The aim of this study is to evaluate the effectiveness of virtual reality (VR) for learning ophthalmic anatomy and to determine whether peer-assisted facilitation produces learning outcomes comparable to expert-assisted facilitation among preclinical medical students. A secondary objective was to contextualize learning outcomes by comparing performance of preclinical students with that of senior medical students receiving expert-assisted VR instruction. This is a prospective controlled experimental study with repeated-measures assessments. Second-year (preclinical) medical students without prior formal ophthalmic anatomy instruction were recruited voluntarily (peer-assisted n = 31, expert-assisted n = 32). Exclusion criteria included previous VR-based ophthalmic anatomy training, history of severe motion sickness or vertigo, or refusal to provide consent. In addition, fifth-year medical students undertaking their ophthalmology clerkship participated in a parallel prospective pre-post cohort (n = 61 baseline; n = 55 completed the intervention). All participants first attended a conventional didactic lecture on ophthalmic anatomy. Second-year students then completed an immersive VR learning session exploring a stereoscopic 3D model of the globe and adnexa using a head-mounted display. Sessions were facilitated either by an anatomy faculty expert or by trained peer facilitators. Fifth-year students completed the same instructional sequence with expert-assisted VR only. The primary outcome was change in anatomy knowledge measured by a 20-item assessment administered at baseline (T0), after didactic instruction (T1), and after VR (T2). Among second-year students, knowledge scores improved significantly across timepoints (repeated-measures ANOVA: F(2,124) = 251.0, p<.001, η²ₚ=0.802). Post-VR scores were comparable between peer-assisted and expert-assisted groups (15.1 ± 3.1 vs. 15.2 ± 3.4; t(61 =-0.12, p=.905, d=-0.03). Simulator sickness scores were low and did not differ between groups (4.2 ± 4.0 vs. 3.7 ± 3.7; p=.649), and satisfaction ratings were high in both conditions. Among fifth-year students, knowledge scores also increased significantly across instructional stages (F(2,106) = 33.4, p<.001, η²ₚ=0.387). Despite higher baseline scores among senior students (t(121)=-3.17, p=.002), post-VR performance was comparable between cohorts (t(115) = 1.11, p=.269). Peer-assisted facilitation produced learning outcomes comparable to expert-assisted instruction while maintaining high learner satisfaction and minimal simulator sickness. These findings suggest that peer facilitation may represent a scalable approach for implementing VR-based anatomy education.
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The prostatic urethra and distal sphincteric complex are often overlooked compartments that influence symptoms, treatment response, and uncommon complications of benign prostatic hyperplasia (BPH). Emerging anatomical studies suggest that the prostatic urethra is a dynamic structure where differences in length, curvature, and angulation alter local hydrodynamics and contribute to symptoms inadequately predicted by prostate volume alone. Real-time imaging further suggests that the periverumontanal region is responsible for creating an antichamber in which semen accumulates and directs antegrade flow. Therefore, anatomical distortion, surgical modification, or local physiological barriers disruption in this region may alter ejaculatory mechanics or permit reflux phenomena involving urine or seminal fluid. Distal to this region, the external urethral sphincter may present anterior and lateral extensions beyond conventional landmarks. These considerations should be studied when planning obstructive surgery and may help explain atypical continence patterns, pelvic discomfort, or dysorgasmia not captured by conventional lower urinary tract symptoms. PATIENT SUMMARY: We reviewed anatomical features of the prostatic urethra and sphincter, which are usually overlooked in standard evaluation of benign prostatic hyperplasia. Recognizing such anatomic variants may help explain unusual symptoms and improve surgical treatment.
Persistent primitive olfactory artery (PPOA)-associated aneurysms are rare lesions in which treatment risk is determined not only by aneurysm morphology, but also by the anomalous parent vessel and its distal territory. These lesions should therefore be approached as anatomy-defined aneurysms rather than ordinary anterior cerebral artery aneurysms in an unusual location. Based on the available literature, PPOA-associated lesions most often arise at the hairpin turn or A1-PPOA origin, where abrupt curvature, branching, and parent-vessel dependence may influence treatment selection. We propose a practical anatomy-led framework that begins with recognition of the PPOA, followed by assessment of rupture status, lesion certainty, morphology, distal-territory dependence, and feasibility of parent-vessel preservation or reconstruction. Until stronger evidence is available, management should remain individualized, anatomy-led, and supported by long-term vascular surveillance.
Although most Patient-Reported Outcome Measures (PROMs) in sports medicine are anatomy-specific and limited in scope, the 4-Domain Sports PROM (4-DSP) offers a comprehensive, athlete-centered, and anatomy-independent alternative. Validating the Persian version addresses a critical need for Iran's substantial athletic community, which experiences a high prevalence of sports-related injuries. To translate, culturally adapt, and validate the Persian 4-DSP for Persian-speaking athletes. Cross-sectional observational study following COSMIN and STROBE guidelines. Following Beaton and ISPOR guidelines, the 4-DSP underwent forward-backward translation. Psychometric evaluation involved 112 Persian-speaking athletes (61 men, 51 women; mean age: 27.45±4.52 years) with orthopedic injuries 3-12 months prior. Face validity was assessed by 20 athletes using I-FVI. Content validity was evaluated by 10 experts using I-CVI, S-CVI/Ave, S-CVI/UA, and modified Kappa. Test-retest reliability was assessed using ICC with 24-48-hour intervals. Internal consistency (Cronbach's alpha), measurement error (SEM, MDC), feasibility (missing data), and interpretability (floor/ceiling effects) were also evaluated. Analyses were performed using SPSS v29. All items showed acceptable face validity (I-FVI≥0.83); scale-level indices were excellent (S-FVI/Ave=0.95, S-FVI/UA=0.36). Content validity was robust (I-CVI≥0.78, S-CVI/Ave=0.95, modified kappa=0.94; S-CVI/UA=0.45). Test-retest reliability was excellent for the total score (ICC=0.91; 95% CI: 0.87-0.94) and good-to-excellent across domains (ICC: 0.84-0.93). Internal consistency was acceptable (α=0.77). Missing data were <2%, and no floor/ceiling effects were detected (<15%). SEM and MDC values supported clinical interpretation. The Persian 4-DSP demonstrates excellent face and content validity, very good reliability, and acceptable internal consistency, supporting its use as a feasible, culturally adapted tool for assessing treatment outcomes in Persian-speaking athletes. Future research should address convergent validity and responsiveness to fully establish construct validity.
The nasal passages of bats that emit their echolocation call through their nostrils have adapted for sound emission as well as standard respiratory and olfactory functions. Rhinolophids, hipposiderids and rhinonycterids all use a high duty cycle (HDC) echolocation strategy. In this study we used computational fluid dynamics (CFD) to simulate airflow through models of the nasal passages of 12 members of Rhinolophoidea, with the aim of gaining a greater insight into how differences in nasal passage anatomy and echolocation strategy influence airflow. We also aimed to gain greater insight into the function of the unique strands housed in the rhinolophid nasal passage, by comparing models with the strands intact and digitally removed. We found that nasal passage anatomy (e.g., the presence or lack of an ethmoturbinal I projecting into the rostral part of the nasal chamber), not echolocation strategy (HDC vs. low duty cycle) appeared to influence simulated airflow patterns and rates. Further, our results revealed digital removal of the unique strands within the nasal passages of the rhinolophids resulted in a reduction in the overall pressure gradient across the nasal passage models and altered the airflow patterns. How this pressure gradient change influences either the functions of echolocation and/or respiration warrants further investigation.
Traditionally defined as attaching to the mandibular coronoid process, the temporalis muscle (TM) has instead been shown, through anatomical evidence, including dissection, histology, and imaging, to have more variable distal insertions relevant to mastication, deglutition, temporomandibular disorders, and facial reanimation. We have assembled this evidence and propose a classification based on insertion. A systematic review of the medical literature was conducted using PubMed, Embase, Scopus, and LILACS to identify studies that reported distal TM insertions in humans by dissection, histology, or imaging; case reports, animal studies, and studies involving major craniofacial anomalies were excluded. PRISMA and Evidence-Based Anatomy guidelines were followed, with risk of bias assessed using the Anatomical Quality Assessment (AQUA) Tool; data on sample characteristics, detection method, definition, and insertion sites were collected. From 276 records reviewed, only 22 met the inclusion criteria, with 815 cadaveric TMs recorded by dissection, 26 TMs recorded histologically, and 183 TMs recorded by use of imaging across multiple regions. Overall, AQUA ratings for study objectives, descriptive anatomy, and reporting were rated as low risk but were rated higher risk regarding methodological characterisation. Three bony insertions were identified: (1) on or through the coronoid; (2) between the coronoid and ramus; and (3) between the coronoid, ramus, and retromolar triangle of the mandible. These bony insertions may be modified by accompanying soft-tissue attachments. This information could assist in standardising anatomical communication and aid in research on the TM region. It may also help clarify the function of the TM during chewing and swallowing and improve understanding of temporomandibular joint disorders.
Deep brain stimulation (DBS) is an established treatment for essential tremor (ET), with the ventral intermediate nucleus (Vim) of the thalamus and the posterior subthalamic area (PSA), including the zona incerta and dentato-rubro-thalamic tract (DRTT), serving as the primary stimulation targets. These structures lie along the cerebello-thalamo-cortical pathway but differ in anatomical location and fibre composition, potentially influencing clinical effects and side effect profiles. We aim to compare the anatomical and physiological considerations of Vim and PSA targeting in ET, explore the impact of pulse width modulation on the therapeutic window, and highlight the importance of a fibre-informed, anatomically guided approach to programming. PSA targeting, particularly toward the DRTT, may offer improved tremor control over Vim. While clinical studies suggest shorter pulse widths can widen the therapeutic window when defined by amplitude, modelling and neurophysiological data indicate that longer pulse widths may better engage target neural elements in the PSA. Variability in study design, anatomical target and stimulation parameters complicates direct comparison across trials. A nuanced understanding of target anatomy and neurophysiology may inform DBS programming to improve clinical outcomes. Based on biophysical and anatomical considerations, we propose an initial algorithm to guide DBS programming to substitute the conventional monopolar review.
Atypical femoral fracture (AFF) is a rare yet potentially devastating complication associated with long-term antiresorptive therapy for osteoporosis. Given the substantial differences between Asian and Western populations in femoral anatomy, genetic background, and patterns of anti-osteoporotic medication use, the Asia Federation of Osteoporosis Societies (AFOS) officially released the AFOS 2025 Consensus on "Atypical Femoral Fracture in Patients with Osteoporosis", based on multinational expert surveys and the latest available evidence. This consensus provides region-specific recommendations tailored to Asian populations, focusing on key aspects of AFF management, including early recognition and imaging surveillance, risk-stratified intervention for incomplete fractures, surgical fixation strategies for complete fractures, and individualized sequential anti-osteoporotic therapy after surgery. The present article offers an in-depth interpretation of the core principles and clinical implications of this consensus, with the aim of assisting Chinese clinicians in more precisely balancing the long-term benefits and risks of anti-osteoporotic treatment, and in providing an advanced reference for systematically optimizing the prevention and management of AFF. 非典型股骨骨折（atypical femoral fracture，AFF）是长期应用抗骨吸收药物治疗骨质疏松的一种罕见但后果严重的并发症。鉴于亚洲人群在股骨解剖形态、遗传背景及用药习惯上与西方人群存在显著差异，亚洲骨质疏松学会联合会（AFOS）于2025年结合多国专家调研与最新文献证据，正式发布了《亚洲骨质疏松学会联合会2025年关于骨质疏松患者非典型股骨骨折的共识》。该共识针对AFF的早期识别与影像筛查、不完全骨折的分层干预、完全骨折的手术固定策略，以及术后抗骨质疏松药物的个体化序贯管理等核心环节，提出了极具亚洲区域特异性的推荐意见。本文将对该共识的核心精髓进行深度剖析，旨在帮助中国临床医师更精准地平衡抗骨质疏松治疗的长期获益与风险，为系统优化AFF的临床防治策略提供前沿参考。.
Asian elephants possess a unique pulmonary anatomy that presents challenges for diagnosing respiratory diseases, particularly when reared under human care where environmental stressors, poor hygiene and limited physical activity predispose them to respiratory pathologies. Conventional diagnostic tools such as radiography, computed tomography (CT), and magnetic resonance imaging (MRI) are impractical for elephants due to their large body size. Diagnosis of lung pathologies is often delayed until postmortem. This study evaluated the diagnostic utility of lung ultrasound (LUS) as a noninvasive, real-time imaging modality in assessing lung health in Asian elephants. A total of 68 noncardiac transthoracic ultrasound scans were performed on 28 elephants to develop a systematic approach for pulmonary imaging. LUS demonstrated high sensitivity in detecting lung lesions, including interstitial syndrome, pulmonary edema, consolidation, pneumothorax, and pleural effusion, even in apparently healthy, asymptomatic individuals. Specific thoracic zones serving as acoustic windows were successfully mapped to improve consistency in lesion localization. Additionally, a semi-quantitative LUS score was developed for the objective assessment of lung aeration across 24 thoracic regions. Despite species-specific challenges such as narrow intercostal spaces and large lung volume, key sonographic features, including A-lines, B-lines, lung sliding, and bronchograms, were visualized. This study establishes LUS as a practical, field-adaptable tool for antemortem detection and monitoring of respiratory disease in elephants. Its ability to detect subclinical pathology offers significant benefits for early intervention, improved clinical outcomes, and support for conservation efforts. LUS has the potential to transform pulmonary diagnostics in elephant healthcare, bridging a critical gap in veterinary medicine for this endangered species.
Cardiopulmonary resuscitation is a critical intervention for cardiac arrest, but its forceful chest compressions can lead to skeletal injuries, including rare vertebral fractures CASE PRESENTATION: This case report details a 78-year-old woman with a history of cardiac surgery and obesity who suffered a fatal cardiac arrest due to a DeBakey type II aortic dissection. Despite 30 minutes of advanced manual CPR, she succumbed to cardiogenic shock. Autopsy revealed an incidental transvertebral fracture of the 8th thoracic vertebra alongside multiple bilateral rib fractures, with no evidence of pre-existing trauma LITERATURE REVIEW: A systematic literature search was conducted in three major scientific databases and reported according to PRISMA 2020, with structured eligibility criteria and methodological quality appraisal of included reports. Results were evaluated by two independent reviewers. Data on demographics, anatomy, bone comorbidities, and CPR were extracted independently and reviewed collectively CONCLUSIONS: A systematic literature review of 16 studies identified 23 cases of CPR-related vertebral fractures, predominantly in the mid-to-lower thoracic spine, with Th10 being the most affected level. Pre-existing conditions such as osteopenia, osteoporosis, and kyphosis increase susceptibility to these injuries by compromising spinal integrity. The biomechanical forces of CPR, combined with structural vulnerabilities, contribute to this rare complication. This case underscores the importance of post-mortem examinations in distinguishing CPR-related injuries from traumatic causes, aiding forensic investigations. Clinicians and forensic pathologists should remain vigilant for vertebral fractures as a potential CPR complication, particularly in elderly patients with predisposing bone conditions, to ensure accurate diagnosis and avoid medico-legal issues.
This focused update from the Korean Society of Myocardial Infarction provides consensus recommendations for revascularization in acute coronary syndrome (ACS), integrating major trial evidence since 2021 with Korean real-world practice. A multidisciplinary writing committee reviewed randomized trials, meta-analyses, and recent guidelines, and achieved consensus document. Key recommendations are as follows: 1) Cardiogenic shock: prioritize culprit-first revascularization with early reassessment; apply mechanical circulatory support selectively, guided by shock phenotype and escalation criteria rather than routine use; 2) Non-ST segment elevation ACS: use risk-stratified invasive timing with clear triggers for urgent versus early angiography; 3) Access and imaging: adopt radial-first access and broaden intravascular imaging for complex anatomy, ambiguous culprit lesions, and optimization of stent expansion; 4) Non-culprit lesion: favor complete revascularization in ST-segment elevation myocardial infarction (MI) with multivessel disease; select immediate versus staged procedures based on hemodynamics, ischemic burden, renal function, and contrast load. (5) Special scenarios: implement mechanism-based pathways for MI with non-obstructive coronary arteries and spontaneous coronary artery dissection (SCAD), incorporating intracoronary imaging, functional testing, vasospasm provocation, and cardiac magnetic resonance imaging; prefer conservative treatment for SCAD unless ongoing ischemia persists. The document provides concise "do" statements, and a summary of changes from 2021 to facilitate bedside adoption. These recommendations aim to standardize high-value, patient-centered ACS care in Korea, reduce practice variability, and improve outcomes while acknowledging areas requiring further evidence.
Trigeminal nerve injury (TNI) complicates oral and maxillofacial surgery (OMS) and dental procedures; accurate neurosensory testing (NST) using the Medical Research Council Scale (MRCS) guides diagnosis and referral. It is unclear if a standardized neurosensory training programme for residents can improve the accuracy of diagnosing trigeminal nerve injuries. To measure the effect of standardized training on trigeminal NST accuracy among OMS residents. A prospective cohort study at the University of Illinois Chicago. OMS residents completed NST on adult subjects with stable unilateral TNI before and after training. NST training status (pre vs post). The 15-minute training comprised a didactic on trigeminal anatomy and MRCS, a demonstration video, and supervised practice. Two faculty examiners served as the reference standard. Mean absolute error (MAE) of resident MRCS scores relative to the faculty median; smaller MAE indicates greater accuracy. Sex and postgraduate year (PGY) of training. Examination duration, self-reported confidence (5-point Likert), and inter-rater reliability (intraclass correlation coefficient). Paired t-tests compared pre/post values. Mann-Whitney U (sex) and Spearman correlation (PGY) assessed covariate associations; a mixed-effects model adjusted for both. Statistical significance was set at α = 0.05. Nine OMS residents (6 male [67%], 3 female [33%]; 6 PGY-1, 1 PGY-3, 2 PGY-4) and 4 subjects participated. MAE decreased from 0.4 (SD 0.3) to 0.1 (SD 0.1) (P = .01); intraclass correlation coefficient improved from 0.20 to 0.65. Neither sex (P = .7) nor PGY (P = .8) was associated with MAE; the training effect remained statistically significant after adjustment (β = -0.31, P = .001). Confidence increased from 3.0 (SD 1.3) to 4.0 (SD 0.6) (P = .02); duration shortened from 202 (SD 70) to 133 (SD 48) seconds (P = .006). A 15-minute standardized training programme reduced resident MRCS scoring error and improved inter-rater reliability from poor to moderate. OMS residency programmes should incorporate brief structured NST training to improve TNI assessment.
Posterior spinal accessory nerve (SAN) to suprascapular nerve (SSN) transfer is a well-established procedure for restoration of shoulder function in upper brachial plexus injuries. Nerve localization traditionally relies on anatomical surface landmarks, which may be influenced by surgeon experience and patient-specific anatomy. Ultrasound provides direct visualization of neural and vascular landmarks before incision. We compared ultrasound-guided preoperative localization with conventional anatomical landmark-based localization during posterior SAN-to-SSN nerve transfer. In this prospective, nonrandomized comparative cohort study, 40 consecutive patients undergoing posterior SAN-to-SSN transfer were allocated in an alternating sequence to ultrasound-guided or landmark-based preoperative skin marking (20 patients per group). Outcomes included time to SAN and SSN identification, total operative time, and requirement for wider exploratory dissection. Baseline demographic and injury characteristics were comparable between the groups. Ultrasound localization was associated with shorter time to SAN identification (12.0 ± 2.1 vs. 20.1 ± 3.0 min), SSN identification (58.2 ± 5.3 vs. 72.4 ± 6.1 min), and total operative time (110.4 ± 9.5 vs. 132.6 ± 11.3 min) (all p < 0.001). Wider exploratory dissection was required less frequently in the ultrasound group (15% vs. 60%; p = 0.004). Ultrasound mapping required a mean of 3.0 ± 0.5 min and did not eliminate the overall procedural time advantage when included in workflow analysis. Preoperative ultrasound-guided skin marking was associated with more directed nerve localization, reduced exploratory dissection, and improved operative efficiency during posterior SAN-to-SSN nerve transfer. Ultrasound appears to be a useful adjunct that provides anatomically informed pre-incision guidance while maintaining an overall procedural time benefit. III, prospective nonrandomized comparative cohort study.
Branching patterns of the adrenal artery exhibit interspecies and individual variations. As Eulipotyphla species have distinctive morphological characteristics, observations in this group may provide insights into the comparative anatomy of this artery. This study used 15 house musk shrews (Suncus murinus). In most cases, adrenal arteries arose from a single parent artery, namely the caudal phrenic artery, abdominal aorta, or renal artery. In one left case, adrenal arteries emerged from both the abdominal aorta and renal artery. The most common pattern of adrenal arterial supply was one middle and one caudal adrenal artery on both sides, with no cranial one. The house musk shrew exhibited a simpler branching pattern than other species, offering comparative anatomical insights into the adrenal artery.
The global expansion of highly pathogenic avian influenza (HPAI) virus A(H5N1) underscores the need for rapid surveillance at high-risk wildlife interfaces. Taiaroa Head (45.7828° S, 170.7333° E) in the South Island of Aotearoa New Zealand hosts a plethora of aquatic wildlife including a large red-billed gull (Chroicocephalus novaehollandiae scopulinus) colony as well as the only mainland breeding colony of northern royal albatross (Diomedea sanfordi). The Royal Albatross Centre is also a major nature tourism destination, attracting tens of thousands of visitors annually, thereby creating a dense ecological and human-wildlife interface vulnerable to viral incursion. We evaluated the GeneXpert II platform using the Xpert® Xpress Flu/RSV cartridge as a field-deployable tool for avian influenza virus detection in environmental and wildlife-associated samples. The assay detected synthetic influenza A viral RNA and multiple endemic low pathogenic avian influenza virus subtypes (A(H3N8), A(H1N9), A(H5N2) and A(H7N7)) circulating in New Zealand birds in controlled spiking experiments. Influenza A virus was reliably identified in spiked environmental water samples with no consistent RT-qPCR inhibition as well as naturally occurring avian influenza virus in duck pond water. Field deployment demonstrated that the system could be operated by non-laboratory personnel with minimal training in a non-clinical setting. This study establishes the feasibility of near-real-time environmental monitoring. Repurposing clinical cartridge-based point-of-care diagnostics offers a practical early warning approach for avian influenza virus surveillance at ecologically and economically significant locations.
Necrotizing enterocolitis (NEC) is a life-threatening intestinal inflammatory disease in preterm infants. Inositol hexakisphosphate kinase 1 (IP6K1) regulates platelet polyphosphate (polyP) homeostasis, yet its roles in NEC remain unclear. This study aimed to investigate the regulatory mechanism of platelet IP6K1 in neutrophil-platelet aggregate (NPA) formation and NEC pathogenesis, and to evaluate the therapeutic potential of IP6K1 inhibition. Clinical samples from patients with NEC were analyzed to assess circulating mitochondrial DNA, anticardiolipin IgG levels, platelet alterations, platelet cell death patterns, and NPA formation. A mouse model of NEC was used to evaluate the effects of genetic IP6K1 deficiency and pharmacological IP6K inhibition with TNP on survival, intestinal injury, neutrophil infiltration, neutrophil extracellular trap (NET) formation, and inflammatory responses. Mechanistic experiments were performed using exogenous polyP supplementation and P-selectin neutralization RESULTS: Patients with NEC exhibited significantly increased circulating mitochondrial DNA levels, elevated anticardiolipin IgG levels, enhanced NPA formation, reduced platelet counts, abnormal platelet morphological parameters, and platelet pyroptosis as the predominant mode of cell death. In NEC mice, both IP6K1 deficiency and TNP treatment improved survival, preserved intestinal mucosal architecture, reduced disease severity, and markedly attenuated neutrophil infiltration and NET formation. Mechanistically, IP6K1 promoted NPA formation and downstream inflammatory responses by regulating the release of platelet-derived short-chain polyP. Exogenous polyP supplementation restored the impaired NPA formation observed in IP6K1⁻/⁻ mice. Moreover, P-selectin neutralization suppressed NPA formation and reduced NET production in inflamed intestinal tissues. Platelet IP6K1 is a key regulator of NPA formation and NET release in NEC through its control of platelet-derived short-chain polyP. Targeting IP6K1 may represent a promising therapeutic strategy for mitigating local and systemic inflammation in severe NEC.
Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited therapeutic options. Kaempferol shows potential in suppressing HCC progression via glycolysis regulation, yet its molecular targets and mechanisms are unclear. Transcriptomic data were analyzed to identify HCC-related DEGs. Intersection with kaempferol's glycolysis-related targets yielded candidate genes. A prognostic risk model was constructed and validated by ROC curves and survival analysis. GSEA and single-cell RNA sequencing explored mechanisms and cellular heterogeneity. Mendelian randomization assessed causality between prognostic genes and HCC. After HCC cells were treated with different concentrations of kaempferol, the effects of kaempferol on proliferation, invasion, and migration of HCC cells were detected by CCK-8, cell clone formation, and Transwell cell scratch healing experiments. The expression levels of key proteins in the AKT-mTOR signaling pathway and glycolytic rate-limiting enzymes were detected by Western blot. The spectrophotometric method was used to detect the effect of kaempferol on glucose uptake and lactate production of HCC cells. Finally, the impact of knocking down CA9 on glucose uptake and lactic acid production in liver cancer cells was analyzed. The prognostic risk model identified GRK6, ABCC1, CA9, and CDK5R1 as prognostic genes. GSEA implicated cell cycle and PI3K-Akt pathways in HCC progression driven by these genes. Single-cell analysis revealed pronounced upregulation of prognostic genes in hepatocytes. Finally, MR analysis confirmed that CDK5R1 was a risk factor for the incidence of HCC. Kaempferol significantly inhibited the proliferation, invasion, and migration of MHCC97H and Huh7 cells, as well as the expression levels of PKM2, HK2, p-AKT, p-mTOR, and p-RPS6. Kaempferol significantly reduced glucose uptake and lactic acid production in MHCC97H and Huh7 cells. Knockdown of CA9 inhibited the uptake of glucose and lactic acid production, along with suppressing the expression of HK2 and PKM2 in MHCC97H and Huh7 cells. This study found that kaempferol targeted the AKT-mTOR pathway and downregulated the CA9 gene, thereby modulating glycolysis and ultimately suppressing the proliferation, invasion, and migration of hepatocellular carcinoma.
Vascular cognitive impairment (VCI) is a devastating clinical endpoint of microvascular senescence. However, the mechanisms by which age-related focal vascular insults cause systemic brain network failure and molecular vulnerability remain unknown. To decode the multi-scale neurobiology of VCI, we conducted a systematic review and meta-analysis of whole-brain voxel-based morphometry studies comparing patients with VCI and healthy controls. We used coordinate-based network mapping on a normative functional connectome to identify convergent structural atrophy networks. To decode multi-scale biological substrates, we checked the resulting macroscopic topography against the Allen Human Brain Atlas and 28 positron emission tomography-derived neurotransmitter maps. 18 studies contributed to the analysis, including 682 VCI patients and 643 healthy controls. VCI-related atrophy, despite appearing disparate, functionally converges onto a robust macroscopic architecture that is anchored predominantly in the somatomotor and salience networks. Transcriptomic profiling further showed that this network colocalizes significantly with Layer 6 corticothalamic and subcortical projection neurons. These neuron populations feature exceptionally long axonal projections, a property that heightens their metabolic susceptibility to chronic hypoperfusion. At the neurochemical level, this structural degradation exhibited profound spatial coherence with the macroscopic distribution of dopamine transporter (DAT) and 5-hydroxytryptamine transporter (5‑HTT). These findings suggest that VCI may represent a quintessential "disconnection syndrome" associated with the vulnerability of long-range projection pathways to vascular aging, providing a novel multi-scale neurobiological template to identify network-level targets for intervention.
Broad-spectrum antibiotics are invaluable tools for treating pathogenic infections, but their sustained use can contribute to changes in gut microbiome membership and the emergence of antimicrobial resistance. While these unintended side effects are independently well documented, the relationship between them has seldom been investigated. To address this, we quantified the effects of 28-d antibiotic cocktail exposure on metagenome-assembled genomes and antibiotic resistance genes in common marmosets using a custom whole-genome shotgun sequencing pipeline and quantitative polymerase chain reaction assays. We observed contrasting genus-level reductions in Bifidobacterium abundance and Fusobacterium growth, both during antibiotic treatment and a 2-week post-treatment period. Total bacterial abundance was not significantly affected by antibiotics, likely due to the presence of antibiotic-resistant opportunists. Genes for vancomycin resistance and multidrug efflux pumps were identified in metagenome-assembled genomes of an unclassified Sarcina sp. and Escherichia coli, respectively, and were accompanied by increased abundance of these species during treatment. Additionally, we detected 11 dysregulated metagenomic pathways related to carbohydrate metabolism, including 2 pathways relevant to short-chain fatty acid production, following antibiotic exposure. This study provides insights into the species-dependent emergence of antimicrobial resistance mechanisms in non-human primates following antibiotic exposure that could be relevant for antibiotic therapies and resistance management.