ROS exhaustion reverses the effects of hyperbaric oxygen on hemorrhagic transformation through reactivating microglia in post-stroke hyperglycemic mice.

Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-L-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.

Reducing the uncertainty in estimating soil microbial-derived carbon storage.

Soil organic carbon (SOC) is the largest carbon pool in terrestrial ecosystems and plays a crucial role in mitigating climate change and enhancing soil productivity. Microbial-derived carbon (MDC) is the main component of the persistent SOC pool. However, current formulas used to estimate the proportional contribution of MDC are plagued by uncertainties due to limited sample sizes and the neglect of bacterial group composition effects. Here, we compiled the comprehensive global dataset and employed machine learning approaches to refine our quantitative understanding of MDC contributions to total carbon storage. Our efforts resulted in a reduction in the relative standard errors in prevailing estimations by an average of 71% and minimized the effect of global variations in bacterial group compositions on estimating MDC. Our estimation indicates that MDC contributes approximately 758 Pg, representing approximately 40% of the global soil carbon stock. Our study updated the formulas of MDC estimation with improving the accuracy and preserving simplicity and practicality. Given the unique biochemistry and functioning of the MDC pool, our study has direct implications for modeling efforts and predicting the land-atmosphere carbon balance under current and future climate scenarios.

Global, regional, and national burden of stroke attributable to diet high in sodium from 1990 to 2019: a systematic analysis from the global burden of disease study 2019.

Purpose: Given the increasing occurrence of stroke and high-sodium diets (DHIS) over the past 30 years, it is crucial to assess the global, national, and regional impact of DHIS on the burden of stroke. Methods and materials: The Global Burden of Diseases Study 2019 provided the study's data. We used the Bayesian meta-regression tool DisMod-MR 2.1 to evaluate the burden of stroke attributable to DHIS. Age-standardized disability-adjusted life years (ASDR) and age-standardized mortality rate (ASMR) were used to quantify the burden. We perform correlation analysis utilizing the Spearman rank-order correlation method, and we calculate the estimated annual percentage change (EAPC) to evaluate temporal trends. Results: Globally, DHIS accounts for 17,673.33 thousand disability-adjusted life years (DALYs) and 700.98 thousand deaths of stroke in 2019. The burden of stroke attributable to DHIS has declined between 1990 and 2019 globally and in the majority of regions, with the largest declines seen in regions with high sociodemographic indexes (SDI). Both ASMR and ASDR were higher regionally in regions with moderate SDI than those in developed regions. Furthermore, the absolute values of EAPC, reflecting the rate of decrease, were notably lower in these regions compared to developed nations. High-income North America, categorized within the SDI regions, notably witnessed the smallest decline in ASDR over the last three decades. Additionally, from 1990 to 2019, males consistently bore a larger burden of stroke attributable to DHIS. Conclusion: The burden of stroke attributable to DHIS remained a major concern despite advancements in public knowledge of stroke and their utilization of emergency medical services. Over the past 30 years, more burden has been placed on males and regions with moderate SDI values; in males, higher EAPC values for both ASMR and ASDR have been found. This underscores the urgent need for effective interventions to alleviate the burden of stroke associated with DHIS.

Assessment of pathological grade and variants of bladder cancer with a continuous-time random-walk diffusion model.

Purpose: To evaluate the efficacy of high b-value diffusion-weighted imaging (DWI) with a continuous-time random-walk (CTRW) diffusion model in determining the pathological grade and variant histology (VH) of bladder cancer (BCa). Methods: A total of 81 patients (median age, 70 years; range, 35-92 years; 18 females; 66 high grades; 30 with VH) with pathologically confirmed bladder urothelial carcinoma were retrospectively enrolled and underwent bladder MRI on a 3.0T MRI scanner. Multi-b-value DWI was performed using 11 b-values. Three CTRW model parameters were obtained: an anomalous diffusion coefficient (D) and two parameters reflecting temporal (α) and spatial (ß) diffusion heterogeneity. The apparent diffusion coefficient (ADC) was calculated using b0 and b800. D, α, ß, and ADC were statistically compared between high- and low-grade BCa, and between pure urothelial cancer (pUC) and VH. Comparisons were made using the Mann-Whitney U test between different pathological states. Receiver operating characteristic curve analysis was used to assess performance in differentiating the pathological states of BCa. Results: ADC, D, and α were significantly lower in high-grade BCa compared to low-grade, and in VH compared to pUC (p < 0.001), while ß showed no significant differences (p > 0.05). The combination of D and α yielded the best performance for determining BCa grade and VH (area under the curves = 0.913, 0.811), significantly outperforming ADC (area under the curves = 0.823, 0.761). Conclusion: The CTRW model effectively discriminated pathological grades and variants in BCa, highlighting its potential as a noninvasive diagnostic tool.

Enhancing Photoreduction of Cr(VI) through a Multivalent Manganese(II)-Organic Framework Incorporating Anthracene Moieties.

Exploiting a photocatalyst with high stability and excellent activity for Cr(VI) reduction under mild conditions is crucial yet challenging. Herein, the rigid aromatic multicarboxylate ligand with chromophore anthracene was selected to coordinate with multivalent metal ion manganese and to obtain a stable two-dimensional (2D) Mn-based metal-organic framework (MOF), LCUH-120, which can efficiently and quickly convert Cr(VI) into Cr(III) under light without the need for any additional photosensitizer. The efficient photosensitive anthracene group serves as a photosensitizer center and multivalent Mn(II) ion as a photocatalyst center in LCUH-120, and the conversion of Cr(VI) to Cr(III) can be realized completely in just 40 min. Specifically, the rate constant (k) and reduction rate of the Cr(VI) photocatalytic reaction can be high up to 0.134 min-1 and 2.50 mgCr(VI) g-1cata min-1 in an acidic environment (pH = 2), respectively. Compared to our previously reported three-dimensional (3D) Sm-MOF, LCUH-120 exhibits a significantly higher catalytic reaction rate, which might be ascribed to the fact that the photocatalyst center Mn node can improve the rate of electron transfer and promote the separation of holes and photogenerated electrons. In an acidic environment, the reaction mechanism can be verified through various contrast experiments and theoretical simulations.

Ketamine ameliorates post-traumatic social avoidance by erasing the traumatic memory encoded in VTA-innervated BLA engram cells.

Erasing traumatic memory during memory reconsolidation is a promising retrieval-extinction strategy for post-traumatic stress disorder (PTSD). Here, we developed an acute social defeat stress (SDS) mouse model with short-term and re-exposure-evoked long-term social avoidance. SDS-associated traumatic memories were identified to be stored in basolateral amygdala (BLA) engram cells. A single intraperitoneal administration of subanesthetic-dose ketamine within, but not beyond, the re-exposure time window significantly alleviates SDS-induced social avoidance, which reduces the activity and quantity of reactivated BLA engram cells. Furthermore, activation or inhibition of dopaminergic projections from the ventral tegmental area to the BLA effectively mimics or blocks the therapeutic effect of re-exposure with ketamine and is dopamine D2 receptor dependent. Single-cell RNA sequencing reveals that re-exposure with ketamine triggered significant changes in memory-related pathways in the BLA. Together, our research advances the understanding of how ketamine mitigates PTSD symptoms and offers promising avenues for developing more effective treatments for trauma-related disorders.

Evaluating extractable work of quantum batteries via entropic uncertainty relations.

In this study, we investigate the effectiveness of entropic uncertainty relations (EURs) in discerning the energy variation in quantum batteries (QBs) modelled by battery-charger field in the presence of bosonic and fermionic reservoirs. Our results suggest that the extractable works (exergy and ergotropy) have versatile characteristics in different scenarios, resulting in a complex relationship between tightness and extractable work. It is worth noting that the tightness of the lower bound of entropic uncertainty can be a good indicator for energy conversion efficiency in charging QBs. Furthermore, we disclose how the EUR including uncertainty and lower bound contributes to energy conversion efficiency in the QB system. It is believed that these findings will be beneficial for better understanding the role of quantum uncertainty in evaluating quantum battery performance.

A Survey of Mean Glandular Doses and Suggestions on National Diagnostic Reference Levels for Digital Mammography in China.

ABSTRACT: The primary purpose of this study was to report the mean glandular doses and to determine the national diagnostic reference levels for digital mammography based on data between 2016 and 2018 in China. The data from 19,076 mammograms (4,769 examinations) by random sampling from 118 digital mammography systems were compiled. Exposure factors included age, compressed breast thickness, kVp, mAs, target/filter combination, entrance surface air kerma, and mean glandular doses, which were retrospectively surveyed and recorded from the monitor. The national diagnostic reference levels (75th percentiles) in mean glandular dose were calculated across median value obtained for all included data and stratified to specific compressed breast thickness ranges. The patients' ages ranged from 22 to 88 y, with a median age of 45. The applied voltage and output medians were 28 kVp and 75.1 mAs for all exposure, respectively. The median CBTs were 45 mm and 48 mm for craniocaudal views and mediolateral oblique views, and the corresponding median mean glandular doses were 1.32 mGy and 1.40 mGy, respectively. The national diagnostic reference level at compressed breast thickness of 40-50 mm was 1.67 mGy for CC views and 1.71 mGy for MLO views. The median mean glandular doses varied significantly and increased with compressed breast thickness, demonstrating the necessity of establishing DRL according to breast thickness and optimizing the clinic's digital mammography practice in China.

Designing NIR AIEgens for lysosomes targeting and efficient photodynamic therapy of tumors.

Cancer is the most severe health problem facing most people today. Photodynamic therapy (PDT) for tumors has attracted attention because of its non-invasive nature, negligible adverse reactions, and high spatiotemporal selectivity. Developing biocompatible photosensitizers that can target, guide, and efficiently kill cancer cells is desirable in PDT. Here, two amphiphilic organic compounds, PS-I and PSS-II, were synthesized based on the D-π-A structure with a positive charge. The two AIEgens exhibited near-infrared emission, large Stokes shift, high 1O2 and O2-∙ generation efficiency, good biocompatibility, and photostability. They were co-incubated with cancer cells and eventually accumulated to lysosomes by cell imaging experiments. In vitro and in vivo experiments demonstrated that PS-I and PSS-II could effectively kill cancer cells and sufficiently inhibit tumor growth under light irradiation. PS-I had a higher fluorescence quantum yield in the aggregated state, which made it better for bio-imaging in imaging-guided photodynamic therapy. In contrast, PSS-II with a longer conjugated structure had more ROS generation to kill tumor cells under illumination, and the tumor growth inhibition of mice reached 71.95% during the treatment. No observable injury or undesirable outcomes were detected in the vital organs of the mice within the treatment group, suggesting that PSS-II/PS-I had a promising future in efficient imaging-guided PDT for cancer.

The Development of Gesture Skills in Chinese Autistic Children: The Predictive Roles of Age and Language Ability.

PURPOSE: Gesture delay in autistic infants and toddlers has been widely reported. The developmental trajectory of gesture production during early childhood is understudied. Thus, little is known about the possible changes of gesture production over time. The present study aimed to document the development of gesture production in autistic children and examine whether child-based factors (chronological age and initial language skills) predicted gesture development. METHOD: A total of 33 Chinese-speaking autistic children (Mage = 56.39 months, SD = 8.54 months) played with their parents at four time points over a 9-month period. Their speech was transcribed, and their gestures were coded from parent-child interaction. Multilevel modeling analysis was used to investigate the development of gesture and its associated factors. RESULTS: The total number of gestures produced by autistic children decreased over time. Among different factors, children's initial age significantly and negatively predicted children's gesture production, while initial language positively predicted children's gesture production. CONCLUSIONS: Gesture delay persists in preschool age. The decline in gesture production was associated with children's age and initial language ability. These findings shed light on the difficulties surrounding gesture use in autistic children.

Ultrasensitive Ratiometric Fluorescent Nanothermometer with Reverse Signal Changes for Intracellular Temperature Mapping.

Sensing temperature at the subcellular level is pivotal for gaining essential thermal insights into diverse biological processes. However, achieving sensitive and accurate sensing of the intracellular temperature remains a challenge. Herein, we develop a ratiometric organic fluorescent nanothermometer with reverse signal changes for the ultrasensitive mapping of intracellular temperature. The nanothermometer is fabricated from a binary mixture of saturated fatty acids with a noneutectic composition, a red-emissive aggregation-caused quenching luminogen, and a green-emissive aggregation-induced emission luminogen using a modified nanoprecipitation method. Different from the eutectic mixture with a single phase-transition point, the noneutectic mixture possesses two solid-liquid phase transitions, which not only allows for reversible regulation of the aggregation states of the encapsulated luminogens but also effectively broadens the temperature sensing range (25-48 °C) across the physiological temperature range. Remarkably, the nanothermometer exhibits reverse and sensitive signal changes, demonstrating maximum relative thermal sensitivities of up to 63.66% °C-1 in aqueous systems and 44.01% °C-1 in the intracellular environment, respectively. Taking advantage of these outstanding thermometric performances, the nanothermometer is further employed to intracellularly monitor minute temperature variations upon chemical stimulation. This study provides a powerful tool for the exploration of dynamic cellular thermal activities, holding great promise in unveiling intricate physiological processes.

Characterization of prostatic cancer lesion and gleason grade using a continuous-time random-walk diffusion model at high b-values.

Background: Distinguishing between prostatic cancer (PCa) and chronic prostatitis (CP) is sometimes challenging, and Gleason grading is strongly associated with prognosis in PCa. The continuous-time random-walk diffusion (CTRW) model has shown potential in distinguishing between PCa and CP as well as predicting Gleason grading. Purpose: This study aimed to quantify the CTRW parameters (α, ß & Dm) and apparent diffusion coefficient (ADC) of PCa and CP tissues; and then assess the diagnostic value of CTRW and ADC parameters in differentiating CP from PCa and low-grade PCa from high-grade PCa lesions. Study type: Retrospective (retrospective analysis using prospective designed data). Population: Thirty-one PCa patients undergoing prostatectomy (mean age 74 years, range 64-91 years), and thirty CP patients undergoing prostate needle biopsies (mean age 68 years, range 46-79 years). Field strength/Sequence: MRI scans on a 3.0T scanner (uMR790, United Imaging Healthcare, Shanghai, China). DWI were acquired with 12 b-values (0, 50, 100, 150, 200, 500, 800, 1200, 1500, 2000, 2500, 3000 s/mm2). Assessment: CTRW parameters and ADC were quantified in PCa and CP lesions. Statistical tests: The Mann-Whitney U test was used to evaluate the differences in CTRW parameters and ADC between PCa and CP, high-grade PCa, and low-grade PCa. Spearman's correlation of the pathologic grading group (GG) with CTRW parameters and ADC was evaluated. The usefulness of CTRW parameters, ADC, and their combinations (Dm, α and ß; Dm, α, ß, and ADC) to differentiate PCa from CP and high-grade PCa from low-grade PCa was determined by logistic regression and receiver operating characteristic curve (ROC) analysis. Delong test was used to compare the differences among AUCs. Results: Significant differences were found for the CTRW parameters (α, Dm) between CP and PCa (all P<0.001), high-grade PCa, and low-grade PCa (α:P=0.024, Dm:P=0.021). GG is correlated with certain CTRW parameters and ADC(α:P<0.001,r=-0.795; Dm:P<0.001,r=-0.762;ADC:P<0.001,r=-0.790). Moreover, CTRW parameters (α, ß, Dm) combined with ADC showed the best diagnostic efficacy for distinguishing between PCa and CP as well as predicting Gleason grading. The differences among AUCs of ADC, CTRW parameters and their combinations were not statistically significant (P=0.051-0.526). Conclusion: CTRW parameters α and Dm, as well as their combination were beneficial to distinguish between CA and PCa, low-grade PCa and high-grade PCa lesions, and CTRW parameters and ADC had comparable diagnostic performance.

Corrigendum: Comparative study of alginate and type I collagen as biomaterials for cartilage stem/progenitor cells to construct tissue-engineered cartilage in vivo.

[This corrects the article DOI: 10.3389/fbioe.2022.1057199.].

Research on High-Precision Resonant Capacitance Bridge Based on Multiple Transformers.

The Taiji program is dedicated to the detection of middle and low-frequency gravitational waves, targeting the 0.1 mHz to 1 Hz frequency band. The project requires an acceleration residual sensitivity of 3 × 10-15 ms-2/Hz1/2, which necessitates a capacitance sensing resolution of 1 aF/Hz1/2 for the capacitive sensing system within the specified frequency range. The noise level of the resonant bridge significantly influences the resolution. Addressing the challenges in enhancing transformer performance parameters in existing resonant capacitance bridges and the constraints on improving the characteristics of resonant capacitance bridges, this study introduces a novel approach to reduce bridge thermal noise without optimizing existing parameters. The simulation results demonstrate that this scheme can reduce the noise to 0.7 times the original level and further reduce bridge thermal noise when other parameters affecting noise are optimized. This not only mitigates the demands for other performance parameters but also increases the range of maximum acceptable resonant frequency deviations and reduces its sensitivity to such variations. Experimental validation confirms that the proposed scheme effectively reduces noise by 0.7 times and improves the resolution of capacitance sensing to 0.6 aF/Hz1/2, thereby advancing the Taiji program gravitational wave detection capabilities.

Transcobalamin 2 orchestrates monocyte proliferation and TLR4-driven inflammation in systemic lupus erythematosus via folate one-carbon metabolism.

Background: SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear. Methods: We collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR, and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione, and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS, and CD14 changes. Results: Elevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response. Conclusion: Our study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation, and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.

Real-time monitoring of intracellular biochemical response in locally stretched single cell by a nanosensor.

Mechanotransduction is the essential process that cells convert mechanical force into biochemical responses, and electrochemical sensor stands out from existing techniques by providing quantitative and real-time information about the biochemical signals during cellular mechanotransduction. However, the intracellular biochemical response evoked by mechanical force has been poorly monitored. In this paper, we report a method to apply local stretch on single cell and simultaneously monitor the ensuing intracellular biochemical signals. Specifically, a ferromagnetic micropipette was fabricated to locally stretch a single cell labeled with Fe3O4 nanoparticles under the external magnetic field, and the SiC@Pt nanowire electrode (SiC@Pt NWE) was inserted into the cell to monitor the intracellular hydrogen peroxide (H2O2) production induced by the local stretch. As a proof of concept, this work quantitatively investigated the elevated amount of H2O2 levels in single endothelial cell under different stretching amplitudes. This work puts forward a new research modality to manipulate and monitor the mechanotransduction at the single-cell level.

Changes in planta K nutrient content altered the interaction pattern between Nicotiana benthamiana and Alternaria longipes.

Potassium (K) fertilisation has frequently been shown to enhance plant resistance against pathogens, though the mechanisms remain elusive. This study investigates the interaction dynamics between Nicotiana benthamiana and the pathogen Alternaria longipes under different planta K levels. On the host side, adding K activated the expressions of three NLR (nucleotide-binding domain and leucine-rich repeat-containing proteins) resistance genes, including NbRPM1, NbR1B23 and NbNBS12. Silencing these NLRs attenuated resistance in high-K (HK, 40.8 g/kg) plant, whereas their overexpression strengthened resistance in low-K (LK, 23.9 g/kg) plant. Typically, these NLRs mainly strengthened plant resistance via promoting the expression of pathogenesis-related genes (PRs), ROS burst and synthesis of antifungal metabolites in HK plant. On the pathogen side, the expression of effectors HKCSP1, HKCSP2 and LKCSP were shown to be related to planta K content. A. longipes mainly expressed effectors HKCSP1 and HKCSP2 in HK plant to interfere host resistance. HKCSP1 physically interacted with NbRPM1 to promote the degradation of NbRPM1, then attenuated related resistance in HK N. benthamiana. Meanwhile, HKCSP2 directly interacted with NbPR5 to suppress resistance in HK plant. In LK plant, A. longipes mainly deployed LKCSP that interacted with NbR1B23 to interfere reduce resistance in N. benthamiana. Overall, our research insights that both pathogen and host mobilise distinct strategies to outcompete each other during interactions in different K nutrient environments.