Investigation of the safety and protective efficacy of an attenuated and marker M. bovis-BoHV-1 combined vaccine in bovines.

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.

Longitudinal vibration control of a double-rod system by employing nonlinear energy sinks.

This study aims to potential the potential utilization of nonlinear energy sinks (NESs) for controlling longitudinal vibrations in a double-rod system. The research introduces a longitudinal vibration prediction model for a double-rod system equipped with NESs. The generalized Hamilton principle is employed to derive governing equations of the double-rod system. The longitudinal vibration responses of the double-rod system are numerically solved through the application of Galerkin truncation method. The longitudinal vibration responses of the double-rod system are impacted by NESs, as they yield accurate numerical results. The installation of both NES 1 and NES 2 concurrently is recommended for mitigating the vibration of the double-rod system. Under reasonable single-frequency excitations, modifying the parameters of NESs can significantly alter both the vibration state and magnitudes of vibration in the double-rod system. Furthermore, the synchronous optimization of parameters in NES 1 and NES 2 is crucial for effectively controlling vibrations in the double-rod system. Sensitive parameter areas of NESs provide the possibility of controlling the vibration of the double-rod system by utilizing NESs.

A study of analyzing longitudinal dynamic behavior of a double-rod system with longitudinal nonlinear supports.

In engineering, shafting systems are typically subjected to longitudinal vibration excitations, which may result in unwanted vibration. To study the control of longitudinal vibration in shafting systems, they can be simplified to rod structures. Currently, engineers have attempted to apply the nonlinear principle to design nonlinear supports to control the vibration of flexible structures. However, the flexible structures referenced in the literature are usually composed of a single component, which limits the application of nonlinear supports to more complex structures. To explore the potential application of nonlinear supports in marine engineering, this work introduces a longitudinal vibration prediction model for a double-rod system equipped with longitudinal nonlinear supports. The generalized Hamilton principle is used to derive the governing equations for the double-rod system with longitudinal nonlinear supports. The longitudinal vibration responses of the double-rod system are numerically solved using the Galerkin truncation method. The numerical results confirm that a 1-term truncation number guarantees the stability of the longitudinal vibration prediction model. Under certain conditions, the longitudinal vibration responses are significantly affected by longitudinal nonlinear supports. It is recommended to install longitudinal nonlinear supports on both Rod 1 and Rod 2 simultaneously to suppress vibration in the first two main resonance orders. With reasonable excitations, the vibration state and magnitudes of the double-rod system can be effectively controlled by adjusting the longitudinal nonlinear supports. Complex longitudinal vibration responses are more readily induced by altering the parameters of the longitudinal nonlinear support installed on Rod 1. Choosing appropriate parameters for the nonlinear supports on Rod 1 and Rod 2 positively contributes to the reduction of vibration in the double-rod system.

Prevalence, Molecular Characteristics and Virulence Identification of Bovine Parainfluenza Virus Type 3 in China.

Bovine parainfluenza virus type 3 (BPIV-3) is one of the major pathogens of the bovine respiratory disease complex (BRDC). BPIV-3 surveillance in China has been quite limited. In this study, we used PCR to test 302 cattle in China, and found that the positive rate was 4.64% and the herd-level positive rate was 13.16%. Six BPIV-3C strains were isolated and confirmed by electron microscopy, and their titers were determined. Three were sequenced by next-generation sequencing (NGS). Phylogenetic analyses showed that all isolates were most closely related to strain NX49 from Ningxia; the genetic diversity of genotype C strains was lower than strains of genotypes A and B; the HN, P, and N genes were more suitable for genotyping and evolutionary analyses of BPIV-3. Protein variation analyses showed that all isolates had mutations at amino acid sites in the proteins HN, M, F, and L. Genetic recombination analyses provided evidence for homologous recombination of BPIV-3 of bovine origin. The virulence experiment indicated that strain Hubei-03 had the highest pathogenicity and could be used as a vaccine candidate. These findings apply an important basis for the precise control of BPIV-3 in China.

Land-use change interacts with island biogeography to alter bird community assembly.

Anthropogenic activities have reshaped biodiversity on islands worldwide. However, it remains unclear how island attributes and land-use change interactively shape multiple facets of island biodiversity through community assembly processes. To answer this, we conducted bird surveys in various land-use types (mainly forest and farmland) using transects on 34 oceanic land-bridge islands in the largest archipelago of China. We found that bird species richness increased with island area and decreased with isolation, regardless of the intensity of land-use change. However, forest-dominated habitats exhibited lower richness than farmland-dominated habitats. Island bird assemblages generally comprised species that share more similar traits or evolutionary histories (i.e. functional and/or phylogenetic clustering) than expected if assemblages were randomly assembled. Contrary to our expectations, we observed that bird assemblages in forest-dominated habitats were more clustered on large and close islands, whereas assemblages in farmland-dominated habitats were more clustered on small islands. These contrasting results indicate that land-use change interacts with island biogeography to alter the community assembly of birds on inhabited islands. Our findings emphasize the importance of incorporating human-modified habitats when examining the community assembly of island biota, and further suggest that agricultural landscapes on large islands may play essential roles in protecting countryside island biodiversity.

Diselenide-Containing Polymer Based on New Antitumor Mechanism as Efficient GSH Depletion Agent for Ferroptosis Therapy.

Glutathione (GSH) depletion-induced ferroptosis has emerged as a promising treatment for malignant cancer. It works by inactivating glutathione peroxidase 4 (GPX4) and facilitating lipid peroxidation. However, effectively delivering inducers and depleting intracellular GSH remains challenging due to the short half-lives and high hydrophobicity of small-molecule ferroptosis inducers. These inducers often require additional carriers. Herein, diselenide-containing polymers can consume GSH to induce ferroptosis for pancreatic cancer therapy. The diselenide bonds are controllably built into the backbone of the polycarbonate with a targeting peptide CRGD (Cys-Arg-Gly-Asp), which allows for self-assembly into stable nanoparticles (denoted CRNSe) for self-delivery. Significantly, at a concentration of 12 µg mL-1, CRNSe binds to the active site cysteine of GSH resulting in a thorough depletion of GSH. In contrast, the disulfide-containing analog only causes a slight decrease in GSH level. Moreover, the depletion of GSH inactivates GPX4, ultimately inducing ferroptosis due to the accumulation of lipid peroxide in BxPC-3 cells. Both in vitro and in vivo studies have demonstrated that CRNSe exhibits potent tumor suppressive ability with few side effects on normal tissue. This study validates the anti-tumor mechanism of diselenide-containing polymers in addition to apoptosis and also provides a new strategy for inherently inducing ferroptosis in cancer therapy.

Exosomal hsa_circ_0093884 derived from endothelial progenitor cells promotes therapeutic neovascularization via miR-145/SIRT1 pathway.

Therapeutic neovascularization is a strategy to promote blood vessel growth and improve blood flow, which is critical to tissue repair and regeneration in ischemic diseases. Here, we investigated the role of endothelial progenitor cell - derived exosomes (EPC-Exos) in therapeutic neovascularization and clarified the mechanism of hsa_circ_0093884 in EPC-Exos mediated neovascularization. Injection of EPC-Exos improved mouse ischemic hindlimb perfusion, promoted angiogenesis in Matrigel plugs and mouse skin wound healing. In vitro coculture with EPC-Exos improved HUVEC proliferation, angiogenic and migration ability, while alleviated hypoxia-induced apoptosis. hsa_circ_0093884 was identified from eleven types of circRNA derived from SIRT1 and proved to be enriched in EPC-Exos. Overexpression of hsa_circ_0093884 in EPC-Exos further enhanced the angiogenic capacity, while knockdown of hsa_circ_0093884 abolished the benefits. Mechanistically, EPC-Exos mediated shuttling of hsa_circ_0093884 induced cytoplasmic sponge of miR-145, thereby releasing repression of SIRT1. In vitro co-transfection indicated silence of miR-145 further strengthened the angiogenic effect of hsa_circ_0093884, while overexpression of miR-145 inhibited hsa_circ_0093884 mediated angiogenesis and abolished the beneficial effect of EPC-Exos. Furthermore, in vivo experiments using endothelial specific SIRT1 conditional knockout mice indicated hsa_circ_0093884 overexpressing EPC-Exos failed to promote therapeutic neovascularization in SIRT1cKO mice. Collectively, our results demonstrated that EPC-Exos promoted therapeutic neovascularization through hsa_circ_0093884/miR-145/SIRT1 axis.

Isolation and Characterization of Paenibacillus polymyxa B7 and Inhibition of Aspergillus tubingensis A1 by Its Antifungal Substances.

Screening of Bacillus with antagonistic effects on paddy mold pathogens to provide strain resources for biological control of mold in Oryza sativa L. screening of Bacillus isolates antagonistic towards Aspergillus tubingensis from rhizosphere soil of healthy paddy; classification and identification of antagonistic strains by biological characteristics and 16S rDNA sequence analysis; transcriptome sequencing after RNA extraction from Bacillus-treated Aspergillus tubingensis; and extraction of inhibitory crude proteins of Bacillus by ammonium sulfate precipitation; inhibitory crude protein and Bacillus spp. were treated separately for A. tubingensis and observed by scanning electron microscopy (SEM). An antagonistic strain of Bacillus, named B7, was identified as Paenibacillus polymyxa by 16S rDNA identification and phylogenetic evolutionary tree comparison analysis. Analysis of the transcriptome results showed that genes related to secondary metabolite biosynthesis such as antifungal protein were significantly downregulated. SEM results showed that the mycelium of A. tubingensis underwent severe rupture after treatment with P. polymyxa and antifungal proteins, respectively. In addition, the sporocarp changed less after treatment with P. polymyxa, and the sporangium stalks had obvious folds. P. polymyxa B7 has a good antagonistic effect against A. tubingensis and has potential for biocontrol applications of paddy mold pathogens.

-COOH & -OH Condensation Reaction Utilization for Biomass FDCA-based Polyesters.

A green and sustainable -COOH & -OH condensation solution polymerization method was hereby reported for FDCA-based polyesters to avoid discoloration and toxic solvents. First, taking poly(ethylene 2,5-furandicarboxylate) (PEF) as the representative of FDCA-based polyester, enabling good white appearance PEF with Mn =6.51×103  g mol-1 from FDCA and ethylene glycol in green solvent γ-valerolactone (GVL), catalyzed by 4-dimethylaminopyridine (DMAP) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC). Additionally, the molecular weight of PEF was rapidly improved (Mn >2.5×104  g mol-1 ) via remelting polycondensation within minutes, with the dispersity still kept relatively low dispersity (D<1.40). Importantly, the -COOH & -OH condensation solution polymerization method was successfully applied for the synthesis of various FDCA-based polyesters, including diols with varying carbon chain lengths (3 to 11 carbons) and cycloalkyl diols, especially the applicability of this method to diols containing C=C double bonds, which was found to exhibit low heat resistance. Lastly, assisting with 13 C labeled 1,4-succinic acid and in-situ 13 C-NMR, an in-depth study of the possible catalytic mechanism was proposed, by which, EDC activated FDCA, and then DMAP catalyzed it with diol to yield macromolecular chain of polyester. Overall, the results provided a green and sustainable strategy for the synthesis of FDCA-based polyesters.

Identification of Reduced mTOR T1262 Phosphorylation as a Novel Mechanism and Therapeutic Target of Apoptosis in Senescent Cardiomyocytes: Aging and Cardiomyocyte Apoptosis.

The mechanisms through which aging increases heart injury remain partially understood. Protein phosphorylation plays a critical regulatory role in cell survival and death. Using an unbiased phosphoproteomics approach, we aimed to identify the proteins whose phosphorylation could be causatively related to aging-related cardiomyocyte apoptosis and elucidate the underlying mechanisms. Comparative phosphoproteomics was conducted on cardiac tissues obtained from young (8 weeks) and aged (24 months) mice. Our findings revealed that the Mammalian Target of Rapamycin phosphorylation at T1262 (mTORT1262) was reduced in the aging heart. Immunohistochemical and Western blot analyses confirmed these findings in aging myocardia and D-galactose-induced senescent AC16 cardiomyocytes. In hypoxia/reoxygenation cardiomyocytes, mTORT1262 phosphorylation deficiency (mTORT1262A, lentivirus-mediated transfection) inhibited AKT1, suppressed NF-κB, activated FOXO1/3a signaling, and ultimately exacerbated apoptosis. Conversely, mTORT1262 pseudophosphorylation (mTORT1262E) exhibited opposite effects. Through bioinformatics and CO-IP, purinergic receptor P2X4 (P2X4R) was found to be the possible receptor responsible for mTORT1262 phosphorylation. Knockdown of P2X4R increased apoptosis, whereas its overexpression decreased it. In senescent cardiomyocytes, P2X4R expression and mTORT1262 and AKT1S473 phosphorylation were reduced, NF-κB signaling was suppressed, and FOXO1/3a signaling was activated. We demonstrated that P2X4R downregulation and the subsequent reduction of mTORT1262 phosphorylation is a novel mechanism contributing to cardiomyocyte apoptosis in aging hearts. The P2X4R-mTOR-AKT1 signaling pathway represents a potential therapeutic target against accelerated cardiac injury in aging.

Uncovering widespread Anthropocene dietary shifts in Chinese large mammalian herbivores.

The Anthropocene's human-dominated habitat expansion endangers global biodiversity. However, large mammalian herbivores experienced few extinctions during the 20th century, hinting at potentially overlooked ecological responses of a group sensitive to global change. Using dental microwear as a proxy, we studied large herbivore dietary niches over a century across mainland China before (1880s-1910s) and after (1970s-1990s) the human population explosion. We uncovered widespread and significant shifts (interspecific microwear differences increased and intraspecific microwear dispersion expanded) within dietary niches linked to geographical areas with rapid industrialization and population growth in eastern China. By contrast, in western China, where human population growth was slower, we found no indications of shifts in herbivore dietary niches. Further regression analysis links the intensity of microwear changes to human land-use expansion. These analyses highlight dietary adjustments of large herbivores as a likely key factor in their adaptation across a century of large-scale human-driven changes.

A multi-center, single-blinded, randomized, parallel-group, superiority study to compare the efficacy of manipulation under anesthesia versus intra-articular steroid injection in the treatment of patients with frozen shoulder and a diagnosis of rotator cuff injury or tear by MRI: study protocol for a randomized controlled trial.

BACKGROUND: Frozen shoulder (FS) is a common condition that can cause severe pain and limited range of motion in the shoulder joint. While intra-articular steroid injection has been shown to be an effective treatment for FS, manipulation under anesthesia (MUA) is an alternative treatment that has gained popularity in recent years. However, there is a lack of evidence regarding the effectiveness of MUA on FS patients with concomitant rotator cuff injury or tear. Though a few studies have shown that MUA is not associated with rotator cuff tears, and will not exacerbate the injury, more high-quality studies with bigger sample sizes are needed. Therefore, the aim of this multi-center, single-blinded, randomized, parallel-group, superiority study is to compare the efficacy of MUA versus intra-articular steroid injection in the treatment of FS patients with a diagnosis of rotator cuff injury or tear by MRI. METHODS: A parallel, single-blinded, multi-center randomized controlled trial of 320 patients will be conducted at three hospitals of China. Eligible patients with frozen shoulder and rotator cuff injury or tear diagnosed by MRI will be randomly assigned to, in equal proportions, the manipulation under anesthesia group and the intra-articular steroid injection group via a central randomization system, undergoing a corresponding operation on day one and a sequent physical exercise for 14 days. The primary outcome is the comprehensive efficacy evaluation (total effective rate) and the change of Constant-Murley Score. Outcome assessors and data analysts will be blinded, and participants will be asked not to reveal their allocation to assessors. DISCUSSION: This study aims to explore the superiority of manipulation under anesthesia in reducing pain and improving shoulder function in frozen shoulder patients accompanied with rotator cuff injury. To provide a scientific basis for the dissemination and application of manipulation under anesthesia, and a better knowledge for the role of MUA in the treatment of frozen shoulder accompanied with rotator cuff injury. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2200067122 . Registered on 27 December 2022. ChiCTR is a primary registry of the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) network and includes all items from the WHO Trial Registration data set in Trial registration.

Habitat fragmentation increases specialization of multi-trophic interactions by high species turnover.

Habitat fragmentation is altering species interactions worldwide. However, the mechanisms underlying the response of network specialization to habitat fragmentation remain unknown, especially for multi-trophic interactions. We here collected a large dataset consisting of 2670 observations of tri-trophic interactions among plants, sap-sucking aphids and honeydew-collecting ants on 18 forested islands in the Thousand Island Lake, China. For each island, we constructed an antagonistic plant-aphid and a mutualistic aphid-ant network, and tested how network specialization varied with island area and isolation. We found that both networks exhibited higher specialization on smaller islands, while only aphid-ant networks had increased specialization on more isolated islands. Variations in network specialization among islands was primarily driven by species turnover, which was interlinked across trophic levels as fragmentation increased the specialization of both antagonistic and mutualistic networks through bottom-up effects via plant and aphid communities. These findings reveal that species on small and isolated islands display higher specialization mainly due to effects of fragmentation on species turnover, with behavioural changes causing interaction rewiring playing only a minor role. Our study highlights the significance of adopting a multi-trophic perspective when exploring patterns and processes in structuring ecological networks in fragmented landscapes.

Joint associations of asthma and sleep duration with cardiovascular disease and all-cause mortality: a prospective cohort study.

PURPOSE: This study aimed to investigate the joint association of asthma and sleep duration with cardiovascular disease (CVD) and mortality risk. METHODS: This prospective cohort study included 366,387 participants from the UK Biobank. The participants were divided into three groups based on their sleep duration (short: <7 h/d; referent: 65+ years: 7-8 h/d; ages 39-64 years: 7-9 h/d; and long: 65+ years: >8 h/d; ages 39-64 years: >9 h/d). Cox proportional hazards models were used to examine the association between asthma and sleep duration on CVD and all-cause mortality. RESULTS: Participants with asthma and short sleep duration showed increased risk of CVD (hazard ratio [HR] 1.42; 95% confidence interval [CI] 1.34-1.51) and all-cause mortality (HR, 1.26; 95% CI, 1.17-1.36), compared with participants with no asthma in the referent sleep duration group. We documented significant additive interactions between asthma and short sleep duration in relation to CVD (relative excess risk due to interaction [RERI], 0.13; 95% CI, 0.04-0.23) and all-cause mortality (RERI, 0.12; 95% CI, 0.01-0.23). CONCLUSIONS: Asthma and short sleep duration may have additive interactions on CVD and all-cause mortality risk, highlighting the importance of controlling asthma in combination with improving sleep duration.

Structural properties of the Late Pleistocene Liujiang femoral diaphyses from southern China.

The characterization of the femoral diaphysis in Pleistocene hominins with chronoecogeographical diversity plays a crucial role in evaluating evolutionary shifts in locomotor behavior and body shape. However, Pleistocene hominin fossil remains in East Asia are scarce and are widely dispersed temporally and spatially, impeding our comprehension of the nature and polarity of morphological trends. Here, we present qualitative and quantitative analyses of the cross-sectional properties and structural organization of diaphyses in two Late Pleistocene hominin femora (Liujiang PA91 and PA92) from southern China, comparing them to other Eurasian and African Pleistocene hominins. By integrating surface features and internal structure, our findings reveal that the Liujiang femora exhibit modern human-like characteristics, including a developed pilaster, a gluteal buttress, and minimum mediolateral breadth located at the midshaft. The presence of a femoral pilaster may relate to posterior cortical reinforcement and an increased anteroposterior bending rigidity along the mid-proximal to mid-distal portion of the diaphysis. Compared to archaic Homo, Liujiang and other Late Pleistocene modern human femora show a thinner mediolateral cortex and lower bending rigidity than the anteroposterior axis, and a lack of medial buttress, potentially indicating functionally related alterations in a range of pelvic and proximal femoral features throughout the Pleistocene. The femoral robusticity of the Liujiang individual resembles that of other Pleistocene hunter-gatherers from East Asia, implying comparable overall mobility or activity levels. The investigation of Liujiang femoral diaphyseal morphology contributes to a more comprehensive understanding of early modern human postcranial structural morphology in East Asia.

Advances in immunotherapy for biliary tract cancers.

ABSTRACT: Biliary tract cancers (BTC) are a heterogeneous disease with poor prognosis, including gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC). Although surgery is currently the primary regimen to treat BTC, most BTC patients are diagnosed at an advanced stage and miss the opportunity of surgical eradication. As a result, non-surgical therapy serves as the main intervention for advanced BTC. In recent years, immunotherapy has emerged as the one of the most promising therapies in a number of solid cancers, and it includes immune checkpoint inhibitors (ICIs) monotherapy or combined therapy, tumor vaccines, oncolytic virus immunotherapy, adoptive cell therapy (ACT), and cytokine therapy. However, these therapies have been practiced in limited clinical settings in patients with BTC. In this review, we focus on the discussion of latest advances of immunotherapy in BTC and update the progress of multiple current clinical trials with different immunotherapies.

Artificial intelligence based multimodal language decoding from brain activity: A review.

Decoding brain activity is conducive to the breakthrough of brain-computer interface (BCI) technology. The development of artificial intelligence (AI) continually promotes the progress of brain language decoding technology. Existent research has mainly focused on a single modality and paid insufficient attention to AI methods. Therefore, our objective is to provide an overview of relevant decoding research from the perspective of different modalities and methodologies. The modalities involve text, speech, image, and video, whereas the core method is using AI-built decoders to translate brain signals induced by multimodal stimuli into text or vocal language. The semantic information of brain activity can be successfully decoded into a language at various levels, ranging from words through sentences to discourses. However, the decoding effect is affected by various factors, such as the decoding model, vector representation model, and brain regions. Challenges and future directions are also discussed. The advances in brain language decoding and BCI technology will potentially assist patients with clinical aphasia in regaining the ability to communicate.

Ischemic Stroke and Cerebral Microbleeds: A Two-Sample Bidirectional Mendelian Randomization Study.

INTRODUCTION: Recent observational studies have reported the association between ischemic stroke (IS) and cerebral microbleeds (CMBs). Whether this reflects a causal association remains to be established. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) analysis to comprehensively evaluate the causal association of IS and CMBs. METHODS: The summary-level genome-wide association studies (GWASs) data of IS were obtained from the GIGASTROKE consortium (62,100 European ancestry cases and 1,234,808 European ancestry controls). All IS cases could be further divided into large-vessel atherosclerosis stroke (LVS, n = 6399), cardio-embolic stroke (CES, n = 10,804) and small-vessel occlusion stroke (SVS, n = 6811). Meanwhile, we used publicly available summary statistics from published GWASs of CMBs (3556 of the 25,862 European participants across 2 large initiatives). A bidirectional MR analysis was conducted using inverse-variance weighting (IVW) as the major outcome, whereas MR-Egger and weighted median (WM) were used to complement the IVW estimates as they can provide more robust estimates in a broader set of scenarios but are less efficient (wider CIs). A Bonferroni-corrected threshold of p < 0.0125 was considered significant, and p values between 0.0125 and 0.05 were considered suggestive of evidence for a potential association. RESULTS: We detected that higher risk of IS [IVW odds ratio (OR) 1.47, 95% confidence interval (CI) 1.04-2.07, p = 0.03] and SVS (IVW OR 1.62, 95% CI 1.07-2.47, p = 0.02) were significantly associated with CMBs. Reverse MR analyses found no significant evidence for a causal effect of CMBs on IS and its subtypes. CONCLUSIONS: Our study provides potential evidence that IS and SVS are causally linked to increased risk of CMBs. Further research is needed to determine the mechanisms of association between IS and CMBs.

Exosomal miR-218 derived from mesenchymal stem cells inhibits endothelial-to-mesenchymal transition by epigenetically modulating of BMP2 in pulmonary fibrosis.

Endothelial-to-mesenchymal transition (EndMT), the process by which endothelial cells lose their characteristics and acquire mesenchymal phenotypes, participates in the pathogenic mechanism of idiopathic pulmonary fibrosis. Recently, exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos) has been introduced as a promising treatment in organ fibrosis. This study aimed to explore the effects as well as the molecular mechanism for hucMSC-Exo in pulmonary fibrosis. The intravenous administration of hucMSC-Exos alleviated bleomycin-induced pulmonary fibrosis in vivo. Moreover, hucMSC-Exos elevated miR-218 expression and restored endothelial properties weakened by TGF-ß in endothelial cells. Knockdown of miR-218 partially abrogated the inhibition effect of hucMSC-Exos on EndMT. Our mechanistic study further demonstrated that MeCP2 was the direct target of miR-218. Overexpressing MeCP2 aggravated EndMT and caused increased CpG islands methylation at BMP2 promoter, which lead to BMP2 post-transcriptional gene silence. Transfection of miR-218 mimic increased BMP2 expression as well, which was downregulated by overexpression of MeCP2. Taken together, these findings indicate exosomal miR-218 derived from hucMSCs may possess anti-fibrotic properties and inhibit EndMT through MeCP2/BMP2 pathway, providing a new avenue of preventive application in pulmonary fibrosis.

A review on surgical treatment options in gliomas.

Gliomas are one of the most common primary central nervous system tumors, and surgical treatment remains the principal role in the management of any grade of gliomas. In this study, based on the introduction of gliomas, we review the novel surgical techniques and technologies in support of the extent of resection to achieve long-term disease control and summarize the findings on how to keep the balance between cytoreduction and neurological morbidity from a list of literature searched. With modern neurosurgical techniques, gliomas resection can be safely performed with low morbidity and extraordinary long-term functional outcomes.