Acute intracerebral hemorrhage (ICH) often induces a hyperadrenergic response, resulting in a significantly increased cardiac workload. This study aimed to assess the relationship between early cardiac workload and long-term outcomes following ICH, utilizing the rate-pressure product (RPP) as a simple surrogate indicator. We conducted an analysis of data from a large multicenter, prospective cohort comprising 1364 ICH patients. Heart rate (HR) and systolic blood pressure (SBP) were recorded to calculate the RPP. Multivariable logistic regression and Cox proportional hazards models were used to evaluate the associations of RPP with unfavorable functional outcome (modified Rankin Scale score >3) and all-cause mortality at 90 days and 1 year, respectively. Elevated RPP was independently associated with unfavorable functional outcomes and all-cause mortality at 90 days and 1 year (all p < 0.05). RPP exhibited superior predictive performance, as indicated by higher C-statistics for all outcomes when compared to HR or SBP alone (all p < 0.05). A significant interaction was noted with in-hospital β-blocker treatment (p for interaction < 0.05), indicating that the association between high RPP and primary outcomes was attenuated in patients receiving β-blockers. Early cardiac workload, quantified by the RPP, is a potent independent predictor of long-term unfavorable functional outcome and all-cause mortality in patients with ICH.
Allergic conjunctivitis (AC) is an ocular surface disease characterized by immune-mediated inflammation that can significantly impair quality of life. This review explores recent advances in understanding the immunological and molecular mechanisms underlying AC, highlighting local and systemic immune responses and their roles in disease pathogenesis and progression. Particular attention is given to the influence of genetic and epigenetic factors, which may contribute to individual susceptibility and variability in clinical presentation. Finally, this review discusses emerging evidence on clinical phenotypes and immunological endotypes in ocular allergy, emphasizing their relevance for the development of targeted, personalized, and precision therapies.
Arts-based interventions create meaningful opportunities for emotional expression, strengthening personal competencies that can enhance prison social climate and support reintegration. This study examined the perceived feasibility and acceptability of RadioACTIVITY, a co-creative arts-based program combining radio theatre production with participatory practices (RadioLAB, RadioSTUDIO, RadioDIFFUSION), implemented across three 10-month editions in a Portuguese prison. Twenty-eight incarcerated individuals (53.6% female; 46.4% male) participated in focus groups. Thematic analysis indicated that feasibility was supported by sustained engagement facilitated through non-judgmental facilitation, collaborative processes, and dynamic sessions. Acceptability was reflected in positive evaluations of the program as meaningful and appropriate, alongside interest in its continuation. Participants also reported intrapersonal (e.g., self-regulation, language skills) and interpersonal (e.g., empathy) gains, as well as perceived social impacts, including reduced stigma. Findings highlight the potential of arts-based approaches to foster rehabilitation and more constructive prison environments. A Participant-Led Radio Program in Prison: What Worked and WhyCreative arts programs can help people in prison express their thoughts and emotions, build personal skills, and improve relationships with others. These benefits may also contribute to a more positive prison environment and support successful reintegration into society. This study explored how people in prison experienced RadioACTIVITY, an innovative arts-based program that uses radio theatre and collaborative creative activities. RadioACTIVITY was implemented over three editions (i.e., three groups of participants), each lasting 10 months, in a Portuguese prison. The program involved three main stages: experimenting with ideas and voices (RadioLAB), creating radio productions together (RadioSTUDIO), and sharing the final content with others (RadioDIFFUSION). A total of 28 incarcerated participants (men and women) took part in group discussions to share their views about the program. Overall, participants found the program easy to engage with and highly meaningful. They highlighted the importance of facilitators who showed respect, listened without judgment, and worked collaboratively with the group. The creative and varied structure of the sessions also helped maintain motivation and interest. Participants reported several personal benefits. On an individual level, they described improvements in emotional control, self-discipline, and language skills. On a social level, they noted better understanding of others, increased empathy, and more positive interactions. Beyond personal change, participants felt the program had a wider impact by helping to challenge negative stereotypes about people in prison and by creating content that could be shared with other prisons. These findings suggest that arts-based programs like RadioACTIVITY can play an important role in rehabilitation by fostering personal growth, improving relationships, and contributing to healthier and more constructive prison environments.
In mechanically ventilated patients, the clinical and echocardiographic presentation of pericardial tamponade differs from the classic spontaneous-breathing paradigm. Positive-pressure ventilation (PPV) increases pleural and pericardial pressures, narrows the transmural filling gradient, augments ventricular interdependence, and can precipitate tamponade physiology at smaller effusion volumes. Consequently, the classic Doppler cues, such as large respiratory variation in mitral/tricuspid inflow, are commonly blunted, reversed, or absent, and right-sided chamber collapse can be intermittent or phase-shifted across the ventilatory cycle. Therefore, diagnosis depends on integrating clinical suspicion, hemodynamics, and multiple echocardiographic features, including effusion morphology (often loculated/posterior in the postoperative setting), right-atrial systolic and right-ventricular diastolic collapse (timed to the cardiac cycle), venous congestion surrogates (inferior vena cava plethora and superior vena cava/hepatic venous Doppler findings), and direct evidence of reduced stroke volume. Transthoracic echocardiography (TTE) is fast and, when the window is good, can provide a safe guide to life-saving pericardiocentesis. Thus, TTE is established as a first-line approach in both intra-hospital emergencies and in prehospital settings. However, in the context of PPV, tamponade may be underrecognized because suboptimal acoustic windows, postoperative dressings, emphysema, thoracic trauma, or prone positioning can limit TTE. Across 40 physiological, diagnostic accuracy, and impact studies, early TTE after cardiac surgery showed only modest performance in surgically confirmed tamponade (area under the curve of approximately 0.64 and a positive predictive value of approximately 58%). Meanwhile, about half of the postoperative effusions were predominantly posterior or loculated. In mechanically ventilated intensive care unit cohorts, transesophageal echocardiography (TEE) resolved almost all prespecified clinical questions and changed therapy more often than TTE (97% vs. 38% and 36% vs. 16%, respectively). These findings support a physiology-anchored approach in which TTE remains first-line; meanwhile, TEE should be considered early when clinical suspicion is moderate-to-high, and TTE is nondiagnostic or when posterior/loculated or regional tamponade is suspected during PPV.
Contemporary classification systems differ in their conceptualization of ADHD as either an externalizing or neurodevelopmental condition, with both perspectives promoting the common cause model as an explanation of ADHD's comorbidity. An alternative theory, dynamic mutualism, proposes that ADHD's comorbidity emerges through reciprocal interactions among symptoms over time, as opposed to a common cause. We tested the common cause and the dynamic mutualism theories in explaining the associations between aspects of ADHD (i.e., ADHD, inattention, hyperactivity/impulsivity, cognitive disengagement) and the neurodevelopmental and externalizing spectra across four waves of the Adolescent Brain Cognitive Development (ABCD) Study data (n = 11,878 youths aged 9-10 at baseline; 48% female). Results largely supported the common cause theory in explaining the developmental links between ADHD and both the externalizing and neurodevelopmental spectra. Findings varied across ADHD subdimensions, although not substantially, with hyperactivity/impulsivity more closely linked to the externalizing spectrum and cognitive disengagement more closely linked to the neurodevelopmental spectrum. ADHD is best conceptualized as a disorder that bridges both the externalizing and neurodevelopmental domains, rather than fitting exclusively within either category. Given the assessment structure of the ABCD Study, there was more support for the common cause model compared with dynamic mutualism.
Heart failure with preserved ejection fraction (HFpEF) has emerged as the predominantform of heart failure (HF) worldwide and is increasingly recognized as a systemic syndrome closely linked to metabolic dysfunction. Furthermore, metabolic dysfunction-associated steatotic liver disease (MASLD), a highly prevalent yet often underrecognized comorbidity in patients with HFpEF, has attracted increasing attention. Accumulating epidemiological evidence demonstrates a significant association between MASLD and HFpEF, suggesting shared pathophysiological foundations that extend beyond coincidental coexistence. Mechanistically, MASLD contributes to the development and progression of HFpEF through a network of interconnected pathways, including chronic low-grade inflammation, insulin resistance (IR), dysregulated lipid metabolism, endothelial dysfunction, the gut-liver-heart axis, and as liver-derived mediators that influence cardiac structure and function. These overlapping mechanisms underlie the pronounced clinical and phenotypic heterogeneity of HFpEF and may help explain the limited efficacy of conventional heart failure therapies. This review summarizes current diagnostic and therapeutic strategies for HFpEF and MASLD and proposes an integrated, multiorgan framework to improve clinical recognition and management. A deeper understanding of liver-heart interactions is essential to redefining cardiometabolic disease, shifting from an organ-centric perspective toward a more integrated, mechanism-based approach.
Intraoperative cerebral ischemia is a critical complication that can arise during cerebral aneurysm clipping surgery. Although intraoperative neuromonitoring (IONM) can detect resulting functional deficits, these alerts may occur minutes after the initial ischemic event. We aimed to demonstrate the clinical utility of laser speckle contrast imaging (LSCI) for continuous, real-time monitoring of cerebral blood flow (CBF) during aneurysm surgery. In this case study, a 67-year-old female underwent a craniotomy for a left-sided cerebral aneurysm. A microscope-integrated LSCI system was used to continuously monitor cortical perfusion. After surgery, LSCI data were correlated with IONM alerts, indocyanine green angiography (ICGA), and surgical events, including an ischemic period following clip placement. A paired t-test, mixed effects model, and changepoint analysis were used to compare mean perfusion between the pre-ischemic and ischemic periods across seven regions of interest (ROIs) on the cortical surface. LSCI detected a widespread drop in cortical perfusion immediately following the application of an aneurysm clip. This perfusion deficit was detected by LSCI ∼ 8    min before the corresponding IONM alert. During the ischemic period, blood flow decreased across six of the seven ROIs, with reductions ranging from 7.9% to 28.0%. The overall decrease in perfusion from the pre-ischemic to the ischemic period was statistically significant ( p < 0.0001 ). LSCI can provide continuous imaging of tissue perfusion during surgery, enabling the detection of developing ischemia before functional deficits may be evident on IONM. The ability of LSCI to track tissue perfusion changes highlights its potential as a valuable complementary tool for enhancing surgical safety alongside IONM and ICGA.
Downbeat nystagmus varies with head position, a phenomenon termed gravity-dependent modulation. We aimed to clarify its mechanism using a velocity-storage model. In 10 patients with downbeat nystagmus due to cerebellar disorders, we recorded eye movements at different pitch- and roll-axis head positions. Sine-wave fitting of the nystagmus intensity as a function of head position decomposed the slow-phase velocity of nystagmus into a gravity-dependent component-the amplitude and phase shift of the sine-wave term-and a gravity-independent constant offset. To probe mechanisms, we applied a velocity-storage model simulating the estimation of rotational velocity, gravity orientation, and inertial acceleration, and incorporated a gravity-estimator lesion that produced a gravity-estimation bias. The gravity-dependent component during pitch-axis modulation had a median amplitude of 3.8°/s (interquartile range [IQR] = 2.6) and a phase shift of 158.5° (57.9). During roll-axis modulation, it had an amplitude of 2.1°/s (1.5) and a phase shift of -0.9° (147.6), with two subgroups showing phase shifts near ±90°. The amplitude was significantly larger during pitch- than roll-axis modulation (p < 0.05). The lesion model generated persistent rotational cues that modulated downbeat nystagmus intensity as observed in the patients and additionally explained the interindividual variation in phase shifts and the weaker modulation of downbeat nystagmus during head roll. These findings refine our understanding of cerebellar vestibular processing and provide a computational framework for positional modulation of downbeat nystagmus. The concept of a biased gravity estimate may further account for several clinical phenomena, including atypical patterns of positional nystagmus.
We present a systematic and exhaustive exploration of transition metal tetramer low-energy minima (M, M' = Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, Au, x = 0-4), combining stochastic structural searches with density functional theory. Our results reveal a pronounced structural diversity, multiple low-lying spin states, and widespread fluxionality at the subnanometric scale. While binding energies broadly follow periodic trends, selected heterometallic combinations exhibit enhanced cohesion, identifying "magic" compositions with increased stability. Time-dependent DFT calculations predict intense UV-visible absorptions in several tetramers and distinctive and potentially useful optical signatures in a number of Ni-containing heterotetramers. Conceptual DFT descriptors uncover a wide range of electrophilic and nucleophilic behaviors across the series, offering initial, qualitative insights into potential reactivity patterns across the series. These results establish clear links between atomic-scale composition, geometry, and functionality in transition metal subnanoclusters, providing transferable insights relevant to nanocatalysis, optical nanomaterials, and the rational design of functional nanoalloys.
During land colonisation, plants evolved new microtubule structures that have no functional analogues in opisthokonts, namely animals and fungi. The appearance of these unique structures, such as cortical microtubule arrays, the preprophase band, and the phragmoplast, coincided with the family expansion of kinesin motors. While most plant kinesins are classified into the same families as their opisthokont orthologues, many plant kinesins have not only increased functional redundancy but acquired additional or completely new functionality in various cellular processes. Although many opisthokont kinesins have been scrutinised down to the mechanics of a single motor, much less is known about the molecular details of plant kinesins. Insights from opisthokont kinesins are often used to infer how their corresponding plant kinesin counterparts might work in vivo with little molecular verification. In this review, we summarise current advances in in vitro characterisation of plant kinesins and highlight examples of how A. thaliana kinesins have diverged functionally. These examples illustrate that insights from opisthokont kinesins cannot be easily transferred to plant kinesins. Furthermore, they motivate the in vitro characterisation of each individual plant kinesin, a challenge we hope to overcome by promoting the use of reconstituted plant-kinesin assays.
Understanding resilience in pre-adolescence is important for informing interventions to promote good mental health. Middle childhood is a critical developmental phase, characterised by significant emotional and behavioural development. However, there is limited research on children's perceptions and diverse experiences of resilience which could inform interventions. Qualitative methods can enable meaningful engagement of children and provide rich insights into perceptions of resilience. This study involved Muslim children in East London, a population disproportionately affected by deprivation and racial and cultural discrimination yet underrepresented in resilience research. This study aimed to explore (1) children's perceptions, meanings and experiences of resilience, and (2) the factors and resources that constrain and contribute to resilience in Black and South Asian Muslim children aged 7-12 living in East London. Data were collected through a one-day workshop at a community centre, during which one of the activities was body mapping with children (n = 12). Body mapping, a visual arts-based research method, was used to explore children's subjective and embodied experiences of resilience. Here, we report on the findings from body mapping with children. Themes were developed using systematic visuo-textual analysis and reflexive thematic analysis. Findings are grouped into (1) Conceptualising resilience and (2) Personal and social resources for resilience. Children viewed resilience as personal strength, and related it to nature, sports and physical health. External support from family, friends, teachers and role models was also highlighted as important for resilience. This study provides insights into how children conceptualise resilience and the resources they view as important for promoting it. The findings contribute to understanding resilience in middle childhood and highlight the value of resource-oriented approaches for resilience-supporting interventions. Body mapping emerged as an effective method for engaging children creatively and non-verbally on this topic.
Human Streptococcus suis infections occur worldwide but are most common in East and Southeast Asia. In Europe, most cases are linked to occupational contact with pigs and are usually caused by serotype 2 sequence type 1 (ST1) and ST20 strains, whereas other serotype 2 genotypes seldom cause human disease on the continent. A 55-year-old male pig farmer from Brittany, France, presented with acute confusion, fever, and nuchal rigidity consistent with meningitis. Cerebrospinal fluid cultures were negative, but blood cultures grew S. suis. Empirical treatment with cefotaxime and dexamethasone was initiated, followed by high-dose amoxicillin once antimicrobial susceptibility results confirmed β-lactam sensitivity. The patient required 5 days of intensive care and 7 additional days in a general ward and then completed 8 days of home intravenous ceftriaxone, fully recovering without hearing loss, a frequent sequela of S. suis meningitis. The isolate was typed as serotype 2. It belonged to the ST25 lineage and was genetically closely related to North American strains. This case serves as a reminder that S. suis should be considered in meningitis among swine-exposed individuals and expands the known range of ST25 human infections to Western Europe, providing useful insights for regional surveillance efforts.
Magnetic field sensors based on the magnetoimpedance (MI) effect are attracting increasing attention for next-generation healthcare, environmental monitoring, industrial automation, and wearable electronic systems because of their exceptional sensitivity and rapid response to weak magnetic fields. However, achieving high-performance and miniaturized MI sensors requires precise control of magnetic domain structures and anisotropy, particularly in microscale magnetic conductors. Here, we demonstrate a current-assisted strategy for enhancing the MI effect through transverse domain engineering in amorphous Fe-Si-C microwires with widths ranging from 250 down to 40 µm. By combining laser-assisted microfabrication, magnetic characterization, impedance measurements, and MuMax3 micromagnetic simulations, we systematically reveal how geometric confinement and direct-current (DC) bias cooperatively regulate domain evolution and transverse magnetization dynamics. The results suggest that reducing the microwire width strengthens shape anisotropy, suppresses demagnetizing effects, and promotes the formation of refined stripe-like and helical magnetic domains. Under a DC bias, the induced circumferential magnetic field further enhances transverse magnetic permeability, significantly amplifying the MI response. Notably, the narrowest microwire of 40 µm exhibits a maximum MI ratio of 26.7% under a 70 mA bias current, more than double its unbiased value and significantly higher than the ratio observed in wider microwires. Micromagnetic simulations reveal that current-induced helical domain formation and enhanced transverse magnetization are the key mechanisms responsible for the observed performance improvement. In addition, the optimized microwires demonstrate enhanced field sensitivity and angular response, highlighting the important interplay between shape anisotropy and current-driven magnetostatic effects. This work establishes a scalable and physically intuitive approach for tailoring magnetic domain configurations in microscale amorphous alloys, offering valuable insights for designing compact, highly sensitive MI sensors for flexible electronics, biomedical diagnostics, and intelligent sensing technologies.
This qualitative study explores the barriers and facilitators experienced by adults with hearing loss in accessing hearing-related information and services. Findings were interpreted using the Theoretical Domains Framework, which will be used to inform the design of a novel consumer-centred website-Hear4Health. A total of 13 participants (19-78 years) were recruited. Nine consumers with hearing loss participated in the focus groups, four of whom also served as representatives of consumer organisations. 12 of the 13 participants were subsequently interviewed (51.25 ± 20.35 years), including seven consumers, two consumer organisation representatives, and three who fulfilled dual roles. Nine themes emerged from the interviews under seven theoretical domains: knowledge, environmental context and resources, social influence, beliefs about capabilities, beliefs about consequences, social/professional role and identity, and behavioural regulation. Barriers to access included the themes poor awareness of hearing loss, low-quality information, mistrust in the hearing industry, stigma, unrealistic expectations for hearing technologies, and deaf identity. Facilitators identified included peer support and the value of lived experience, informed decision-making, and self-efficacy. These findings provide crucial insights for the development of Hear4Health. Grounded in the Theoretical Domains Framework, this research underscores the importance of addressing both individual and systemic factors to improve digital access to hearing healthcare and empower adults with hearing loss to make confident and informed choices.
Microplastics (MPs) are emerging contaminants of increasing concern, yet their in vivo fate and mechanisms of intestinal toxicity remain poorly defined. Here, we demonstrate that polystyrene nanoplastics (PS-NPs) undergo a previously overlooked enterohepatic recirculation pathway that markedly enhances their intestinal retention. Using oral exposure and a Zombie mouse model with intravenous PS-NPs delivery, we show that systemically absorbed PS-NPs are efficiently captured by the liver, concentrated in the gallbladder, and subsequently reintroduced into the intestine via bile. Chronic PS-NPs exposure caused pronounced epithelial injury, including goblet cell loss, tight-junction disruption, and robust cytokine-mediated inflammation. Multiomics analyses revealed gut microbial dysbiosis, extensive shifts in metabolite profiles, and enrichment of neuroactive signaling pathways, suggesting microbiome-metabolite contributions to toxicity. We further identified significant enteric neurotoxicity characterized by reduced expression of vasoactive intestinal peptide, increased expression of tyrosine hydroxylase, and downregulation of the mechanosensitive PIEZO1 channel. Together, these findings establish hepatobiliary recycling as a key driver of intestinal PS-NPs accumulation and demonstrate that epithelial damage, microbiome-metabolite imbalance, and enteric nervous system dysfunction collectively mediate PS-NPs-induced gut pathology. This work provides mechanistic insights essential for evaluating the health risks of environmental PS-NPs exposure.
 Medicine shortages and governance failures in low- and middle-income countries continue to hinder progress towards universal health coverage.  To explore healthcare professionals' perceptions and experiences of medicines governance in South African healthcare facilities.  The study was conducted at the public healthcare sectors in Eastern Cape province, South Africa.  A qualitative exploratory cross-sectional design was used. Twenty healthcare professionals were purposively selected. Semi-structured interviews were conducted, audio-recorded, transcribed verbatim and thematically analysed using Braun and Clarke's framework.  Four major themes emerged: systemic governance constraints; pharmaceutical supply chain vulnerabilities; weak accountability mechanisms; and gaps in protocol implementation. Key determinants of medicine shortages included weak budget governance, supplier payment delays, limited pharmacy support staff and inconsistent implementation of standard treatment guidelines (STG) and limited functionality of Pharmacy and Therapeutics Committees (PTCs).  Medicine shortages result from systemic governance failures rather than isolated logistical issues. Strengthening pharmaceutical governance requires transparent budgeting, timely supplier payment systems, functional PTCs, and STG training to improve equitable access to essential medicines.Contribution: This study deepens the understanding of pharmaceutical governance, revealing systemic, interrelated factors that collectively lead to the shortage of pharmaceuticals in South Africa. Unlike previous research that focused primarily on supply chain logistics, the study showed that stock-outs were rooted not simply in operational inefficiency, but also in structural governance weaknesses. This study presents practical insights to strengthen pharmaceutical governance and supports national efforts to achieve universal health coverage by identifying specific governance obstacles and proposing system-level reforms.
Heart failure remains a major cause of morbidity and mortality worldwide despite substantial advances in pharmacological and device-based therapies. Distinct phenotypes, including heart failure with reduced ejection fraction, mildly reduced ejection fraction, and preserved ejection fraction, differ markedly in underlying pathophysiology, clinical presentation, and therapeutic responsiveness. Therefore, a deeper understanding of disease mechanisms is essential for guiding evolving management strategies and identifying novel therapeutic targets. This narrative review synthesizes contemporary evidence on the pathogenesis and management of heart failure, integrating mechanistic biology with phenotype-specific treatment effects and acute-chronic disease transitions to provide a translational framework for care. Key clinical trials, guideline documents, and mechanistic studies were identified through structured searches of major medical databases and review of international guideline updates, with emphasis on recent advances in disease-modifying therapies, inflammatory mechanisms, and emerging treatment strategies across heart failure phenotypes. Heart failure with reduced ejection fraction is characterized predominantly by myocyte loss, adverse ventricular remodeling, and neurohormonal activation, with robust evidence supporting combined disease-modifying pharmacotherapy and selected device-based interventions. In contrast, heart failure with preserved ejection fraction is driven largely by systemic comorbidities, endothelial dysfunction, and myocardial fibrosis, contributing to impaired ventricular compliance and limited evidence-based treatment options. Sodium-glucose cotransporter 2 inhibitors have demonstrated consistent reductions in symptoms and hospitalizations across the spectrum of ejection fractions, representing a major advance in management. However, translation of mechanistic insights into effective therapies has been variable. Broad anti-inflammatory strategies targeting cytokine pathways have yielded mixed or neutral outcomes. In contrast, more targeted approaches, including interleukin-1 inhibition, inflammasome modulation, and mitochondrial-directed therapies, show emerging but heterogeneous signals that warrant phenotype-specific evaluation. Heart failure is a heterogeneous syndrome that requires biologically informed, phenotype-specific approaches. Thus, by linking dominant mechanisms to therapeutic response and highlighting the limitations of current evidence, this review aims to advance understanding beyond descriptive summaries and to outline priorities for future precision-oriented heart failure care.
So far, combining gastroscopy with biopsy remains the gold-standard for screening gastric cancer. Recently, the study of circulating microRNAs (miRNAs or miRs) has yielded valuable insights into gastric cancer prognosis. However, because these molecules are common to multiple cancer types, their clinical applicability remains uncertain. We investigated the pertinent literature dealing with gastric juice microRNAs in gastric cancer patients. Only five original articles have investigated the feasibility of using gastric juice miRNAs as potential biomarkers to assist in screening for gastric cancer. Gastric juice microRNAs proved correlated with high reliability, high sensitivity, high specificity and relative stability. MicroRNAs found in gastric juice may offer a promising alternative approach for gastric cancer screening without the need for biopsy. More studies are needed to reach safe conclusions. However, it seems that this novel potential biomarkers' testing is reliable and reproducible.
Adult neurogenesis is predominantly restricted to two neurogenic regions in the mammalian brain: the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG) within the hippocampus. The hippocampus serves as a critical brain structure involved in learning and memory processes, and the continuous generation of new neurons contributes to enhanced synaptic plasticity. Accumulating evidence has demonstrated that impaired hippocampal neurogenesis is closely associated with various neuropsychiatric disorders, including Alzheimer's disease, epilepsy, and traumatic brain injury. Although the precise molecular and cellular mechanisms underlying adult neurogenesis remain incompletely elucidated, extensive research over the past several decades has identified numerous endogenous, exogenous, and environmental factors that modulate this process. Notably, exercise training, as a key exogenous stimulus, has been shown to promote adult hippocampal neurogenesis by influencing the neurochemical environment and functional integration of newly generated neurons. This review aims to summarize the relationship between cell cycle dynamics and adult hippocampal neurogenesis, with a particular emphasis on how physical exercise regulates the cell cycle to activate and promote the proliferation of neural stem cells (NSCs) in the DG, thereby facilitating the differentiation and lineage progression of neural progenitor cells. A deeper understanding of the regulatory mechanisms by which exercise enhances adult hippocampal neurogenesis may provide novel insights into the development of therapeutic strategies for neurological and psychiatric disorders.
Persistent local tissue hypoperfusion and chronic inflammation are central challenges in diabetic wound management. The development of effective therapeutic strategies to mitigate prolonged inflammation and enhance tissue vascularization is crucial for accelerating diabetic wound healing. This study aimed to develop soluble microneedle materials that simultaneously target both aspects to improve the clinical prognosis of diabetic wounds. A stable macrophage cell line overexpressing basic fibroblast growth factor (bFGF) was established using lentiviral transfection. After M2 polarization was induced with interleukin-4 (IL-4) and IL-10, exosomes were isolated via ultracentrifugation and surface-functionalized with arginine-glycine-aspartic acid (RGD)-targeting peptides. The reparative effects of these exosomes on human umbilical vein endothelial cells (HUVECs) with high glucose-induced injury were evaluated using scratch test, 5-ethynyl-2'-deoxyuridine (EdU) staining, and cell counting kit-8 assays. A delivery system based on soluble hyaluronic acid microneedles (MNs) loaded with engineered exosomes was then developed. Its therapeutic efficacy was evaluated in a diabetic wound mouse model, and the underlying mechanisms were explored via ribonucleic acid (RNA) sequencing. Targeted engineered exosomes (TE-Exos) derived from bFGF-overexpressing M2 macrophages with surface RGD modification were successfully prepared. Assays revealed that TE-Exos exhibited specific targeting to HUVECs with high glucose-induced injury and significantly enhanced cellular proliferation, migration, and tube formation. Furthermore, the polarization ratio of macrophages improved after TE-Exos treatment. In vivo, the MN-mediated delivery of TE-Exos markedly accelerated diabetic wound healing by enhancing re-epithelialization, collagen deposition, and angiogenesis. Furthermore, the treatment modulated the wound microenvironment by reducing the infiltration of proinflammatory M1 macrophages while increasing the proportion of reparative M2 macrophages. RNA sequencing analysis indicated that the therapeutic effects were mediated primarily through the inhibition of excessive inflammation and the activation of angiogenesis-related signaling pathways. This innovative strategy breaks the vicious cycle of impaired angiogenesis and chronic inflammation in diabetic wounds through a synergistic mechanism involving 'angiogenesis, inflammation regulation, and precise delivery'. The combination of targeted exosome engineering with an MN delivery system not only overcomes the limitations of conventional growth factor therapies but also enables intelligent modulation of the wound microenvironment, offering novel theoretical insights and practical approaches for clinical translation.