnosis of PSP.

Rho4 interacts with BbGDI and is essential for the biocontrol potential of Beauveria bassiana by maintaining intracellular redox homeostasis.

Rho4 is a member of the Rho-family small GTPases. In this study, we revealed the function of Rho4 and explored its mechanism involved in intracellular redox homeostasis in Beauveria bassiana, one of the most widely utilized filamentous entomopathogenic fungi. The disruption of Rho4 in B. bassiana resulted in significant phenotypic changes, such as fungal virulence, growth rate on different media, thermotolerance, germination, and conidiation. Integrated analysis of proteomic and transcriptomic data unveiled differential expression patterns of various redox-related genes and proteins in Δrho4, including the down-regulation of GST shown in proteomic and transcriptomic data, and the down-regulated gene expression levels of NOX, SOD, CAT, and GR in the transcriptome. Based on the bi-omics analysis, we focused on the impact of Rho4 in maintaining intracellular redox homeostasis. A decreased ROS content observed in Δrho4 might be attributed to the reduced NOX activity, which subsequently affects the GSH-producing/consuming metabolisms, with the attenuated activities of GR and GST. The imbalanced redox homeostasis also resulted in the reduced enzyme activities of SOD and CAT. Exogenous oxides could partially complement the ROS level and rescue the growth defect in Δrho4 to a certain extent. Besides, BbGDI was initially identified as an interacting protein of Rho4 in entomopathogenic fungi. Our results provide a comprehensive understanding of the function and regulating mechanism of Rho4 in B. bassiana.

Macropinocytosis mediates resistance to loss of glutamine transport in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) metabolism and cell growth uniquely rely on glutamine uptake by the transporter ASCT2. Despite previous data reporting cell growth inhibition after ASCT2 knockdown, we here show that ASCT2 CRISPR knockout is tolerated by TNBC cell lines. Despite the loss of a glutamine transporter and low rate of glutamine uptake, intracellular glutamine steady-state levels were increased in ASCT2 knockout compared to control cells. Proteomics analysis revealed upregulation of macropinocytosis, reduction in glutamine efflux and increased glutamine synthesis in ASCT2 knockout cells. Deletion of ASCT2 in the TNBC cell line HCC1806 induced a strong increase in macropinocytosis across five ASCT2 knockout clones, compared to a modest increase in ASCT2 knockdown. In contrast, ASCT2 knockout impaired cell proliferation in the non-macropinocytic HCC1569 breast cancer cells. These data identify macropinocytosis as a critical secondary glutamine acquisition pathway in TNBC and a novel resistance mechanism to strategies targeting glutamine uptake alone. Despite this adaptation, TNBC cells continue to rely on glutamine metabolism for their growth, providing a rationale for targeting of more downstream glutamine metabolism components.

Nonreciprocal Acoustic Devices with Asymmetric Peierls Phases.

Nonreciprocity in acoustics is of paramount importance in many practical applications and has been experimentally realized using nonlinear media, moving fluids, or time modulation, which regrettably suffer from large volumes and high-power consumption, difficulty in integration, and inevitable vibrations or phase noise. In modern Hamiltonian theory, the violation of system's reciprocity can be achieved via asymmetric Peierls phases, which typically involves with non-Hermiticity or time-reversal symmetry breaking. Here, we propose a framework for designing nonreciprocal acoustic devices based on the asymmetric Peierls phases that can be fully controlled via active acoustic components. The fully controlled Peierls phases enable various high-performance acoustic devices, including non-Hermitian extensions of isolators, gyrators, and circulators, which are otherwise impossible in previous approaches that are bound by Hermiticity or passivity. We reveal that the transmission phases in isolators are equivalent to the Peierls phase plus a constant. The nonreciprocal phase delay in gyrators and the unirotational transmission behavior in circulators result from the gauge-invariant Aharonov-Bohm phases determined by Peierls phases. Our work not only uncovers multiple intriguing physics related to Peierls phases but also provides a general approach to compact, integratable, nonreciprocal acoustic devices.

Nerve agent exposure and physiological stress alter brain microstructure and immune profiles after inflammatory challenge in a long-term rat model of Gulf War Illness.

Gulf War Illness (GWI) is a disorder experienced by many veterans of the 1991 Gulf War, with symptoms including fatigue, chronic pain, respiratory and memory problems. Exposure to toxic chemicals during the war, such as oil well fire smoke, pesticides, physiological stress, and nerve agents, is thought to have triggered abnormal neuroinflammatory responses that contribute to GWI. Previous studies have examined the acute effects of combined physiological stress and chemical exposures using GWI rodent models and presented findings related to neuroinflammation and changes in diffusion magnetic resonance imaging (MRI) measures, suggesting a neuroimmune basis for GWI. In the current study, using ex vivo MRI, cytokine mRNA expression, and immunohistological analyses of brain tissues, we examined the brain structure and immune function of a chronic rat model of GWI. Our data showed that a combination of long-term corticosterone treatment (to mimic high physiological stress) and diisopropyl fluorophosphate exposure (to mimic sarin exposure) primed the response to subsequent systemic immune challenge with lipopolysaccharide resulting in elevations of multiple cytokine mRNAs, an increased activated glial population, and disrupted brain microstructure in the cingulate cortex and hippocampus compared to control groups. Our findings support the critical role of neuroinflammation, dysregulated glial activation, and their relationship to disrupted brain microstructural integrity in the pathophysiology of GWI and highlight the unique consequences of long-term combined exposures on brain biochemistry and structural connectivity.

A novel fungal sensor (Ngs1) of N-acetylglucosamine (GlcNAc) mediates the fungal response to GlcNAc in the interaction between entomopathogenic Beauveria bassiana and insect host.

As N-acetylglucosamine (GlcNAc) ubiquitously exists in both insect cuticle and fungal cell walls, the GlcNAc sensor (Ngs1) potentially plays important roles in the interactions between entomopathogenic fungi and their insect hosts. However, the roles of the Ngs1 derived from the entomopathogens in response to the host's cuticle remain completely unexplored. In this study, a putative Ngs1 homolog was identified in the entomopathogenic fungus Beauveria bassiana. Deletion of Ngs1 significantly reduced virulence towards Galleria mellonella larvae either through cuticle infection (by 23%) or by bypassing the cuticle (by 44%). To investigate the role of Ngs1 in fungal virulence, an analysis of the transcriptome induced by Locusta migratoria exoskeleton was conducted, highlighting the regulatory mechanism of Ngs1 in carbohydrate metabolic process, particularly chitin metabolism and GlcNAc metabolism. Consistent with the transcriptomic data, Ngs1-deletion mutants showed reduced activities of both secreted chitinase (17% reduction) and Pr1 protease (35% reduction). Loss of Ngs1 down-regulated the transcript levels of GlcNAc-catabolism genes, resulting in a 17% decrease in fungal growth on GlcNAc-supported media. Furthermore, Ngs1 deficiency attenuated the fungal response to GlcNAc, leading to the alteration of fungal resistance to diverse stress cues. All of these changes contribute to the reduction in virulence in Ngs1-deficient B. bassiana. These findings support that Ngs1 plays a critical role in responding to insect-derived GlcNAc, affecting the production of cuticle-degrading enzymes to penetrate insect epidermis, GlcNAc-induced changes of stress resistance, and contribute to the fungal virulence against insects.

Rad6 Regulates Conidiation by Affecting the Biotin Metabolism in Beauveria bassiana.

Rad6 is a canonical ubiquitin-conjugating enzyme known for its role in regulating chromosome-related cellular processes in yeast and has been proven to have multiple functions in Beauveria bassiana, including insect-pathogenic lifestyle, UV damage repair, and conidiation. However, previous studies have only reported the key role of Rad6 in regulating conidial production in a nutrient-rich medium, without any deep mechanism analyses. In this study, we found that the disruption of Rad6 leads to a profound reduction in conidial production, irrespective of whether the fungus is cultivated in nutrient-rich or nutrient-poor environments. The absence of rad6 exerts a suppressive effect on the transcription of essential genes in the central developmental pathway, namely, brlA, abaA, and wetA, resulting in a direct downregulation of conidiation capacity. Additionally, mutant strains exhibited a more pronounced decline in both conidial generation and hyphal development when cultured in nutrient-rich conditions. This observation correlates with the downregulation of the central developmental pathway (CDP) downstream gene vosA and the upregulation of flaA in nutrient-rich cultures. Moreover, single-transcriptomics analyses indicated that irregularities in biotin metabolism, DNA repair, and tryptophan metabolism are the underlying factors contributing to the reduced conidial production. Comprehensive dual transcriptomics analyses pinpointed abnormal biotin metabolism as the primary cause of conidial production decline. Subsequently, we successfully restored conidial production in the Rad6 mutant strain through the supplementation of biotin, further confirming the transcriptomic evidence. Altogether, our findings underscore the pivotal role of Rad6 in influencing biotin metabolism, subsequently impacting the expression of CDP genes and ultimately shaping the asexual life cycle of B. bassiana.

Three-dimensional valley-contrasting sound.

Spin and valley are two fundamental properties of electrons in crystals. The similarity between them is well understood in valley-contrasting physics established decades ago in two-dimensional (2D) materials like graphene-with broken inversion symmetry, the two valleys in graphene exhibit opposite orbital magnetic moments, similar to the spin-1/2 behaviors of electrons, and opposite Berry curvature that leads to a half topological charge. However, valley-contrasting physics has never been explored in 3D crystals. Here, we develop a 3D acoustic crystal exhibiting 3D valley-contrasting physics. Unlike spin that is fundamentally binary, valley in 3D can take six different values, each carrying a vortex in a distinct direction. The topological valley transport is generalized from the edge states of 2D materials to the surface states of 3D materials, with interesting features including robust propagation, topological refraction, and valley-cavity localization. Our results open a new route for wave manipulation in 3D space.

[Buyang Huanwu Decoction attenuates cerebral ischemia-reperfusion injury in rats via miR-26a-5p mediated PTEN/PI3K/Akt signaling pathway].

This study aims to investigate the mechanism of Buyang Huanwu Decoction in treatment of cerebral ischemia-reperfusion injury in rats. A total of 180 SD rats were randomly divided into 5 different groups: sham group, model group, Buyang Huanwu Decoction group, Buyang Huanwu Decoction + miR-26a-5p agomir(agomir) group, Buyang Huanwu Decoction + miR-26a-5p agomir negative control(agomir NC) group. There were 36 rats in each group. Each group was then subdivided into three subgroups for the duration of reperfusion(3, 7, 14 d). A ligature-induced middle cerebral artery occlusion(MCAO) model was carried out on all groups other than sham group. Reperfusion was performed following ischemia for 90 min. Buyang Huanwu Decoction group, agomir group, and agomir NC group were given Buyang Huanwu Decoction twice daily by gavage 24 h after the formation of the model. Sham group and model group were given an equal amount of physiological saline by gavage until the day before sacrifice. At 24 h after ischemia induction, miR-26a-5p agomir was injected into the lateral ventricle in agomir group, miR-26a-5p NC in agomir NC group, and equal amounts of physiological saline in the other groups. 24 h after ischemia induction, BrdU was intraperitoneally injected once daily until the day before sacrifice. Modified neurological severity score(mNSS) was used to evaluate neurological deficits, 2,3,5-triphenyltetrazolium chloride(TTC) staining was used to determine the cerebral infarct volume, TUNEL staining was used to assess the apoptosis of parenchymal ischemic brain tissue, and double immunofluorescence staining was used to examine BrdU/NeuN double positive neurons in the parenchymal ischemic brain tissue to evaluate the neuronal regeneration. We employed a luciferase reporter assay to identify and validate that the target gene of miR-26a-5p is PTEN. Real-time quantitative polymerase chain reaction(RT-qPCR) was used to assess gene expression levels of PTEN and miR-26a-5p and Western blot to assess the protein levels of PTEN, PI3K, p-PI3K, Akt, and p-Akt. The results revealed that compared with model group, Buyang Huanwu Decoction treatment promoted neural function recovery, reduced the cerebral infarct volume, increased the number of BrdU~+/NeuN~+ neurons, upregulated the expression of miR-26a-5p, regulated the PTEN/PI3K/Akt signaling pathway, and promoted neuronal regeneration in the cerebral ischemia-reperfusion rats. These effects were significantly enhanced after lateral ventricle injection of miR-26a-5p agomir. The findings prove that Buyang Huanwu Decoction treatment can promote neural function recovery, reduce the cerebral infarct volume, and promote neuronal regeneration in a cerebral ischemia-reperfusion rat model, which is likely to be achieved via miR-26a-5p mediated PTEN/PI3K/Akt signaling pathway.

Developing an integrated model relating substrate water content to indoor temperature reduction for irrigation-decision support of a green roof.

This study analyzes the influences of evapotranspiration or substrate moisture variation on the indoor-temperature reduction of green roofs compared to the control group. A multiple linear regression (MLR) model for the operation stage based on observation and an integrated MLR model for the planning stage based on simulation are verified. The MLR model shows 0.64 °C of the Root Mean Square Error (RMSE) in predicting the hourly difference of temperature reduction based on the measured change in evapotranspiration and air temperature. The contributions of the hourly increment of air temperature (ΔTa) and increment of evapotranspiration (ΔET) are similar to the hourly increment of temperature reduction (ΔTdif). Then, the feasibility of the integrated MLR model is demonstrated based on the evapotranspiration and substrate moisture of a green roof simulated by a hydrological model as well as the indoor-temperature reduction simulated by a building energy model, which has fair performances in capturing the heat-transfer and water-balance physical process within a green roof. The integrated MLR model shows that evapotranspiration is relatively essential, followed by substrate moisture, air temperature, and vapor pressure. Despite the modeling bias, the integrated model quantitatively relates the influential factors to temperature reduction and predicts temperature reduction with an RMSE of 1.02 °C. The integrated model can quantify the influence of irrigation on temperature reduction under various climate conditions and green roof structures. This study demonstrates the procedure of establishing the integrated model. It shows the potential of the integrated model to provide decision support on irrigation for multi-purpose optimization of green roof performances.

Music Therapy and Music Intervention for NSCLC Patients Undergoing PET with Fear of Cancer Recurrence.

Background: Cancer and psychiatric symptoms are associated. Fear of cancer recurrence (FCR) is the most common psychological problem for cancer survivors. Pharmacological interventions can help, but also have major drawbacks. Music therapy and music interventions have been shown to be a safe and practical complementary treatment. Objective: This randomized, controlled trial aimed to investigate the effects of music therapy and music intervention in attenuating non-small cell lung cancer (NSCLC) patients' anxiety related to FCR. Methods: NSCLC patients with FCR were randomly allocated to a music therapy and intervention group (G1) and Control group (G2). Patients' anxiety was measured using the State-Trait Anxiety Inventory scores and heart rates. Primary outcome measure were PET scans. Secondary measures were salivary cortisol, salivary α-amylase levels and heart rate. Findings: Patients in G1 showed higher glucose metabolism of 18F-FDG in the superior frontal gyrus, anterior cingulate, superior temporal gyrus, and parahippocampal gyrus, compared to those in G2 (all P < .001). Heart rates and salivary α-amylase area under the curve (AUC) and relative variation (VAR) in G1 were significantly lower than those in G2 (all P < .05). State-Trait Anxiety Inventory scores and cortisol AUC in G1 were significantly lower than those in G2 (all P < .05). Conclusions: Music therapy and interventions can reduce anxiety and endocrinological responses and change glucose metabolism of 18F-FDG in fear-related brain regions.Trial registration: Registered retrospectively, ISRCTN Registry, www.isrctn.com, ISRCTN23276302Clinical Implications: Cancer treatment centers and physical examination centers should consider providing music therapy and intervention to the appropriate patients as a routine component of a comprehensive clinical care during medical examinations.

Five-year longitudinal surveillance reveals the continual circulation of both alpha- and beta-coronaviruses in Plateau and Gansu pikas (Ochotona spp.) at Qinghai Lake, China1.

The discovery of alphacoronaviruses and betacoronaviruses in plateau pikas (Ochotona curzoniae) expanded the host range of mammalian coronavirus (CoV) to a new order - Lagomorpha. However, the diversity and evolutionary relationships of CoVs in these plateau-region-specific animal population remains uncertain. We conducted a five-year longitudinal surveillance of CoVs harboured by pikas around Qinghai Lake, China. CoVs were identified in 33 of 236 plateau pikas and 2 of 6 Gansu pikas (Ochotona cansus), with a total positivity rate of 14.5%, and exhibiting a wide spatiotemporal distribution across seven sampling sites and six time points. Through meta-transcriptomic sequencing and RT-PCR, we recovered 16 near-complete viral genome sequences. Phylogenetic analyses classified the viruses as variants of either pika alphacoronaviruses or betacoronaviruses endemic to plateau pikas from the Qinghai-Tibet Plateau region. Of particular note, the pika-associated betacoronaviruses may represent a novel subgenus within the genus Betacoronavirus. Tissue tropism, evaluated using quantitative real-time PCR, revealed the presence of CoV in the rectal and/or lung tissues, with the highest viral loads at 103.55 or 102.80 RNA copies/µL. Surface plasmon resonance (SPR) assays indicated that the newly identified betacoronavirus did not bind to human or pika Angiotensin-converting enzyme 2 (ACE2) or Dipeptidyl peptidase 4 (DPP4). The findings highlight the ongoing circulation and broadening host spectrum of CoVs among pikas, emphasizing the necessity for further investigation to evaluate their potential public health risks.

Impact of proximity of left atrium to descending aorta on left inferior pulmonary vein triggers or drivers of atrial fibrillation: A risk score model.

BACKGROUND: Prior studies have investigated cardiac anatomy and clinical parameters as predictors for pulmonary vein and non-pulmonary vein triggers. OBJECTIVE: We aimed to assess the link between the descending aorta to left inferior pulmonary vein (Dao-LIPV) distance and the occurrence of triggers and drivers in atrial fibrillation (AF) ablation procedures. METHODS: Drug-refractory AF patients who underwent first-time index catheter ablation from January 2010 to December 2019 were retrospectively assembled. The Dao-LIPV distance was measured from preablation pulmonary vein computed tomography. Patients were assigned to groups on the basis of the presence of LIPV triggers or drivers. Multivariate logistic regression was used to identify risk factors. RESULTS: A total of 886 consecutive patients with drug-refractory AF were studied, and 63 (7.1%) patients were identified to have LIPV triggers or drivers. The Dao-LIPV distance had a better predictive performance (area under the curve, 0.70) compared with persistent AF (area under the curve, 0.57). Multivariate logistic regression analysis showed that Dao-LIPV distance ≤2.5 mm (odds ratio, 3.96; 95% CI, 2.15-7.29; P < .001) and persistent AF (odds ratio, 1.73; 95% CI, 1.02-2.94]; P = .044) were independent predictors for the presence of LIPV triggers or drivers. A risk score model was established to predict the probability of LIPV triggers or drivers with persistent AF (10.2%), Dao-LIPV distance ≤2.5 mm (11.4%), and both (15.0%). CONCLUSION: The proximity of the Dao-LIPV was correlated to the presence of LIPV triggers or drivers. We developed a risk score model indicating that persistent AF and Dao-LIPV distances ≤2.5 mm significantly increase the risk of LIPV triggers or drivers, aiding electrophysiologists in preparing for and performing catheter ablation more effectively.

Optimized microbial fuel cell-powered electro-Fenton processes to enhance electricity and bisphenol A removal by varying external resistance and electrolyte concentrations.

This study is the first to investigate the effects of external resistance and electrolyte concentration on the performance of a bioelectro-Fenton (BEF) system, involving measurements of power density, H2O2 generation, and bisphenol A (BPA) removal efficiency. With optimized operating conditions (external resistance of 1.12 kΩ and cathodic NaCl concentration of 1,657 mg/L), the BEF system achieved a maximum power density of 38.59 mW/m2, which is about 3.5 times higher than with 1 kΩ external resistance and no NaCl. This system featured a 71.7 % reduction in total internal resistance. The optimized BEF also accelerated the oxygen reduction reaction rate, increasing H2O2 generation by 4.4 times compared to the unoptimized system. Moreover, it exhibited superior BPA degradation performance, removing over 99 % of BPA within 14 hs, representing a 1.1 to 3.3-fold improvement over the unoptimized BEF. By the fifth cycle (70 h), the optimized BEF still removed 70 % of BPA. Optimizing the operating conditions significantly increased the abundance of electrochemically active bacteria (Pseudomonadaceae) from 2.2 % to 20 %, facilitating rapid acclimation. The study demonstrates the strong potential of an optimized BEF system for removing persistent pollutants.

N-acetylglucosamine kinase (BbHxk1) has pleiotropic effects on vegetative growth, cell wall integrity, morphological transition, cuticle infection, and metabolic modulation in the biological pesticide Beauveria bassiana.

Beauveria bassiana is a popular and eco-friendly biopesticide. During its pathogen-pest interaction, both N-acetylglucosamine (GlcNAc) catabolism and anabolism are crucial for nutrient supply and cell-wall construction. The initiation of GlcNAc metabolism relies on the catalysis of GlcNAc kinase, which has been extensively studied in the human pathogen Candida albicans. However, the physiological function of GlcNAc kinase remains poorly understood in entomopathogenic fungi. In the present study, a GlcNAc kinase homolog was identified and designated as BbHxk1 in B. bassiana. Deletion of BbHxk1 resulted in viable but reduced vegetative growth on various carbon sources. ΔBbHxk1 mutants displayed severe defects in cell wall integrity, making them more susceptible to cell wall stress cues. Furthermore, the absence of BbHxk1 resulted in an increase in conidial yield and blastospore production, and a faster rate of germination and filamentation, potentially attributed to higher intracellular ATP levels. BbHxk1 deficiency led to a reduction in the activities of cuticle-degrading enzymes, which might contribute to the attenuated pathogenicity specifically through cuticle penetration rather than hemocoel infection towards Galleria mellonella larvae. Being different from C. albicans Hxk1, which facultatively acts as a catalyzing enzyme and transcriptional regulator, BbHxk1 primarily acts as a catalyzing enzyme and metabolic regulator. The altered metabolomic profiling correlated with the phenotypic defects in ΔBbHxk1 mutants, further implicating a potential metabolism-dependent mechanism of BbHxk1 in mediating physiologies of B. bassiana. These findings not only unveil a novel role for GlcNAc kinase in B. bassiana, but also provide a solid theoretical basis to guide metabolic reprogramming in order to maintain or even enhance the efficiency of fungi for practical applications.

A cryptic site in class 5 epitope of SARS-CoV-2 RBD maintains highly conservation across natural isolates.

The emergence of SARS-CoV-2 variants raises concerns about the efficacy of existing COVID-19 vaccines and therapeutics. Previously, we identified a conserved cryptic class 5 epitope of SARS-CoV-2 receptor binding domain (RBD) by two cross-neutralizing antibodies 7D6 and 6D6. Intriguingly, this site remains resistant to substantial mutations occurred in ever-changing SARS-CoV-2 subvariants. As compared to class 3 antibody S309, 6D6 maintains broad and consistent neutralizing activities against SARS-CoV-2 variants. Furthermore, 6D6 effectively protected hamster from the virulent Beta strain. Sequence alignment of approximately 6 million documented SARS-CoV-2 isolates revealed that 6D6 epitope maintains an exceptionally high conservation rate (99.92%). Structural analysis demonstrated that all 33 mutations accumulated in XBB.1.5 since the original strain do not perturb the binding 6D6 to RBD, in line with the sequence analysis throughout the antigenicity evolution of SARS-CoV-2. These findings suggest the potential of this epitope serving as a critical determinant for vaccines and therapeutic design.

Effects of walking on epigenetic age acceleration: a Mendelian randomization study.

INTRODUCTION: Walking stands as the most prevalent physical activity in the daily lives of individuals and is closely associated with physical functioning and the aging process. Nonetheless, the precise cause-and-effect connection between walking and aging remains unexplored. The epigenetic clock emerges as the most promising biological indicator of aging, capable of mirroring the biological age of the human body and facilitating an investigation into the association between walking and aging. Our primary objective is to investigate the causal impact of walking with epigenetic age acceleration (EAA). METHODS: We conducted a two-sample two-way Mendelian randomization (MR) study to investigate the causal relationship between walking and EAA. Walking and Leisure sedentary behavior data were sourced from UK Biobank, while EAA data were gathered from a total of 28 cohorts. The MR analysis was carried out using several methods, including the inverse variance weighted (IVW), weighted median, MR-Egger, and robust adjusted profile score (RAPS). To ensure the robustness of our findings, we conducted sensitivity analyses, which involved the MR-Egger intercept test, Cochran's Q test, and MR-PRESSO, to account for and mitigate potential pleiotropy. RESULTS: The IVW MR results indicate a significant impact of usual walking pace on GrimAge (BETA = - 1.84, 95% CI (- 2.94, - 0.75)), PhenoAge (BETA = - 1.57, 95% CI (- 3.05, - 0.08)), Horvath (BETA = - 1.09 (- 2.14, - 0.04)), and Hannum (BETA = - 1.63, 95% CI (- 2.70, - 0.56)). Usual walking pace is significantly associated with a delay in epigenetic aging acceleration (EAA) (P < 0.05). Moreover, the direction of effect predicted by the gene remained consistent across RAPS outcomes and sensitivity MR analyses. There is a lack of robust causal relationships between other walking conditions, such as walking duration and walking frequency, on EAA (P > 0.05). CONCLUSION: Our evidence demonstrates that a higher usual walking pace is associated with a deceleration of the acceleration of all four classical epigenetic clocks acceleration.