Genome-wide analysis of in vivo-evolved Candida auris reveals multidrug-resistance mechanisms.

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.

The role of sialidase Neu1 in respiratory diseases.

Neu1 is a sialidase enzyme that plays a crucial role in the regulation of glycosylation in a variety of cellular processes, including cellular signaling and inflammation. In recent years, numerous evidence has suggested that human NEU1 is also involved in the pathogenesis of various respiratory diseases, including lung infection, chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis. This review paper aims to provide an overview of the current research on human NEU1 and respiratory diseases.

Inhibition mechanism of fusarium graminearum growth by g-C3N4 homojunction and its application in barley malting.

The increase of deoxynivalenol (DON) caused by Fusarium graminearum (F. graminearum) during the malting process is a serious safety problem. In our work, the inhibition mechanism of F. graminearum growth by g-C3N4 homojunction and its application in barley malting were studied. The reason why the growth activity of F. graminearum decreased after photocatalysis by g-C3N4 homojunction was that under visible light irradiation, a large amount of •O2- elicited by g-C3N4 homojunction destroyed the cell structure of F. graminearum, leading to the deficiency of cell membrane selective permeability and serious disorder of intracellular metabolism. The application of photocatalysis technology in malting can effectively inhibit the growth of F. graminearum and the accumulation of ergosterol was reduced by 30.55 %, thus reducing the DON content in finished malt by 31.82 %. Meanwhile, the physicochemical indexes of barley malt after photocatalytic treatment still met the requirements of second class barley malt in Chinese light industry standard QB/T 1686-2008. Our work provides a new idea for the control of fungal contamination in barley malt.

Multicenter comparative genomic study of Klebsiella oxytoca complex reveals a highly antibiotic-resistant subspecies of Klebsiellamichiganensis.

BACKGROUND: The Klebsiella oxytoca complex is an opportunistic pathogen that has been recently identified as an actual complex. However, the characteristics of each species remain largely unknown. We aimed to study the clinical prevalence, antimicrobial profiles, genetic differences, and interaction with the host of each species of this complex. METHODS: One hundred and three clinical isolates of the K. oxytoca complex were collected from 33 hospitals belonging to 19 areas in China from 2020 to 2021. Species were identified using whole genome sequencing based on average nucleotide identity. Clinical infection characteristics of the species were analyzed. Comparative genomics and pan-genome analyses were performed on these isolates and an augmented dataset, including 622 assemblies from the National Center for Biotechnology Information. In vitro assays evaluating the adhesion ability of human respiratory epithelial cells and survivability against macrophages were performed on randomly selected isolates. RESULTS: Klebsiella michiganensis (46.6%, 48/103) and K. oxytoca (35.92%, 37/103) were the major species of the complex causing human infections. K. michiganensis had a higher genomic diversity and larger pan-genome size than did K. oxytoca. K. michiganensis isolates with blaoxy-5 had a higher resistance rate to various antibiotics, antimicrobial gene carriage rate, adhesion ability to human respiratory epithelial cells, and survival rate against macrophages than isolates of other species. CONCLUSION: Our study revealed the genetic diversity of K. michiganensis and firstly identified the highly antimicrobial-resistant profile of K. michiganensis carrying blaoxy-5.

Multiple brain abscesses caused by Nocardia asiatica: Case report and literature review.

Nocardia are opportunistic pathogens mainly affecting immunocompromised individuals. Nocardia asiatica, a novel species, can cause severe infections. We present a case of multiple brain abscesses due to Nocardia asiatica, discussing its diagnosis and treatment. In January 2022, a 27-year-old Chinese woman with a history of atypical membranous nephropathy presented with low-grade fever, cough, limb weakness, and headaches. Imaging revealed lung and brain lesions. Neurological symptoms worsened over time, culminating in recurrent seizures and severe headaches. A brain MRI confirmed multiple abscesses. Craniotomy and lesion removal were performed, leading to a diagnosis of brain abscesses caused by Nocardia asiatica. Empirical antibiotics were followed by targeted regimen. After successful treatment, the patient remained symptom-free during follow-ups. Nocardia asiatica multiple brain abscesses are exceedingly rare. This case underscores the importance of considering nocardiosis in immunosuppressed patients presenting with neurological symptoms. Timely neurosurgical intervention and effective antibiotic therapy are crucial. Metagenomic next-generation sequencing proved invaluable for rapid diagnosis. Treatment with trimethoprim-sulfamethoxazole (TMP-SMX) and a carbapenem followed by TMP-SMX alone achieved disease control. This case contributes to the understanding of Nocardia asiatica infections and highlights the role of neurosurgical procedures in managing disseminated nocardiosis.

Ru-W Pair Sites Enabling the Ensemble Catalysis for Efficient Hydrogen Evolution.

Simultaneously optimizing elementary steps, such as water dissociation, hydroxyl transferring, and hydrogen combination, is crucial yet challenging for achieving efficient hydrogen evolution reaction (HER) in alkaline media. Herein, Ru single atom-doped WO2 nanoparticles with atomically dispersed Ru-W pair sites (Ru-W/WO2 -800) are developed using a crystalline lattice-confined strategy, aiming to gain efficient alkaline HER. It is found that Ru-W/WO2 -800 exhibits remarkable HER activity, characterized by a low overpotential (11 mV at 10 mA cm-2 ), notable mass activity (5863 mA mg-1 Ru at 50 mV), and robust stability (500 h at 250 mA cm-2 ). The highly efficient activity of Ru-W/WO2 -800 is attributed to the synergistic effect of Ru-W sites through ensemble catalysis. Specifically, the W sites expedite rapid hydroxyl transferring and water dissociation, while the Ru sites accelerate the hydrogen combination process, synergistically facilitating the HER activity. This study opens a promising pathway for tailoring the coordination environment of atomic-scale catalysts to achieve efficient electro-catalysis.

Direct Observation of Transition Metal Ions Evolving into Single Atoms: Formation and Transformation of Nanoparticle Intermediates.

Understanding the dynamical evolution from metal ions to single atoms is of great importance to the rational development of synthesis strategies for single atom catalysts (SACs) against metal sintering during pyrolysis. Herein, an in situ observation is disclosed that the formation of SACs is ascertained as a two-step process. There is initially metal sintering into nanoparticles (NPs) (500-600 °C), followed by the conversion of NPs into metal single atoms (Fe, Co, Ni, Cu SAs) at higher temperature (700-800 °C). Theoretical calculations together with control experiments based on Cu unveil that the ion-to-NP conversion can arise from the carbon reduction, and NP-to-SA conversion being steered by generating more thermodynamically stable Cu-N4 configuration instead of Cu NPs. Based on the evidenced mechanism, a two-step pyrolysis strategy to access Cu SACs is developed, which exhibits excellent ORR performance.

External-Shell Oxygen Enabling the Local Environment Modulation of Unsaturated NbN3 for Efficient Electrosynthesis of Hydrogen Peroxide.

Single-atom catalysts with a tunable coordination structure have shown grand potential in flexibly altering the selectivity of oxygen reduction reaction (ORR) toward the desired pathway. However, rationally mediating the ORR pathway by modulating the local coordination number of the single-metal sites is still challenging. Herein, we prepare the Nb single-atom catalysts (SACs) with an external-shell oxygen-modulated unsaturated NbN3 site in carbon nitride and the NbN4 site anchored in nitrogen-doped carbon carriers, respectively. Compared with typical NbN4 moieties for 4e- ORR, the as-prepared NbN3 SACs exhibit excellent 2e- ORR activity in 0.1 M KOH, with the onset overpotential close to zero (9 mV) and the H2O2 selectivity above 95%, making it one of the state-of-the-art catalysts in the electrosynthesis of hydrogen peroxide. Density functional theory (DFT) theoretical calculations indicate the unsaturated Nb-N3 moieties and the adjacent oxygen groups optimize the interface bond strength of pivotal intermediates (OOH*) for producing H2O2, thus accelerating the 2e- ORR pathway. Our findings may provide a novel platform for developing SACs with high activity and tunable selectivity.

Serum Metabolic Correlates of the Antibody Response in Subjects Receiving the Inactivated COVID-19 Vaccine.

BACKGROUND: Metabolites are involved in biological process that govern the immune response to infection and vaccination. Knowledge of how metabolites interact with the immune system during immunization with the COVID-19 vaccine is limited. Here, we report that the serum metabolites are correlated with the magnitude of the antibody response in recipients receiving the inactivated COVID-19 vaccine, which provides critical information for studying metabolism regarding the human immune response to vaccination. METHODS: 106 healthy volunteers without history of SARS-CoV-2 infection or vaccination were prospectively enrolled to receive the primary series of two doses of inactivated whole-virion SARS-CoV-2 vaccine. The serum samples were collected 2-4 weeks after the second dose. The magnitude of the anti-RBD antibody was quantified using surrogate virus neutralization tests. The profile of metabolites in serum was identified using untargeted metabolomics analysis. RESULTS: The level of anti-RBD antibody 14-28 days after the second dose was significantly elevated and its interpersonal variability was diverse in a wide range. Thirty-two samples at extremes of the anti-RBD antibody titer were selected to discover the metabolic correlates. Two hundred and fifteen differential metabolites associated with antibody response independent of body mass index were identified. Pregnenolone and sphingolipid metabolism might be involved in the modulation of the human antibody response to the inactivated COVID-19 vaccine. CONCLUSION: We discovered key metabolites as well as those with a related functional significance that might modulate the human immune response to vaccination.

Overexpression of the Zygophyllum xanthoxylum Aquaporin, ZxPIP1;3, Promotes Plant Growth and Stress Tolerance.

Drought and salinity can result in cell dehydration and water unbalance in plants, which seriously diminish plant growth and development. Cellular water homeostasis maintained by aquaporin is one of the important strategies for plants to cope with these two stresses. In this study, a stress-induced aquaporin, ZxPIP1;3, belonging to the PIP1 subgroup, was identified from the succulent xerophyte Zygophyllum xanthoxylum. The subcellular localization showed that ZxPIP1;3-GFP was located in the plasma membrane. The overexpression of ZxPIP1;3 in Arabidopsis prompted plant growth under favorable condition. In addition, it also conferred salt and drought tolerance with better water status as well as less ion toxicity and membrane injury, which led to more efficient photosynthesis and improved growth vigor via inducing stress-related responsive genes. This study reveals the molecular mechanisms of xerophytes' stress tolerance and provides a valuable candidate that could be used in genetic engineering to improve crop growth and stress tolerance.

A graphene assembled porous fiber-based Janus membrane for highly effective solar steam generation.

Owing to the shortage of clean water as the global problem, the exploration of photothermal substances with high performance solar steam generation for sustainable water purification is essential and urgent. Herein, we demonstrate the assembly of two-dimensional graphene into one-dimensional rough, loose, and porous fibers and further use the assembled fibers to fabricate Janus membrane evaporator. The specific configuration guarantees an enhanced light harvesting property through multiple reflections, and improves the vapor transport ability through the constructed interlaced network. As a result, the as-obtained evaporator exhibits high solar absorbance, superior photothermal property and energy conversion efficiency, which is much higher than those of other reported Janus membrane evaporators and also better than the fabricated carbon nanotube-, and graphene sheet-based Janus membrane evaporator. The water purification results indicate that the fabricated graphene fiber-based Janus membrane is highly effective in seawater desalination without obvious salt accumulation and heavy metal wastewater purification. This study proposes a neotype graphene assembly for the fabrication of Janus membrane evaporator, which has potential applications in desalination and wastewater decontamination.

SAUR15 Promotes Lateral and Adventitious Root Development via Activating H+-ATPases and Auxin Biosynthesis.

SMALL AUXIN-UP RNAs (SAURs) comprise the largest family of early auxin response genes. Some SAURs have been reported to play important roles in plant growth and development, but their functional relationships with auxin signaling remain unestablished. Here, we report Arabidopsis (Arabidopsis thaliana) SAUR15 acts downstream of the auxin response factors ARF6,8 and ARF7,19 to regulate auxin signaling-mediated lateral root (LR) and adventitious root (AR) formation. The loss-of-function mutant saur15-1 exhibits fewer LRs and ARs. By contrast, plants overexpressing SAUR15 exhibit more LRs and ARs. We find that the SAUR15 promoter contains four tandem auxin-responsive elements, which are directly bound by ARF6 and ARF7 and are essential for SAUR15 expression. LR and AR impairment in arf6 and arf7 mutants is partially reduced by ectopic expression of SAUR15 Additionally, we demonstrate that the ARF6,7-upregulated SAUR15 promotes LR and AR development using two mechanisms. On the one hand, SAUR15 interacts with PP2C-D subfamily type 2C protein phosphatases to inhibit their activities, thereby stimulating plasma membrane H+-ATPases, which drives cell expansion and facilitates LR and AR formation. On the other hand, SAUR15 promotes auxin accumulation, potentially by inducing the expression of auxin biosynthesis genes. A resulting increase in free auxin concentration likely triggers LR and AR formation, forming a feedback loop. Our study provides insights and a better understanding of how SAURs function at the molecular level in regulating auxin-mediated LR and AR development.

Calibration and evaluation of Quigley's hybrid housing price model in Microsoft Excel.

Quigley derived his hybrid price model to improve the precision of predicted prices of sold homes by statistically merging data of resold homes in a repeat sales model with that of once-sold homes in a single sales hedonic price model. The literature has few applications of the hybrid model aside from those by Quigley and his collaborators. Two reasons for this underuse may be its computational intensiveness and its marginal empirical improvement in comparison with two other models. This paper first demystifies this computational intensiveness by calibrating models in Microsoft Excel with transferable procedures into other software. It second evaluates the hybrid price model's empirical improvement as a reason for its underuse by predicting prices of 2,559 sold and resold homes observed in two inner-city neighbourhoods in Windsor, Ontario, during a 30-year period. The results as hypothesized are its lower standard errors of regression coefficients and higher simple R-squared than those of a single sales hedonic price model. Moreover, the hybrid model's predictions have higher correlations than those of the single sales model with not only in-sample observed prices or changes in prices but also out-of-sample ones. The conclusion speculates in plans for future research about reasons for two models' similar or dissimilar regression coefficients and standard errors predicting correspondingly similar or dissimilar sale prices of homes through time.

Transcriptome analysis reveals regulatory framework for salt and osmotic tolerance in a succulent xerophyte.

BACKGROUND: Zygophyllum xanthoxylum is a succulent xerophyte with remarkable tolerance to diverse abiotic stresses. Previous studies have revealed important physiological mechanisms and identified functional genes associated with stress tolerance. However, knowledge of the regulatory genes conferring stress tolerance in this species is poorly understood. RESULTS: Here, we present a comprehensive analysis of regulatory genes based on the transcriptome of Z. xanthoxylum roots exposed to osmotic stress and salt treatments. Significant changes were observed in transcripts related to known and obscure stress-related hormone signaling pathways, in particular abscisic acid and auxin. Significant changes were also found among key classes of early response regulatory genes encoding protein kinases, transcription factors, and ubiquitin-mediated proteolysis machinery. Network analysis shows a highly integrated matrix formed by these conserved and novel gene products associated with osmotic stress and salt in Z. xanthoxylum. Among them, two previously uncharacterized NAC (NAM/ATAF/CUC) transcription factor genes, ZxNAC083 (Unigene16368_All) and ZxNAC035 (CL6534.Contig1_All), conferred tolerance to salt and drought stress when constitutively overexpressed in Arabidopsis plants. CONCLUSIONS: This study provides a unique framework for understanding osmotic stress and salt adaptation in Z. xanthoxylum including novel gene targets for engineering stress tolerance in susceptible crop species.

Blockade of receptor for advanced glycation end products promotes oligodendrocyte autophagy in spinal cord injury.

Receptor for advanced glycation end product (RAGE) is involved in neuronal inflammation, cell cycle and differentiation. However, the role of RAGE in autophagy in the process of spinal cord injury (SCI) is yet unknown. The present study investigated the effect of RAGE blockade on autophagy in SCI. A rat Allen SCI model was established and the animals were micro-injected with rabbit RAGE neutralizing antibody or rabbit polyclonal Ig G immediately after the injury. The oligodendrocytes(OLs) marker, 2', 3'-cyclic nucleotide 3'-phosphodiesterase(CNPase) and autophagy-related marker microtubule associated protein light chain 3B(LC3B) were evaluated by Western blot. Furthermore, myelin basic protein (MBP) and LC3B double staining were observed in the SCI via immunofluorescence. The results showed that RAGE blockade reduced the expression of CNPase, promoted LC3B-II/I and p62 expression after SCI. In addition, the MBP/LC3B double positive oligodendrocytes-expressing LC3B was up-regulated by RAGE blockade. Moreover, RAGE blockade attenuated the neuronal survival at ventral horn after SCI. The present study revealed the role of RAGE in maintaining oligodendrocyte autophagy to promote neuronal regeneration post-SCI.

Modulating Effects of Contextual Emotions on the Neural Plasticity Induced by Word Learning.

Recently, numerous studies have investigated the neurocognitive mechanism of learning words in isolation or in semantic contexts. However, emotion as an important influencing factor on novel word learning has not been fully considered in the previous studies. In addition, the effects of emotion on word learning and the underlying neural mechanism have not been systematically investigated. Sixteen participants were trained to learn novel concrete or abstract words under negative, neutral, and positive contextual emotions over 3 days; then, fMRI scanning was done during the testing sessions on day 1 and day 3. We compared the brain activations in day 1 and day 3 to investigate the role of contextual emotions in learning different types of words and the corresponding neural plasticity changes. Behaviorally, the performance of the words learned in the negative context was lower than those in the neutral and positive contexts, which indicated that contextual emotions had a significant impact on novel word learning. Correspondingly, the functional plasticity changes of the right angular gyrus (AG), bilateral insula, and anterior cingulate cortex (ACC) induced by word learning were modulated by the contextual emotions. The insula also was sensitive to the concreteness of the learned words. More importantly, the functional plasticity changes of the left inferior frontal gyrus (left IFG) and left fusiform gyrus (left FG) were interactively influenced by the contextual emotions and concreteness, suggesting that the contextual emotional information had a discriminable effect on different types of words in the neural mechanism level. These results demonstrate that emotional information in contexts is inevitably involved in word learning. The role of contextual emotions in brain plasticity for learning is discussed.

Seed-Mediated Synthesis of Tunable-Aspect-Ratio Gold Nanorods for Near-Infrared Photoacoustic Imaging.

Tunable-aspect ratio gold nanorods have been synthesized by a modified seed-mediated synthesis method. Ascorbic acid was employed as a shape controller to induce anisotropic growth, which made the aspect ratio of the synthesized gold nanorods range from 8.5 to 15.6. These nanorods possess tunable longitudinal surface plasmon resonance absorption band, covering a broad near-infrared (NIR) range, from ~ 680 to 1100 nm. When modified with thiol-polyethylene glycol (SH-PEG), the synthesized Au nanorods showed excellent biocompatibility and stability, which foreshadowed the great potential of their NIR application as photoacoustic contrast agent. Due to their adjustable absorbance in the NIR, the synthesized Au nanorods could offer stronger contrast (3.1 times to the control group without contrast agent used) and higher signal-noise ratio values (SNR; 5.6 times to the control group) in photoacoustic imaging, both in vitro and in vivo experiments. Our work presented here not only added some novel Au-based photoacoustic contrast agents but also described a possibility of contrast agent preparation covering the whole biological NIR window.

MP Resulting in Autophagic Cell Death of Microglia through Zinc Changes against Spinal Cord Injury.

Methylprednisolone pulse therapy (MPPT), as a public recognized therapy of spinal cord injury (SCI), is doubted recently, and the exact mechanism of MP on SCI is unclear. This study sought to investigate the exact effect of MP on SCI. We examined the effect of MP in a model of SCI in vivo and an LPS induced model in vitro. We found that administration of MP produced an increase in the Basso, Beattie, and Bresnahan scores and motor neurons counts of injured rats. Besides the number of activated microglia was apparently reduced by MP in vivo, and Beclin-1 dependent autophagic cell death of microglia was induced by MP in LPS induced model. At the same time, MP increases cellular zinc concentration and level of ZIP8, and TPEN could revert effect of MP on autophagic cell death of microglia. Finally, we have found that MP could inhibit NF-κß in LPS induced model. These results show that the MP could result in autophagic cell death of microglia, which mainly depends on increasing cellular labile zinc, and may be associated with inhibition of NF-κß, and that MP can produce neuroprotective effect in SCI.

VEGF inhibits the inflammation in spinal cord injury through activation of autophagy.

Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis and re-vascularization of spinal cord injury (SCI). VEGF has long been thought to be a potent neurotrophic factor for the survival of spinal cord neuron. However, the neuroprotective mechanism of VEGF is still unclear. The aim of this study was to investigate the effect of VEGF on spinal cord injury and its mechanisms. Young male Wistar rats were subjected to SCI and then VEGF165 were injected directly into the lesion epicenter 24 h post injury. We detected Basso, Beattie and Bresnahan (BBB) scores and numbers of motor neuron via Nissl staining. The expressions of autophagy related protein Beclin1 and LC3B were determined by Western blot and RT-PCR. We also detected the contents of inflammation factors interleukin-1ß (IL-1ß), tumor necrosis factor alpha (TNF-α) and interleukin-10(IL-10) in LPS (Lipopolysaccharide) treated spinal neuron-glia co-culture by ELISA. We found that VEGF165 administration increased the BBB score and reduced the loss of motor neuron of rats induced by SCI. VEGF decreased the protein expressions of IL-1ß, TNF-α and IL-10 and up-regulated the expressions of Beclin1 and LC3B of rats. In the in vitro study, VEGF165 decreased the levels of IL-1ß, IL-10 and TNF-a in the medium of LPS treated spinal neuron-glia co-culture, which was partially blocked by 3-MA, the inhibitor of autophagy. In addition, VEGF165 up-regulate the expressions of Beclin1 and LC3B in co-culture cells. The results suggested that VEGF165 attenuated the spinal cord injury by inhibiting the inflammation and increasing the autophagy function.