Cortical structure reorganization and correlation with attention deficit in subcortical stroke: An underlying pattern analysis.

BACKGROUND: Subcortical stroke may significantly alter the cerebral cortical structure and affect attention function, but the details of this process remain unclear. The study aimed to investigate the neural substrates underlying attention impairment in patients with subcortical stroke. MATERIALS AND METHODS: In this prospective observational study, two distinct datasets were acquired to identify imaging biomarkers underlying attention deficit. The first dataset consisted of 86 patients with subcortical stroke, providing a cross-sectional perspective, whereas the second comprised 108 patients with stroke, offering longitudinal insights. All statistical analyses were subjected to false discovery rate correction upon P < 0.05. RESULTS: In the chronic-stage data, the stroke group exhibited significantly poorer attention function compared with that of the control group. The cortical structure analysis showed that patients with stroke exhibited decreased cortical thickness of the precentral gyrus and surface area of the cuneus, along with an increase in various frontal, occipital, and parietal cortices regions. The declined attention function positively correlated with the superior frontal gyrus cortical thickness and supramarginal gyrus surface area. In the longitudinal dataset, patients with stroke showed gradually increasing cortical thickness and surface area within regions of obvious structural reorganization. Furthermore, deficient attention positively correlated with supramarginal gyrus surface area both at the subacute and chronic stages post-stroke. CONCLUSIONS: Subcortical stroke can elicit dynamic reorganization of cortical areas associated with attention impairment. Moreover, the altered surface area of the supramarginal gyrus is a potential neuroimaging biomarker for attention deficits.

PARP1 inhibition prevents oxidative stress in age-related hearing loss via PAR-Ca2+-AIF axis in cochlear strial marginal cells.

Studies have highlighted oxidative damage in the inner ear as a critical pathological basis for sensorineural hearing loss, especially the presbycusis. Poly(ADP-ribose) polymerase-1 (PARP1) activation responds to oxidative stress-induced DNA damage with pro-repair and pro-death effects resembling two sides of the same coin. PARP1-related cell death, known as parthanatos, whose underlying mechanisms are attractive research hotspots but remain to be clarified. In this study, we observed that aged rats showed stria vascularis degeneration and oxidative damage, and PARP1-dependent cell death was prominent in age-related cochlear disorganization and dysfunction. Based on oxidative stress model of primary cultured stria marginal cells (MCs), we revealed that upregulated PARP1 and PAR (Poly(ADP-ribose)) polymers are responsible for MCs oxidative death with high mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane potential (MMP) collapse, while inhibition of PARP1 ameliorated the adverse outcomes. Importantly, the PARylation of apoptosis-inducing factor (AIF) is essential for its conformational change and translocation, which subsequently causes DNA break and cell death. Concretely, the interaction of PAR and truncated AIF (tAIF) is the mainstream in the parthanatos pathway. We also found that the effects of AIF cleavage and release were achieved through calpain activity and mPTP opening, both of which could be regulated by PARP1 via mediation of mitochondria Ca2+ concentration. In conclusion, the PAR-Ca2+-tAIF signaling pathway in parthanatos contributes to the oxidative stress damage observed in MCs. Targeting PAR-Ca2+-tAIF might be a potential therapeutic strategy for the early intervention of presbycusis and other oxidative stress-associated sensorineural deafness.

Altered static and dynamic cerebellar-cerebral functional connectivity in acute pontine infarction.

This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.

Artificial Domain Patterning in Ultrathin Ferroelectric Films via Modifying the Surface Electrostatic Boundary Conditions.

Nanoscale spatially controlled modulation of the properties of ferroelectrics via artificial domain pattering is crucial to their emerging optoelectronics applications. New patterning strategies to achieve high precision and efficiency and to link the resultant domain structures with device functionalities are being sought. Here, we present an epitaxial heterostructure of SrRuO3/PbTiO3/SrRuO3, wherein the domain configuration is delicately determined by the charge screening conditions in the SrRuO3 layer and the substrate strains. Chemical etching of the top SrRuO3 layer leads to a transition from in-plane a domains to out-of-plane c domains, accompanied by a giant (>105) modification in the second harmonic generation response. The modulation effect, coupled with the plasmonic resonance effect from SrRuO3, enables a highly flexible design of nonlinear optical devices, as demonstrated by a simulated split-ring resonator metasurface. This domain patterning strategy may be extended to more thin-film ferroelectric systems with domain stabilities amenable to electrostatic boundary conditions.

Immobilization mechanisms of Sr(II), Ni(II), and Cd(II) on glomalin-related soil protein in mangrove sediments at the microscopic scale.

Glomalin-related soil protein (GRSP) is a significant component in the sequestration of heavy metal in soils, but its mechanisms for metal adsorption are poorly known. This study combined spectroscopic data with molecular docking simulations to reveal metal adsorption onto GRSP's surface functional groups at the molecular level. The EXAFS combined with FTIR and XPS analyses indicated that the adsorption of Cd(II), Sr(II), and Ni(II) by GRSP occurred mainly through the coordination of -OH and -COOH groups with the metal. The -COOH and -OH groups bound to the metal as electron donors and the electron density of the oxygen atom decreased, suggesting that electrostatic attraction might be involved in the adsorption process. Two-dimensional correlation spectroscopy revealed that preferential adsorption occurred on GRSP for the metal in sequential order of -COOH groups followed by -OH groups. The presence of the Ni-C shell in the Ni EXAFS spectrum suggested that Ni formed organometallic complexes with the GRSP surface. However, Sr-C and Cd-C were absent in the second shell of the Sr and Cd spectra, which was attributed to the adsorption of Sr and Cd ions with large hydration ion radius by GRSP to form outer-sphere complexes. Through molecular docking simulations, negatively charged residues such as ASP151 and ASP472 in GRSP were found to provide electrostatic attraction and ligand combination for the metal adsorption, which was consistent with the spectroscopic analyses. Overall, these findings provided new insights into the interaction mechanisms between GRSP and metals, which will help deepen our understanding of the ecological functions of GRSP in metal sequestration.

ß-Sitosterol targets ASS1 for Nrf2 ubiquitin-dependent degradation, inducing ROS-mediated apoptosis via the PTEN/PI3K/AKT signaling pathway in ovarian cancer.

The exploration of drugs derived from natural sources holds significant promise in addressing current limitations in ovarian cancer (OC) treatments. While previous studies have highlighted the remarkable anti-cancer properties of the natural compound ß-sitosterol (SIT) across various tumors, its specific role in OC treatment remains unexplored. This study aims to investigate the anti-tumor activity of SIT in OC using in vitro and in vivo models, delineate potential mechanisms, and establish a preclinical theoretical foundation for future clinical trials, thus fostering further research. Utilizing network pharmacology, we pinpoint SIT as a promising candidate for OC treatment and predict its potential targets and pathways. Through a series of in vitro and in vivo experiments, we unveil a novel mechanism through which SIT mitigates the malignant biological behaviors of OC cells by modulating redox status. Specifically, SIT selectively targets argininosuccinate synthetase 1 (ASS1), a protein markedly overexpressed in OC tissues and cells. Inhibiting ASS1, SIT enhances the interaction between Nrf2 and Keap1, instigating the ubiquitin-dependent degradation of Nrf2, subsequently diminishing the transcriptional activation of downstream antioxidant genes HO-1 and NQO1. The interruption of the antioxidant program by SIT results in the substantial accumulation of reactive oxygen species (ROS) in OC cells. This, in turn, upregulates PTEN, exerting negative regulation on the phosphorylation activation of AKT. The suppression of AKT signaling disrupted downstream pathways associated with cell cycle, cell survival, apoptosis, migration, and invasion, ultimately culminating in the death of OC cells. Our research uncovers new targets and mechanisms of SIT against OC, contributing to the existing knowledge on the anti-tumor effects of natural products in the context of OC. Additionally, this research unveils a novel role of ASS1 in regulating the Nrf2-mediated antioxidant program and governing redox homeostasis in OC, providing a deeper understanding of this complex disease.

Enhanced Cr(VI) stabilization by terrestrial-derived soil protein: Photoelectrochemical properties and reduction mechanisms.

Glomalin-related soil protein (GRSP) is a stable iron-organic carbon mixture that can enhance heavy metal sequestration in soils. However, the roles of GRSP in the transformation and fate of Cr(VI) have been rarely reported. Herein, we investigated the electrochemical and photocatalytic properties of GRSP and its mechanisms in Cr(VI) adsorption and reduction. Results showed that GRSP had a stronger ability for Cr(VI) adsorption and reduction than other biomaterials, with the highest adsorption amount of up to 0.126 mmol/g. The removal efficiency of Cr(VI) by GRSP was enhanced (4-7%) by ultraviolet irradiation due to the hydrated electrons produced by GRSP. Fe(II) ions, persistent free radicals, and oxygen-containing functional groups on the GRSP surface as electron donors participated in the reduction of Cr(VI) under dark condition. Moreover, Cr(III) was mainly adsorbed on the -COOH groups of GRSP via electrostatic interactions. Based on 2D correlation spectroscopy, the preferential adsorption occurred on the GRSP surface for Cr(VI) in the sequential order of CO → COO- → O-H → C-O. This work provides new insights into the Cr(VI) adsorption and reduction mechanism by GRSP. Overall, GRSP can serve as a natural iron-organic carbon for the photo-reduction of Cr(VI) pollution in environments.

Dynamic brain activity states of memory impairment in stroke patients with varying motor outcomes.

Introduction: The objective of this study was to characterize the alteration patterns of dynamic spatiotemporal activity in chronic subcortical stroke patients with varying motor outcomes, while investigating the imaging indicators relevant to the assessment of potential cognitive deficits in these patients. Methods: A total of 136 patients and 88 normal controls were included in the analysis of static and dynamic intrinsic brain activity, determined by amplitude of low-frequency fluctuations. Results: The findings unveiled that subcortical stroke patients exhibited significantly aberrant temporal dynamics of intrinsic brain activity, involving regions within multiple brain networks. These spatiotemporal patterns were found to be contingent upon the side of the lesion. In addition, these aberrant metrics demonstrated potential in discerning cognitive deficits in stroke patients with memory impairment, with the dynamic indices exerting more influence than the static ones. The observe findings may indicate that subcortical stroke can trigger imbalances in the segregation and integration of spatiotemporal patterns across the entire brain with multi-domain networks, especially in patients with poor motor outcomes. Conclusion: It suggests that the temporal dynamics indices of intrinsic brain activity could serve as potential imaging indicators for assessing cognitive impairment in patients with chronic subcortical stroke, which may be associated with the motor outcomes.

Cochlear metabolomics, highlighting novel insights of purine metabolic alterations in age-related hearing loss.

Aging is an inevitable phase in mammals that leads to health impairments, including hearing loss. Age-related hearing loss (AHL) leads to psychosocial problems and cognitive decline in the elderly. In this study, mean thresholds of auditory brainstem responses (ABR) and distortion-product otoacoustic emissions (DPOAE) increased at multiple frequencies in aged rats (14 months old) compared to young rats (2 months old). Using untargeted ultra-high performance liquid chromatography-mass spectroscopy (LC-MS), we quantified molecular metabolic markers in the cochlea of aged rats with hearing loss. A total of 137 different metabolites were identified in two groups, highlighting several prominent metabolic pathways related to purine metabolism; glycine, serine, and threonine metabolism; arginine and proline metabolism; and pyrimidine metabolism. In addition, the beneficial effects of purine supplementation were demonstrated in a mimetic model of senescent marginal cells (MCs). Overall, altered metabolic profiling is both the cause and manifestation of pathology, and our results suggest that cellular senescence and dysfunctional cochlear metabolism may contribute to the progression of AHL. These findings are seminal in elucidating the pathophysiological mechanisms underlying AHL and serve as a basis for future clinical predictions and interventions in AHL.

The gap-free genome of mulberry elucidates the architecture and evolution of polycentric chromosomes.

Mulberry is a fundamental component of the global sericulture industry, and its positive impact on our health and the environment cannot be overstated. However, the mulberry reference genomes reported previously remained unassembled or unplaced sequences. Here, we report the assembly and analysis of the telomere-to-telomere gap-free reference genome of the mulberry species, Morus notabilis, which has emerged as an important reference in mulberry gene function research and genetic improvement. The mulberry gap-free reference genome produced here provides an unprecedented opportunity for us to study the structure and function of centromeres. Our results revealed that all mulberry centromeric regions share conserved centromeric satellite repeats with different copies. Strikingly, we found that M. notabilis is a species with polycentric chromosomes and the only reported polycentric chromosome species up to now. We propose a compelling model that explains the formation mechanism of new centromeres and addresses the unsolved scientific question of the chromosome fusion-fission cycle in mulberry species. Our study sheds light on the functional genomics, chromosome evolution, and genetic improvement of mulberry species.

Associations between long-term blood pressure trajectory and all-cause and CVD mortality among old people in China.

Background: Optimal blood pressure (BP) management strategy among the elderly remains controversial, with insufficient consideration of long-term BP trajectory. This study aimed to identify BP trajectory patterns as well as terminal BP trajectory among the Chinese elderly and to explore the relationships between BP trajectories and all-cause mortality and cardiovascular disease (CVD) mortality. Methods: We included 11,181 participants older than 60 at baseline (mean age, 80.98 ± 10.71) with 42,871 routine BP measurements from the Chinese Longitudinal Healthy Longevity Survey. Latent class trajectory analysis and Cox proportional hazard model were conducted to identify trajectory patterns and their associations with mortality. Furthermore, we also applied mixed-effects model to identify terminal BP trajectories among the elderly. Results: Compared with stable at normal high level trajectory, excess systolic BP (SBP) trajectory with decreasing trend was associated with a 34% (HR = 1.34, 95% CI: 1.23-1.45) higher risk of all-cause mortality. Considering the competing risk of non-CVD death, excess BP trajectory with decreasing trend had a more pronounced effect on CVD mortality, in which HR (95% CI) was 1.67 (1.17, 2.37). Similar results were also found in diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP) trajectories. We further conducted a mixed-effects model and observed that SBP and PP trajectories first increased and began to decline slightly six years before death. In contrast, DBP and MAP showed continuous decline 15 years before death. Conclusion: Long-term BP trajectory was associated with all-cause mortality, especially CVD mortality. Keeping a stable BP over time may be an important way for CVD prevention among the elderly.

Spatiotemporal Trends and Age-Period-Cohort Analysis for the Burden of Endometriosis-Related Infertility: An Analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Endometriosis is a common nonfatal gynecological disease, and infertility is one of its main dangers. Endometriosis-related infertility causes serious damage to women's health and places a burden on women of reproductive age. The aim of this study was to describe the current burden of endometriosis-associated infertility and to analyze its spatiotemporal trends. METHODS: Age-standardized prevalence rate (ASPR) data from 1990 to 2019 for Endometriosis-related primary infertility (ERPI) and secondary infertility (ERSI) were obtained from the Global Burden of Disease Study (GBD) 2019. These data spanning three decades cover the global, sociodemographic index (SDI) regions, GBD regions, and 204 countries and territories. Spatiotemporal trends were analyzed by calculating the estimated annual percentage change (EAPC) and using a time-period-cohort model. RESULTS: Globally, the ASPR of ERPI and ERSI showed a weak downward trend from 1990 to 2019, with EAPCs of -1.25 (95% CI: -1.39 to -1.11) and -0.6 (95% CI: -0.67 to -0.53), respectively. The spatiotemporal trends in ERPI and ERSI varied substantially between regions and age groups. When endometriosis-related infertility burden was linked to SDI values, a strong negative correlation was observed between the ASPR of ERSI and its EAPC and SDI values. When modeling with age-period-cohort, ERPI burden was found to be highest at ages 20-25 years, while ERSI burden was persistently higher at ages 20-45 years. Using 2000-2004 as the reference period, both ERPI and ERSI burden decreased with each year among women. Significant variability in burden between regions was found for the birth cohort factor. CONCLUSIONS: The global burden of endometriosis-related infertility declined minimally from 1990 to 2019. However, this burden varied considerably across regions, age groups, periods, and birth cohorts. The results of this study reflect spatiotemporal trends in the burden of endometriosis-related infertility over the study period and may be used to help improve health management, develop timely and effective prevention and control strategies, and provide epidemiologic theoretical evidence for reducing the burden for endometriosis-related infertility.

Paeonol repurposing for cancer therapy: From mechanism to clinical translation.

Paeonol (PAE) is a natural phenolic monomer isolated from the root bark of Paeonia suffruticosa that has been widely used in the clinical treatment of some inflammatory-related diseases and cardiovascular diseases. Much preclinical evidence has demonstrated that PAE not only exhibits a broad spectrum of anticancer effects by inhibiting cell proliferation, invasion and migration and inducing cell apoptosis and cycle arrest through multiple molecular pathways, but also shows excellent performance in improving cancer drug sensitivity, reversing chemoresistance and reducing the toxic side effects of anticancer drugs. However, studies indicate that PAE has the characteristics of poor stability, low bioavailability and short half-life, which makes the effective dose of PAE in many cancers usually high and greatly limits its clinical translation. Fortunately, nanomaterials and derivatives are being developed to ameliorate PAE's shortcomings. This review aims to systematically cover the anticancer advances of PAE in pharmacology, pharmacokinetics, nano delivery systems and derivatives, to provide researchers with the latest and comprehensive information, and to point out the limitations of current studies and areas that need to be strengthened in future studies. We believe this work will be beneficial for further exploration and repurposing of this natural compound as a new clinical anticancer drug.

Combined use of positive matrix factorization and 13C15N stable isotopes to trace organic matter-bound potential toxic metals in the urban mangrove sediments.

Coastal sediments act as sinks of sediment organic matter (SOM) and metals because of their special land-sea location and depositional properties. However, there are few reports on the correlation between the sources of organic matter (OM) and associated potential toxic metals (PTMs). In this study, we combined CN stable isotope analysis and positive matrix factorization to identify the matter and metal sources of OM and glomalin-related soil protein (GRSP) in an estuary under several decades of urbanization. The results of the positive matrix factorization (PMF) reveal a correlation between the sources of total sediment metals and the sources of OM-related metals. The sources of both SOM-bound PTMs and GRSP-bound PTMs are significantly related to the sources of total PTMs. OM sources were elucidated through 13C-15 N stable isotopes, and the potential sources of different types of OM differed. In addition, there is a significant correlation between OM-associated PTMs and organic matter sources. Interestingly, the functional groups of SOM were mainly influenced by multiple PTM sources but no OM source, while the functional groups of GRSP were regulated by a single metal source and OM source. This study deepened the understanding of the coupling between PTMs and SOM. The possibility of combined use of positive matrix factorization and 13C-15 N stable isotope tracing of metals as well as the sources of each metal fractions has been evaluated, which will provide new insights for the transportation of PTMs.

Association of sleep behavior with depression: a cross-sectional study in northwestern China.

Background: This study aimed to examine the association between sleep duration, sleep problems, and depression in Northwest China. Method: Depression was diagnosed at the hospital and self-reported by the participants in the baseline survey. Sleep duration and problems, including difficulty initiating and maintaining sleep, early morning awakening, daytime dysfunction, use of sleeping pills or drugs, and any sleep problems, were obtained by a self-reported questionnaire. Logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals (CIs) for exploring the association between sleep duration, sleep problems, and depression, adjusting for demographic and socioeconomic characteristics and health behaviors. The association between depression and sleep duration was also evaluated continuously with restricted cubic spline curves based on logistic models. Results: 36,515 adults from Regional Ethnic Cohort Study in Northwest China were included. About 24.04% of participants reported short sleep duration (<7 h), and 15.64% reported long sleep duration (≥9 h). Compared with standard sleep duration (7-9 h), short sleep duration was associated with a higher risk of depression (OR: 1.69, 95%CI: 1.26-2.27, p = 0.001). Self-reported sleep problems were also related to four times depression risk increased (OR: 4.02, 95%CI: 3.03-5.35, p < 0.001) compared with no sleep problems. In addition, a nonlinear relationship was found between sleep duration and depression after adjusting covariates (p = 0.043). Conclusion: Sleep duration and sleep problems are associated with depression. Enough sleep time and healthy sleep habits in life course might be a practical health promotion approach to reduce depression risk in Northwest Chinese adults. A further study from cohort study is needed to verify the temporal association.

Altered resting-state neurovascular coupling in patients with pontine infarction.

The risk for motor and cognitive impairment is increased in patients with chronic pontine infarction (PI). In this study, we attempted to explore the alterations of neurovascular coupling (NVC) in order to understand the neural basis of behavioral impairment after PI. Three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL) and resting-state functional magnetic resonance imaging (rs-fMRI) were applied in 49 patients with unilateral PI (left-sided, n = 26; right-sided, n = 23) and 30 matched normal subjects to assess whole-brain cerebral blood flow (CBF) and functional connectivity strength (FCS). We evaluated NVC in each subject by calculating the correlation coefficient between the whole-brain CBF and FCS (CBF-FCS coupling) and the ratio between voxel-wise CBF and FCS (CBF/FCS ratio). The FCS maps were then divided into long-range and short-range FCS to identify the influence of connection distance. The results indicated that the CBF-FCS coupling in the whole-brain level was significantly interrupted in PI patients, and the CBF/FCS ratio in cognition-related brain regions was abnormal. Distance-dependent results demonstrated that PI had a more serious effect on long-range neurovascular coupling. Correlation analysis revealed that the changes in neurovascular coupling were correlated with working memory scores. These findings imply that disruption of neurovascular coupling in the remote-infarction brain regions may underlie the impaired cognitive functions in chronic PI.

Change in glomalin-related soil protein along latitudinal gradient encompassing subtropical and temperate blue carbon zones.

Glomalin-related soil protein (GRSP), an abundant and eco-friendly bioproduct associated with arbuscular mycorrhizal fungi (AMF), contributes significantly to the soil particle aggregation and carbon sequestration. Although much research has been conducted on the storage of GRSP at different spatio-temporal scales in terrestrial ecosystems. However, the deposition of GRSP in large-scale coastal environments has not been revealed, which hinders an in-depth understanding of GRSP storage patterns and environmental controls, and this knowledge gap has become one of the key uncertainties in understanding the ecological functions of GRSP as blue carbon components in coastal environments. Therefore, we conducted large-scale experiments (spanning subtropical and warm temperate climate zones, coastlines over 2500 km) to test the relative contributions of environmental drivers that shape unique GRSP storage. In salt marshes of China, we found that the abundance of GRSP ranges from 0.29 mg g-1 to 1.10 mg g-1, and its concentration decreases with increasing latitude (R2 = 0.30, p < 0.01). The GRSP-C/SOC of salt marshes ranged from 4 % to 43 % and increased with the increase in latitude (R2 = 0.13, p < 0.05). The carbon contribution of GRSP does not follow the trend of increasing abundance, but is limited by the total amount of background organic carbon. In salt marsh wetlands, precipitation, clay content and pH are the main factors influencing GRSP storage. GRSP is positively correlated with precipitation (R2 = 0.42, p < 0.01) and clay content (R2 = 0.59, p < 0.01), but negatively correlated with pH (R2 = 0.48, p < 0.01). The relative contributions of the main factors to the GRSP differed across climatic zones. Soil properties, such as clay content and pH, explained 19.8 % of the GRSP in subtropical salt marshes (20°N < 34°N), however, in warm temperate salt marshes (34°N < 40°N), precipitation explained 18.9 % of the GRSP variation. Our study provides insight into the distribution and function of GRSP in coastal environments.

Dynamic reorganization of cortical structure in multi-domain regions after capsular and pontine stroke.

Subcortical stroke may cause widespread structural changes to the cerebral cortex in multiple domains; however, the details of this process remain unclear. In this prospective observational study, we acquired two datasets to investigate the effect of lesion location on cortical structure. One was cross-sectional, comprising 269 patients with chronic stroke, either capsular stroke (CS) or pontine stroke (PS), and the other was longitudinal, comprising 119 patients with CS or PS. In the chronic-stage data, both CS and PS exhibited reduced cortical thickness in the precentral gyrus and increased cortical thickness and area in the frontal, temporal, occipital and insular cortices. Cortical thicknesses were correlated with motor outcomes in the precentral and lingual gyri, and early impairment of the corticospinal tract was associated with cortical thickness in the middle frontal gyrus. In the longitudinal dataset, CS showed gradually decreasing cortical thickness in the precentral gyrus, and both CS and PS showed gradually increasing cortical thickness and area in regions with significant structural reorganization. Subcortical stroke can therefore cause complex cortical structural changes in multi-domain regions involved in motor, primary and higher cognitive areas and have different evolution patterns depending on the subcortical level of the lesion affecting the motor pathways.

ß-Sitosterol as a Promising Anticancer Agent for Chemoprevention and Chemotherapy: Mechanisms of Action and Future Prospects.

Cancer is one of the primary causes of death worldwide, and its incidence continues to increase yearly. Despite significant advances in research, the search for effective and nontoxic preventive and therapeutic agents remains greatly important. Cancer is a multimodal disease, where various mechanisms play significant roles in its occurrence and progression. This highlights the need for multitargeted approaches that are not only safe and inexpensive but also provide effective alternatives for current therapeutic regimens. ß-Sitosterol (SIT), the most abundant phytosterol found in various plant foods, represents such an option. Preclinical evidence over the past few decades has overwhelmingly shown that SIT exhibits multiple anticancer activities against varied cancers, such as liver, cervical, colon, stomach, breast, lung, pancreatic, and prostate cancers, in addition to leukemia, multiple myeloma, melanoma, and fibrosarcoma. In this article, we present the latest advances and perspectives on SIT-systematically summarizing its antitumor mechanisms of action into 7 main sections and combining current challenges and prospects-for its use as a promising agent for cancer prevention and treatment. In particular, SIT plays a role in cancer prevention and treatment mainly by enhancing apoptosis, inducing cell cycle arrest, bidirectionally regulating oxidative stress, improving metabolic reprogramming, inhibiting invasion and metastasis, modulating immunity and inflammation, and combating drug resistance. Although SIT holds such great promise, the poor aqueous solubility and bioavailability coupled with low targeting efficacy limit its therapeutic efficacy and clinical application. Further research on novel drug delivery systems may improve these deficiencies. Overall, through complex and pleiotropic mechanisms, SIT has good potential for tumor chemoprevention and chemotherapy. However, no clinical trials have yet proven this potential. This review provides theoretical basis and rationality for the further design and conduct of clinical trials to confirm the anticancer activity of SIT.

Comprehensive Analysis of Purine-Metabolism-Related Gene Signature for Predicting Ovarian Cancer Prognosis, Immune Landscape, and Potential Treatment Options.

Purine metabolism is an important branch of metabolic reprogramming and has received increasing attention in cancer research. Ovarian cancer is an extremely dangerous gynecologic malignancy for which there are no adequate tools to predict prognostic risk. Here, we identified a prognostic signature consisting of nine genes related to purine metabolism, including ACSM1, CACNA1C, EPHA4, TPM3, PDIA4, JUNB, EXOSC4, TRPM2, and CXCL9. The risk groups defined by the signature are able to distinguish the prognostic risk and the immune landscape of patients. In particular, the risk scores offer promising personalized drug options. By combining risk scores with clinical characteristics, we have created a more detailed composite nomogram that allows for a more complete and individualized prediction of prognosis. In addition, we demonstrated metabolic differences between platinum-resistant and platinum-sensitive ovarian cancer cells. In summary, we have performed the first comprehensive analysis of genes related to purine metabolism in ovarian cancer patients and created a feasible prognostic signature that will aid in risk prediction and support personalized medicine.