Less spatial exploration is associated with poorer spatial memory in midlife adults.

Introduction: Despite its importance for navigation, very little is known about how the normal aging process affects spatial exploration behavior. We aimed to investigate: (1) how spatial exploration behavior may be altered early in the aging process, (2) the relationship between exploration behavior and subsequent spatial memory, and (3) whether exploration behavior can classify participants according to age. Methods: Fifty healthy young (aged 18-28) and 87 healthy midlife adults (aged 43-61) freely explored a desktop virtual maze, learning the locations of nine target objects. Various exploration behaviors (object visits, distance traveled, turns made, etc.) were measured. In the test phase, participants navigated from one target object to another without feedback, and their wayfinding success (% correct trials) was measured. Results: In the exploration phase, midlife adults exhibited less exploration overall compared to young adults, and prioritized learning target object locations over maze layout. In the test phase, midlife adults exhibited less wayfinding success when compared to the young adults. Furthermore, following principal components analysis (PCA), regression analyses indicated that both exploration quantity and quality components were associated with wayfinding success in the midlife group, but not the young adults. Finally, we could classify participants according to age with similar accuracy using either their exploration behavior or wayfinding success scores. Discussion: Our results aid in the understanding of how aging impacts spatial exploration, and encourages future investigations into how pathological aging may affect spatial exploration behavior.

Extracellular Vesicles Derived from H2O2-Stimulated Adipose-Derived Stem Cells Alleviate Senescence in Diabetic Bone Marrow Mesenchymal Stem Cells and Restore Their Osteogenic Capacity.

Introduction: Autologous stem cell transplantation has emerged as a promising strategy for bone repair. However, the osteogenic potential of mesenchymal stem cells derived from diabetic patients is compromised, possibly due to hyperglycemia-induced senescence. The objective of this study was to assess the preconditioning effects of extracellular vesicles derived from H2O2-stimulated adipose-derived stem cells (ADSCs) and non-modified ADSCs on the osteogenic potential of diabetic bone marrow mesenchymal stem cells (BMSCs). Methods: Sprague-Dawley (SD) rats were experimentally induced into a diabetic state through a high-fat diet followed by an injection of streptozotocin, and diabetic BMSCs were collected from the bone marrow of these rats. Extracellular vesicles (EVs) were isolated from the conditioned media of ADSCs, with or without hydrogen peroxide (H2O2) preconditioning, using density gradient centrifugation. The effects of H2O2 preconditioning on the morphology, marker expression, and particle size of the EVs were analyzed. Furthermore, the impact of EV-pretreatment on the viability, survivability, migration ability, osteogenesis, cellular senescence, and oxidative stress of diabetic BMSCs was examined. Moreover, the expression of the Nrf2/HO-1 pathway was also assessed to explore the underlying mechanism. Additionally, we transplanted EV-pretreated BMSCs into calvarial defects in diabetic rats to assess their in vivo bone formation and anti-senescence capabilities. Results: Our study demonstrated that pretreatment with EVs from ADSCs significantly improved the viability, senescence, and osteogenic differentiation potential of diabetic BMSCs. Moreover, in-vitro experiments revealed that diabetic BMSCs treated with H2O2-activated EVs exhibited increased viability, reduced senescence, and enhanced osteogenic differentiation compared to those treated with non-modified EVs. Furthermore, when transplanted into rat bone defects, diabetic BMSCs treated with H2O2-activated EVs showed improved bone regeneration potential and enhanced anti-senescence function t compared to those treated with non-modified EVs. Both H2O2-activated EVs and non-modified EVs upregulated the expression of the Nrf2/HO-1 pathway in diabetic BMSCs, however, the promoting effect of H2O2-activated EVs was more pronounced than that of non-modified EVs. Conclusion: Extracellular vesicles derived from H2O2-preconditioned ADSCs mitigated senescence in diabetic BMSCs and enhanced their bone regenerative functions via the activation of the Nrf2/HO-1 pathway.

Evaluating the efficacy of mesenchymal stem cells for diabetic neuropathy: A systematic review and meta-analysis of preclinical studies.

Diabetic neuropathy affects nearly half of all diabetics and poses a significant threat to public health. Recent preclinical studies suggest that mesenchymal stem cells (MSCs) may represent a promising solution for the treatment of diabetic neuropathy. However, an objective assessment of the preclinical effectiveness of MSCs is still pending. We conducted a comprehensive search of PubMed, Web of Science, Embase, and Cochrane library to identify preclinical studies that investigate the effects of MSCs on diabetic neuropathy up until 15 September 2023. Outcome indicators consisted of motor and sensory nerve conduction velocities, intra-epidermal nerve fiber density, sciatic nerve blood flow, capillary-to-muscle fiber ratio, neurotrophic factors, angiogenic factors and inflammatory cytokines. The literature review and meta-analysis were conducted independently by two researchers. 23 studies that met the inclusion criteria were included in this system review for qualitative and quantitative analysis. Pooled analyses indicated that MSCs exhibited an evident benefit in diabetic neuropathy in terms of motor (SMD = 2.16, 95% CI: 1.71-2.61) and sensory nerve conduction velocities (SMD = 2.93, 95% CI: 1.78-4.07), intra-epidermal nerve fiber density (SMD = 3.17, 95% CI: 2.28-4.07), sciatic nerve blood flow (SMD = 2.02, 95% CI: 1.37-2.66), and capillary-to-muscle fiber ratio (SMD = 2.28, 95% CI: 1.55 to 3.01, p < 0.00001). Furthermore, after MSC therapy, the expressions of neurotrophic and angiogenic factors increased significantly in most studies, while the levels of inflammatory cytokines were significantly reduced. The relevance of this review relies on the fact that summarizes an extensive body of work entailing substantial preclinical evidence that supports the efficacy of MSCs in mitigating diabetic neuropathy. While MSCs emerge as a promising potential treatment for diabetic neuropathy, further research is essential to elucidate the underlying mechanisms and the best administration strategy for MSCs.

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 first global multi-timescale daily SPEI dataset from 1982 to 2021.

Global warming accelerates water cycle, causing more droughts globally that challenge monitoring and forecasting. The Standardized Precipitation Evapotranspiration Index (SPEI) is used to assess drought characteristics and response time of natural and economic systems at various timescales. However, existing SPEI datasets have coarse spatial or temporal resolution or limited spatial extent, restricting their ability to accurately identify the start or end dates or the extent of drought at the global scale. To narrow these gaps, we developed a global daily SPEI dataset (SPEI-GD), with a 0.25° spatial resolution from 1982 to 2021 at multiple timescales (5, 30, 90, 180 and 360 days), based on the precipitation from European Center for Medium Weather Forecasting Reanalysis V5 (ERA5) dataset and the potential evapotranspiration from Singer's dataset. Compared to widely used SPEIbase dataset, the SPEI-GD can improve the spatial-temporal resolution and the accuracy of SPEI in areas where meteorological sites are lacking. The SPEI-GD significantly correlates with site-based SPEI and soil moisture. Our dataset solidly supports sub-seasonal and daily-scale global and regional drought research.

Development and Evaluation of a Novel Hyaluronic Acid and Chitosan-modified Phytosome for Co-delivery of Oxymatrine and Glycyrrhizin for Combination Therapy.

BACKGROUND: Multidrug resistance (MDR) of cancer cells is a major obstacle to efficient cancer chemotherapy. Combination therapy is expected to enhance the anticancer effect and reverse MDR. Numerous patents involve different kinds of nanoparticles for the co-delivery of multiple chemotherapeutics, but the FDA has approved none. OBJECTIVE: In this study, oxymatrine (OMT) and glycyrrhizin (GL) were co-loaded into phytosomes as the core of nanocarriers, and the shell was cross-linked with chitosan (CS) and hyaluronic acid (HA) with the capability for the controlled, sequential release and the targeted drug uptake. METHODS: Phospholipid complexes of OMT and GL (OGPs) were prepared by a solvent evaporation technique and could self-assemble in an aqueous solution to form phytosomes. CS and HA were sequentially coated on the surface of OGPs via electrostatic interactions to obtain CS coated OGPs (CS-OGPs) and HA modified CS-OGPs (HA-CS-OGPs), respectively. The particle size and zeta potential were measured to optimize the formulations. In vitro cytotoxicity and cellular uptake experiments on HepG2 cells were performed to evaluate the anticancer activity. RESULTS: OGPs were obtained with nano-size around 100 nm, and CS and HA coating on phytosomes could change the particle size and surface potential. The drug loading of OMT and GL showed that the nanocarriers could maintain a fixed ratio of 1:1. The in vitro release experiments indicated the release of OMT and GL was pH-dependent and sequential: the release of OMT from CS-OGPs and HA-CS-OGPs was significantly increased at pH 5.0 compared to the release at pH 7.4, while GL exhibited sustained released from CS-OGPs and HA-CS-OGPs at pH 5.0. Furthermore, in vitro cytotoxicity and cellular uptake experiments on HepG2 cells demonstrated that the co-delivery system based on phytosomes had significant synergistic anti-tumor activities, and the effects were enhanced by CS and HA modification. CONCLUSION: The delivery of OMT and GL via HA-CS-OGPs might be a promising treatment to reverse MDR in cancer therapy.

Emergence of multiple fluconazole-resistant Candida parapsilosis sensu stricto clones with persistence and transmission in China.

OBJECTIVES: We explored the epidemiological and molecular characteristics of Candida parapsilosis sensu stricto isolates in China, and their mechanisms of azole resistance. METHODS: Azole susceptibilities of 2318 non-duplicate isolates were determined using CLSI broth microdilution. Isolates were genotyped by a microsatellite typing method. Molecular resistance mechanisms were also studied and functionally validated by CRISPR/Cas9-based genetic alterations. RESULTS: Fluconazole resistance occurred in 2.4% (n = 56) of isolates, and these isolates showed a higher frequency of distribution in ICU inpatients compared with susceptible isolates (48.2%, n = 27/56 versus 27.8%, 613/2208; P = 0.019). Microsatellite-genotyping analysis yielded 29 genotypes among 56 fluconazole-resistant isolates, of which 10 genotypes, including 37 isolates, belonged to clusters, persisting and transmitting in Chinese hospitals for 1-29 months. Clusters harbouring Erg11Y132F (5/10; 50%) were predominant in China. Among these, the second most dominant cluster MT07, including seven isolates, characteristically harbouring Erg11Y132F and Mrr1Q625K, lent its carriage to being one of the strongest associations with cross-resistance and high MICs of fluconazole (>256 mg/L) and voriconazole (2-8 mg/L), causing transmission across two hospitals. Among mutations tested, Mrr1Q625K led to the highest-level increase of fluconazole MIC (32-fold), while mutations located within or near the predicted transcription factor domain of Tac1 (D440Y, T492M and L518F) conferred cross-resistance to azoles. CONCLUSIONS: This study is the first Chinese report of persistence and transmissions of multiple fluconazole-resistant C. parapsilosis sensu stricto clones harbouring Erg11Y132F, and the first demonstration of the mutations Erg11G307A, Mrr1Q625K, Tac1L263S, Tac1D440Y and Tac1T492M as conferring resistance to azoles.

Exploring watershed ecological risk bundles based on ecosystem services: A case study of Shanxi Province, China.

Humans are having an increasingly profound impact on the environment along with the advent of the Anthropocene. Ecological risk assessment (ERA) as a method to quantify ecological problems can provide support for decision-makers, and it is one of key issues to integrate ecosystem services into ERA. In this study, an ERA framework was proposed under the loss-probability paradigm from the perspective of ecosystem services risk bundles. The results showed that initiatives aimed at ecological protection in Shanxi Province had been effective, the number of watersheds with low-risk bundles increased significantly (from 16.09% to 34.49%) and the watersheds basically overlapped with key forestation areas. However, the effects of forestation activities may no longer be as significant as they once were, as the relationship between forestation and water supply was becoming increasingly contradictory. Meanwhile, the conflict between urban expansion and natural ecosystem protection was intensifying, habitat degradation risks were gradually polarized, and the risk bundles dominated by high carbon emission and habitat degradation were increasing significantly (from 15.88% to 33.54%). Strengthening the construction of urban green space and controlling the expansion of human activities may be the next focus of ecological conservation in Shanxi Province. This study enriched the ERA framework with an ecosystem services risk bundle approach.

Systematic investigation of the emerging pathogen of Tsukamurella species in a Chinese tertiary teaching hospital.

Tsukamurella species have been clinically regarded as rare but emerging opportunistic pathogens causing various infections in humans. Tsukamurella pneumonia has often been misdiagnosed as pulmonary tuberculosis due to its clinical presentation resembling tuberculosis-like syndromes. Tsukamurella species have also been confused in the laboratory with other phylogenetic bacteria, such as Gordonia. This study aimed to investigate the clinical, microbiological, and molecular characteristics; species distribution; and antimicrobial susceptibility of Tsukamurella species. Immunodeficiency and chronic pulmonary disease appeared to be risk factors for Tsukamurella pneumonia, and the presence of bronchiectasis and pulmonary nodules on imaging was highly correlated with this infection. The study confirmed that groEL (heat shock protein 60) and secA (the secretion ATPase) genes are reliable for identifying Tsukamurella species. Additionally, the ssrA (stable small RNA) gene showed promise as a tool for discriminating between different Tsukamurella species with the shortest sequence length. In terms of antimicrobial susceptibility, quinolones, trimethoprim/sulfamethoxazole, amikacin, minocycline, linezolid, and tigecycline demonstrated potent in vitro activity against Tsukamurella isolates in our study. The study also proposed a resistance mechanism involving a substitution (S91R) within the quinolone-resistance-determining region of the gyrA gene, which confers resistance to levofloxacin and ciprofloxacin. Furthermore, we found that disk diffusion testing is not suitable for testing the susceptibilities of Tsukamurella isolates to ciprofloxacin, imipenem, and minocycline. In conclusion, our systematic investigation may contribute to a better understanding of this rare pathogen. Tsukamurella species are rare but emerging human pathogens that share remarkable similarities with other mycolic acid-containing genera of the order Actinomycetales, especially Mycobacterium tuberculosis. Consequently, misdiagnosis and therapeutic failures can occur in clinical settings. Despite the significance of accurate identification, antimicrobial susceptibility, and understanding the resistance mechanism of this important genus, our knowledge in these areas remains fragmentary and incomplete. In this study, we aimed to address these gaps by investigating promising identification methods, the antimicrobial susceptibility patterns, and a novel quinolone resistance mechanism in Tsukamurella species, utilizing a collection of clinical isolates. The findings of our study will contribute to improve diagnosis and successful management of infections caused by Tsukamurella species, as well as establishing well-defined performance and interpretive criteria for antimicrobial susceptibility testing.

The first established microsatellite markers to distinguish Candida orthopsilosis isolates and detection of a nosocomial outbreak in China.

The infection proportion of Candida orthopsilosis, a member of the C. parapsilosis complex, has increased globally in recent years, and nosocomial outbreaks have been reported in several countries. This study aimed to establish microsatellite loci-based typing method that was able to effectively distinguish among C. orthopsilosis isolates. Three reference C. orthopsilosis genome sequences were analyzed to identify repeat loci. DNA sequences containing over eight bi- or more nucleotide repeats were selected. A total of 51 loci were initially identified, and locus-specific primers were designed and tested with 20 epidemiologically unrelated isolates. Four loci with excellent reproducibility, specificity, and resolution for molecular typing purposes were identified, and the combined discriminatory power (DP, based on 20 epidemiologically unrelated isolates) of these four loci was 1.0. Reproducibility was demonstrated by consistently testing three strains each in triplicate, and stability, demonstrated by testing 10 successive passages. Then, we collected 48 C. orthopsilosis non-duplicate clinical isolates from the China Hospital Invasive Fungal Surveillance Net study to compare the DP of the microsatellite-based typing with internal transcribed spacer (ITS) and amplified fragment length polymorphism (AFLP) typing analyses, using ATCC 96139 as a reference strain. These 49 isolates were subdivided into 12 microsatellite types (COMT1-12), six AFLP types, and three ITS types, while all the isolates with the same COMT belonged to consistent AFLP and ITS type, demonstrating the high DP of our microsatellite-type method. According to our results, COMT12 was found to be the predominant type in China, and COMT5 was the second largest and responsible for causing a nosocomial outbreak. This microsatellite-type method is a valuable tool for the differentiation of C. orthopsilosis and could be vital for epidemiological studies to determine strain relatedness and monitor transmission.

Understanding Differences in Wayfinding Strategies.

Navigating to goal locations in a known environment (wayfinding) can be accomplished by different strategies, notably by taking habitual, well-learned routes (response strategy) or by inferring novel paths, such as shortcuts, from spatial knowledge of the environment's layout (place strategy). Human and animal neuroscience studies reveal that these strategies reflect different brain systems, with response strategies relying more on activation of the striatum and place strategies associated with activation of the hippocampus. In addition to individual differences in strategy, recent behavioral studies show sex differences such that men use place strategies more than women, and age differences such that older adults use more response strategies than younger adults. This paper takes a comprehensive multilevel approach to understanding these differences, characterizing wayfinding as a complex information processing task. This analysis reveals factors that affect navigation strategy, including availability of the relevant type of environmental knowledge, momentary access to this knowledge, trade-offs between physical and mental effort in different navigation contexts, and risk taking. We consider how strategies are influenced by the computational demands of a navigation task and by factors that affect the neural circuits underlying navigation. We also discuss limitations of laboratory studies to date and outline priorities for future research, including relating wayfinding strategies to independent measures of spatial knowledge, and studying wayfinding strategies in naturalistic environments.

Antifungal susceptibility profiles and drug resistance mechanisms of clinical Candida duobushaemulonii isolates from China.

Candida duobushaemulonii, type II Candida haemulonii complex, is closely related to Candida auris and capable of causing invasive and non-invasive infections in humans. Eleven strains of C. duobushaemulonii were collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), VITEK 2 Yeast Identification Card (YST), and internal transcribed spacer (ITS) sequencing. Whole genome sequencing of C. duobushaemulonii was done to determine their genotypes. Furthermore, C. duobushaemulonii strains were tested by Sensititre YeastOne™ and Clinical and Laboratory Institute (CLSI) broth microdilution panel for antifungal susceptibility. Three C. duobushaemulonii could not be identified by VITEK 2. All 11 isolates had high minimum inhibitory concentrations (MICs) to amphotericin B more than 2 µg/ml. One isolate showed a high MIC value of ≥64 µg/ml to 5-flucytosine. All isolates were wild type (WT) for triazoles and echinocandins. FUR1 variation may result in C. duobushaemulonii with high MIC to 5-flucytosine. Candida duobushaemulonii mainly infects patients with weakened immunity, and the amphotericin B resistance of these isolates might represent a challenge to clinical treatment.

Correlation of Moraxella catarrhalis macrolide susceptibility with the ability to adhere and invade human respiratory epithelial cells.

Recently, the prevalence of macrolide-resistant Moraxella catarrhalis has been reported, especially among Chinese children. The fitness cost of resistance is reported to render the resistant bacteria less virulent. To investigate the correlation between macrolide susceptibility of M. catarrhalis and pathogenicity, the whole genome of 70 M. catarrhalis isolates belonging to four clonal complexes with different macrolide susceptibilities was sequenced. The gene products were annotated with the Gene Ontology terms. Based on 46 extracted essential virulence genes, 19 representative isolates were selected to infect type II alveolar cells (A549 cells). The ability of these isolates to adhere and invade human epithelial cells and to produce cytokines was comparatively analysed. Furthermore, mice were infected with a pair of M. catarrhalis isolates with different pathogenic behaviours and macrolide susceptibilities to examine pulmonary clearance, histological findings, and the production of cytokines. The percentages of annotations for binding, metabolic process, cellular process, and cell were non-significantly different between the macrolide-resistant and macrolide-susceptible groups. The presence of uspA2, uspA2H, pilO, lbpB, lex1, modM, mboIA, and mboIB significantly differed among the four clonal complexes and macrolide susceptibility groups. Furthermore, compared with those in macrolide-susceptible isolates, the adhesion ability was stronger (P = 0.0019) and the invasion ability was weaker (P < 0.0001) in the macrolide-resistant isolates. Mouse experiments revealed that pulmonary macrophages elicit immune responses against M. catarrhalis infection by significantly upregulating the Csf2, Il4, Il13, Il1b, Il6, Tnf, and Il18. Therefore, M. catarrhalis populations exhibited diverse pathogenicity in vitro and in vivo.

Histone Acetylation Regulator Gcn5 Mediates Drug Resistance and Virulence of Candida glabrata.

Candida glabrata is poised to adapt to drug pressure rapidly and acquire antifungal resistance leading to therapeutic failure. Given the limited antifungal armamentarium, there is an unmet need to explore new targets or therapeutic strategies for antifungal treatment. The lysine acetyltransferase Gcn5 has been implicated in the pathogenesis of C. albicans. Yet how Gcn5 functions and impacts antifungal resistance in C. glabrata is unknown. Disrupting GCN5 rendered C. glabrata cells more sensitive to various stressors, partially reverted resistance in drug-resistant mutants, and attenuated the emergence of resistance compared to wild-type cells. RNA sequencing (RNA-seq) analysis revealed transcriptomic changes involving multiple biological processes and different transcriptional responses to antifungal drugs in gcn5Δ cells compared to wild-type cells. GCN5 deletion also resulted in reduced intracellular survival within THP-1 macrophages. In summary, Gcn5 plays a critical role in modulating the virulence of C. glabrata and regulating its response to antifungal pressure and host defense. IMPORTANCE As an important and successful human pathogen, Candida glabrata is known for its swift adaptation and rapid acquisition of resistance to the most commonly used antifungal agents, resulting in therapeutic failure in clinical settings. Here, we describe that the histone acetyltransferase Gcn5 is a key factor in adapting to antifungal pressure and developing resistance in C. glabrata. The results provide new insights into epigenetic control over the drug response in C. glabrata and may be useful for drug target discovery and the development of new therapeutic strategies to combat fungal infections.

Neuroprotective effects of CysLTR antagonist on Streptococcus pneumoniae-induced meningitis in rats.

Cysteinyl leukotrienes (CysLTs) modulate central nervous system inflammatory responses via their receptors, CysLT1R and CysLT2R. It has been demonstrated that CysLTR participates in the infection process of Streptococcus pneumoniae (SP)-induced meningitis. In the present study, the effects and possible underlying mechanisms of CysLTR antagonists (pranlukast and HAMI 3379) on SP meningitis were further determined. SP meningitis was induced by intracerebroventricular injection of serotype III SP in Sprague-Dawley rats which were administrated intraperitoneally with 0.1 mg/kg antagonists. The clinical disease status of rats was evaluated by body weight and behavioral changes with neurological scoring. Survival neuron density, activated microglial and astrocytes were assessed by Nissl staining and immunohistochemical staining. The expression levels of inflammatory cytokines and NLRP3 inflammasome were detected by reverse transcription-quantitative PCR and western blotting, respectively. Pranlukast and HAMI 3379 treatment markedly alleviated the clinical disease status, which was manifested by improving body weight loss and neurological deficit. Furthermore, pranlukast and HAMI 3379 treatment ameliorated neuronal injury and inhibited microgliosis and astrogliosis. In addition, significant downregulation of inflammatory cytokines and NLRP3 expression was observed in pranlukast and HAMI 3379-treated rats. These in vivo findings indicated the neuroprotective effects of CysLTR antagonists against experimental SP-induced meningitis, and the mechanism of anti-inflammatory effects may partly be by inhibiting NLRP3 inflammasome overactivation.

Elevation dependency of ecosystem services supply efficiency in great lake watershed.

Although it is well acknowledged that the improvement of ecosystem services is conducive to human well-being, there is still a lack of approach to determining reasonable improvement goals, especially for ecosystem services with trade-off relationship. Based on the method of production possibility frontier (PPF), this study presented a novel approach to identifying the improvement goals of interacting ecosystem services with considering their context dependency. By calculating the gap between the current supply of ecosystem services and the reasonable improvement goal, the ecosystem services supply efficiency was defined and measured to identify the optimization potentials of ecosystem services with trade-off relationship. The results showed that the supply efficiency of ecosystem services (grain production and water purification) decreased and then increased significantly along with the increasing of farmland area ratio in the Dongting Lake Basin (DLB). Meanwhile, the inflection point appeared when the farmland area ratio was 0.16. The change of farmland area ratio was significantly influenced by the change of elevation, with the regression coefficients of elevation on the left and right sides of the inflection point being -1.28 and -0.5 respectively, which were higher than that of other factors. Along with the increasing of elevation, the ecosystem services supply efficiency decreased but increased when the elevation exceeded 721.74 m. Furthermore, the sub-watersheds with farmland area ratio below the inflection point, i.e. mainly high elevation areas, were located around national or provincial level poor counties, posing a great challenge for improving ecosystem services with trade-off relationship. Development strategies for sub-watersheds should consider the non-linear trade-offs of ecosystem services, especially the opposite stages of supply efficiency. This study highlighted the elevation dependency of ecosystem services supply efficiency through farmland area ratio in great lake watershed.

A wavelet coherence approach to detecting ecosystem services trade-off response to land use change.

Clarifying the complex land use impacts on ecosystem services (ESs) trade-off will be beneficial to watershed sustainable development, especially through scientific land use management and decision making. Dongting Lake Basin (DLB) is not only one of the most significant ecological barriers for the Yangtze River Economic Belt, but also an important grain production base of China. The trade-off between the grain production (GP) and water purification (WP) has become increasingly prominent. Here, we chose DLB as a case study area, applied spatial continuous wavelet transform and wavelet coherence analysis, characterized the ES trade-off intensity by wavelet coherence coefficient, and explored the influence of land use type, conflict and intensity on the trade-off between GP and WP. The results showed that the trade-off intensity between GP and WP in the DLB in 2015 had alleviated compared with 2005, and the coherence coefficient had increased while maitaining the negative value. The trade-off intensity was the strongest in farmland and forest land, and weaker in grassland and water body. The impact of land use conflict mainly depended on the specific types of land use conversions. For the transects where land use conversions mainly appeared between farmland and forest land, the intensification of land use conflict would increase the trade-off intensity (2005: R2 = 0.3862, p < 0.05; 2015: R2 = 0.2543, p < 0.05), while for the transects dominated by conversions to water body and grassland, stronger land use conflicts would reduce the trade-off intensity (2005: R2 = 0.3438, p < 0.05; 2015: R2 = 0.2668, p < 0.05). The impact of land use intensity was also realized through the land use type, with lower interpretation ratio. In addition, the wavelet coherence analysis showed that the scale about 10.51 km was the most suitable for exploring the trade-off between GP and WP, which was equivalent to the scale of the secondary watershed in the study area.

Species distribution and antifungal susceptibilities of clinical isolates of Penicillium and Talaromyces species in China.

Morphologically identified Penicillium (n = 103) and Talaromyces marneffei (n = 8) isolates were collected from various clinical sources between 2016 and 2017 at a medical centre in Beijing, China. Identification to species level was confirmed by sequencing of the internal transcribed spacer (ITS) region, ß-tubulin gene (benA) and RNA polymerase II second largest subunit (RPB2) gene. Of the 111 isolates, 56 (50.5%) were identified as Penicillium spp. and 55 (49.5%) as Talaromyces spp. Eleven species of Penicillium were detected, of which Penicillium oxalicum was the commonest, accounting for 51.8% (29/56), followed by Penicillium rubens (10.7%; 6/56) and Penicillium citrinum (10.7%; 6/56). Among the 55 Talaromyces isolates, nine species were identified, with Talaromyces funiculosus (36.4%; 20/55), Talaromyces stollii (27.3%; 15/55) and Talaromyces marneffei (14.5%; 8/55) being the most common. Of note, 89.3% (50/56) of the Penicillium isolates and 98.2% (54/55) of the Talaromyces isolates exhibited growth at 37°C. The isolates were mainly recovered from patients with pulmonary disorders (56.8%; 63/111), autoimmune disease (12.6%; 14/111) and AIDS (5.4%; 6/111). The azoles and amphotericin B exhibited potent activity against T. marneffei, while various levels of activity were observed against Penicillium and other Talaromyces species The echinocandins had the lowest MECs (MEC90, ≤0.12 mg/L) against most Penicillium and Talaromyces species, with the exception of T. marneffei whose MEC90 (4 mg/L) was five or more dilutions higher than that of the other species tested. These data on the species distribution and antifungal susceptibility expand the current clinical knowledge of Penicillium and Talaromyces species.

Age-Related Changes in Spatial Navigation Are Evident by Midlife and Differ by Sex.

Accumulating evidence suggests that distinct aspects of successful navigation-path integration, spatial-knowledge acquisition, and navigation strategies-change with advanced age. Yet few studies have established whether navigation deficits emerge early in the aging process (prior to age 65) or whether early age-related deficits vary by sex. Here, we probed healthy young adults (ages 18-28) and midlife adults (ages 43-61) on three essential aspects of navigation. We found, first, that path-integration ability shows negligible effects of sex or age. Second, robust sex differences in spatial-knowledge acquisition are observed not only in young adulthood but also, although with diminished effect, at midlife. Third, by midlife, men and women show decreased ability to acquire spatial knowledge and increased reliance on taking habitual paths. Together, our findings indicate that age-related changes in navigation ability and strategy are evident as early as midlife and that path-integration ability is spared, to some extent, in the transition from youth to middle age.

Evaluation of Autof MS 1000 and Vitek MS MALDI-TOF MS System in Identification of Closely-Related Yeasts Causing Invasive Fungal Diseases.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been accepted as a rapid, accurate, and less labor-intensive method in the identification of microorganisms in clinical laboratories. However, there is limited data on systematic evaluation of its effectiveness in the identification of phylogenetically closely-related yeast species. In this study, we evaluated two commercially available MALDI-TOF systems, Autof MS 1000 and Vitek MS, for the identification of yeasts within closely-related species complexes. A total of 1,228 yeast isolates, representing 14 different species of five species complexes, including 479 of Candida parapsilosis complex, 323 of Candida albicans complex, 95 of Candida glabrata complex, 16 of Candida haemulonii complex (including two Candida auris), and 315 of Cryptococcus neoformans complex, collected under the National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) program, were studied. Autof MS 1000 and Vitek MS systems correctly identified 99.2% and 89.2% of the isolates, with major error rate of 0.4% versus 1.6%, and minor error rate of 0.1% versus 3.5%, respectively. The proportion of isolates accurately identified by Autof MS 1000 and Vitek MS per each yeast complex, respectively, was as follows; C. albicans complex, 99.4% vs 96.3%; C. parapsilosis complex, 99.0% vs 79.1%; C glabrata complex, 98.9% vs 94.7%; C. haemulonii complex, 100% vs 93.8%; and C. neoformans, 99.4% vs 95.2%. Overall, Autof MS 1000 exhibited good capacity in yeast identification while Vitek MS had lower identification accuracy, especially in the identification of less common species within phylogenetically closely-related species complexes.