Exploration and Validation of Immune and Therapeutic-Related Hub Genes in Aortic Valve Calcification and Carotid Atherosclerosis.

Background: Cardiovascular diseases, such as aortic valve calcification (AVC) and carotid atherosclerosis (CAS), impose substantial health challenges on a global scale. Both disorders have overlapping risk factors, which might trigger similar immune-inflammatory reactions in both diseases. Methods: Shared differentially expressed genes (DEGs) were identified in the AVC and CAS datasets from the Gene Expression Omnibus (GEO). Candidate hub genes associated with immunity were identified using LASSO and immune cell infiltration analysis, and single gene set enrichment analysis (GSEA) was performed on the datasets. Subsequently, the hub genes were confirmed by qRT‒PCR validation in tissue samples. Results: A total of 140 upregulated and 65 downregulated common genes were screened. Enrichment analyses highlighted immune system processes, response to stress, and cytokine pathways among the identified CEGs. LASSO identified candidate hub genes, including ANGPTL1, CX3CR1, and CCL4. Immune cell infiltration analysis emphasized the participation of immune cells, including macrophages, γδ T cells, and resting NK cells. The three hub genes were validated by qRT‒PCR analysis. Conclusion: Our study explored immunological processes, including immune-related genes and cells, involved in the development of AVC and CAS. In particular, the identified hub genes ANGPTL1, CX3CR1, and CCL4 play crucial roles in mediating immune-inflammatory responses, which are central to the pathogenesis of these cardiovascular diseases, and the involvement of these genes in key immune pathways suggests that they could serve as potential biomarkers for early diagnosis or as targets for therapeutic strategies.

White matter microstructural and inflammation-based subgroups in bipolar disorder II depression differentiate in depressive and psychotic symptoms.

BACKGROUND: Elevated inflammation and impaired white matter (WM) microstructure have been observed in bipolar disorder (BD). The link between inflammation, WM integrity, and psychiatric symptoms in BD-II depression (BDII-D) remains unknown. We aimed to define BDII-D subgroups through the interplay of inflammation and WM microstructure, and to explore differences in psychiatric symptoms between subgroups, thus offering insight into elucidating the explanatory measures linked to BDII-D. METHODS: WM differences were compared between 146 BDII-D individuals and 151 health controls (HCs) by Tract-Based Spatial Statistics. Partial correlation with multiple comparison corrections was used to explore associations between WM, inflammation, and psychiatric symptoms. The canonical correlation analysis metrics of WM and inflammation followed by k-means clustering were used to define WM microstructural-inflammation subgroups of BDII-D. The differences in clinical profiles were compared between the subgroups. RESULTS: Compared with HCs, BDII-D showed significant WM alterations in the anterior thalamic radiation (ATR), cingulum, forceps, and inferior fronto-occipital fasciculus. In BDII-D, lower fraction anisotropy (FA) within the right ATR and cingulum were significantly associated with higher interleukin-6, while lower FA in the cingulum and lower axial diffusivity in the forceps major exhibited significant links with higher C-reactive protein. Among the subgroups identified, subgroup II characterized by elevated inflammation and impaired WM integrity displayed greater psychiatric symptoms. CONCLUSIONS: WM alterations are concentrated in emotional neurocircuits and are linked to inflammation in BDII-D. WM-inflammation subgroups exhibit distinct variations in psychiatric symptoms. Thus, WM alterations and inflammation might be an explanatory process in the pathophysiology of BDII-D.

A systematic review of the application of machine learning techniques to ultrasound tongue imaging analysis.

B-mode ultrasound has emerged as a prevalent tool for observing tongue motion in speech production, gaining traction in speech therapy applications. However, the effective analysis of ultrasound tongue image frame sequences (UTIFs) encounters many challenges, such as the presence of high levels of speckle noise and obscured views. Recently, the application of machine learning, especially deep learning techniques, to UTIF interpretation has shown promise in overcoming these hurdles. This paper presents a thorough examination of the existing literature, focusing on UTIF analysis. The scope of our work encompasses four key areas: a foundational introduction to deep learning principles, an exploration of motion tracking methodologies, a discussion of feature extraction techniques, and an examination of cross-modality mapping. The paper concludes with a detailed discussion of insights gleaned from the comprehensive literature review, outlining potential trends and challenges that lie ahead in the field.

The transcription factor CAMTA2 interacts with the histone acetyltransferase GCN5 and regulates grain weight in wheat.

Grain weight and size are major traits targeted in breeding to improve wheat (Triticum aestivum L.) yield. Here, we find that the histone acetyltransferase GENERAL CONTROL NONDEREPRESSIBLE 5 (GCN5) physically interacts with the calmodulin-binding transcription factor CAMTA2 and regulates wheat grain size and weight. gcn5 mutant grains were smaller and contained less starch. GCN5 promoted the expression of the starch biosynthesis genes SUCROSE SYNTHASE 2 (Sus2) and STARCH-BRANCHING ENZYME Ic (SBEIc) by regulating H3K9ac and H3K14ac levels in their promoters. Moreover, immunoprecipitation followed by mass spectrometry (IP-MS) revealed that CAMTA2 physically interacts with GCN5. The CAMTA2-GCN5 complex activated Sus2 and SBEIc by directly binding to their promoters and depositing H3K9ac and H3K14ac marks during wheat endosperm development. camta2 knockout mutants exhibited similar phenotypes to gcn5 mutants, including smaller grains that contained less starch. In gcn5 mutants, transcripts of high molecular weight (HMW) Glutenin (Glu) genes were downregulated, leading to reduced HMW glutenin protein levels, gluten content, and sodium dodecyl sulfate (SDS) sedimentation volume. However, the association of GCN5 with Glu genes was independent of CAMTA2, since GCN5 enrichment on Glu promoters was unchanged in camta2 knockouts. Finally, we identified a CAMTA2-AH3 elite allele that corresponded with enhanced grain size and weight, serving as a candidate gene for breeding wheat varieties with improved grain weight.

New insights in lipid metabolism: potential therapeutic targets for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is increasingly recognized as being intertwined with the dysregulation of lipid metabolism. Lipids are a significant class of nutrients vital to all organisms, playing crucial roles in cellular structure, energy storage, and signaling. Alterations in the levels of various lipids in AD brains and dysregulation of lipid pathways and transportation have been implicated in AD pathogenesis. Clinically, evidence for a high-fat diet firmly links disrupted lipid metabolism to the pathogenesis and progression of AD, although contradictory findings warrant further exploration. In view of the significance of various lipids in brain physiology, the discovery of complex and diverse mechanisms that connect lipid metabolism with AD-related pathophysiology will bring new hope for patients with AD, underscoring the importance of lipid metabolism in AD pathophysiology, and promising targets for therapeutic intervention. Specifically, cholesterol, sphingolipids, and fatty acids have been shown to influence amyloid-beta (Aß) accumulation and tau hyperphosphorylation, which are hallmarks of AD pathology. Recent studies have highlighted the potential therapeutic targets within lipid metabolism, such as enhancing apolipoprotein E lipidation, activating liver X receptors and retinoid X receptors, and modulating peroxisome proliferator-activated receptors. Ongoing clinical trials are investigating the efficacy of these strategies, including the use of ketogenic diets, statin therapy, and novel compounds like NE3107. The implications of these findings suggest that targeting lipid metabolism could offer new avenues for the treatment and management of AD. By concentrating on alterations in lipid metabolism within the central nervous system and their contribution to AD development, this review aims to shed light on novel research directions and treatment approaches for combating AD, offering hope for the development of more effective management strategies.

Positional differences in the micro- and ultra-structural variations of ray parenchyma cells during the transformation from sapwood to heartwood.

Ray parenchyma cells are involved in the initiation of heartwood formation. The position within a ray influences the timing of ray parenchyma cell differentiation and function; however, there is little information concerning the positional influence on the cellular changes of ray parenchyma cells from sapwood and heartwood. In this study, radial variations in morphology, size, and ultrastructure of ray parenchyma cells were studied by combined transmission electron microscopy and optical microscopy. Results showed that cellular traits of ray parenchyma cells in Populus tomentosa were all affected by both radial position in the secondary xylem and position within a ray. Specifically, radial variations in cellular traits were more evident in isolation cells, which were not adjacent to vessel elements. Both cell length and cell width/length ratio of isolation cells were bigger than contact cells, which contacted adjacent vessel elements via pits. Moreover, the secondary wall thickening and lignification of contact cells developed in the current-year xylem, much earlier than isolation cells. Secondary walls in contact cells were in a polylamellate structure with a protective layer on the inner side. No alteration in the ultrastructure of contact cells occurred in the sapwood-heartwood transition zone, except that most contact cells died. By contrast, in the transition zone, isolation cells still lived. A thin secondary wall began to deposit on the thick primary wall of isolation cells, with two isotropic layers on the inner side of the primary wall and secondary wall respectively being characteristic. Meanwhile, starch grains in isolation cells were depleted, and dark polyphenolic droplets lost their spherical shape and flowed together. Furthermore, the intercellular spaces of isolation cells became densified in the transition zone. Overall, cellular changes suggested that the positional information of ray parenchyma cells appeared to be an important factor in the transformation from sapwood to heartwood. Unlike contact cells, isolation cells were more elongated, specialized in radial transport, had a delayed formation of secondary walls, and were involved in the synthesis of heartwood substances. Our result promotes the elucidation of the involvement of xylem rays in heartwood formation.

Biomechanical Study of Three Cannulated Screws Configurations for Femur Neck Fracture: A Finite Element Analysis.

Background: To improve the performance of cannulated screws (CSs) in the treatment of femoral neck fractures (FNF), a number of new screw configurations have been proposed. However, most of the studies have only analyzed the biomechanical performance of different screw configurations under static conditions. This study aimed to investigate the biomechanical performance of three cannulated screws configurations under different loadings through finite element analysis. Methods: In this FEA study, nine numerical models of proximal femur were employed to analyze the mechanical response of various fracture types and different fixation strategies (three inverted triangular parallel cannulated screws (TCS), four non-parallel cannulated screws (FCS) and biplane double-supported screw fixation (BDSF) respectively). The maximum principal strain (MPS) on the proximal femur and the von Mises stress on the screws were compared for different models. Results: In Pauwels I and II fractures, FCS had the lowest peak MPS on the proximal femur and the BDSF had highest peak MPS value. In Pauwels III fractures, BDSF performance in MPS is improved and better than FCS under partial loading conditions. FCS exhibits the lowest von Mises stress in all load conditions for all fracture types, demonstrating minimal risk of screws breakage. Conclusions: FCS is an ideal screw configuration for the treatment of FNF. And BDSF has shown potential in the treatment of Pauwels type III FNF.

Research advances in the function and anti-aging effects of nicotinamide mononucleotide. / çƒŸé °èƒºå•æ ¸è‹·é ¸çš„åŠŸèƒ½åŠå ¶æŠ—è¡°è€ä½œç”¨çš„ç ”ç©¶è¿›å±•.

Aging and age-related ailments have emerged as critical challenges and great burdens within the global contemporary society. Addressing these concerns is an imperative task, with the aims of postponing the aging process and finding effective treatments for age-related degenerative diseases. Recent investigations have highlighted the significant roles of nicotinamide adenine dinucleotide (NAD+) in the realm of anti-aging. It has been empirically evidenced that supplementation with nicotinamide mononucleotide (NMN) can elevate NAD+ levels in the body, thereby ameliorating certain age-related degenerative diseases. The principal anti-aging mechanisms of NMN essentially lie in its impact on cellular energy metabolism, inhibition of cell apoptosis, modulation of immune function, and preservation of genomic stability, which collectively contribute to the deferral of the aging process. This paper critically reviews and evaluates existing research on the anti-aging mechanisms of NMN, elucidates the inherent limitations of current research, and proposes novel avenues for anti-aging investigations.

Brief research report: WGCNA-driven identification of histone modification genes as potential biomarkers in AQP4-Associated optic neuritis.

Introduction: Neuromyelitis Optica spectrum disorder (NMOSD) is an autoimmune disease characterized by anti-aquaporin-4 (AQP4) auto-antibodies. The discovery of antibodies AQP4 and myelin oligodendrocyte glycoprotein (MOG) has expanded our understanding of the pathogenesis of neuromyelitis optica. However, the molecular mechanisms underlying the disease, particularly AQP4-associated optic neuritis (AQP4-ON), remain to be fully elucidated. Methods: In this study, we utilized Weighted Gene Co-expression Network Analysis (WGCNA) to investigate the transcriptomic profiles of peripheral blood samples from patients with AQP4-ON and MOG-positive optic neuritis (MOG-ON), compared to healthy controls. Results: WGCNA revealed a brown module (ME brown) strongly associated with AQP4-ON, which correlated positively with post-onset visual acuity decline. A total of 132 critical genes were identified, mainly involved in histone modification and microtubule dynamics. Notably, genes HDAC4, HDAC7, KDM6A, and KDM5C demonstrated high AUC values in ROC analysis, indicating their potential as biomarkers for AQP4-ON. Conclusion: Our findings provide novel insights into the molecular signature of AQP4-ON and highlight the potential of systems biology approaches in identifying biomarkers for NMOSD. The identified histone modification genes warrant further investigation for their role in disease pathogenesis and as therapeutic targets.

Comparative transcriptome analysis of differentially expressed genes and pathways in male and female flowers of Fraxinus mandshurica.

Fraxinus mandshurica Rupr. (F. mandshurica) is a dioecious tree species with important ecological and application values. To delve deeper into the regulatory pathways and genes responsible for male and female flowers in F. mandshurica, we conducted transcriptome sequencing on male and female flowers at four distinct stages. The analysis revealed that the female database generated 38,319,967 reads while the male database generated 43,320,907 reads, resulting in 2930 differentially expressed genes with 1441 were up-regulated and 1489 down-regulated in males compared to females. Following an analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), four distinct pathways (hormone signal transduction, energy metabolism, flavonoid biosynthesis, and photoperiod) linked to female and male flowers were identified. Subsequently, qRT-PCR verification revealed that FmAUX/IAA, FmEIN3, and FmA-ARR genes in hormone signal transduction pathway are related to female flower development. Meanwhile, FmABF genes in hormone signal transduction pathway, FmGS and FmGDH genes in energy metabolism pathway, FmFLS genes in flavonoid biosynthesis pathway, and FmCaM, FmCRY, and FmPKA genes in photoperiod pathway are related to male flower development. This study was the first to analyze the transcriptome of male and female flowers of F. mandshurica, providing a reference for the developmental pathways and gene expression levels of male and female plants.

Unraveling the impact of the design of current collector on dry-processed lithium-ion battery electrodes.

Dry processing emerges as a cost-effective technique for achieving high material loading in the field of lithium-ion battery fabrication. Nevertheless, insight into the role of current collectors in this process is still scarce. Herein, a set of dry-processed electrodes with three different current collectors is accordingly prepared and comprehensively studied. This work novelly reveals that the current collectors exhibit significant influence on the interface adhesion strength and the electron conductivity, which leads to difference in the mechanical strength and electrochemical performance of dry-processed electrodes. Consequently, it is recommended that carbon-coated current collector is preferred for dry-processed high energy density lithium-ion battery electrodes.

Synthesis and Evaluation of Novel 1-Methyl-1H-pyrazol-5-amine Derivatives with Disulfide Moieties as Potential Antimicrobial Agents.

Sulfur-containing compounds have diverse biological functions and are crucial in crop protection chemistry. In this study, a series of novel 1-methyl-1H-pyrazol-5-amine derivatives incorporating disulfide moieties were synthesized and evaluated for their antimicrobial properties. In vitro bioassays demonstrated that compound 7f displayed potent antifungal activity against Valsa mali, with an EC50 value of 0.64 mg/L, outperforming allicin (EC50 = 26.0 mg/L) but lower than tebuconazole (EC50 = 0.33 mg/L). In vivo experiments confirmed that compound 7f could effectively inhibit V. mali infection on apples at a concentration of 100 mg/L, similar to the positive control tebuconazole. Mechanistic studies revealed that compound 7f could induce hyphal shrinkage and collapse, trigger intracellular reactive oxygen species accumulation, modulate antioxidant enzyme activities, initiate lipid peroxidation, and ultimately cause irreversible oxidative damage to the cells of V. mali. Additionally, compound 7b exhibited notable antibacterial activity, particularly against Pseudomonas syringae pv. actinidiae, with a MIC90 value of 1.56 mg/L, surpassing the positive controls allicin, bismerthiazol, and streptomycin sulfate. These findings suggest that 1-methyl-1H-pyrazol-5-amine derivatives containing disulfide moieties hold promise as potent candidates for the development of novel antimicrobial agents.

Simultaneous Detection of Major Greenhouse Gases with Multiresonator Photoacoustic Spectroscopy.

Greenhouse gas (GHG) detection plays an important role in climate change research and industry applications. A novel photoacoustic spectroscopy (PAS) sensor based on multiple resonators has been developed for the detection of GHGs. The major GHGs CO2, CH4, and N2O were measured simultaneously using only one acoustic sensor by coupling three acoustic resonators into a photoacoustic cell. A sinusoidal voltage signal-driven noise source was integrated into a multiresonator photoacoustic cell, allowing convenient calibration of the resonant frequency of the photoacoustic cell. The performance of the sensor was further enhanced by reflecting a laser beam four times in the photoacoustic cell. Allan deviation analysis showed that the minimum detection limits of 2.7 ppm, 90 ppb, and 1 ppb could be achieved for CO2, CH4, and N2O, respectively, over a 300 s integration time. The feasibility of the system was confirmed by continuous measurements of the three major GHGs from different sources for up to 10 h.

On-chip multi-degree-of-freedom control of two-dimensional materials.

Two-dimensional materials (2DM) and their heterostructures offer tunable electrical and optical properties, primarily modifiable through electrostatic gating and twisting. Although electrostatic gating is a well-established method for manipulating 2DM, achieving real-time control over interfacial properties remains challenging in exploring 2DM physics and advanced quantum device technology1-6. Current methods, often reliant on scanning microscopes, are limited in their scope of application, lacking the accessibility and scalability of electrostatic gating at the device level. Here we introduce an on-chip platform for 2DM with in situ adjustable interfacial properties, using a microelectromechanical system (MEMS). This platform comprises compact and cost-effective devices with the ability of precise voltage-controlled manipulation of 2DM, including approaching, twisting and pressurizing actions. We demonstrate this technology by creating synthetic topological singularities, such as merons, in the nonlinear optical susceptibility of twisted hexagonal boron nitride (h-BN)7-10. A key application of this technology is the development of integrated light sources with real-time and wide-range tunable polarization. Furthermore, we predict a quantum analogue that can generate entangled photon pairs with adjustable entanglement properties. Our work extends the abilities of existing technologies in manipulating low-dimensional quantum materials and paves the way for new hybrid two- and three-dimensional devices, with promising implications in condensed-matter physics, quantum optics and related fields.

Neural Network Based Aliasing Spectral Decoupling Algorithm for Precise Mid-Infrared Multicomponent Gases Sensing.

Owing to the overlapping and cross-interference of absorption lines in multicomponent gases, the simultaneous measurement of such gases via laser absorption spectroscopy frequently necessitates the use of supplementary pressure sensors to distinguish the spectral lines. Alternatively, it requires multiple lasers combined with time-division multiplexing to independently scan the absorption peaks of each gas, thereby preventing interference from other gases. This inevitably escalates both the cost of the system and the complexity of the gas pathway. In response to these challenges, a mid-infrared sensor employing a neural network-based decoupling algorithm for aliasing spectral is developed, enabling the simultaneous detection of methane(CH4), water vapor(H2O), and ethane(C2H6). The sensor system underwent evaluation in a controlled laboratory environment. Allan deviation analysis revealed that the minimum detection limits for CH4,H2O, and C2H6 were 6.04, 118.44, and 1 ppb, respectively, with an averaging time of 3 s. The performance of the proposed sensor demonstrates that the aliasing spectral decoupling algorithm based on neural network combined with wavelength-modulated spectroscopy technology has the advantages of high sensitivity, low cost and low complexity, showing its potential for simultaneous detection of multicomponent trace gases in various fields.

Comparison of different immobilisation durations following open surgery for acute achilles tendon rupture: a prospective cohort study.

BACKGROUND: In recent decades, early rehabilitation after Achilles tendon rupture (ATR) repair has been proposed. The aim of this prospective cohort study was to compare different immobilisation durations in order to determine the optimal duration after open surgery for ATR repair. METHODS: This study included 1088 patients (mean age, 34.9 ± 5.9 years) who underwent open surgery for acute ATR repair. The patients were categorised into four groups (A, B, C, and D) according to postoperative immobilisation durations of 0, 2, 4, and 6 weeks, respectively. All patients received the same suture technique and a similar rehabilitation protocol after brace removal,; they were clinically examined at 2, 4, 6, 8, 10, 12, 14, and 16 weeks postoperatively, with a final follow-up at a mean of 19.0 months. The primary outcome was the recovery time for the one-leg heel-rise height (OHRH). Secondary outcomes included the time required to return to light exercise (LE) and the recovery times for the range of motion (ROM). Data regarding the surgical duration, complications, the visual analogue scale (VAS) score for pain, the Achilles tendon Total Rupture Score (ATRS), and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale score were also collected. RESULTS: The recovery times for OHRH, LE, and ROM were significantly shorter in groups A and B than in groups C and D (P < 0.001). The VAS scores decreased over time, reaching 0 in all groups by 10 weeks. The mean scores in groups A and B were higher than those in the other groups at 2 and 4 weeks (P < 0.001), whereas the opposite was true at 8 weeks (P < 0.001). ATRS and the AOFAS Ankle-Hindfoot scale score increased across all groups over time, showing significant between-group differences from weeks 6 to 16 (P < 0.001) and weeks 6 to 12 (P < 0.001). The mean scores were better in groups A and B than in groups C and D. Thirty-eight complications (3.5%) were observed, including 20 re-ruptures and 18 superficial infections. All complications were resolved at the last follow-up, with no significant between-group differences. CONCLUSIONS: Immobilisation for 2 weeks after open surgery for ATR repair may be the optimal strategy for early rehabilitation with relatively minimal pain and other complications. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04663542).

Cerebral blood flow alterations and host genetic association in individuals with long COVID: A transcriptomic-neuroimaging study.

Neuroimaging studies have indicated that altered cerebral blood flow (CBF) was associated with the long-term symptoms of postacute sequelae of SARS-CoV-2 infection (PASC), also known as "long COVID". COVID-19 and long COVID were found to be strongly associated with host gene expression. Nevertheless, the relationships between altered CBF, clinical symptoms, and gene expression in the central nervous system (CNS) remain unclear in individuals with long COVID. This study aimed to explore the genetic mechanisms of CBF abnormalities in individuals with long COVID by transcriptomic-neuroimaging spatial association. Lower CBF in the left frontal-temporal gyrus was associated with higher fatigue and worse cognition in individuals with long COVID. This CBF pattern was spatially associated with the expression of 2,178 genes, which were enriched in the molecular functions and biological pathways of COVID-19. Our study suggested that lower CBF is associated with persistent clinical symptoms in long COVID individuals, possibly as a consequence of the complex interactions among multiple COVID-19-related genes, which contributes to our understanding of the impact of adverse CNS outcomes and the trajectory of development to long COVID.

Hepatocyte-derived tissue extracellular vesicles safeguard liver regeneration and support regenerative therapy.

Tissue-derived extracellular vesicles (EVs) are emerging as pivotal players to maintain organ homeostasis, which show promise as a next-generation candidate for medical use with extensive source. However, the detailed function and therapeutic potential of tissue EVs remain insufficiently studied. Here, through bulk and single-cell RNA sequencing analyses combined with ultrastructural tissue examinations, we first reveal that in situ liver tissue EVs (LT-EVs) contribute to the intricate liver regenerative process after partial hepatectomy (PHx), and that hepatocytes are the primary source of tissue EVs in the regenerating liver. Nanoscale and proteomic profiling further identify that the hepatocyte-specific tissue EVs (Hep-EVs) are strengthened to release with carrying proliferative messages after PHx. Moreover, targeted inhibition of Hep-EV release via AAV-shRab27a in vivo confirms that Hep-EVs are required to orchestrate liver regeneration. Mechanistically, Hep-EVs from the regenerating liver reciprocally stimulate hepatocyte proliferation by promoting cell cycle progression through Cyclin-dependent kinase 1 (Cdk1) activity. Notably, supplementing with Hep-EVs from the regenerating liver demonstrates translational potential and ameliorates insufficient liver regeneration. This study provides a functional and mechanistic framework showing that the release of regenerative Hep-EVs governs rapid liver regeneration, thereby enriching our understanding of physiological and endogenous tissue EVs in organ regeneration and therapy.

Ameliorative effects of mesenchymal stromal cells on senescence associated phenotypes in naturally aged rats.

BACKGROUND: Aging is a multifaceted process that affects all organ systems. With the increasing trend of population aging, aging-related diseases have resulted in significant medical challenges and socioeconomic burdens. Mesenchymal stromal cells (MSCs), due to their antioxidative stress, immunoregulatory, and tissue repair capabilities, hold promise as a potential anti-aging intervention. METHODS: In this study, we transplanted MSCs into naturally aged rats at 24 months, and subsequently examined levels of aging-related factors such as ß-galactosidase, superoxide dismutase, p16, p21 and malondialdehyde in multiple organs. Additionally, we assessed various aging-related phenotypes in these aged rats, including immune senescence, lipid deposition, myocardial fibrosis, and tissue damage. We also conducted a 16 S ribosomal ribonucleic acid (rRNA) analysis to study the composition of gut microbiota. RESULTS: The results indicated that MSCs significantly reduced the levels of aging-associated and oxidative stress-related factors in multiple organs such as the heart, liver, and lungs of naturally aging rats. Furthermore, they mitigated chronic tissue damage and inflammation caused by aging, reduced levels of liver lipid deposition and myocardial fibrosis, alleviated aging-associated immunodeficiency and immune cell apoptosis, and positively influenced the gut microbiota composition towards a more youthful state. This research underscores the diverse anti-aging effects of MSCs, including oxidative stress reduction, tissue repair, metabolic regulation, and improvement of immune functions, shedding light on the underlying anti-aging mechanisms associated with MSCs. CONCLUSIONS: The study confirms that MSCs hold great promise as a potential anti-aging approach, offering the possibility of extending lifespan and improving the quality of life in the elderly population.

Phenotypes Associated with NOTCH3 Cysteine-Sparing Mutations in Patients with Clinical Suspicion of CADASIL: A Systematic Review.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is caused by NOTCH3 mutations affecting the number of cysteines. The pathogenic role of cysteine-sparing NOTCH3 mutations with typical clinical CADASIL syndrome is still debated. This review aimed to characterize NOTCH3 cysteine-sparing mutations in patients with clinical suspicion of CADASIL. Articles on NOTCH3 cysteine-sparing mutations with clinical suspicion of CADASIL were reviewed. Clinical and radiological cerebral phenotypes data were extracted and characterized across regions and compared with phenotypes of typical CADASIL patients. We screened 298 NOTCH3 cysteine-sparing mutation individuals from 20 publications, and mutations in exon 3 were the most frequently reported (21.46%). Gait impairment (76.47%), cognitive impairment (67.47%), and stroke (62.37%) were the three most common clinical phenotypes; the most frequent radiological cerebral phenotypes were lacunes (74.29%) and cerebral microbleeds (72.73%). Compared with CADASIL patients, cognitive impairment and cerebral microbleed frequencies were significantly higher in patients with NOTCH3 cysteine-sparing mutations, while the white matter hyperintensities in anterior temporal polar and external capsule were rarely observed. Compared with Western patients, radiological phenotypes were more common than clinical phenotypes in cysteine-sparing Asian patients. More than half of cysteine-sparing patients had positive granular osmiophilic material deposits. NOTCH3 cysteine-sparing mutations in patients with clinical suspicion of CADASIL mainly manifested with gait and cognitive impairment but rare white matter hyperintensities in anterior temporal pole and external capsule. Further studies are warranted to pay attention to atypical NOTCH3 variants, which could guide specific diagnosis and help unravel underlying mechanisms.