Comparison of Microbial Diversity of Two Typical Volcanic Soils in Wudalianchi, China.

Volcanic lava is an excellent model of primary succession, in which basalt-associated microorganisms drive the cycling of different elements such as nitrogen, carbon, and other nutrients. Microbial communities in volcanic soils are of particular interest for study on the emergence and evolution of life within special and extreme conditions. The initial processes of colonization and subsequent rock weathering by microbial communities are still poorly understood. We analyzed the soil bacterial and fungal communities and diversities associated with lava (LBL) and kipuka (BK) sites in Wudalianchi using 16S and ITS rRNA Illumina Miseq sequencing techniques. The results showed that soil physical and chemical properties (pH, MC, TOC, TN, TP, AP, DOC, and DON) significantly differed between LBL and BK. The Shannon, Ace, and Pd indexes of fungi in the two sites showed a significant difference (p < 0.05). The dominant bacterial phyla forming communities at LBL and BK sites were Acidobacteria, Proteobacteria, Actinobacteria, and Basidiomycota, and their differences were driven by Gemmatimonadetes and Verrucomicrobia. The dominant fungal phyla of LBL and BK sites were Ascomycota, Zygomycota, and Rozellomcota, which differed significantly between the two sites. The microbial communities showed extremely significant differences (p < 0.05), with MC, pH, and nitrogen being the main influencing factors according to RDA/CCA and correlation analysis. Microbial functional prediction analysis across the two sites showed that the relative abundance of advantageous functional groups was significantly different (p < 0.05). The combined results drive us to conclude that the volcanic soil differences in the deposits appear to be the main factor shaping the microbial communities in Wudalianchi (WDLC) volcanic ecosystems.

G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis.

G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.

Platinum-Loaded Cerium Oxide Capable of Repairing Neuronal Homeostasis for Cerebral Ischemia-Reperfusion Injury Therapy.

Effective neuroprotective agents are required to prevent neurological damage caused by reactive oxygen species (ROS) generated by cerebral ischemia-reperfusion injury (CIRI) following an acute ischemic stroke. Herein, it is aimed to develop the neuroprotective agents of cerium oxide loaded with platinum clusters engineered modifications (Ptn -CeO2 ). The density functional theory calculations show that Ptn -CeO2 could effectively scavenge ROS, including hydroxyl radicals (·OH) and superoxide anions (·O2 - ). In addition, Ptn -CeO2 exhibits the superoxide dismutase- and catalase-like enzyme activities, which is capable of scavenging hydrogen peroxide (H2 O2 ). The in vitro studies show that Ptn -CeO2 could adjust the restoration of the mitochondrial metabolism to ROS homeostasis, rebalance cytokines, and feature high biocompatibility. The studies in mice CIRI demonstrate that Ptn -CeO2 could also restore cytokine levels, reduce cysteine aspartate-specific protease (cleaved Caspase 3) levels, and induce the polarization of microglia to M2-type macrophages, thus inhibiting the inflammatory responses. As a result, Ptn -CeO2 inhibits the reperfusion-induced neuronal apoptosis, relieves the infarct volume, reduces the neurological severity score, and improves cognitive function. Overall, these findings suggest that the prominent neuroprotective effect of the engineered Ptn -CeO2 has a significant neuroprotective effect and provides a potential therapeutic alternative for CIRI.

Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: A cohort study.

OBJECTIVES: To explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival. METHODS: This is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, and evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival. RESULTS: A total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. Thirty-seven of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%; p < 0.001) and more likely to develop pulmonary mass lesions with a diameter >3 centimetres (42.9% vs. 6.5%; p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR, 2.66; 95% CI, 1.34-5.27; p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR, 5.44; 95% CI, 1.23-24.10; p 0.026 and HR, 5.09; 95% CI, 1.95-13.26; p 0.001). DISCUSSION: Presence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex.

Macrophage-Derived Extracellular Vesicles-Coated Palladium Nanoformulations Modulate Inflammatory and Immune Homeostasis for Targeting Therapy of Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease mainly involving the colon and rectum, which features recurrent mucosal inflammation. The excessive production of reactive oxygen species (ROS) is a trigger for pathological changes such as cell apoptosis and disordered immune microenvironments, which are crucial for the progression of UC and can be a promising therapeutic target. Nowadays, the development of targeted therapeutic strategies for UC is still in its infancy. Thus, developing effective therapies based on ROS scavenging and elucidating their molecular pathways are urgently needed. Herein, a biomimetic nanoformulation (Pd@M) with cubic palladium (Pd) as the core and macrophage-derived extracellular vesicles (MEVs) as the shell is synthesized for the treatment of UC. These Pd@M nanoformulations exhibit multienzyme-like activities for effective ROS scavenging, excellent targeting ability as well as good biocompatibility. It is verified that Pd@M can regulate the polarization state of macrophages by inhibiting glycolysis, and decrease neutrophil infiltration and recruitment. In this way, the colonic inflammatory and immune microenvironment is remodeled, and apoptosis is prevented, ultimately improving colonic mucosal barrier function and alleviating colitis in the mouse model. This finding provides a promising alternative option for the treatment of UC patients.

Multi-nodes dissemination of stable radio frequency with 10-17 instability over 2000 km optical fiber.

To meet the demand of flexible access for high-precision synchronization frequency, we demonstrate multi-node stable radio frequency (RF) dissemination over a long-distance optical fiber. Stable radio frequency signals can be extracted at any node along the optical fiber, not just at the endpoint. The differential mixing structure (DMS) is employed to avoid the frequency harmonic leakage and enhance the precision. The phase-locked loop (PLL) provides frequency reference for the DMS while improving the signal to noise ratio (SNR) of dissemination signal. We measure the frequency instability of multi-node stable frequency dissemination system (MFDS) at different locations along the 2,000 km optical fiber. The measured short-term instability with average time of 1 s are 1.90 × 10-14 @ 500 km, 2.81 × 10-14 @ 1,000 km, 3.46 × 10-14 @ 1,500 km, and 3.84 × 10-14 @ 2,000 km respectively. The long-term instability with average time of 10,000 s are basically the same at any position of the optical fiber, which is about (6.24 ± 0.05) × 10-17. The resulting instability is sufficient for the propagation of precision active hydrogen masers.

Measuring Productivity and Relative Efficiency of Public Tertiary Traditional Chinese Medicine Hospitals in Hubei, China.

Improving the productivity and relative efficiency of traditional Chinese medicine (TCM) hospitals is pivotal for hospital managers and policymakers to optimize the utilization of TCM resources in China. This study aimed to measure the productivity and relative efficiency of public tertiary TCM hospitals in Hubei Province. The input and output indicators data were extracted from the Health Commission of Hubei Province (HCHP) from 2019 to 2021. The Bootstrap-Malmquist-DEA model was employed to measure the productivity and relative efficiency of the hospitals. The statistical significance was set at P < .05. The numbers of total diagnostic patients and discharged patients declined by 23.44% and 28.34% from 2019 to 2020, and then increased by 25.76% and 20.44% respectively from 2020 to 2021. The average bias-corrected technical efficiency (TE) scores of the TCM hospitals from 2019 to 2021 were 0.8391, 0.8048, and 0.8559, indicating good efficiency. The average total factor productivity (TFP) in 2020 and 2021 decreased compared to that in 2019, with scores of 0.7479 and 0.8996, respectively. Between 2019 and 2020, the TFP changes among 19 out of 21 (90.48%) TCM hospitals and the technological changes (TC) among 20 out of 21 (95.24%) were less than 1.0000 (P < .05). The TFP changes of 17 out of 21 (80.95%) TCM hospitals and the TC of 20 out of 21 (95.24%) were less than 1.0000 (P < .05) between 2019 and 2021. COVID-19 might have constrained the provision of healthcare services by the public tertiary TCM hospitals in Hubei Province. Priority should be given to the utilization of healthcare resources, performance evaluation, information system strengthening, and internal hospital management to boost technical efficiency. TCM hospitals need to focus further on technology innovation to improve their technological progress.

Conformal in-ear bioelectronics for visual and auditory brain-computer interfaces.

Brain-computer interfaces (BCIs) have attracted considerable attention in motor and language rehabilitation. Most devices use cap-based non-invasive, headband-based commercial products or microneedle-based invasive approaches, which are constrained for inconvenience, limited applications, inflammation risks and even irreversible damage to soft tissues. Here, we propose in-ear visual and auditory BCIs based on in-ear bioelectronics, named as SpiralE, which can adaptively expand and spiral along the auditory meatus under electrothermal actuation to ensure conformal contact. Participants achieve offline accuracies of 95% in 9-target steady state visual evoked potential (SSVEP) BCI classification and type target phrases successfully in a calibration-free 40-target online SSVEP speller experiment. Interestingly, in-ear SSVEPs exhibit significant 2nd harmonic tendencies, indicating that in-ear sensing may be complementary for studying harmonic spatial distributions in SSVEP studies. Moreover, natural speech auditory classification accuracy can reach 84% in cocktail party experiments. The SpiralE provides innovative concepts for designing 3D flexible bioelectronics and assists the development of biomedical engineering and neural monitoring.

Circular RNAs with protein-coding ability in oncogenesis.

As ubiquitously expressed transcripts in eukaryotes, circular RNAs (circRNAs) are covalently closed and lack a 5'-cap and 3'-polyadenylation (poly (A)) tail. Initially, circRNAs were considered non-coding RNA (ncRNA), and their roles as sponging molecules to adsorb microRNAs have been extensively reported. However, in recent years, accumulating evidence has demonstrated that circRNAs could encode functional polypeptides through the initiation of translation mediated by internal ribosomal entry sites (IRESs) or N6-methyladenosine (m6A). In this review, we collectively discuss the biogenesis, cognate mRNA products, regulatory mechanisms, aberrant expression and biological phenotypes or clinical relevance of all currently reported, cancer-relevant protein-coding circRNAs. Overall, we provide a comprehensive overview of circRNA-encoded proteins and their physiological and pathological functions.

Systematic evaluation of the toxicological effects of deltamethrin exposure in zebrafish larvae.

Deltamethrin (DM) is a widely used pesticide and has been generally detected in aquatic systems. To systematically investigate the toxic effects, zebrafish embryos were treated with various concentrations of DM for 120 h. The LC50 was determined to be 102 µg L-1. Lethal concentrations of DM induced severe morphological defects in the surviving individuals. Under non-lethal concentrations, DM suppressed the development of neurons in the larvae, which was associated with the reduction in locomotor activity. DM exposure induced cardiovascular toxicity, including suppressed growth of blood vessels and enhanced heart rates. DM also disrupted the development of bones in the larvae. Moreover, liver degeneration, apoptosis and oxidative stress were observed in the larvae treated with DM. Correspondingly, the transcriptional levels of the genes related to the toxic effects were altered by DM. In conclusion, the results obtained in this study provided evidence that DM showed multiple toxic effects on aquatic organisms.

High-Output Single-Electrode Droplet Triboelectric Nanogenerator Based on Asymmetrical Distribution Electrostatic Induction Enhancement.

Droplet-based triboelectric nanogenerators (D-TENGs) have recently gained much attention due to their great potential in harvesting energy. However, the output performance of conventional single-electrode droplet-based TENGs is limited owing to low induced electrification efficiency. The asymmetric distribution of electric fields on both sides of the electrode edge enhances the electrostatic induction process and improves the output performance of D-TENG. Herein, an induced electrification-enhanced droplet-based triboelectric nanogenerator (IED-TENG) is developed to effectively enhance the output performance by simultaneously optimizing the electrode structure and the dynamics of the water droplet. One droplet falling from a height of 30 cm results in a -70 V output voltage and -6 µA short-circuit current, which is 70 times and 20 times the full-inductive-electrode mode, respectively. The working principle and the relationship between electric signal and droplet dynamics are analyzed in detail. Moreover, the peak output voltage can reach -110 V, and the peak current can get -140 µA by using the power generation of multiple water droplets. The present protocol provides an easy and reproducibility strategy in energy harvesting and sensing areas.

Pyrrolysine-Inspired in Cellulo Synthesis of an Unnatural Amino Acid for Facile Macrocyclization of Proteins.

Macrocyclization has been touted as an effective strategy to enhance the in vivo stability and efficacy of protein therapeutics. Herein, we describe a scalable and robust system based on the endogenous biosynthesis of a noncanonical amino acid coupled to the pyrrolysine translational machinery for the generation of lasso-grafted proteins. The in cellulo biosynthesis of the noncanonical amino acid d-Cys-ε-Lys was achieved by hijacking the pyrrolysine biosynthesis pathway, and then, its genetical incorporation into proteins was performed using an optimized PylRS/tRNAPyl pair and cell line. This system was then applied to the structurally inspired cyclization of a 23-mer therapeutic P16 peptide engrafted on a fusion protein, resulting in near-complete cyclization of the target cyclic subunit in under 3 h. The resulting cyclic P16 peptide fusion protein possessed much higher CDK4 binding affinity than its linear counterpart. Furthermore, a bifunctional bicyclic protein harboring a cyclic cancer cell targeting RGD motif on the one end and the cyclic P16 peptide on the other is produced and shown to be a potent cell cycle arrestor with improved serum stability.

Diagnostic Laboratory Features and Performance of an Aspergillus IgG Lateral Flow Assay in a Chronic Pulmonary Aspergillosis Cohort.

Chronic pulmonary aspergillosis (CPA) is a chronic and progressive fungal disease with high morbidity and mortality. Avoiding diagnostic delay and misdiagnosis are concerns for CPA patients. However, diagnostic practice is poorly evaluated, especially in resource-constrained areas where Aspergillus antibody testing tools are lacking. This study aimed to investigate the diagnostic laboratory findings in a retrospective CPA cohort and to evaluate the performance of a novel Aspergillus IgG lateral flow assay (LFA; Era Biology, Tianjin, China). During January 2016 and December 2021, suspected CPA patients were screened at the Center for Infectious Diseases at Huashan Hospital. A total of 126 CPA patients were enrolled. Aspergillus IgG was positive in 72.1% with chronic cavitary pulmonary aspergillosis, 75.0% with chronic necrotizing pulmonary aspergillosis, 41.7% with simple aspergilloma, and 30.3% with Aspergillus nodule(s). The cavitary CPA subtypes had significantly higher levels of Aspergillus IgG. Aspergillus IgG was negative in 52 patients, who were finally diagnosed by histopathology, respiratory culture, and metagenomic next-generation sequencing (mNGS). Sputum culture was positive in 39.3% (42/107) of patients and Aspergillus fumigatus was the most common species (69.0%, 29/42). For CPA cohort versus controls, the sensitivity and specificity of the LFA were 55.6% and 92.7%, respectively. In a subgroup analysis, the LFA was highly sensitive for A. fumigatus-associated chronic cavitary pulmonary aspergillosis (CCPA; 96.2%, 26/27). Given the complexity of the disease, a combination of serological and non-serological tests should be considered to avoid misdiagnosis of CPA. The novel LFA has a satisfactory performance and allows earlier screening and diagnosis of CPA patients. IMPORTANCE There are concerns on avoiding diagnostic delay and misdiagnosis for chronic pulmonary aspergillosis due to its high morbidity and mortality. A proportion of CPA patients test negative for Aspergillus IgG. An optimal diagnostic strategy for CPA requires in-depth investigation based on real-world diagnostic practice, which has been rarely discussed. We summarized the clinical and diagnostic laboratory findings of 126 CPA patients with various CPA subtypes. Aspergillus IgG was the most sensitive test for diagnosing CPA. However, it was negative in 52 patients, who were finally diagnosed by non-serological tests, including biopsy, respiratory culture, and metagenomic next-generation sequencing. We also evaluated a novel Aspergillus IgG lateral flow assay, which showed a satisfactory performance in cavitary CPA patients and was highly specific to Aspergillus fumigatus. This study gives a full picture of the diagnostic practice for CPA patients in Chinese context and calls for early diagnosis of CPA with combined approaches.

Herbicide atrazine impairs metabolic plasticity of mixotrophic organisms: Evidence in photochemistry, morphology, and gene expression.

Herbicide pollution is a main form of water pollution. As a result of additional harms to other non-target organisms, it threatens the function and structure of ecosystems. Previous researches mainly focused on the assessment of the toxicity and ecological effect of herbicides on monotrophic organisms. Responses of mixotrophs as an important component of functional groups are rarely understood in contaminated waters, although their metabolic plasticity and unique ecological functions in ecosystem stability are a major concern. This work aimed to investigate the trophic plasticity of mixotrophic organisms in atrazine-contaminated waters, and a primarily heterotrophic Ochromonas was used as the tested organism. Results showed that the herbicide atrazine significantly inhibited the photochemical activity and impaired the photosynthetic machine of Ochromonas, and photosynthesis activated by light was sensitive to atrazine. However, phagotrophy was unaffected by atrazine and closely correlated with growth rate, indicating that heterotrophy helped population maintenance during herbicide exposure. Mixotrophic Ochromonas upregulated the gene expression level involved in photosynthesis, energy synthesis, and antioxidation to adapt to increasing atrazine after long-term exposure. Compared with bacterivory, herbivory increased atrazine tolerance of photosynthesis under mixotrophic status. This study systematically illustrated the mechanism by which mixotrophic Ochromonas respond to the herbicide atrazine at population, photochemical activity, morphology, and gene expression levels and demonstrated the potential effect of atrazine on the metabolic flexibility and ecological niches of mixotrophs. These findings will provide important theoretical reference for governance and management decision-making in contaminated environments.

Shape and texture analyses based on conventional MRI for the preoperative prediction of the aggressiveness of pituitary adenomas.

OBJECTIVES: Pituitary adenomas can exhibit aggressive behavior, characterized by rapid growth, resistance to conventional treatment, and early recurrence. This study aims to evaluate the clinical value of shape-related features combined with textural features based on conventional MRI in evaluating the aggressiveness of pituitary adenomas and develop the best diagnostic model. METHODS: Two hundred forty-six pituitary adenoma patients (84 aggressive, 162 non-aggressive) who underwent preoperative MRI were retrospectively reviewed. The patients were divided into training (n = 193) and testing (n = 53) sets. Clinical information, shape-related, and textural features extracted from the tumor volume on contrast-enhanced T1-weighted images (CE-T1WI), were compared between aggressive and non-aggressive groups. Variables with significant differences were enrolled into Pearson's correlation analysis to weaken multicollinearity. Logistic regression models based on the selected features were constructed to predict tumor aggressiveness under fivefold cross-validation. RESULTS: Sixty-five imaging features, including five shape-related and sixty textural features, were extracted from volumetric CE-T1WI. Forty-seven features were significantly different between aggressive and non-aggressive groups (all p values < 0.05). After feature selection, four features (SHAPE_Sphericity, SHAPE_Compacity, DISCRETIZED_Q3, and DISCRETIZED_Kurtosis) were put into logistic regression analysis. Based on the combination of these features and Knosp grade, the model yielded an area under the curve value of 0.935, with a sensitivity of 94.4% and a specificity of 82.9%, to discriminate between aggressive and non-aggressive pituitary adenomas in the testing set. CONCLUSION: The radiomic model based on tumor shape and textural features study from CE-T1WI might potentially assist in the preoperative aggressiveness diagnosis of pituitary adenomas. KEY POINTS: • Pituitary adenomas with aggressive behavior exhibit rapid growth, resistance to conventional treatment, and early recurrence despite gross resection and may require multiline treatments. • Shape-related features and texture features based on CE-T1WI were significantly correlated with the Ki-67 labeling index, mitotic count, and p53 expression, and the proposed model achieved a favorable prediction of the aggressiveness of PAs with an AUC value of 0.935. • The prediction model might provide valuable guidance for individualized treatment in patients with PAs.

Diagnostic performance of noncultural methods for central nervous system aspergillosis.

BACKGROUND: Central nervous system (CNS) aspergillosis is an uncommon but fatal disease, the diagnosis of which is still difficult. OBJECTIVES: We aim to explore the diagnositic performance of noncultural methods for CNS aspergillosis. METHODS: In this retrospective study, all pathologically confirmed rhinosinusitis patients in whom cerebrospinal fluid (CSF) galactomannan (GM) test and metagenomic next-generation sequencing (mNGS) had been performed were included. We evaluated the diagnostic performances of CSF GM optical density indexes (ODI) at different cut-off values and compared performance with mNGS in patients with and without CNS aspergillosis, as well as in patients with different manifestations of CNS aspergillosis. RESULTS: Of the 21 proven and probable cases, one had positive culture result, five had positive mNGS results and 10 had a CSF GM ODI of >0.7. Sample concordance between mNGS and GM test was poor, but best diagnostic performance was achieved by combination of GM test (ODI of >0.7) and mNGS, which generated a sensitivity of 61.9% and specificity of 82.6%. Further investigation of combination diagnostic performances in different kind of CNS aspergillosis was also conducted. Lowest sensitivity (42.9%) was identified in abscess group, while increased sensitivity (60.0%) was achieved in abscess with encephalitis groups. Combination test exhibited the best performance for encephalitis patients who had only CSF abnormalities, in whom the sensitivity and specificity were 77.8% and 82.6%, respectively. CONCLUSIONS: In conclusion, combination of these two tests might be useful for diagnosis of CNS aspergillosis associated with fungal rhinosinusitis, especially in encephalitis patients.

Induction therapy with high-dose fluconazole plus flucytosine for human immunodeficiency virus-uninfected cryptococcal meningitis patients: Feasible or not?

BACKGROUND: Cryptococcal meningitis (CM) is increasingly recognised in human immunodeficiency virus (HIV)-uninfected patients with high mortality. The efficacy and safety profiles of induction therapy with high-dose fluconazole plus flucytosine remain unclear. METHODS: HIV-uninfected CM patients who received high-dose fluconazole (800 mg/d) for initial therapy in Huashan Hospital were included in this retrospective study from January 2013 to December 2018. Efficacy and safety of initial therapy, clinical outcomes and risk factors were evaluated. RESULTS: Twenty-seven (71.1%) patients who received high-dose fluconazole with flucytosine combination therapy and 11 (28.9%) having fluconazole alone for induction therapy were included. With a median duration of 42 days (IQR, 28-86), the successful response rate of initial therapy was 76.3% (29/38), while adverse drug reactions occurred in 14 patients (36.8%). The rate of persistently positive cerebrospinal fluid (CSF) culture results was 30.6% at 2 weeks, which was significantly associated with CSF CrAg titre >1:1280 (OR 9.56; 95% CI 1.40-103.65; p = .010) and CSF culture of Cryptococcus >3.9 log10 CFU/ml (OR 19.20; 95% CI 1.60-920.54; p = .011), and decreased to 8.6% at 4 weeks. One-year mortality was 15.8% (6/38), and low serum albumin (35 g/L) was found as an independent risk factor for 1-year mortality (HR 6.31; 95% CI 1.150-34.632; p = .034). CONCLUSIONS: Induction therapy with high-dose fluconazole (800 mg/d), combined with flucytosine, effectively treated HIV-uninfected CM and was well tolerated. Long-term fluconazole treatment with continued monitoring is beneficial for patients with persistent infection.

Altered mean apparent propagator-based microstructure and the corresponding functional connectivity of the parahippocampus and thalamus in Crohn's disease.

Crohn's disease (CD) is a chronic and relapsing inflammatory bowel disorder that has been shown to generate neurological impairments, which has the potential to signify disease activity in an underlying neurological manner. The objective of this study was to investigate the abnormalities of brain microstructure and the corresponding functional connectivity (FC) in patients with CD, as well as their associations with disease condition. Twenty-two patients with CD and 22 age-, gender-, and education-matched healthy controls (HCs) were enrolled in this study. All subjects underwent mean apparent propagator (MAP)-MRI and resting-state functional magnetic resonance imaging (MRI) (rs-fMRI) data collection. Each patient was evaluated clinically for the condition and duration of the disease. The MAP metrics were extracted and compared between two groups. Pearson's correlation analysis was conducted to determine the relationship between disease characteristics and significantly abnormal MAP metrics in the CD group. Regions of interest (ROIs) for ROI-wise FC analysis were selected based on their correlation with MAP metrics. Results showed that multiple brain regions, including the parahippocampus and thalamus, exhibited statistically significant differences in MAP metrics between CD patients and HCs. Additionally, CD patients exhibited decreased FC between the left parahippocampus and bilateral thalamus, as well as the right parahippocampus and bilateral thalamus. The findings of this work provide preliminary evidence that structural abnormalities in the parahippocampal gyrus (PHG) and thalamus, as well as decreased FC between them, may reflect the degree of inflammatory of the disease and serve as brain biomarkers for evaluating CD activity.

Control of triboelectrification on Al-metal surfaces through microstructural design.

The instantaneous discharge of accumulated static charge due to contact electrification can cause irreversible damage to electrostatic-sensitive systems. Despite major advances in reducing tribo-charges, the problem remains intractable. Here, four alumina microstructures are fabricated on aluminum (Al) by combining chemical etching and anodic oxidation, and the effects of surface composition and structure on the triboelectric performance are studied by assembling them with a polytetrafluoroethylene membrane into a solid-solid triboelectric nanogenerator. The results show that the short-circuit current of the hierarchical nanoporous anodic aluminum oxide (micro/nano-AAO) modified Al is 8.77 times smaller than that of pristine Al, which is attributed to the reduced contact area and presence of an oxide film on the surface of the modified metal. By regulating the diameter of alumina nanotubes, a positive correlation between the contact area and the measured charge density is theoretically demonstrated, which establishes the size of the contact area as the main factor affecting triboelectric outputs. In addition, the micro/nano-AAO based phone shell could provide more effective electrostatic protection than that based on an acrylic coating. This novel regulation of the triboelectric output by microstructural design provides a new direction for the development of antistatic materials in a vacuum and non-grounded environment.