Social bonding in groups of humans selectively increases inter-status information exchange and prefrontal neural synchronization.

Social groups in various social species are organized with hierarchical structures that shape group dynamics and the nature of within-group interactions. In-group social bonding, exemplified by grooming behaviors among animals and collective rituals and team-building activities in human societies, is recognized as a practical adaptive strategy to foster group harmony and stabilize hierarchical structures in both human and nonhuman animal groups. However, the neurocognitive mechanisms underlying the effects of social bonding on hierarchical groups remain largely unexplored. Here, we conducted simultaneous neural recordings on human participants engaged in-group communications within small hierarchical groups (n = 528, organized into 176 three-person groups) to investigate how social bonding influenced hierarchical interactions and neural synchronizations. We differentiated interpersonal interactions between individuals of different (inter-status) or same (intra-status) social status and observed distinct effects of social bonding on inter-status and intra-status interactions. Specifically, social bonding selectively increased frequent and rapid information exchange and prefrontal neural synchronization for inter-status dyads but not intra-status dyads. Furthermore, social bonding facilitated unidirectional neural alignment from group leader to followers, enabling group leaders to predictively align their prefrontal activity with that of followers. These findings provide insights into how social bonding influences hierarchical dynamics and neural synchronization while highlighting the role of social status in shaping the strength and nature of social bonding experiences in human groups.

Atg16l2 augments Nlrc4 inflammasome activation by facilitating NAIPs-NLRC4 association.

As cytoplasmic protein complexes that are pivotal for innate immunity, inflammasomes act primarily through the detection of pathogen- or danger-associated molecular patterns. Nucleotide oligomerisation domain-like receptor family and caspase activation recruitment domain-containing protein 4 (NLRC4) inflammasomes identify and eliminate intracellular pathogens, a process contingent on the ligand-recognition capabilities of neuronal apoptosis inhibitory proteins (NAIPs). Upon detection of specific molecules indicative of intracellular infection, NAIPs discern distinct pathogenic components and subsequently transmit signals to NLRC4, thus initiating their activation and triggering an inflammatory response. However, the mechanisms underlying NLRC4 inflammasome remain unclear. In this study, we elucidated the critical role of ATG16L2 in activating the NLRC4 inflammasome. ATG16L2-deficient macrophages exhibited reduced NLRC4 inflammasome activation, characterised by decreased oligomerisation of apoptosis-associated speck-like protein containing a CARD and attenuated cleavage of Pro-caspase-1, Pro-IL-1ß and gasdermin D. Co-immunoprecipitation assays revealed an interaction between ATG16L2 and NAIPs. Furthermore, ATG16L2 enhanced the association between NAIPs and NLRC4 by binding to NAIPs. For ATG16L2-knockout mice infected with Salmonella typhimurium, pathogen clearance and survival rates markedly decreased. Collectively, our findings suggest that ATG16L2 is a significant modulator of the innate immune system, influencing the activity of the NLRC4 inflammasome and the host's defensive response to intracellular pathogens.

Genome-Wide Mendelian Randomization Study Reveals Druggable Genes for Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is a group of neurological disorders that affect the small blood vessels within the brain, for which no effective treatments are currently available. We conducted a Mendelian randomization (MR) study to identify candidate therapeutic genes for CSVD. METHODS: We retrieved genome-wide association study data from 6 recently conducted, extensive investigations focusing on CSVD magnetic resonance imaging markers and performed a 2-sample MR analysis to assess the potential causal effects of gene expression and protein level within druggable genes on CSVD in blood and brain tissues. Colocalization analyses and repeat studies were undertaken to verify the relationship. Additionally, mediation analysis was conducted to explore the potential mechanisms involving druggable genes and known risk factors for CSVD. Finally, phenome-wide MR analyses were applied to evaluate the potential adverse effects related to the identified druggable genes for CSVD treatment. RESULTS: Overall, 5 druggable genes consistently showed associations with CSVD in MR analyses across both the discovery and validation cohorts. Notably, the ALDH2 and KLHL24 genes were identified as associated with CSVD in both blood and brain tissues, whereas the genes ADRB1, BTN3A2, and EFEMP1 were exclusively detected in brain tissue. Moreover, mediation analysis elucidated the proportion of the total effects mediated by CSVD risk factors through candidate druggable genes, which ranged from 5.5% to 18.5%, and offered potential explanations for the observed results. A comprehensive phenome-wide MR analysis further emphasized both the therapeutic benefits and potential side effects of targeting these candidate druggable genes. CONCLUSIONS: This study provides genetic evidence supporting the potential therapeutic benefits of targeting druggable genes for treating CSVD, which will be useful for prioritizing CSVD drug development.

Interleukin-17A educated hepatic stellate cells promote hepatocellular carcinoma occurrence through fibroblast activation protein expression.

BACKGROUND: Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin-17A (IL-17A), a pivotal pro-inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL-17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL-17A and HSCs in the context of HCC. METHODS: An HCC model was established in male Sprague-Dawley rats using diethylnitrosamine to explore the roles of IL-17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno-associated virus. A suite of molecular techniques, including RT-qPCR, enzyme-linked immunosorbent assays, Western blotting, cell counting kit-8 assays and colony formation assays, was employed for in vitro analyses. RESULTS: The study findings indicate that IL-17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro-tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL-17A-induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL-17A-stimulated HSCs was observed to reverse the HCC-promoting effects of HSCs. CONCLUSIONS: The collective evidence from this study implicates the IL-17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL-17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.

Automated diffusion-weighted image analysis along the perivascular space index reveals glymphatic dysfunction in association with brain parenchymal lesions.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

Short-Term Efficacy of Cerebello-spinal tDCS and Body Weight-Supported Treadmill Training in the Hypertrophic Olivary Degeneration: a Rare Case Report.

The present case study reported a patient diagnosed with hypertrophic olivary degeneration, a rare condition characterized by a trans-neuronal degeneration and signal enhancement in T2-weighted images on magnetic resonance imaging, usually caused by cerebral hemorrhage, cerebral infarction, and trauma. Furthermore, the relevant literature review was performed. The existing pharmacological treatment has limited clinical benefits on the patient. Since spontaneous remission hardly occurs in the disease, there are no other effective treatments. In this case, the patient was a 55-year-old Chinese male who presented progressive gait difficulty for several months due to both-sided ataxia. Neurological examination revealed upper extremity and lower limb bilateral spasticity, ataxia, slurred speech, and dysmetria. Therefore, our study treated the patient through the inventive application of cerebello-spinal transcranial direct current stimulation and body weight-supported treadmill training. After a 4-week treatment, the patient could walk independently, without aid, speeding up by 7%, as well as the ataxia symptoms, and balance has improved significantly. It was demonstrated in this case report that the combination of cerebello-spinal tDCS and body weight-supported treadmill training can be an effective treatment for patients with Hypertrophic olivary degeneration.

Polysubstitution Induced Centrosymmetric-to-Noncentrosymmetric Structural Transformation and Nonlinear-Optical Behavior: The Case of Na0.45Ag0.55Ga3Se5.

Obtaining compounds with large nonlinear-optical (NLO) coefficients and wide band gaps is challenging due to their competitive requirements for chemical bonds. Herein, the first member with mixed cations on the A site in the A-M3-Q5 or A-Ag-M6-Q10 (A = alkali metal; M = Ga, In; Q = S, Se, Te) family, viz. Na0.45Ag0.55Ga3Se5 (NAGSe), was obtained by a solid-state reaction. Its structure features [GaSe4] tetrahedra built three-dimensional {[Ga3Se5]-}∞ network, with Na and Na/Ag cations located at the octahedral cavities. Noncentrosymmetric (R32) NAGSe can also be transformed from centrosymmetric RbGa3S5 (P21/c) via multiple-site cosubstitution. NAGSe exhibits the highest NLO response (1.9 × AGS) in the A-Ag-M-Q family. Crystal structure analysis and theoretical calculations suggest that the NLO response is mainly contributed by the regularly arranged [GaSe4] units. This work enriches the exploration of the undeveloped A-M3-Q5 or A-Ag-M6-Q10 family as potential infrared NLO materials.

Cerebral venous thrombosis at high altitude: more severe symptoms and specific predisposing factors than plain areas.

BACKGROUND: Exposure to a high-altitude environment is a risk factor for cerebral venous thrombosis (CVT) probably due to hypercoagulability. The study aims to explore the unique characteristics of CVT patients in high-altitude areas of China by comparing them with those in plain areas. METHODS: We retrospectively included consecutive patients with CVT admitted to Tibet Autonomous Region People's Hospital (altitude 3650 m) and Peking Union Medical College Hospital (altitude 43.5 m) between January 2015 and December 2023. Patients from the plateau and the plain were considered two independent groups in this study. The risk factors, clinical and radiological presentations, treatment, and outcomes were analyzed and compared between the two groups. RESULTS: A total of 169 patients with CVT were included in the study, 48 patients from plateau and 121 patients from plain. The median age was 27 and 34 years old, and women accounted for 66.7% and 54.5% respectively. Headache (91.7% vs. 71.1%, P = 0.004), altered consciousness (31.3% vs. 16.5%, P = 0.033), hemorrhage (41.7% vs. 19.0%, P = 0.002), and venous infarction (50.0% vs. 25.6%, P = 0.002) on imaging were more common in patients from plateau than those from plain. Pregnancy or puerperium was significantly more common in highland patients (25% vs. 5.8%, P < 0.001). The levels of D-Dimer (1.7 vs. 0.8 mg/L FEU, P = 0.01), fibrinogen (3.7 vs. 3.0 g/L, P < 0.001), hemoglobin (157 vs. 129 g/L, P = 0.01), white blood cells (9.6 vs. 7.5*1012/L, P < 0.001) and highly sensitive C-reactive protein (20.2 vs. 3.2 mg/L, P = 0.005) were remarkably higher in highland patients. The percentage of receiving anticoagulant therapy was lower in high-altitude patients (70.8% vs. 93.4%, P < 0.001). Favorable outcome at follow-up was observed in 81.4% of highland patients and 90.7% of lowland patients, with a median follow-up time of 330 days and 703 days respectively. CONCLUSIONS: The more severe clinical and imaging manifestations along with prominent inflammatory and hypercoagulable states were observed in plateau CVT patients, probably due to exposure to the hypoxic environment at high altitude. Pregnancy or puerperium were more common in highland patients. The overall prognosis of CVT patients from both groups were favorable.

Study on lattice dynamics and thermal conductivity of fluorite AF2 (A = Ca, Sr, Ba) based on first principles calculations.

Fluorite materials have received particular attention in electron optics due to their favorable optical properties. However, further exploration of these materials in the thermoelectric (TE) field is hampered by the lack of studies on their lattice thermal transport properties. In this work, we use first-principles calculations, combined with self-consistent phonon theory, compressive sensing lattice dynamics and the Boltzmann transport equation, to study the microscopic mechanism of lattice thermal transport properties in AF2 (A = Ca, Sr, Ba) with a fluorite structure. We investigate the effects of three-phonon and four-phonon scattering and quartic anharmonic renormalization of phonon frequencies on this system. The results show that the bonding strength of atoms A (Ca, Sr, and Ba) plays an important role in the thermal transport process, and the third-order anharmonicity also plays an important role in this system. Meanwhile, the role of the quartic anharmonicity cannot be ignored. Our findings not only fill in the gaps in the study of lattice thermal transport of fluorite materials, but also deepen the comprehensive understanding of the high κL value of fluorite materials.

Effects of Pd atom vibration in the Sr-Te octahedral interstitial space in Zintl compound SrPdTe on lattice anharmonicity and thermoelectric properties.

Based on first-principles calculations, the current study deeply explores the thermoelectric properties of the Zintl compound SrPdTe. We found that the anharmonic vibration of Pd atoms plays an important role in the quartic anharmonic effect and the temperature dependence of the thermal conductivity. In the crystalline structure, Sr atoms form octahedra with eight surrounding Te atoms, while Pd atoms are located in the gaps between the octahedra. This structure makes the strong atomic mean square displacement of Pd atoms the main factor leading to the ultralow thermal conductivity. The study also reveals the effects of phonon frequency renormalization and four-phonon scattering on heat transfer performance. Even considering the spin-orbit coupling effect, multiple secondary valence band tops maintain the power factor of the material at high temperatures, providing a potential opportunity for achieving excellent thermoelectric performance.

Thiostrepton suppresses triple-negative breast cancer through downregulating c-FLIP/SMAD2/3 signaling pathway.

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.

Study on the Effect of Cations on the Surface Energy of Nano-SiO2 Particles for Oil/Gas Exploration and Development Based on the Density Functional Theory.

Although nano SiO2 exhibits excellent application potential in the field of oil and gas exploration and development, such as drilling fluid, enhanced oil/gas recovery, etc., it is prone to agglomeration and loses its effectiveness due to the action of cations in saline environments of oil and gas reservoirs. Therefore, it is crucial to study the mechanism of the change in energy between nano SiO2 and cations for its industrial application. In this paper, the effect of cations (Na+, K+, Ca2+, and Mg2+) on the surface energy of nano SiO2 particles is investigated from the perspective of molecular motion and electronic change by density functional theory. The results are as follows: Due to the electrostatic interactions, cations can migrate towards the surface of nano SiO2 particles. During the migration process, monovalent cations are almost unaffected by water molecules, and they can be directly adsorbed on the surface by nano SiO2 particles. However, when divalent cations migrate from a distance to the surface of nano SiO2 particles, they can combine with water molecules to create an energy barrier, which can prevent them from moving forward. When divalent cations break through the energy barrier, the electronic kinetic energy between them and nano SiO2 particles changes more strongly, and the electrons carried by them are more likely to break through the edge of the atomic nucleus and undergo charge exchange with nano SiO2 particles. The change in interaction energy is more intense, which can further disrupt the configuration stability of nano SiO2. The interaction energy between cations and nano SiO2 particles mainly comes from electrostatic energy, followed by Van der Waals energy. From the degree of influence of four cations on nano SiO2 particles, the order from small to large is as follows: K+ < Na+ < Mg2+ < Ca2+. The research results can provide a theoretical understanding of the interaction between nano SiO2 particles and cations during the application of nano SiO2 in the field of oil and gas exploration and development.

Myocardial Work for Dynamic Monitoring of Myocardial Injury in Neonatal Asphyxia.

To assess the value of parameters of myocardial work for dynamic monitoring of myocardial injury after neonatal asphyxia. Fifty-three neonates with asphyxia admitted within 24 h after delivery were divided into a mild asphyxia group (n = 40) and severe asphyxia group (n = 13). Echocardiography was performed within 24 h post-birth, within 72 h post-birth (48 h after first echo), and during recovery. The left ventricular ejection fraction on M-mode echocardiography and by Simpson's biplane method (LVEF and Bi-EF, respectively), stroke volume (SV), cardiac output (CO), cardiac index (CI), global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), and other parameters were measured. Echocardiographic indicators were compared between groups and over time. GWI was significantly increased at 72 h in the mild asphyxia group (P < 0.05) but showed no significant change over time in the severe asphyxia group (P > 0.05). While GCW increased significantly over time in both groups (P < 0.05), it increased earlier in the mild asphyxia group. Time and grouping factors had independent effects on GWI and GCW (P > 0.05). The characteristics of differences in GWI and GCW between the two groups were different from those for LVEF, Bi-EF, SV, CO, CI, and GLS and their change characteristics with improvement from treatment. GWI and GCW changed significantly during recovery from neonatal asphyxia, and their change characteristics differed between mild and severe asphyxia cases. Myocardial work parameters can be used as valuable supplements to traditional indicators of left ventricular function to dynamically monitor the recovery from myocardial injury after neonatal asphyxia.

RNF213 in moyamoya disease: Genotype-phenotype association and the underlying mechanism.

ABSTRACT: Moyamoya disease (MMD) is a cerebrovascular disorder characterized by a steno-occlusive internal carotid artery and compensatory vascular network formation. Although the precise pathogenic mechanism remains elusive, genetic association studies have identified RNF213 as the principal susceptibility gene for MMD, with the single nucleotide polymorphism p.R4810K recognized as the founder variant predominantly in the Asian populations. Distinct genotype-phenotype correlations are observable in RNF213-related MMD. The clinical manifestations linked to p.R4810K bear commonalities within Asian cohort, including familial predisposition, earlier age of onset, ischemic episodes, and involvement of the posterior cerebral artery (PCA). However, despite these shared phenotypic characteristics, there is significant heterogeneity in RNF213-related MMD presentations. This diversity manifests as variations across ethnic groups, inconsistent clinical symptoms and prognosis, and occurrence of other vasculopathies involving RNF213. This heterogeneity, in conjunction with the observed low disease penetrance of RNF213 mutations, suggests that the presence of these mutations may not be sufficient to cause MMD, underscoring the potential influence of other genetic or environmental factors. Although the current research might not have fully identified these additional contributors, experimental evidence points toward the involvement of RNF213 in angiogenesis, lipid metabolism, and the immune response. Future research is required to unveil the molecular mechanisms and identify the factors that synergize with RNF213 in the pathogenesis of MMD.

Optimizing energy storage plant discrete system dynamics analysis with graph convolutional networks.

Addressing the challenges of suboptimal model performance and excessive parameters and operations in the optimization of energy storage power plants utilizing Graph Convolutional Network (GCN), this paper introduces a novel approach - the packet-switched graph convolutional network. Initially, a GCN extreme learning machine is established. Drawing inspiration from this solid foundation, we have innovatively crafted a group exchange graph convolution module. This module leverages group graph convolution techniques to amalgamate unique node feature information, tailored to diverse topology graph matrices based on various groupings. This innovative approach ensures that information flows freely and effectively among distinct groupings. Furthermore, we have designed a cutting-edge timing depth separation convolution module, comprising two innovative components. The first component introduces timing depth separation convolution, revolutionizing the original timing convolution module. The second component, the packet-switching graph convolutional network, revolutionizes the time sequence depth separation convolution process. It achieves this by employing 1 × 1 convolutional layers between different feature fusion packets, enabling seamless information exchange between distinct packets. Experimental results demonstrate the efficacy of the proposed model, with root mean square error (RMSE) metrics and root mean square error (MAE) metrics for single-step prediction reaching 46.08 and 26.22 at 60 min, respectively. In multi-step testing, the proposed model exhibits a 14.71 % reduction in RMSE error at the 15-min scale and a 9.29 % reduction at the 60-min scale compared to the benchmark model. This performance improvement enhances the operational efficiency and reliability of the energy storage plant, particularly under dynamic changes in the time series.

Plant-soil hydraulic interaction and rhizosphere bacterial community under biochar and CO2 enrichment.

The increasing atmospheric CO2 concentration is a global concern that affects the plant-bacteria-soil system. Previous studies have investigated plant growth and bacteria activity under CO2 enrichment. However, the effects of coupled elevated CO2 and biochar amendment on the interactions of soil and medicinal plants are not well understood. This study aims to investigate the medicinal plant-soil hydraulic interactions and rhizosphere bacteria communities under coupled CO2 enrichment and biochar conditions. Two levels of CO2 concentration (400, 1000 ppm) and two biochar dosages (3%, 5% by mass) were considered. Pseudostellaria heterophylla was used as the tested medicinal plant. During plant growth, coupled CO2 enrichment and biochar at 3% and 5% dosage increased the volumetric water content at a matric suction of 33 kPa by 97% and 82% respectively, which indicates enhanced water retention. The transpiration rate of P. heterophylla was slightly reduced by 11-30% with an increase in biochar dosage due to higher total suction, while it was significantly reduced by up to 57% due to CO2 enrichment. In the rhizosphere of P. heterophylla, elevated CO2 (1000 ppm) coupled with 3% biochar dramatically increase the relative abundance of Thaumarchaeota, which played an important role in C and N cycles. Moreover, coupled CO2 enrichment and biochar addition resulted in the highest bacterial richness, while 3% biochar at ambient CO2 induced the highest bacterial diversity. This study provides a basis for understanding the medicinal plant-bacteria-soil system under CO2 enrichment and biochar conditions.

Circulating inflammatory biomarkers and risk of intracranial aneurysm: a Mendelian randomization study.

BACKGROUND: Intracranial aneurysm (IA) accounts for a substantial source of non-traumatic subarachnoid hemorrhage, with inflammation postulated as a potential factor in its pathogenesis. The present study aims at evaluating the association between circulating inflammatory cytokines and risk of IA under a bidirectional two-sample Mendelian randomization (MR) design. METHODS: For primary analysis, summary statistics of inflammatory regulators was obtained from a genome-wide association study (GWAS) comprising 8293 Finnish participants. Summary data of IA were extracted from a GWAS which comprised 7495 cases and 71,934 controls in European descent. For targeted analysis, summary statistics were extracted from two proteomic studies, which recruit 3301 and 5368 European participants, respectively. Summary data of IA were acquired from FinnGen study with 5342 cases and 342,673 controls. We employed inverse variance weighted (IVW) method as main approach, with sensitivity analyses using weighted median, MR-Egger, and MR-PRESSO methods. Reverse MR analyses were conducted to minimize bias from reverse causality. RESULTS: No causation of cytokines with IA subtypes was identified in both primary and targeted analysis after Bonferroni correction. In primary analysis, vascular endothelial growth factor (VEGF) and fibroblast growth factor basic (bFGF) levels were suggestively associated with aneurysmal subarachnoid hemorrhage (aSAH) [VEGF → aSAH: OR = 1.15, 95%CI 1.04-1.26, P = 0.005; bFGF → aSAH: OR = 0.62, 95% CI 0.42-0.92, P = 0.02]. Statistical significance failed to replicate in targeted analysis. Instead, suggestive protective effects for aSAH were identified in FGF-9 (FGF-9 → aSAH: OR = 0.74, 95% CI 0.62-0.89, P = 0.001) and FGF-16 (FGF-16 → aSAH: OR = 0.84, 95% CI 0.72-0.97, P = 0.017). Furthermore, reverse analyses identified suggestive effect of unruptured IA on RANTES, MIF, GRO-alpha, FGF-16, and FGF-19. Result remained robust after applying sensitivity tests. CONCLUSIONS: No causality of inflammatory biomarkers on the risk of IA subtypes was identified. Future large-scale studies are in need to evaluate the temporal dynamics of cytokines in conjunction with IA.

Assessment of lower limb proprioception after fibula free flap harvest: A pilot study.

BACKGROUND: After undergoing fibula-free flap harvest, patients may experience complications such as ankle instability. It remains unclear whether these patients have deficits of proprioception, and the recovery process is also uncertain. OBJECTIVE: This study aimed to objectively evaluate proprioception on the donor and normal side of surgical patients during long-term follow-up using the Pro-kin system. METHODS: This study enrolled 36 patients who underwent reconstruction of the head and neck using osseous free flaps harvested from the fibula. Each patient underwent pre-operative evaluations and was subsequently evaluated at postoperative months 1, 3, 6, and 12. The study assessed the proprioceptive evaluation of the lower limbs, muscle function, range of motion of the ankle, and donor side complications. RESULTS: On the donor side, the average trace error (ATE) at postoperative month 1 was significantly higher than pre-operation, postoperative months 6 and 12 (P< 0.05). The test execution time (TTE) at postoperative month 1 was significantly increased by 9.875s compared to the pre-operative levels (P= 0.012, 95% confidence interval [CI] 4: 1.877-17.873) and by 11.583s compared to postoperative month 12 (P= 0.007, 95% CI: 2.858-20.309). The reduction in range of motion of ankle dorsiflexion was most pronounced at postoperative month 1, exhibiting an 11.25∘ decrease compared to pre-operative levels (P< 0.001, 95% CI: 6.304-16.16). Although the range of motion of ankle dorsiflexion gradually improved over time at postoperative months 3, 6, and 12, it remained lower than pre-operative levels (P< 0.05). CONCLUSION: The study revealed that the patients exhibited proprioceptive disturbances in both lower limbs at postoperative month 1. The proprioceptive function gradually improved over time, with a gradual decrease in donor site complications.

Tumor Cell-Derived Exosomal miR-191-5p Activates M2-Subtype Macrophages Through SOCS3 to Facilitate Breast Cancer.

Differential activation of macrophages is associated with poor progression of breast cancer (BC). Many reports have elucidated the important involvement of exosomes produced by cancer cells in remodeling the macrophage activation phenotype to promote tumor expansion and invasion. However, the underlying mechanisms by which exosomes secreted by BC cells facilitate macrophage M2 polarization remain enigmatic and worth exploring. In this study, quantitative real-time PCR (RT-qPCR) was used to investigate miR-191-5p expression in BC tumor tissues and cells. Cell counting kit 8 (CCK-8), transwell, and flow cytometry were applied to assess the functional role of miR-191-5p in BC. Isolated nano-vesicles were identified using transmission electron microscopy and western blotting. We also observed that miR-191-5p was significantly elevated in BC clinical samples and that inhibition of miR-191-5p hindered the growth and metastasis of BC cells. Importantly, BC cells successfully accelerated macrophage M2-like polarization by directly transferring exosomes to macrophages, resulting in increased miR-191-5p levels in macrophages. Mechanistically, exosomal miR-191-5p directly inhibited the suppressors of cytokine signaling 3 (SOCS3) expression in macrophages and aggravated macrophage M2 polarization. Similarly, si-SOCS3 transfected macrophages boosted BC cell migration and invasion in a positive feedback manner. Overall, our results manifested a pro-growth and pro-metastatic role between the two cells by elucidating the crucial role of exosomal miR-191-5p in stimulating M2 macrophage polarization and mediating communication between BC cells and macrophages. These findings opened up new horizons for the development of BC therapeutic strategies.