Temporal trends in the prevalence of major birth defects in China: a nationwide population-based study from 2007 to 2021.

BACKGROUND: Birth defects constitute a significant public health issue worldwide, yet there is a lack of comprehensive population-based data for the Chinese population. METHODS: We analyzed data from the China National Population-based Birth Defects Surveillance System from 2007 to 2021, we calculated the prevalence rates of selected birth defects, stratified by maternal residence, geographic region, maternal age, and infant sex. The Joinpoint regression model was utilized to assess trends and annual percent changes in prevalence. RESULTS: From 2007 to 2021, significant downward trends in prevalence were observed for neural tube defects (NTDs), hydrocephalus, cleft lip with or without palate (CL/P), limb reduction defects (LRD), omphalocele, Down syndrome, and tetralogy of Fallot (TOF). Conversely, upward trends were identified for hypospadias, cleft palate (CP), microtia/anotia, polydactyly, syndactyly, ventricular septal defect (VSD), atrial septal defect/patent foramen ovale (ASD/PFO), and patent ductus arteriosus (PDA). Younger mothers exhibited a higher prevalence of hydrocephalus, gastroschisis, CL/P, and polydactyly, while anotia/microtia, Down syndrome, and congenital heart diseases (CHDs) were more common in mothers aged 35 years or older. Significant variations in the prevalence of anencephalus, spina bifida, CL/P, anorectal atresia/stenosis, hypospadias, polydactyly, syndactyly, VSD, ASD/PFO, and PDA were found across different maternal residences and geographic regions. CONCLUSION: This study highlights the diverse trends and prevalence patterns of major birth defects, underscoring the necessity for defect-specific public health interventions.

Recent Advances in Bonding Regulation of Metalloporphyrin-Modified Carbon-Based Catalysts for Accelerating Energy Electrocatalytic Applications.

Metalloporphyrins modified carbon-based materials, owing to the excellent acid-base resistance, optimal electron transfer rates, and superior catalytic performance, have shown great potential in energy electrocatalysis. Recently, numerous efforts have concentrated on employing carbon-based substrates as platforms to anchor metalloporphyrins, thereby fabricating a diverse array of composite catalysts tailored for assorted electrocatalytic processes. However, the interplay through bonding regulation of metalloporphyrins with carbon materials and the resultant enhancement in catalyst performance remains inadequately elucidated. Gaining an in-depth comprehension of the synergistic interactions between metalloporphyrins and carbon-based materials within the realm of electrocatalysis is imperative for advancing the development of innovative composite catalysts. Herein, the review systematically classifies the binding modes (i.e., covalent grafting and non-covalent interactions) between carbon-based materials and metalloporphyrins, followed by a discussion on the structural characteristics and applications of metalloporphyrins supported on various carbon-based substrates, categorized according to their binding modes. Additionally, this review underscores the principal challenges and emerging opportunities for carbon-supported metalloporphyrin composite catalysts, offering both inspiration and methodological insights for researchers involved in the design and application of these advanced catalytic systems.

Unraveling the neuroprotective potential of scalp electroacupuncture in ischemic stroke: A key role for electrical stimulation.

This study aims to explore the neuroprotective effects of scalp Electroacupuncture (EA) on ischemic stroke, with a specific focus on the role of electrical stimulation (ES). Employing a rat model of middle cerebral artery occlusion (MCAO), we used methods such as Triphenyl tetrazolium chloride staining, micro-CT scanning, Enzyme linked immunosorbent assay (ELISA), and immunofluorescence to assess the impacts of EA. We further conducted RNA-seq analysis and in vitro experiments with organotypic brain slices and cerebral organoids to explore the underlying mechanisms. Our research revealed that EA notably reduced cerebral infarct volume and improved regional cerebral blood flow in rats following MCAO. Micro-CT imaging showed improved vascular integrity in EA-treated groups. Histological analyses, including HE staining, indicated reduced brain tissue damage. ELISA demonstrated a decrease in pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, suggesting improved blood-brain barrier function. Immunofluorescence and Western blot analyses revealed that EA treatment significantly inhibited microglial and astrocytic overactivation. RNA-seq analysis of brain tissues highlighted a downregulation of immune pathways and inflammatory responses, confirming the neuroprotective role of EA. This was further corroborated by in vitro experiments using organotypic brain slices and cerebral organoids, which showcased the efficacy of electrical stimulation in reducing neuroinflammation and protecting neuronal cells. The study highlights the potential of scalp EA, particularly its ES component, in treating ischemic stroke. It provides new insights into the mechanisms of EA, emphasizing its efficacy in neuroprotection and modulation of neuroinflammation, and suggests avenues for optimized treatment strategies in stroke therapy.

Providing Insight for Pediatric Ear Surgery: Analysis of Middle Ear Development via HRCT.

OBJECTIVES: Providing insight for pediatric ear surgery via investigations on the development patterns of ossicles, mastoid, and external auditory canal (EAC). METHODS: This retrospective study analyzed high-resolution computed tomography (HRCT) scans of 191 healthy temporal bones ranging from infants to adults. Subjects were grouped by 1-year intervals for developmental regression models and 3-year intervals for stage comparisons using t-tests or Mann-Whitney U tests. RESULTS: The size of auditory ossicles and tympanic cavity (TC) remained stable during development, while the minimum diameter of the tympanic sinus (TS) entrance was reduced. Regarding mastoid pneumatization, the air cells can be observed at birth, became pronounced at 2 years old, and were fully developed around the age of 5, with subsequent growth primarily involving radial expansion. Furthermore, the EAC demonstrated significant growth with age: the width of EAC increased linearly ( y ̂ $$ \hat{y} $$ = 0.12x + 4.01, R2 = 0.85), while the length of EAC followed a polynomial growth pattern ( y ̂ $$ \hat{y} $$ = -0.03x2 + 1.15x + 6.25, R2 = 0.96). CONCLUSIONS: Ossicles and TC remain stable during development. Furthermore, mastoid air cells may have developed in the early stages of life, while their diameter increases synchronously with EAC. All in all, ossicular chain reconstruction surgery and endoscopic ear surgery can be performed in babies. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

snPATHO-seq, a versatile FFPE single-nucleus RNA sequencing method to unlock pathology archives.

Formalin-fixed paraffin-embedded (FFPE) samples are valuable but underutilized in single-cell omics research due to their low RNA quality. In this study, leveraging a recent advance in single-cell genomic technology, we introduce snPATHO-seq, a versatile method to derive high-quality single-nucleus transcriptomic data from FFPE samples. We benchmarked the performance of the snPATHO-seq workflow against existing 10x 3' and Flex assays designed for frozen or fresh samples and highlighted the consistency in snRNA-seq data produced by all workflows. The snPATHO-seq workflow also demonstrated high robustness when tested across a wide range of healthy and diseased FFPE tissue samples. When combined with FFPE spatial transcriptomic technologies such as FFPE Visium, the snPATHO-seq provides a multi-modal sampling approach for FFPE samples, allowing more comprehensive transcriptomic characterization.

Multi-Strategy Improved Harris Hawk Optimization Algorithm and Its Application in Path Planning.

Path planning is a key problem in the autonomous navigation of mobile robots and a research hotspot in the field of robotics. Harris Hawk Optimization (HHO) faces challenges such as low solution accuracy and a slow convergence speed, and it easy falls into local optimization in path planning applications. For this reason, this paper proposes a Multi-strategy Improved Harris Hawk Optimization (MIHHO) algorithm. First, the double adaptive weight strategy is used to enhance the search capability of the algorithm to significantly improve the convergence accuracy and speed of path planning; second, the Dimension Learning-based Hunting (DLH) search strategy is introduced to effectively balance exploration and exploitation while maintaining the diversity of the population; and then, Position update strategy based on Dung Beetle Optimizer algorithm is proposed to reduce the algorithm's possibility of falling into local optimal solutions during path planning. The experimental results of the comparison of the test functions show that the MIHHO algorithm is ranked first in terms of performance, with significant improvements in optimization seeking ability, convergence speed, and stability. Finally, MIHHO is applied to robot path planning, and the test results show that in four environments with different complexities and scales, the average path lengths of MIHHO are improved by 1.99%, 14.45%, 4.52%, and 9.19% compared to HHO, respectively. These results indicate that MIHHO has significant performance advantages in path planning tasks and helps to improve the path planning efficiency and accuracy of mobile robots.

A new model for the inference of biological entities states: Ternary Entity State Inference System.

Understanding the state transitions in biological systems and identifying critical steady states are crucial for investigating disease development and discovering key therapeutic targets. To advance the study of state transitions in specific biological entities, we proposed the Ternary Entity State Inference System (T-ESIS). T-ESIS builds upon the Entity State Inference System by providing richer information on entity states, where states can take values of 0, 1, or 1/2, representing activation, inhibition, and normal states, respectively. This method infers state transition pathways based on interaction relationships and visualizes them through the Entity State Network. Furthermore, the cyclic structures within the Entity State Network capture positive and negative feedback loops, providing a topological foundation for the formation of steady states. To demonstrate the applicability of T-ESIS, entity states were modeled, and attractor analysis was conducted in non-small cell lung cancer (NSCLC) networks. Our analysis provided valuable insights into targeted therapy for NSCLC, highlighting the potential of T-ESIS in uncovering therapeutic targets and understanding disease mechanisms. Moreover, the proposed T-ESIS framework facilitated the inference of entity state transitions and the analysis of steady states in biological systems, offering a novel approach for studying the dynamic principles of these systems. This ternary dynamic modeling approach not only deepened our understanding of biological networks but also provided a methodological reference for future research in the field.

Au Nanorings/TiO2 NPs@MXene-Based Metasurfaces with a Magnetic Mirror-Modulated ECL Strategy for Extracellular Vesicle Detection.

A metasurface as an artificial electromagnetic structure can concentrate optical energy into nanometric volumes to strongly enhance the light-matter interaction, which has been becoming a powerful platform for optical sensing, nonlinear effects, and quantum optics. Herein, we developed a novel hybrid plasmonic-dielectric metasurface consisting of Au nanorings (Au NRs) and TiO2 nanoparticles derived from MXene (TiO2 NPs@MXene). The hybrid metasurface simultaneously benefited from the high near-field enhancement effect of plasmonic materials and the low loss of dielectric materials. Furthermore, the optical modulation efficiency of the hybrid metasurface can be regulated by a magnetic mirror configuration. The magnetic mirror acted like a mirror, confining the electrons to a limited region and increasing the density of the surface plasmon. Moreover, the electrochemiluminescence (ECL) of the Cu2BDC metal-organic framework (Cu2BDC-MOF) served as a light source for the Au NRs/TiO2 NPs@MXene metasurface. Due to the exceptional light manipulation capability of the hybrid metasurface and the coordination of the magnetic mirror, the isotropic ECL signal can be dynamically amplified and converted into polarized emission. Finally, a metasurface-regulated ECL (MECL)-based biosensor with a dual-positive membrane protein recognition strategy was developed for the accurate identification of gastric cancer-derived extracellular vesicles. The novel MECL research opened up a new route in the realization of dynamically tunable metasurfaces for optical sensing and novel nanophotonic devices.

Causal effect of air pollution on the risk of brain health and potential mediation by gut microbiota.

OBJECTIVE: Epidemiologic investigations have examined the correlation between air pollution and neurologic disorders and neuroanatomic structures. Increasing evidence underscores the profound influence of the gut microbiota on brain health. However, the existing evidence is equivocal, and a causal link remains uncertain. This study aimed: to determine if there is a causal connection between four key air pollutants, and 42 neurologic diseases, and 1325 distinct brain structures; and to explore the potential role of the gut microbiota in mediating these associations. METHODS: Univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) models were deployed to estimate the causal impact of air pollutants (including particulate matter [PM] with aerodynamic diameters <2.5 µm [PM2.5], and <10 µm [PM10]; PM2.5 absorbance; and nitrogen oxides [NOx]) on brain health through various Mendelian randomization methodologies. Lastly, the mediating role of the gut microbiome in the connections between the identified pollutants and neurologic diseases and brain structures was systematically examined. RESULTS: The potential causal associations of PM2.5, PM2.5 absorbance, PM10, and exposure to NOx, with the risks of intracerebral hemorrhage, hippocampal perivascular spaces, large artery strokes, generalized epilepsy with tonic-clonic seizures, Alzheimer's disease, multiple sclerosis, anorexia nervosa, post-traumatic stress disorder (PTSD), and 420 brain structures, were investigated by UVMR analysis. Following adjustment for air pollutants by MVMR analysis, the genetic correlations between PM10 exposure and PTSD and multiple sclerosis remained significant and robust. Importantly, we observed that phylum Lentisphaerae may mediate the association between PM10 and multiple sclerosis. Additionally, PM2.5 absorbance with a greater risk of reduced thickness in the left anterior transverse temporal gyrus of Heschl and a decreased area in the right sulcus intermedius primus of Jensen, mediated by genus Senegalimassilia and genus Lachnospiraceae UCG010, respectively. Finally, we provided evidence that Clostridium innocuum and genus Ruminococcus2 may partly mediate the causal effect of NOx on altered thickness in the left transverse temporal cortex and area in the right sulcus intermedius primus of Jensen, respectively. CONCLUSION: This study established a genetic connection between air pollution and brain health, implicating the gut microbiota as a potential mediator in the relationship between air pollution, neurologic disorders, and altered brain structures.

Copper-Surface-Mediated Synthesis of sp2 Carbon-Conjugated Covalent Organic Framework Photocathodes for Photoelectrochemical Hydrogen Evolution.

Sp2-carbon (sp2-c) covalent organic frameworks (COFs), featuring distinctive π-conjugated network structures, facilitate the migration of photo-generated carriers, rendering them exceptionally appealing for applications in photoelectrochemical water splitting. However, owing to the powdery nature of COFs, leaving anchor the sp2-c COFs powder tightly onto a conductive substrate challenging. Here, we propose a method for preparing photoactive substance-conductive substrate integrated photocathodes through copper surface-mediated knoevenagel polycondensation (Cu-SMKP), this approach results in a uniform and stable sp2-c COF film, directly grown on commercial copper foam (COFTh-Cu). The COFTh-Cu demonstrates a high H2-evolution photocurrent density of 56 µA cm-2 at 0.3 V vs. RHE, sustaining stability for 12 h. The as-prepared COFTh-Cu represents a 4.5-fold increase in current density compared to traditional spin-coating methods and outperforms most COF photocathodes without cocatalysts. This innovative copper surface-mediated approach for preparing photocathodes opens up a crucial pathway towards the realization of highly active COF photocathodes.

Swertianin Promotes Anti-Tumor activity by facilitating Macrophage M1 polarization via STING signaling.

To investigate the mechanism by which swertiamarin (swertianin, SWE) regulates the polarization of tumor microenvironment-associated macrophages to M1 phenotype, thereby exerting anti-tumor effects.SWE promoted the formation of M1 cells and increased the proportion of CD86 + cells in both RAW264.7 and primary monocyte-derived macrophages, while activating the STING-NF-κB pathway. When STING or P65 was knocked out, the effects of SWE were antagonized, inhibiting the formation of CD86 + M1 cells. At the animal level, SWE inhibited tumor growth, activated STING-NF-κB, and promoted the formation of CD86 + cells. STING-KO inhibited the effects of SWE.SWE can activate the STING-NF-κB signal to promote macrophage M1 polarization, playing an anti-tumor role.

Descriptive epidemiology of gastroschisis in China from 2007 to 2020: a nationwide surveillance-based study.

BACKGROUND: Gastroschisis is a common abdominal wall defect that increases infant mortality risk and health care costs. However, recent epidemiological data on gastroschisis in China is limited. METHODS: Using 2007-2020 data from the Chinese Birth Defects Monitoring Network (CBDMN), we analyzed gastroschisis prevalence rates stratified by birth year, maternal age group, residence area, geographical region, and infant sex. We also examined the temporal variations in prevalence, pregnancy outcomes of affected infants, prenatal diagnoses, and co-occurring anomalies. RESULTS: From 2007 to 2020, a total of 6,813 cases of gastroschisis were identified among 25,909,000 births, comprising 4,675 isolated and 2,138 non-isolated cases. Prevalence rates per 10,000 live and still births were 2.63, 1.80, and 0.83 for the overall, isolated, and non-isolated gastroschisis, respectively, all showing a decreasing trend over the study period. The prevalence of overall gastroschisis varied significantly by maternal age (< 20 years, 9.88/10,000; 20-24 years, 4.17/10,000; 25-29 year, 2.08/10,000; 30-34 years, 1.88/10,000;≥35 years, 2.24/10,000), maternal residence (urban, 2.45/10,000; rural, 2.85/10,000), geographic region (central, 2.54/10,000; east, 2.57/10,000; west, 2.80/10,000), and infant sex (male, 2.13/10,000; female, 1.79/10,000). Non-isolated gastroschisis cases had a higher early neonatal mortality rate than isolated cases (41.91% vs. 28.10%) and frequently co-occurred with musculoskeletal anomalies. CONCLUSIONS: This study highlights a declining trend in gastroschisis prevalence in Chinese population, a contrast to previous studies, and underscores the need for improved perinatal management due to adverse pregnancy outcomes associated with this condition.

Ginsenoside RD prevents acute liver injury in mice by inhibiting STAT3-mediated NLRP3/GSDMD activation.

We investigated the role and mechanism of ginsenoside RD (GRD) in acute liver injury. Network pharmacology was used to analyze the correlations among GRD-liver injury-pyroptosis targets. A mouse model of acute liver injury was established by lipopolysaccharide + d-galactose（LPS + d/Gal). After pretreatment with GRD, the changes in mouse liver function were detected. The histopathological changes were assayed by hematoxylin and eosin and Masson staining, the tissue expressions of inflammatory cytokines were detected by enzyme-linked immunosorbent assay, and the protein expressions were assayed by immunohistochemical staining and Western blotting. Meanwhile, mechanism research was conducted using STAT3-knockout transgenic mice and STAT3-IN13, a STAT3 inhibitor. GRD inhibited liver injury, mitigated tissue inflammation, and suppressed STAT3-mediated pyroptosis in mice. After applying STAT3-knockout mouse model or STAT3-IN13, GRD did not further inhibit the liver injury. GRD can resist liver injury by inhibiting the STAT3-mediated pyroptosis, which is one of the hepatoprotective mechanisms of GRD.

Novel biomimetic hybrid plasmonic nanocavity-based ECL strategy for the detection of extracellular vesicles.

Tumor-derived extracellular vesicles detection has emerged as an important clinical liquid biopsy approach for cancer diagnosis. In this work, we developed a novel hybrid plasmonic nanocavity consisting of hexagonal Au nanoplates nanoarray, SnS2/Au nanosheet layer and biomimetic lipid bilayer. Firstly, the hybrid plasmonic nanocavity combined the optical confinement for the ECL regulation and the biological recognition for the detection of extracellular vesicles. Secondly, MXene-derived Ti2N QDs have been prepared as ECL nanoprobe to label extracellular vesicles. Moreover, biomimetic lipid bilayer with specific aptamer was used to identify extracellular vesicles and integrate Ti2N QDs into the nanocavity with membrane fusion strategy. Due to the significant electromagnetic field enhancement at the cavity region, the hybrid plasmonic nanocavity provided strong field confinement to concentrate and redistribute the ECL emission of QDs with a 9.3-fold enhancement. The hybrid plasmonic nanocavity-based ECL sensing system improved the spatial controllability of EVs analysis and the accurate resolution of specific protein. It achieved the sensitive detection of extracellular vesicles in ascites and successfully distinguished the peritoneal metastasis of gastric cancer.

The long-term efficacy and safety of balloon dilation eustachian tuboplasty combined with tympanostomy tube insertion for patients with otitis media with effusion: study protocol for a prospective randomized controlled trial.

BACKGROUND: Otitis media with effusion (OME) is a common disease in ear, nose, and throat clinics characterized by aural fullness and hearing loss and mainly caused by eustachian tube dysfunction (ETD). Tympanostomy tube insertion (TTI) is a conventional surgical treatment option that can alleviate symptoms but does not provide a definitive cure, and it is prone to recurrence. Balloon dilation eustachian tuboplasty (BDET) has become a novel procedure for the treatment of ETD, demonstrating significant potential in addressing the aforementioned limitations. However, it is not widely available in the clinic and few high-quality randomized clinical trials was conducted to investigate its long-term efficacy and security in OME. Therefore, the purpose of this study is to verify the efficacy of BDET combined with TTI for patients with OME and its prospects for providing a definitive cure. METHODS AND ANALYSIS: This is a prospective, parallel-group, single-blind, randomized controlled prospective trial. Totally 124 patients with OME will be randomized into either group A or B. Group A will receive conventional therapy (TTI) while group B will use BDET therapy in addition to TTI. Outcome assessments will take place at baseline and at the 3rd, 6th, 12th, and 24th months after surgery. The primary outcome is eustachian tube function, which will be measured by the eustachian tube dysfunction questionnaire (ETDQ-7) and eustachian tube score (ETS). The secondary outcomes include middle ear function, hearing situation, and quality of life, which will be measured by acoustic impedance measurement, pure-tone audiometry, and Chinese-version Chronic Ear Survey (CCES). The main analysis of change in the outcomes will use mixed-model with repeated measures (MMRM) analyses of variance (ANOVAs). DISCUSSION: This is the first prospective trial in Chinese populations that aims to validate the long-term efficacy and safety of BDET-combined TTI therapy in patients with OME. This parallel-group, single-blind, randomized controlled trial may provide an opportunity to decrease the recurrence rate of OME and explore a definitive cure for patients with OME. This trial's rigorous design enhances the reliability of the findings, ensuring a robust answer to the research question. In the future, the research team will further expand upon the clinical evidence and applications of the BDET combined therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400079632. Registered on 8 January 2024, https://www.chictr.org.cn/bin/project/edit?pid=214452 .

Structural basis for linker histone H5-nucleosome binding and chromatin fiber compaction.

The hierarchical packaging of chromatin fibers plays a critical role in gene regulation. The 30-nm chromatin fibers, a central-level structure bridging nucleosomal arrays to higher-order organizations, function as the first level of transcriptional dormant chromatin. The dynamics of 30-nm chromatin fiber play a crucial role in biological processes related to DNA. Here, we report a 3.6-angstrom resolution cryogenic electron microscopy structure of H5-bound dodecanucleosome, i.e., the chromatin fiber reconstituted in the presence of linker histone H5, which shows a two-start left-handed double helical structure twisted by tetranucleosomal units. An atomic structural model of the H5-bound chromatin fiber, including an intact chromatosome, is built, which provides structural details of the full-length linker histone H5, including its N-terminal domain and an HMG-motif-like C-terminal domain. The chromatosome structure shows that H5 binds the nucleosome off-dyad through a three-contact mode in the chromatin fiber. More importantly, the H5-chromatin structure provides a fine molecular basis for the intra-tetranucleosomal and inter-tetranucleosomal interactions. In addition, we systematically validated the physiological functions and structural characteristics of the tetranucleosomal unit through a series of genetic and genomic studies in Saccharomyces cerevisiae and in vitro biophysical experiments. Furthermore, our structure reveals that multiple structural asymmetries of histone tails confer a polarity to the chromatin fiber. These findings provide structural and mechanistic insights into how a nucleosomal array folds into a higher-order chromatin fiber with a polarity in vitro and in vivo.

Astragalin improves cognitive disorder in Alzheimer's disease: Based on network pharmacology and molecular docking simulation.

We investigate the mechanism of action of astragalin (AST) in the treatment of Alzheimer's disease (AD). Network pharmacology was conducted to analyze the relationships among AST, AD, and neuroinflammation, The APP/PS1 transgenic mice with AD were used in the experiments; to be specific, the influence of AST on the behavior of mice was analyzed by Morris water maze and eight-arm radial maze tests, the tissue inflammatory factor levels were detected by ELISA, and pathological changes were analyzed by H&E and immunohistochemical staining. Analysis results of network pharmacology suggested that AST exerted the multi-target effect on neuroinflammation in AD. Through molecular docking and dynamics analyses, COX2 might be the target of AST. Moreover, animal experimental results demonstrated that AST improved the behavior of AD mice, and enhanced the motor and memory abilities, meanwhile, it suppressed the expression of inflammatory factors in tissues and the activation of microglial cells. this study discovers that AST can suppress microglial cell activation via COX2 to improve neuroinflammation in AD.

The sEVs miR-487a/Notch2/GATA3 axis promotes osteosarcoma lung metastasis by inducing macrophage polarization toward the M2-subtype.

Small extracellular vesicles (sEVs) are important mediators of intercellular communication between tumor cells and their surrounding environment. Furthermore, the mechanisms by which miRNAs carried in tumor sEVs regulate macrophage polarization remain largely unknown. To concentrate sEVs, we used the traditional ultracentrifugation method. Western blot, NanoSight, and transmission electron microscopy were used to identify sEVs. To determine the function of sEVs-miR-487a, we conducted in vivo and in vitro investigations. The intercellular communication mechanism between osteosarcoma cells and M2 macrophages, mediated by sEVs carrying miR-487a, was validated using luciferase reporter assays, transwell assays, and Western blot analysis. In vitro, sEVs enriched in miR-487a and delivered miR-487a to macrophages, promoting macrophage polarization toward an M2-like type, which promotes proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. In vivo, sEVs enriched in miR-487a facilitate lung metastasis of osteosarcoma. Moreover, plasma miR-487a in sEVs was shown to be a potential biomarker applicable for osteosarcoma diagnosis. In summary, miR-487a derived from osteosarcoma cells can be transferred to macrophages via sEVs, then promote macrophage polarization towards an M2-like type by targeting Notch2 and activating the GATA3 pathway. In a feedback loop, the activation of macrophages accelerates epithelial-mesenchymal transition (EMT), which in turn promotes the migration, invasion, and lung metastasis of osteosarcoma cells. This reciprocal interaction between activated macrophages and osteosarcoma cells contributes to the progression of the disease. Our data demonstrate a new mechanism that osteosarcoma tumor cells derived exosomal-miR-487a which is involved in osteosarcoma development by regulating macrophage polarization in tumor microenvironment (TME).

The effect of fascial manipulation therapy on lower limb spasticity and ankle clonus in stroke patients.

Lower limb spasticity and clonus are common sequelae after cerebral stroke. An important part of their etiopathogenesis has been related to the peripheral component of spasticity. Rheological properties of the tissues seem to be involved. Several studies highlighted anatomical and functional changes in the connective structures. The fasciae might be implicated in the pathological process. Thus, this study intends to investigate the effect of the Fascial Manipulation (FM) technique on triceps surae in stroke patients through a clinical randomized controlled trial, to provide a reference for clinical treatment of lower limb spasticity and ankle clonus. A total of 40 patients with post-stroke ankle clonus were selected and divided into a control group and an observation group by random number table method, with 20 cases in each group. Both groups received conventional rehabilitation therapy, while the FM group received Fascial Manipulation based on conventional rehabilitation therapy. Before the first treatment and after 3 weeks of treatment, the Comprehensive Spasticity Scale (CSS), the Passive Range Of Motion (PROM), the simplified Fugl-Meyer motor function score (FMA), and the Modified Ashworth Scale (MAS) were used to assess the degree of ankle clonus, ankle passive range of motion, and lower limb motor function of the two groups of patients. Before treatment, there was no statistically significant difference between the control group and the FM group in terms of CSS, PROM, FMA, and MAS of the affected lower limbs (P>0.05). After 3 weeks of treatment, the CSS and MAS of the affected lower limbs in the control group and FM group decreased, while PROM and FMA increased compared to pre-treatment evaluation, with statistically significant differences (P<0.05). Moreover, the FM group showed a statistically significant decrease in CSS and MAS, as well as an increase in PROM and FMA, compared to the control group (P<0.05). Conclusions: Fascial manipulation in addition to conventional therapy can effectively reduce spasticity and ankle clonus in stroke patients in a short time, and improve the passive range of motion of the ankle joint and the function of lower limbs.