The stress granule protein G3BP1 promotes pre-condensation of cGAS to allow rapid responses to DNA.

Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.

A single-cell atlas of immunocytes in the spleen of a mouse model of Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is a disorder characterized by rare X-linked genetic immune deficiency with mutations in the Was gene, which is specifically expressed in hematopoietic cells. The spleen plays a major role in hematopoiesis and red blood cell clearance. However, to date, comprehensive analyses of the spleen in wild-type (WT) and WASp-deficient (WAS-KO) mice, especially at the transcriptome level, have not been reported. In this study, single-cell RNA sequencing (scRNA-seq) was adopted to identify various types of immune cells and investigate the mechanisms underlying immune deficiency. We identified 30 clusters and 10 major cell subtypes among 11,269 cells; these cell types included B cells, T cells, dendritic cells (DCs), natural killer (NK) cells, monocytes, macrophages, granulocytes, stem cells and erythrocytes. Moreover, we evaluated gene expression differences among cell subtypes, identified differentially expressed genes (DEGs), and performed enrichment analyses to identify the reasons for the dysfunction in these different cell populations in WAS. Furthermore, some key genes were identified based on a comparison of the DEGs in each cell type involved in specific and nonspecific immune responses, and further analysis showed that these key genes were previously undiscovered pathology-related genes in WAS-KO mice. In summary, we present a landscape of immune cells in the spleen of WAS-KO mice based on detailed data obtained at single-cell resolution. These unprecedented data revealed the transcriptional characteristics of specific and nonspecific immune cells, and the key genes were identified, laying a foundation for future studies of WAS, especially studies into novel and underexplored mechanisms that may improve gene therapies for WAS.

Prediction of high-grade patterns of stage IA lung invasive adenocarcinoma based on high-resolution CT features: a bicentric study.

OBJECTIVES: This study aims to predict the high-grade pattern (HGP) of stage IA lung invasive adenocarcinoma (IAC) based on the high-resolution CT (HRCT) features. METHODS: The clinical, pathological, and HRCT imaging data of 457 patients (from bicentric) with pathologically confirmed stage IA IAC (459 lesions in total) were retrospectively analyzed. The 459 lesions were classified into high-grade pattern (HGP) (n = 101) and non-high-grade pattern (n-HGP) (n = 358) groups depending on the presence of HGP (micropapillary and solid) in pathological results. The clinical and pathological data contained age, gender, smoking history, tumor stage, pathological type, and presence or absence of tumor spread through air spaces (STAS). CT features consisted of lesion location, size, density, shape, spiculation, lobulation, vacuole, air bronchogram, and pleural indentation. The independent predictors for HGP were screened by univariable and multivariable logistic regression analyses. The clinical, CT, and clinical-CT models were constructed according to the multivariable analysis results. RESULTS: The multivariate analysis suggested the independent predictors of HGP, encompassing tumor size (p = 0.001; OR = 1.090, 95% CI 1.035-1.148), density (p < 0.001; OR = 9.454, 95% CI 4.911-18.199), and lobulation (p = 0.002; OR = 2.722, 95% CI 1.438-5.154). The AUC values of clinical, CT, and clinical-CT models for predicting HGP were 0.641 (95% CI 0.583-0.699) (sensitivity = 69.3%, specificity = 79.2%), 0.851 (95% CI 0.806-0.896) (sensitivity = 79.2%, specificity = 79.6%), and 0.852 (95% CI 0.808-0.896) (sensitivity = 74.3%, specificity = 85.8%). CONCLUSION: The logistic regression model based on HRCT features has a good diagnostic performance for the high-grade pattern of stage IA IAC. KEY POINTS: • The AUC values of clinical, CT, and clinical-CT models for predicting high-grade patterns were 0.641 (95% CI 0.583-0.699), 0.851 (95% CI 0.806-0.896), and 0.852 (95% CI 0.808-0.896). • Tumor size, density, and lobulation were independent predictive markers for high-grade patterns. • The logistic regression model based on HRCT features has a good diagnostic performance for the high-grade patterns of invasive adenocarcinoma.

Application of multi-target positioning algorithm in basketball teaching system and injury prevention.

In today's era, the rapid spread of information and the rise of major network platforms provide good conditions for online learning and at the same time provide a new development idea for basketball teaching. The establishment of modern multimedia teaching theory provides theoretical support for the research and development of this subject. Construct and apply the online learning system of basketball basic technology, provide high-quality education, and can accommodate a large number of basketball fans to study and exchange together, and improve the physical fitness of young people. This thesis combines the multi-target localization algorithm in wireless sensor networks, first introduces the related concepts and basic theories of UWSNs, and then summarizes the related theories of node localization technology. In the course of basketball teaching, the advantages and disadvantages of the wireless sensor network multi-target positioning algorithm and the research direction are introduced. Aiming at the problem of low positioning accuracy and high complexity of the basketball motion prediction positioning algorithm, a multi-target positioning algorithm improved by backtracking search is proposed. The MBSA algorithm improves the positioning accuracy of anchor points, and uses cooperation mechanisms and basketball mobility to locate nodes for unknown actions. An improved BSA algorithm, namely the KLBSA-LoT algorithm, is proposed. The KLBSA-LoT algorithm accurately locates the anchor point and uses a cooperative mechanism to predict the position information of unknown nodes in basketball. Applying this algorithm to basketball teaching can greatly improve the accuracy of its positioning training. Sports teaching provides new methods.

Potential heterogeneity of urban ecological resilience and urbanization in multiple urban agglomerations from a landscape perspective.

Rapid urbanization has reduced the capacity of cities to mitigate and withstand disasters. Strengthening urban ecological resilience (ER) is important for improving urban self-organization. Geographical characteristics and developmental status of different cities lead to a more complex relationship between urbanization and ER. Using the three major urban agglomerations in China, we constructed a new framework for assessing the ER from a landscape and ecological processes perspective, and analyzed the driving heterogeneity of urbanization on ER. The results indicated that the ER of Yangtze River Delta (YRD) and Pearl River Delta (PRD) decreased continuously from 2000 to 2018, while the ER of Beijing-Tianjin-Hebei (BTH) decreased from 2000 to 2010, and then increased from 2010 to 2018. The resilience level of PRD was significantly lower than those of BTH and YRD. The urbanization process had a negative impact on ER, and the contribution of urbanization factors to ER varied significantly across cities, and population factors have the most direct influence. Curve fitting analysis further deepened our understanding of heterogeneity, investigating from the perspective of landscape and driving factors, and suggesting improvement measures. This study can deepen the understanding of the impact of urbanization on resilience and provide scientific guidance for achieving regional sustainability.

Genome-wide characterization and analysis of WRKY transcription factors in Panax ginseng.

BACKGROUND: Panax ginseng is a well-known medicinal plant worldwide. As an herbal medicine, ginseng is also known for its long lifecycle, which can reach several decades. WRKY proteins play regulatory roles in many aspects of biological processes in plants, such as responses to biotic or abiotic stress, plant development, and adaptation to environmental challenges. Genome-wide analyses of WRKY genes in P. ginseng have not been reported. RESULTS: In this study, 137 PgWRKY genes were identified from the ginseng genome. Phylogenetic analysis showed that the PgWRKYs could be clustered into three primary groups and five subgroups. Most of the PgWRKY gene promoters contained several kinds of hormone- and stress-related cis-regulatory elements. The expression patterns of PgWRKY genes in 14 different tissues were analyzed based on the available public RNA-seq data. The responses of the PgWRKY genes to heat, cold, salt and drought treatment were also investigated. Most of the PgWRKY genes were expressed differently after heat treatment, and expression trends changed significantly under drought and cold treatment but only slightly under salt treatment. The coexpression analysis of PgWRKY genes with the ginsenoside biosynthesis pathway genes identified 11 PgWRKYs that may have a potential regulatory role in the biosynthesis process of ginsenoside. CONCLUSIONS: This work provides insights into the evolution, modulation and distribution of the WRKY gene family in ginseng and extends our knowledge of the molecular basis along with modulatory mechanisms of WRKY transcription factors in ginsenoside biosynthesis.

Novel germline mutation KMT2A G3131S confers genetic susceptibility to familial myeloproliferative neoplasms.

The current study analyzed the clinical and genetic characteristics of a family with familial myeloproliferative neoplasms (MPNs). Whole-exome sequencing was conducted, and a germline heterozygous mutation in lysine methyltransferase 2A (KMT2A, also known as MLL1), G3131S (c.9391G > A, p.Gly3131Ser, rs150804738), was identified. Somatic DNA and germline DNA were collected from 8 family members, 120 healthy donors (somatic DNA), and 30 healthy donors (germline DNA). Using Sanger sequencing, the KMT2A G3131S mutation was analyzed. Four individuals, the proband (II-1), his sister (patient II-2), and family members II-3 and III-1 (somatic DNA and germline DNA), tested positive for the KMT2A G3131S mutation. We did not observe the KMT2A G3131S mutation in healthy donors (somatic DNA and germline DNA), indicating that this is not a SNP. Bioinformatics analysis of KMT2A G3131S suggested that protein structure changes could be caused by this mutation. To further elucidate the function of KMT2A G3131S, the CRISPR-Cas9 technique was applied to generate a KMT2A G3131S heterozygous K562 cell line. The colony formation potency, apoptosis, and cell cycle of KMT2A G3131S mutant K562 cells were analyzed. The results demonstrated that KMT2A G3131S mutant K562 cells showed increased proliferation and colony formation ability. Immunophenotyping was performed using flow cytometry to analyze the surface marker expression of gene-edited KMT2A G3131S mutant K562 cells. A significant increase in CD11b and mild increases in CD61 and CD235a were observed in KMT2A G3131S mutant K562 cells, suggesting that the KMT2A G3131S mutant could cause an increase in myeloproliferation. May-Giemsa staining showed that the morphological changes in KMT2A G3131S mutant K562 cells were consistent with the flow cytometry analysis. To verify which downstream genes were affected by the KMT2A G3131S mutant, we performed real-time PCR to evaluate the expression of previously reported KMT2A-related genes and found that C-MYB expression was significantly decreased. Western blotting was applied to investigate the expression of Kmt2a and C-myb proteins, and the results showed that in KMT2A G3131S mutant K562 cells, the expression of C-myb was decreased. Our findings suggested that KMT2A G3131S could affect the myeloproliferation of K562 cells and decrease C-myb expression. In conclusion, KMT2A G3131S could be considered a novel genetic susceptibility gene in familial MPN.

Imaging the Transformation of Ipsilateral Internal Capsule Following Focal Cerebral Ischemia in Rat by Diffusion Kurtosis Imaging.

BACKGROUND: The purpose of our study is to explore the relationship between recovery of neural function and transformation of the internal capsule (IC) after transient middle cerebral artery occlusion (MCAO) by using diffusion kurtosis imaging (DKI). METHODS: Six male adult Sprague-Dawley rats implemented with transient MCAO were used in this study. Sensorimotor function was assessed according to repetitive behavioral testing on day 1, 3, 7, 14, and 28 after cerebral ischemia. Metrics of DKI were acquired, and the time course of the region-to-normal ratio was evaluated in IC. RESULTS: After cerebral ischemia, relative fractional anisotropy in IC decreased on day 3 (P < .01). Relative mean diffusivity (rMD) increased on day 28 (P < .05). Relative mean diffusional kurtosis (rMK) increased on day 3 (P < .01) and decreased on day 7 (P < .05). Relative axial diffusional kurtosis (rKa) increased on day 3 (P < .01) and declined on day 7 (P < .05). Relative radial diffusional kurtosis (rKr) was reduced on day 7 (P < .05). Changes in rMK were larger than changes in rMD on day 3 (P < .05). The factor of rKa and rKr revealed marked difference on day 7 (P < .05) and day 14 (P < .05). Neurological function score showed that rats exhibited functional recovery from day 7 (P < .01) post stroke. CONCLUSIONS: This longitudinal multiparametric magnetic resonance imaging study suggested that K metrics offers information complimentary to conventional diffusion metrics and revealed the procedure during the structural modification in the ipsilateral IC following focal cerebral ischemia. After transient MCAO, the neural transformation occurred in a time-dependent procedure.

Combining systemic and stereotactic MEMRI to detect the correlation between gliosis and neuronal connective pathway at the chronic stage after stroke.

BACKGROUND: The early dysfunction and subsequent recovery after stroke, characterized by the destruction and remodeling of connective pathways between cortex and subcortical regions, is associated with neuroinflammation. As major components of the inflammatory process, reactive astrocytes have double-edged effects on pathological progression. The temporal patterns of astrocyte and neuronal pathway activity can be revealed by systemic and stereotactic manganese-enhanced magnetic resonance imaging (MEMRI), respectively. In the present study, we aimed to detect an association between astrocyte activity and recovery of neuronal connective pathways by combining systemic with stereotactic MEMRI. METHODS: Fifty adult rats, divided into two groups, underwent a 60-min occlusion of the middle cerebral artery. The groups were given either a systemic administration or stereotactic injection of MnCl2 at 1, 3, 7, and 14 days after stroke and underwent MRI 4 and 2 days later, respectively. Immunofluorescence (IF) of group 1 was conducted to corroborate the results. Repetitive behavioral testing was also performed with all rats at 1, 3, 7, and 14 days to obtain a functional score. RESULTS: Ring- or crescent-shaped enhancements formed in the striatal peri-infarct regions (STR) at 11 and 18 days. This was concurrent with the activity of glial fibrillary acidic protein (GFAP)-positive astrocytes, which mainly localized at the peri-infarct region and significantly increased in number at 11 and 18 days after stroke. Microglia/macrophages, detected by IF, mainly localized in the lesion core, rather than in the region of enhancement. The ipsilateral substantia nigra (SN) revealed Mn-related signal enhancement reduction and subsequent signs of the recovery process at 3 to 5 days and 9 to 16 days, respectively. Behavioral testing showed that sensorimotor functions were initially disturbed, but subsequently recovered at 7 and 14 days. CONCLUSIONS: We found a positive temporal correlation between astrogliosis and the recovery of neuronal connective pathways at the chronic stage by using the in vivo method of MEMRI. Our results highlighted the potential contribution of astrocytes to the neuronal recovery of these connective pathways.

Normalization of T2 relaxation time and apparent diffusion coefficient in relation to the inflammatory changes in the substantia nigra of rats with focal cerebral ischemia.

BACKGROUND: Focal cerebral ischemia results in delayed neurodegeneration in remote brain regions, such as the substantia nigra. To date, a reasonable explanation is still lacking regarding the correlation of magnetic resonance (MR) signal pseudo-normalization following a transient abnormal change and subsequent progressive pathological damage. PURPOSE: To characterize the substantia nigra following middle cerebral artery occlusion and to evaluate the potential pathophysiological changes associated with the pseudo-normalization of MR signals in the substantia nigra at the subacute stage after stroke onset. MATERIAL AND METHODS: Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion. During the occlusion of single middle cerebral artery, computed tomography (CT) perfusion was acquired to observe the blood flow perfusion in the primary ischemic striatum and ipsilateral substantia nigra. Next, the MR T2 relaxation time and apparent diffusion coefficient changes within the substantia nigra were determined on days 1, 3, 7, and 14 after stroke onset, and compared with immunohistochemistry for microglia activation and astrogliosis. RESULTS: Twenty-four rats with strong hypoperfusion in the primary ischemic territory and no alterations of the perfusion in the ipsilateral substantia nigra detected both visually and measurably during the middle cerebral artery occlusion were further studied. All animals showed MR pseudo-normalization with T2 relaxation time and apparent diffusion coefficient recovered in the ipsilateral substantia nigra at the subacute phase following focal cerebral ischemia. Normalization of the MR signals corresponded well with the spatio-temporal occurrence of microglia activation and astrogliosis. CONCLUSION: The pseudo-normalization of T2 relaxation time and apparent diffusion coefficient reflects the neuroinflammatory changes that accompany activation of microglia and astrocytes in the ipsilateral substantia nigra following middle cerebral artery occlusion.

Comparison of USPIO-enhanced MRI and Gd-DTPA enhancement during the subacute stage of focal cerebral ischemia in rats.

BACKGROUND: Being one class of magnetic resonance imaging (MRI) contrast agents, ultrasmall superparamagnetic particles of iron oxides (USPIO) bear the potential to study neuroinflammation following stroke, but there is still debate over whether the iron oxides particles may enter the brain tissue passively over a damaged blood-brain barrier (BBB). PURPOSE: To compare the enhancement patterns of USPIO and gadopentate dimeglumine (Gd-DTPA) during the subacute stage of focal cerebral ischemia, to examine the relationship between USPIO enhancement and BBB disturbance, as well as with neuroinflammatory cell response. MATERIAL AND METHODS: Multiple MR sequences were obtained on days 3 and 6 after transient middle cerebral artery occlusion induced in rats with and without the application of USPIO and Gd-DTPA. The enhancement patterns of the two contrast agents were compared and correlated to histology, including IgG for BBB permeability, Prussian Blue staining for iron particle detection, and CD68 immunohistochemistry staining to identify macrophage/microglia. RESULTS: Gd-DTPA enhancement depicted BBB breakdown being in line with IgG leakage. The USPIO enhanced images demonstrated both diffuse and focal signal alteration in ischemic lesions. The diffuse enhanced pattern had a similar spatial and temporal profile as with Gd-DTPA enhancement. In addition, focal enhanced signal loss was visible on T1-, T2-, and T2*-weighted images, with a peak tendency of MR signal loss, macrophage/microglia concentration and iron particle accumulation at a later phase of the study. CONCLUSION: After focal cerebral ischemia, Gd-DTPA-enhanced MRI showed a higher sensitivity in detecting BBB alterations than did USPIO enhancement. USPIO provided complementary information regarding inflammatory cell activity in neuroinflammatory to cerebral ischemia that had not been visualized using conventional Gd-DTPA. The assessment using multiple MR parameters may identify intracellular and extracellular USPIO in vivo.

HACE1 exerts a neuroprotective role against oxidative stress in cerebral ischemia-reperfusion injury by activating the PI3K/AKT/Nrf2 pathway.

HECT domain and Ankyrin repeat-containing E3 ubiquitin protein ligase 1 (HACE1) is an E3 ubiquitin ligase involving oxidative stress, an important contributor in cerebral ischemia-reperfusion injury (CIRI). It was proposed to be associated with the PI3K/AKT pathway and Nrf2 nuclear translocation, which are important players of oxidative stress. Therefore, we supposed that HACE1 might affect CIRI by regulating the PI3K/AKT/Nrf2 pathway. Here, we used the transient middle cerebral artery occlusion-reperfusion (tMCAO/R) model to induce CIRI in rats and found lower HACE1 expression in ischemic rats compared with the control. To explore the exact role of HACE1, the lentivirus vector carrying the HACE1 sequence was administrated to rats by intracerebroventricular injection (1 × 109 TU/mL, 9 µL) one week before tMCAO/R operation. HACE1 overexpression alleviated tMCAO/R-induced brain damage in rats. Further studies revealed that it reduced oxidative stress via activating the PI3K/AKT/Nrf2 pathway, thereby inhibiting neuronal apoptosis in the ischemic penumbra of rats with CIRI. Then, differentiated PC12 cells were cultured in oxygen-glucose deprivation-reoxygenation (OGD/R) conditions (OGD: 1 % O2, 94 % N2, and 5 % CO2; R: normal atmosphere) to simulate CIRI in vitro. Similarly, HACE1 overexpression inhibited neuronal apoptosis caused by OGD/R treatment. The PI3K inhibitor LY294002 reversed the inhibitory effects of HACE1 overexpression on oxidative stress in OGD/R-injured cells, accompanied by the inactivated AKT/Nrf2 pathway. Altogether, our results suggest that HACE1 protects against oxidative stress-induced neuronal apoptosis in CIRI by activating the PI3K/AKT/Nrf2 pathway, providing a new insight into the CIRI treatment.

T1/T2 Proportional Magnetic Resonance Nanoprobe Monitoring Tumor Autophagy during Chemotherapy.

Autophagy leads to cellular tolerance of the therapeutic pressure of chemotherapeutic drugs, resulting in treatment resistance. Therefore, the effective monitoring of the autophagy status of tumors in vivo and the regulating of the autophagy level are crucial for improving the efficacy of chemotherapy. In this work, we grafted nitroxide radicals onto the surface of iron oxide nanoparticles (Fe3O4 NPs) using dendrimer polymers, yielding Fe3O4-NO· NPs that are responsive to reactive oxygen species (ROS) and possess enhanced T1 and T2 signal capabilities in a magnetic resonance imaging (MRI) measurement. The ROS in tumor cells generated by autophagy quenches the nitroxide radicals, thereby weakening the T1 signal. In contrast, Fe3O4 NPs are unaffected by intracellular ROS, leading to a stable T2 signal. By comparing the intensity ratio of T1 to T2 in Fe3O4-NO· NPs, we can evaluate the in vivo autophagy status within tumors in real time. It also revealed that Fe3O4-NO· NPs loaded with doxorubicin (Dox) and combining the autophagy inhibitor exhibited high antitumor activity in cells and tumor-bearing mice. This system, which combines real-time monitoring of tumor cell autophagy with the delivery of chemotherapeutic drugs, provides an innovative and effective strategy for tumor treatment with potential clinical application prospects.

Enhancing multiple myeloma staging: a novel cell death risk model approach.

The prognostication of survival trajectories in multiple myeloma (MM) patients presents a substantial clinical challenge. Leveraging transcriptomic and clinical profiles from an expansive cohort of 2,088 MM patients, sourced from the Gene Expression Omnibus and The Cancer Genome Atlas repositories, we applied a sophisticated nested lasso regression technique to construct a prognostic model predicated on 28 gene pairings intrinsic to cell death pathways, thereby deriving a quantifiable risk stratification metric. Employing a threshold of 0.15, we dichotomized the MM samples into discrete high-risk and low-risk categories. Notably, the delineated high-risk cohort exhibited a statistically significant diminution in survival duration, a finding which consistently replicated across both training and external validation datasets. The prognostic acumen of our cell death signature was further corroborated by TIME ROC analyses, with the model demonstrating robust performance, evidenced by AUC metrics consistently surpassing the 0.6 benchmark across the evaluated arrays. Further analytical rigor was applied through multivariate COX regression analyses, which ratified the cell death risk model as an independent prognostic determinant. In an innovative stratagem, we amalgamated this risk stratification with the established International Staging System (ISS), culminating in the genesis of a novel, refined ISS categorization. This tripartite classification system was subjected to comparative analysis against extant prognostic models, whereupon it manifested superior predictive precision, as reflected by an elevated C-index. In summation, our endeavors have yielded a clinically viable gene pairing model predicated on cellular mortality, which, when synthesized with the ISS, engenders an augmented prognostic tool that exhibits pronounced predictive prowess in the context of multiple myeloma.

In vivo USPIO-enhanced MR signal characteristics of secondary degeneration in the ipsilateral substantia nigra after middle cerebral artery occlusion at 3T.

BACKGROUND AND PURPOSE: Ultrasmall superparamagnetic iron oxide (USPIO) particles to enhance MRI have been used to study neuroinflammation in vivo. Our purpose was to observe the USPIO-enhanced MR signal alterations in the primary ischemic lesion and ipsilateral substantia nigra after middle cerebral artery occlusion (MCAO) to verify the subsequent sequelae of neuroinflammation seen in the primary ischemic focus and secondary degeneration region. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to transient MCAO. In addition to conventional T2-, T1-weighted imaging, USPIO-enhanced MRI was performed in USPIO-injected stroke rats, while Gd-enhanced imaging was acquired in control stroke rats, on days 3, 6 using a 3-T MR scanner. The MR signal characteristics in the primary ischemic striatum, ipsilateral substantia nigra were noted, compared on histopathological H&E, Prussian blue (PB) staining. RESULTS: After MCAO, USPIO-induced T2 hypointensity changes were observed in the primary ischemic region with BBB impairment at both time points. In the substantia nigra ipsilateral to the primary ischemic lesion, there was no evidence of USPIO accumulation detected by MRI and PB staining, and no BBB leakage reflected by Gd-enhanced imaging on days 3 and 6. CONCLUSION: USPIO-enhanced MR signals have variable characteristics in both primary and remote sites after focal cerebral ischemia. This suggests that the neuroinflammatory response to brain ischemia in the primary ischemic focus and secondary degeneration region have different temporal patterns and pathophysiological mechanisms.

Exploring Spatio-Temporal Variations of Ecological Risk in the Yellow River Ecological Economic Belt Based on an Improved Landscape Index Method.

Intense human activities have led to profound changes in landscape patterns and ecological processes, generating certain ecological risks that seriously threaten human wellbeing. Ecological risk assessment from a landscape perspective has become an important tool for macroecosystem landscape management. This research improves the framework and indices of the ecological risk assessment from a landscape perspective, evaluates the land use pattern and landscape ecological risk dynamics in the Yellow River Ecological Economic Belt (YREEB), analyzes the spatiotemporal variation, and identifies key areas for ecological risk management. The results indicate the following: The main land use types in the region are grassland and cropland, but the area of cropland and grassland decreased during the study period, and with the accelerated urbanization, urban land is the only land use type that continued to increase over the 20-year period. The ecological risk in the YREEB tended to decrease, the area of low ecological risk zones increased, while the area of high ecological risk zones gradually decreased. Most areas are at medium risk level, but the risk in central Qinghai and Gansu is obviously higher, and there is a dispersed distribution of local high- and low-risk zones. A total of 37.7% of the study area is identified as critical area for future risk management, and the potential for increased risk in these areas is high. These results can provide a basis for sustainable development and planning of the landscape and the construction of ecological civilization in ecologically fragile areas.

Exploring the relationship between seasonal variations of land surface temperature and urban morphological factors in complex urban areas.

The urban heat island effect is an increasingly serious problem in urban areas. Previous studies suggest that spatial variation in the urban land surface temperature (LST) is determined by interactions among urban morphological factors, but few studies have explored the main factors that affect the LST in different seasons in complex urban areas, especially at a fine scale. By considering the central Chinese city of Jinan as an example, we selected 19 parameters related to the architectural morphological factors, ecological basis factors, and humanistic factors and explored their effects on the LST in different seasons. A correlation model was used to identify the key factors and to analyze the main impact thresholds in different seasons. In the four seasons, the 19 factors all had significant correlations with LST. In particular, architectural morphological factors comprising the average building height and high building ratio had significant negative correlations with the LST in the four seasons. The architectural morphological factors comprising the floor area ratio, spatial concentration degree, building volume density, and urban surface pattern index comprising the mean nearest neighbor distance to green land, as well as humanistic factors comprising the point of interest density, nighttime light intensity, and human activity intensity of land surface had significant positive correlations with LST in the summer and autumn. Ecological basis factors made the main contributions to the LST in the spring, summer, and winter, whereas humanistic factors contributed the most in the autumn. The contributions of architectural morphological factors were relatively low in the four seasons. The dominant factors differed in each season but their thresholds had similar characteristics. The results obtained in this study deepen our understanding of the relationships between urban morphology and the urban heat island effect, and provide practical suggestions for improving the urban thermal environment through reasonable building planning and management.

Advances in the pathogenesis and therapeutic strategies of angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphomas with its cell origin determined to be follicular helper T-cells. AITL is characterized by a prominent tumor microenvironment involving dysregulation of immune cells, signaling pathways, and extracellular matrix. Significant progress has been made in the molecular pathophysiology of AITL, including genetic mutations, immune metabolism, hematopoietic-derived microenvironment, and non-hematopoietic microenvironment cells. Early diagnosis, detection of severe complications, and timely effective treatment are crucial for managing AITL. Treatment typically involves various combination chemotherapies, but the prognosis is often poor, and relapsed and refractory AITL remains challenging, necessitating improved treatment strategies. Therefore, this article provides an overview of the pathogenesis and latest advances in the treatment of AITL, with a focus on potential therapeutic targets, novel treatment strategies, and emerging immunotherapeutic approaches.

Based on bound water characteristics study of microporosity characteristics and mechanical properties evolution of copper-contaminated laterite.

The potential impact of heavy metal ion infiltration on macroscopic and microscopic soil properties is a subject of academic interest. Laterite has an extensive distribution in southern China and is extensively utilized as a vertical containment wall for landfills. Consequently, there is a need to investigate how heavy metal ions affect laterite's microstructure and mechanical properties. To examine the impact of Cu2+ on laterite's microporous characteristics and mechanical properties, laboratory tests were conducted on the permeability, shear strength, microporous characteristics, and strong absorbed water content of Cu2+-contaminated laterite. The results show that Cu2+ hydrolysis generates an acidic environment, which leads to erosion of the cementing substance between the laterite particles, increasing the laterite's porosity and decreasing the soil's cohesive strength, thus affecting the shear strength and permeability of the laterite. When the concentration of Cu2+ is 5.0 g/L, the laterite demonstrated the most significant decrease in shear strength, 43.01%, while the permeability coefficient increased from 3.24 × 10-8 cm/s to 1.32 × 10-7 cm/s. Meanwhile, Cu2+ changes the content of strong absorbed water in laterite. The change of strong absorbed water content will affect the Van der Waals between laterite particles, promote the evolution of soil micropore structure, and lead to a decrease in the proportion of intra-aggregate pores (d < 1 µm) and an increase in the proportion of inter-aggregate pores (1 µm < d < 10 µm), which in turn affects the macroscopic shear strength and permeability. This study has improved our understanding of the mechanisms underlying the microporosity and mechanical property evolution of laterite when subjected to heavy metal attack.