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Vascular calcification and vascular ageing are “silent” diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

Abstract Sophisticated interactions between stromal and immune cells play crucial roles in various biological and pathological processes. In chronic rhinosinusitis with nasal polyps (CRSwNP), the upper airway inflammation in many patients is driven by TH2, ILC2, and eosinophils, thus being treated with glucocorticoids and anti-type 2 inflammation biologics. The resistance to these therapies is often associated with neutrophilic inflammation, which has also been widely identified in CRSwNP, but the underlying mechanisms remain unclear. Using single-cell analysis, spatial transcriptomics, and T-cell receptor sequencing, we identify an increased presence of granzyme K+(GZMK+) CD8+ T cells in NPs, which possess a phenotype distinct from the cytotoxic GZMB+ effector CD8+ T subset. GZMK+CD8+ T cells are found to express CXCR4 and interact with CXCL12-secreting fibroblasts, inducing the latter to produce neutrophil chemoattractants in a manner uniquely mediated by GZMK but not other granzymes. This GZMK+CD8+ T cell-fibroblast crosstalk is also observed in other inflammatory diseases. Furthermore, GZMK+CD8+ T cells exhibit a selective expansion of clones that recognize Epstein-Barr virus. Here, we show that GZMK marks a phenotypically distinct subset of effector CD8+ T cells that promote neutrophilic inflammation.

Abstract Epicardial adipose tissue (EAT) significantly contributes to the progression of cardiovascular diseases (CVDs). However, manually quantifying EAT volume is labor-intensive and susceptible to human error. Although there have been some deep learning-based methods for automatic quantification of EAT, they are mostly uninterpretable and fail to harness the complete anatomical characteristics. In this study, we proposed an enhanced deep learning method designed for EAT quantification on coronary computed tomography angiography (CCTA) scan, which integrated both data-driven method and specific morphological information. A total of 108 patients who underwent routine CCTA examinations were included in this study. They were randomly assigned to training set (n = 60), validation set (n = 8), and test set (n = 40). We quantified and calculated the EAT volume based on the CT attenuation values within the predicted pericardium. The automatic method demonstrated strong agreement with expert manual quantification, yielding a median Dice score coefficients (DSC) of 0.916 (Interquartile Range (IQR): 0.846–0.948) for 2D slices. Meanwhile, the median DSC for the 3D volume was 0.896 (IQR: 0.874–0.908) between these two measures, with an excellent correlation of 0.980 (p

Abstract Introduction Arterial calcification, an independent predictor of cardiovascular events, increases morbidity and mortality in patients with diabetes mellitus (DM), but its mechanisms remain unclear. Extracellular vesicles (EVs) play an important role in intercellular communication. The study investigates the role and potential mechanisms of EVs derived from endothelial cells (ECs) in regulating vascular smooth muscle cell (VSMC) calcification under high glucose (HG) condition, with a goal of developing effective prevention and treatment strategies for diabetic arterial calcification. Results The results showed that EVs derived from HG induced ECs (ECHG-EVs) exhibited a bilayer structure morphology with a mean diameter of 74.08 ± 31.78 nm, expressing EVs markers including CD9, CD63 and TSG101, but not express calnexin. ECHG-EVs was internalized by VSMCs and induced VSMC calcification by increasing Runx2 expression and mineralized nodule formation. The circ_0008362 was enriched in ECHG-EVs, and it can be transmitted to VSMCs to promote VSMC calcification both in vitro and in vivo. Mechanistically, miR-1251-5p might be one of the targets of circ_0008362 and they were co-localization in the cytoplasm of VSMCs. Runx2 was identified as the downstream target of miR-1251-5p, and circ_0008362 acted as a sponge, enhancing Runx2 expression and then promoted VSMC calcification. Besides, circ_0008362 could directly interact with Runx2 to aggravate VSMC calcification. Notably, DiR-labelled ECHG-EVs was detected in the vessels of mice. Meanwhile, the level of circ_0008362 and Runx2 were increased significantly, while the expression of miR-1251-5p was decreased significantly in calcified artery tissues of mice. However, inhibiting the release of EVs by GW4869 attenuated arterial calcification in diabetic mice. Finally, the level of circulation of plasma EVs circ_0008362 was significantly higher in patients with DM compared with normal controls. Elevated levels of plasma EVs circ_0008362 were associated with more severe coronary and aorta artery calcification in patients with DM. Conclusions Our findings suggested that circ_0008362 was enriched in EVs derived from ECs and promoted VSMC calcification under HG conditions, both by sponging miR-1251-5p to upregulate Runx2 expression and through direct interaction with Runx2. Furthermore, elevated levels of plasma EVs circ_0008362 were associated with more severe coronary and aorta artery calcification in patients with DM. These results may serve as a potential prevention and therapeutic target for diabetic arterial calcification. Graphical abstract

Abstract Natural gas hydrate is a promising unconventional natural gas source due to its high energy density and huge global reserves. During exploitation, the drilling fluid may invade the hydrate formation and induce hydrate decomposition, causing reservoir damage. Herein, a novel reservoir protectant made by bio-degradable temporary plugging material (BDTPM) was developed in the form of polymer-ceramic composite microcapsules. As an additive to the drilling fluid, the BDTPM can minimize drilling fluid intrusion by plugging the reservoir during drilling and afterwards maximize permeability recovery by degrading the material. The particle size distribution was in the range of 1–130 μm. The optimal mass ratio between modified ceramic particles, ethyl cellulose and epoxy resin was found to be 4:2:1. The plugging rate was 100% when ethyl cellulose and epoxy resin were mixed to coat the ceramic particles to form BDTPM, and the plugging performance was the best. At a temperature close to the typical hydrate reservoir environment (5 °C), 0.02 wt% low-temperature complex enzyme can degrade BDTPM, and the permeability recovery rate is 64.66%. The efficient reservoir protectant developed in this work could play an important role in the successful drilling of natural gas hydrate reservoirs.

Abstract Background Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. Methods The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. Results We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. Conclusion These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis. Graphical Abstract

Abstract Objective The purpose of this study was to investigate the long-term consequences on the cervical spine after Anterior transcorporeal percutaneous endoscopy cervical discectomy (ATc-PECD) from the biomechanical standpoint. Methods A three-dimensional model of the normal cervical spine C2-T1 was established using finite element method. Subsequently, a disc degeneration model and degeneration with surgery model were constructed on the basis of the normal model. The same loading conditions were applied to simulate flexion, extension, lateral bending and axial rotation of the cervical spine. We calculated the cervical range of motion (ROM), intradiscal pressure, and intravertebral body pressure under different motions for observing changes in cervical spine biomechanics after surgery. At the same time, we combined the results of a long-term follow-up of the ATc-PECD, and used imaging methods to measure vertebral and disc height and cervical mobility, the Japanese Orthopaedic Association (JOA) score and visual analog scale (VAS) score were used to assess pain relief and neurological functional recovery. Results The long-term follow-up results revealed that preoperative JOA score, neck VAS score, hand VAS score, IDH, VBH, and ROM for patients were 9.49 ± 2.16, 6.34 ± 1.68, 5.14 ± 1.48, 5.95 ± 0.22 mm, 15.41 ± 1.68 mm, and 52.46 ± 9.36° respectively. It changed to 15.71 ± 1.13 (P

Abstract Achieving high-luminescence organic light-emitting devices (OLEDs) with narrowband emission and high color purity is important in various optoelectronic fields. Laser displays exhibit outstanding advantages in next-generation display technologies owing to their ultimate visual experience, but this remains a great challenge. Here, we develop a novel OLED based organic single crystals. By strongly coupling the organic exciton state to an optical microcavity, we obtain polariton electroluminescent (EL) emission from the polariton OLEDs (OPLEDs) with high luminance, narrow-band emission, high color purity, high polarization as well as excellent optically pumped polariton laser. Further, we evaluate the potential for electrically pumped polariton laser through theoretical analysis and provide possible solutions. This work provides a powerful strategy with a material–device combination that paves the way for electrically driven organic single-crystal-based polariton luminescent devices and possibly lasers.

Abstract A stable mitochondrial pool is crucial for healthy cell function and survival. Altered redox biology can adversely affect mitochondria through induction of a variety of cell death and survival pathways, yet the understanding of mitochondria and their dysfunction in primary human cells and in specific disease states, including asthma, is modest. Ferroptosis is traditionally considered an iron dependent, hydroperoxy-phospholipid executed process, which induces cytosolic and mitochondrial damage to drive programmed cell death. However, in this report we identify a lipoxygenase orchestrated, compartmentally-targeted ferroptosis-associated peroxidation process which occurs in a subpopulation of dysfunctional mitochondria, without promoting cell death. Rather, this mitochondrial peroxidation process tightly couples with PTEN-induced kinase (PINK)−1(PINK1)-Parkin-Optineurin mediated mitophagy in an effort to preserve the pool of functional mitochondria and prevent cell death. These combined peroxidation processes lead to altered epithelial cell phenotypes and loss of ciliated cells which associate with worsened asthma severity. Ferroptosis-targeted interventions of this process could preserve healthy mitochondria, reverse cell phenotypic changes and improve disease outcomes.

BackgroundPerineural administration of dexmedetomidine (PN-DEX) can enhance the efficacy of local anesthetics used in regional nerve blocks while decreasing the median effective concentration (EC50) of these anesthetics. Intranasal administration of dexmedetomidine (IN-DEX) is more accessible for sedation during regional anesthesia because of its non-invasive systemic administration and demonstrates synergism with local anesthetic. However, it remains unclear whether IN-DEX affects the EC50 of local anesthetics used in caudal blocks.MethodsThis study was a prospective, single-center, double-blind, randomized controlled trial. Patients scheduled to undergo elective hemorrhoidectomy were included and divided into three groups. Furthermore, 0.01 mL/kg of normal saline and 1 μg/kg and 2 μg/kg of dexmedetomidine were dripped into both nostrils of the patients in groups IN-NS, IN-DEX1, and IN-DEX2, respectively. These were administered 15 min before the caudal block. The initial concentration of ropivacaine was set at 0.4%, which was then varied by 0.025% using the up-and-down sequential allocation method. Vital signs, instances of hypotension and bradycardia with treatment, and other adverse reactions were recorded and compared.ResultsThe EC50 values of ropivacaine were 0.275% (95% confidence interval (CI), 0.254–0.296%) in group IN-NS, 0.257% (95% CI, 0.238–0.276%) in group IN-DEX1, and 0.216% (95% CI, 0.195–0.236%) in group IN-DEX2. The EC95 values of ropivacaine were 0.315% (95% CI, 0.295–0.370%) in group IN-NS, 0.297% (95% CI, 0.278–0.351%) in group IN-DEX1, and 0.256% (95% CI, 0.236–0.310%) in group IN-DEX2. Compared to group IN-NS, the EC50 value of ropivacaine in IN-DEX2 was significantly decreased by 21.4% (p = 0.001), while there was no significant difference between group IN-NS and IN-DEX1 (p = 0.125). There were no differences in hypotension and bradycardia with treatment among the different groups.ConclusionIN-DEX decreased the EC50 of ropivacaine for the caudal block, and there was a specific dose-dependent effect for IN-DEX. The side effects were similar across all groups.

BackgroundWith the aging population, the prevalence and impact of osteoporosis are expected to rise, and existing anti-osteoporosis agents have limitations due to adverse events. This study aims to discover novel drug targets for osteoporosis.MethodsThe protein data were obtained from the latest proteome-wide association studies (PWAS) including 54, 219 participants. The osteoporosis data were extracted from a GWAS meta-analysis, characterized by heel bone mineral density (HBMD) comprising 426,824 individuals. Mendelian randomization (MR) was the primary approach used to establish genetic causality between specific traits. Summary-data-based MR (SMR), colocalization analysis, heterogeneity test, and external validation were applied to ensure the findings were reliable. The underlying mechanisms behind these causal associations were investigated by additional analyses. Finally, the druggability of the identified proteins was assessed.ResultsAfter Bonferroni correction, a total of 84 proteins were found to have a genetic association with osteoporosis. With strong colocalization evidence, proteins such as ACHE, HS6ST1, LRIG1, and LRRC37A2 were found to negatively influence HBMD, whereas CELSR2, CPE, FN1, FOXO1, and FSHB exhibited a positive association with HBMD. No significant heterogeneity was found. Additionally, CELSR2, FN1, FSHB, HS6ST1, LRIG1, and LRRC37A2 were replicated in the external validation. The effect of FSHB on HBMD was more pronounced in females compared to males. Interestingly, ACHE, LRIG1, FN1, and FOXO1 were observed to partially act on HBMD through BMI. Phewas analysis indicated that CPE and FOXO1 did not have genetic associations with any phenotypes other than osteoporosis. FN1 was highlighted as the most significant protein by protein-protein interaction network analysis.ConclusionIn conclusion, this study offers valuable insights into the role of specific proteins in the development of osteoporosis, and underscores potential therapeutic targets. Future studies should emphasize exploring these causal relationships and elucidating their underlying mechanisms.

Abstract Although it is well documented that mountains tend to exhibit high biodiversity, how geological processes affect the assemblage of montane floras is a matter of ongoing research. Here, we explore landform-specific differences among montane floras based on a dataset comprising 17,576 angiosperm species representing 140 Chinese mountain floras, which we define as the collection of all angiosperm species growing on a specific mountain. Our results show that igneous bedrock (granitic and karst-granitic landforms) is correlated with higher species richness and phylogenetic overdispersion, while the opposite is true for sedimentary bedrock (karst, Danxia, and desert landforms), which is correlated with phylogenetic clustering. Furthermore, we show that landform type was the primary determinant of the assembly of evolutionarily older species within floras, while climate was a greater determinant for younger species. Our study indicates that landform type not only affects montane species richness, but also contributes to the composition of montane floras. To explain the assembly and differentiation of mountain floras, we propose the ‘floristic geo-lithology hypothesis’, which highlights the role of bedrock and landform processes in montane floristic assembly and provides insights for future research on speciation, migration, and biodiversity in montane regions.

A new spleenwort species, Asplenium guodanum, was found and described from Danxia landform region in Guangdong, China. The new species has close resemblance to A. subcrenatum Ching ex S.H.Wu in morphology, but can be distinguished by having plants small, stipes and rachises not covered with fibrous scales, relatively fewer pairs of pinnae, pinnae short, pinna margin weakly biserrate, pinna apex acute and lower pinnae obviously reduced. Phylogenetic analyses, based on six plastid markers (atpB, rbcL, rps4 & rps4-trnS and trnL & trnL-F) of the new species and its relatives, support a close relationship between A. guodanum and A. subcrenatum. Only one population with no more than 50 individuals were found and, therefore, it is recommended to be classified as Critically Endangered (CR) following IUCN Red List Criteria.

Abstract Objective Full endoscopic techniques are being gradually introduced from single-segment cervical disc herniation surgery to two-segment cervical disc herniation surgery. However, there is no suitable full endoscopic treatment for mixed-type two-segment cervical disc herniation (MTCDH) in which one segment herniates in front of the spinal cord and the other segment herniates behind the spinal cord. Therefore, we introduce a new full endoscopic technique by combining an anterior transcorporeal approach and a posterior translaminar approach. In addition, we provide a brief description of its safety, efficacy, feasibility, and surgical points. Methods Thirty patients with MTCDH were given full endoscopic surgical treatment by a combined transcorporeal and transforaminal approach and were followed up for at least 12 months. Results Clinical assessment scales showed that the patient’s symptoms and pain were significantly reduced postoperatively. Imaging results showed bony repair of the surgically induced bone defect and the cervical Cobb angle was increased. No serious complications occurred. Conclusion This technique enables minimally invasive surgery to relieve the compression of the spinal cord by MTCDH. It avoids the fusion of the vertebral body for internal fixation, preserves the vertebral motion segments, avoids medical destruction of the cervical disc to the greatest extent possible, and expands the scope of adaptation of full endoscopic technology in cervical surgery.

Abstract Background Lumbar revision surgery can be performed by simple lumbar nerve decompression or lumbar interbody fusion, including percutaneous endoscopic lumbar discectomy, transforaminal lumbar interbody fusion (TLIF), etc. However, lumbar revision surgery is very difficult in surgical operation. We sought to explore the technique safety and efficacy of microscope-assisted minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) in lumbar revision surgery. Methods Cases of postoperative recurrence following lumbar spine surgery (n = 63) treated from December 2016 to July 2021 were retrospectively analyzed, including 24 cases of microscope-assisted MI-TLIF (microscopic group) and 39 cases of naked-eye MI-TLIF (naked-eye group). The operation time, intraoperative blood loss, incision length, postoperative drainage, length of hospital stay, initial operation, and visual analog score (VAS) of low back and leg pain before and at 7 days and 3 months after the operation and the last follow-up were compared between the two groups. The Oswestry Dysfunction Index (ODI) and the Japanese Orthopaedic Association (JOA) scores before and after the operation and the Bridwell interbody fusion grades at 1 year were compared. The independent t tests, Mann–Whitney U tests, and Chi-square tests were used for analysis. Results All 63 patients were successfully treated by operation and were followed up for an average of 31.5 ± 8.6 months (range 12–48 months). The two groups had no significant difference in sex, age, incision length, initial operation, or operative segment (P > 0.05). There was no significance in operation time, VAS score, ODI score, and JOA score of low back pain or Bridwell interbody fusion grade between the two groups (P > 0.05). Significant differences in intraoperative blood loss, postoperative drainage, and the lengths of hospital stay were observed between the two groups (P

A new species of the genus Camellia (Theaceae), Camellia zijinica, discovered in the Danxia landscape from Guangdong Province, China, is characterized and illustrated. Phylogenetic analysis based on chloroplast genomes suggested its affinity with C. drupifera, C. oleifera and C. fluviatilis, however, it morphologically differs from all of the latter by leaf shape and size. Phonologically, it most closely resembles C. microphylla, but can be distinguished from the latter by its young branchlets glabrous (vs. densely pubescent), fewer bracteoles and sepals, diverse leaf shape, midvein raised slightly with sparsely pubescent or glabrous (vs. prominently with densely pubescent) and leaf adaxially matt (vs. vernicose) when dried. By morphological and molecular analyses, Camellia zijinica represented a distinct new species of C. sect. Paracamellia.

Lysimachia danxiashanensis, a new Primulaceae species, endemic to the Danxia landscape in Guangdong Province, China, is described and illustrated. This new species is morphologically similar to L. pseudohenryi, L. phyllocephala, L. congestiflora and L. kwangtungensis, but it differs from the similar species by its purplish-red plants, petiole without wings, calyx with orange glandular and the corolla margin serrated on upper half with orange-red glandular punctates. This new species belongs to Lysimachia subgen. Lysimachia sect. Nummularia. Phylogenetic analysis confirmed that L. danxiashanensis is a distinct clade, based on the combined data of ITS and rbcL sequences. The conservation status of the new species was evaluated as Endangered (EN) according to IUCN Red List Categories and Criteria.

Abstract Background The current treatments for adjacent two-segment cervical spondylotic myelopathy (CSM) include two-segment anterior cervical discectomy and fusion (ACDF) and single-segment anterior cervical corpectomy and fusion (ACCF). Long-term follow-up has demonstrated that both procedures have complications such as reduced cervical mobility, accelerated degeneration of adjacent segments and loosening of internal fixation screws. The purpose of this study is to demonstrate the feasibility, safety, and efficacy of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) via one vertebra with two bony channels for the treatment of adjacent two-segment CSM and to present our surgical experience. Methods Anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) via one vertebra with two bony channels was performed for 12 patients with adjacent two-segment CSM with follow-up care for at least 12 months. The Visual analog scale (VAS) and the Japanese Orthopedic Association Score (JOA) were recorded, and modified Macnab criteria were used to evaluate the treatment excellence rate. Radiological examinations, including X-ray, computed tomography (CT) and magnetic resonance imaging (MRI), were used to evaluate spinal cord decompression, intervertebral stability and healing of the bony channel. Results All 12 patients completed the operation successfully. No postoperative complications, such as dysphagia, Horner’s syndrome, or laryngeal recurrent nerve palsy, were found. The postoperative VAS and JOA scores were significantly improved compared with those before surgery(P

Abstract Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFsHPi-Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFsHPi-Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFsHPi-Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFsmiR21M-Exos) significantly accelerate vascular calcification in CRF mice. In general, AFsHPi-Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment. Graphical Abstract

Abstract The effect of niobium ions with high‐valence doping on high‐voltage LiNi0.5Mn1.5O4 (LNMO) materials was investigated. LiNi0.5Mn1.5−xNbxO4 was prepared by doping high‐valent niobium ions into LiNi0.5Mn1.5O4 material using the organic assisted combustion method. The experimental samples were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), electrochemical impedance (EI), and cyclic voltammetry (CV) analysis. The experimental results show that ‐doping with high‐valence niobium ions changes the orientation of the crystal plane growth of spinel particles, and the morphology of these particles changes from the octahedral shape before doping to the spherical shape after doping. With the increase in doping amount, the crystal structure changes gradually, resulting in the Li0.96Nb1.01O3 impurity phase. The doping of high valence‐niobium ions increases the content of Mn3+ in the material, resulting in the appearance of a 4 V discharge platform and the formation of a 4.7 and 4 V discharge platforms. The doping of Nb can improve the cycling stability of LiNi0.5Mn1.5O4 material, but the specific capacity of the material is reduced.

Electrical stimulation (ES) of the spinal cord is a promising therapy for functional rehabilitation after spinal cord injury (SCI). However, the specific mechanism of action is poorly understood. We designed and applied an implanted ES device in the SCI area in rats and determined the effect of ES on the treatment of motor dysfunction after SCI using behavioral scores. Additionally, we examined the molecular characteristics of the samples using proteomic and transcriptomic sequencing. The differential molecules between groups were identified using statistical analyses. Molecular, network, and pathway-based analyses were used to identify group-specific biological features. ES (0.5 mA, 0.1 ms, 50 Hz) had a positive effect on motor dysfunction and neuronal regeneration in rats after SCI. Six samples (three independent replicates in each group) were used for transcriptome sequencing; we obtained 1026 differential genes, comprising 274 upregulated genes and 752 downregulated genes. A total of 10 samples were obtained: four samples in the ES group and six samples in the SCI group; for the proteome sequencing, 48 differential proteins were identified, including 45 up-regulated and three down-regulated proteins. Combined transcriptomic and proteomic studies have shown that the main enrichment pathway is the hedgehog signaling pathway. Western blot results showed that the expression levels of Sonic hedgehog (SHH) (P

Objective: The PRAS40 is an essential inhibitory subunit of the mTORC1 complex, which regulates autophagy. It has been suggested that Erxian Decoction (EXD) could treat spinal cord injury (SCI) via the autophagy pathway. However, the mechanism of whether EXD acts through PRAS40 remains unclear.Methods: With the help of immobilized PRAS40, isothermal titration calorimetry (ITC) and molecular docking, the bioactive metabolites in the EXD were screened. To establish in vitro SCI models, PC12 cells were exposed to hydrogen peroxide (H2O2) and then treated with the identified EXD substances. Furthermore, Western blot assay was carried out to identify potential molecular mechanisms involved. For assessing the effect of metabolites in vivo, the SCI model rats were first pretreated with or without the metabolite and then subjected to the immunohistochemistry (IHC) staining, Basso, Beattie & Bresnahan (BBB) locomotor rating scale, and H&E staining.Results: The immobilized PRAS40 isolated indole, 4-nitrophenol, terephthalic acid, palmatine, sinapinaldehyde, and 3-chloroaniline as the potential ligands binding to PRAS40. Furthermore, the association constants of palmatine and indole as 2.84 × 106 M-1 and 3.82 × 105 M-1 were elucidated via ITC due to the drug-like properties of these two metabolites. Molecular docking results also further demonstrated the mechanism of palmatine binding to PRAS40. Western blot analysis of PC12 cells demonstrated that palmatine inhibited the expression of p-mTOR by binding to PRAS40, activating the autophagic flux by markedly increasing LC3. The injection of palmatine (10μM and 20 μM) indicated notably increased BBB scores in the SCI rat model. Additionally, a dose-dependent increase in LC3 was observed by IHC staining.Conclusion: This research proved that EXD comprises PRAS40 antagonists, and the identified metabolite, palmatine, could potentially treat SCI by activating the autophagic flux.

Background: Eurycomanone (EN) is a diterpenoid compound isolated from the roots of Eurycoma longifolia (E. longifolia). Previous studies have confirmed that E. longifolia can enhance bone regeneration and bone strength. We previously isolated and identified ten quassinoids from E. longifolia, and the result displayed that five aqueous extracts have the effects on promotion of bone formation, among whom EN showed the strongest activity. However, the molecular mechanism of EN on bone formation was unknown, and we further investigated in this study. Methods: After the verification of purity of extracted EN, following experiments were conducted. Firstly, the pharmacologic action of EN on normal bone mineralization and the therapeutic effect of EN on Dex-induced bone loss using zebrafish larvae. The mineralization area and integral optical density (IOD) were evaluated using alizarin red staining. Then the vital signaling pathways of EN relevant to OP was identified through network pharmacology analysis. Eventually in vitro, the effect of EN on cell viability, osteogenesis activities were investigated in human bone marrow mesenchymal stem cells (hMSCs) and C3H10 cells, and the molecular mechanisms by which applying AKT inhibitor A-443654 in hMSCs. Results: In zebrafish larvae, the administration in medium of EN (0.2, 1, and 5 μM) dramatically enhanced the skull mineralization area and integral optical density (IOD), and increased mRNA expressions of osteoblast formation genes (ALP, RUNX2a, SP7, OCN). Meanwhile, exposure of EN remarkably alleviated the inhibition of bone formation induced by dexamethasone (Dex), prominently improved the mineralization, up-regulated osteoblast-specific genes and down-regulated osteoclast-related genes (CTSK, RANKL, NFATc1, TRAF6) in Dex-treated bone loss zebrafish larvae. Network pharmacology outcomes showed the MAPK and PI3K-AKT signaling pathways are closely associated with 10 hub genes (especially AKT1), and AKT/GSK-3β/β-catenin was selected as the candidate analysis pathway. In hMSCs and C3H10 cells, results showed that EN at appropriate concentrations of 0.008–5 μM effectively increased the cell proliferation. In addition, EN (0.04, 0.2, and 1 μM) significantly stimulated osteogenic differentiation and mineralization as well as significantly increased the protein phosphorylation of AKT and GSK-3β, and expression of β-catenin, evidencing by the results of ALP and ARS staining, qPCR and western blotting. Whereas opposite results were presented in hMSCs when treated with AKT inhibitor A-443654, which effectively inhibited the pro-osteogenesis effect induced by EN, suggesting EN represent powerful potential in promoting osteogenesis of hMSCs, which may be closely related to the AKT/GSK-3β/β-catenin signaling pathway. Conclusions: Altogether, our findings indicate that EN possesses remarkable effect on bone formation via activating AKT/GSK-3β/β-catenin signaling pathway in most tested concentrations. The translational potential of this article: This study demonstrates EN is a new effective monomer in promoting bone formation, which may be a promising anabolic agent for osteoporosis (OP) treatment.

Abstract Background Evaluate the effectiveness of posterior percutaneous full-endoscopic technique for patients with thoracic myelopathy caused by ossification of ligamentum flavum (TOLF). Methods A prospective study was conducted for 16 patients with TOLF, who were treated with posterior endoscopic technique from 2017 to 2019. The sagittal and cross-sectional CT images are used to measure the area of ossified ligamentum and evaluate the decompression of surgery, respectively. The effectiveness was evaluated with visual analog scale (VAS), modified Japanese Orthopedic Association scale (mJOA), The Oswestry Disability Index (ODI), and Macnab efficacy evaluation. Results The average area of TOLF on sagittal and cross-sectional CT images in the 16 patients was (116.62 ± 32.72) mm2 and (141.59 ± 27.25) mm2 preoperatively, (15.99 ± 12.54) mm2 and (11.72 ± 8.64) mm2 at 3 days after the operation, (16.78 ± 11.49) mm2 and (10.82 ± 7.57) mm2 postoperative 1 year, respectively. The invasive proportion of spinal canal at preoperative sagittal and cross-sectional CT images was (48.10 ± 10.04) % and (57.58 ± 11.37) %, which decreased to (6.83 ± 4.48) % and (4.40 ± 3.01) % at the final follow-up. The average score of mJOA, VAS and ODI improved. The excellent and good rate was 87.50% according to Macnab evaluation. Compared with preoperative, differences in areas of TOLF, proportions of spinal canal, and clinical assessments of postoperative 3 days and 1 year were all statistically significant. Two cases of dural tear were observed. Conclusion Endoscopic surgery has a good clinical effect on TOLF, which has the advantage of less trauma to the paraspinal muscles and no impact on the spinal structure. The CT-based radiographic measurements can quantitatively evaluate the degree of spinal canal stenosis in TOLF.

BackgroundThe comparative advantages of robotic posterior retroperitoneal adrenalectomy (RPRA) over laparoscopic posterior retroperitoneal adrenalectomy (LPRA) remain a topic of ongoing debate within the medical community. This systematic literature review and meta-analysis aim to assess the safety and efficacy of RPRA compared to LPRA, with the ultimate goal of determining which procedure yields superior clinical outcomes.MethodsA systematic search was conducted on databases including PubMed, Embase, Web of Science, and the Cochrane Library database to identify relevant studies, encompassing both randomized controlled trials (RCTs) and non-RCTs, that compare the outcomes of RPRA and LPRA. The primary focus of this study was to evaluate perioperative surgical outcomes and complications. Review Manager 5.4 was used for this analysis. The study was registered with PROSPERO (ID: CRD42023453816).ResultsA total of seven non-RCTs were identified and included in this study, encompassing a cohort of 675 patients. The findings indicate that RPRA exhibited superior performance compared to LPRA in terms of hospital stay (weighted mean difference [WMD] -0.78 days, 95% confidence interval [CI] -1.46 to -0.10; p = 0.02). However, there were no statistically significant differences observed between the two techniques in terms of operative time, blood loss, transfusion rates, conversion rates, major complications, and overall complications.ConclusionRPRA is associated with a significantly shorter hospital stay compared to LPRA, while demonstrating comparable operative time, blood loss, conversion rate, and complication rate. However, it is important to note that further research of a more comprehensive and rigorous nature is necessary to validate these findings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=453816, identifier CRD42023453816.

To adapt to the extreme conditions of plateau environments, yaks have evolved thick hair, making them an ideal model for investigating the mechanisms involved in hair growth. We can gain valuable insights into how hair follicles develop and their cyclic growth in challenging environments by studying yaks. However, the lack of essential data on yak hair follicle histology and the absence of in vitro cell models for hair follicles serve as a limitation to such research objectives. In this study, we investigated the structure of skin tissue during different hair follicle cycles using the yak model. Additionally, we successfully established in vitro models of hair follicle-associated cells derived from yak skin, including dermal papilla cells (DPCs), preadipocytes, and fibroblasts. We optimized the microdissection technique for DPCs culture by simplifying the procedure and reducing the time required. Furthermore, we improved the methodology used to differentiate yak preadipocytes into mature adipocytes, thus increasing the differentiation efficiency. The introduction of yak as a natural model provides valuable research resources for exploring the mechanisms of hair growth and contributes to a deeper understanding of hair follicle biology and the development of regenerative medicine strategies.

Background There are limited data on low‐density lipoprotein cholesterol (LDL‐C) goal achievement per the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidemia management guidelines and its impact on long‐term outcomes in patients undergoing coronary artery bypass grafting (CABG). We investigated the association between LDL‐C levels attained 1 year after CABG and the long‐term outcomes. Methods and Results A total of 2072 patients diagnosed with multivessel coronary artery disease and undergoing CABG between 2011 and 2020 were included. Patients were categorized by lipid levels at 1 year after CABG, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs) was evaluated. The goal of LDL‐C

Commelina danxiaensis (Commelinaceae), a remarkable new species from Mount Danxia, Guangdong Province, China, is described and illustrated. This species is similar to C. communis in inflorescences and flowers but readily distinguishable in its nearly erect stems, larger flowers, and different petal colouration.

Argostemma ehuangzhangense, a new Rubiaceae species from E’huangzhang Nature Reserve, Guangdong Province, China, is here described and illustrated. A morphological comparison between the new species and its putative relatives, A. lamxayanum, A. laotica and A. verticillatum, is presented. The new species is mostly similar to A. laotica, but they can be distinguished from each other since Argostemma ehuangzhangense presents solitary flower (vs. 2-flowered inflorescences), flower lobes 4 (vs. 5) and anthers opening by longitudinal slits (vs. apical pores). In a preliminary IUCN Red List status of Argostemma ehuangzhangense this species is assigned as Vulnerable (VU).

The new species Eriobotrya crassifolia, collected from Yunnan Province, China, is characterised and illustrated. A phylogeny based on chloroplast genomes supported its closest affinity with E. tengyuehensis, while a phylogeny based on 197 single-copy nuclear genes supported its closest affinity with E. fragrans and E. deflexa. Morphologically, however, it resembles E. angustissima. Nevertheless, it can be easily distinguished from E. angustissima by its abaxially retroflexed and sharply serrate leaf margins, densely rusty tomentose inflorescences, and oblong or elliptic leaves.

A new species, Wikstroemia fragrans (Thymelaeaceae, Daphneae), from Danxiashan National Park, Shaoguan, Guangdong of China is described and illustrated. It is similar to the sympatric W. trichotoma, but can be differentiated easily from the latter by its shorter racemose inflorescences, yellowish green calyx tube, and smaller leaves. It also resembles the allopatric W. fargesii, but differs from it by its strigose-pubescent ovary and disk scale that is 2- or 3-dentate apically. Phylogenetic analysis using the nuclear DNA internal transcribed spacer (ITS) region revealed that W. fragrans falls within the Wikstroemia clade; based on current sampling, W. fragrans is closely-related to W. capitata. It is also the first species of Wikstroemia known to be endemic to the Danxia landform and is classified provisionally as Critically Endangered according to the IUCN Red List Categories and Criteria.

BackgroundCorrelations between posttranslational modifications and atrial fibrillation (AF) have been demonstrated in recent studies. However, it is still unclear whether and how ubiquitylated proteins relate to AF in the left atrial appendage of patients with AF and valvular heart disease.MethodsThrough LC–MS/MS analyses, we performed a study on tissues from eighteen subjects (9 with sinus rhythm and 9 with AF) who underwent cardiac valvular surgery. Specifically, we explored the ubiquitination profiles of left atrial appendage samples.ResultsIn summary, after the quantification ratios for the upregulated and downregulated ubiquitination cutoff values were set at >1.5 and

IntroductionGlioblastoma (GBM) is the most invasive type of glioma, is insensitive to radiotherapy and chemotherapy, and has high proliferation and invasive ability, with a 5-year survival rate of

Abstract Background The purpose of this study was to determine how the drain fluid volume on the first day after surgery (DFV 1) can be used to predict clinically relevant post-operative pancreatic fistula following distal pancreatectomy (DP). Method A retrospective analysis of 175 patients who underwent distal pancreatectomy in hepatobiliary surgery at Chengdu 363 Hospital (China) from January 2015 to January 2021 has been performed. Depending on the presence of pancreatic fistula, all patients were divided into two groups: POPF and non-POPF. The clinical factors were analyzed using SPSS 17.0 and Medcalc software. In order to assess the effectiveness of DFV 1 in predicting POPF after surgery, ROC curves were used to calculate its cut-off point,, which yielded sensitivity and negative predictive value of 100% for excluding POPF. Result Of the 175 patients who underwent distal pancreatectomy, the incidence of overall pancreatic fistula was 36%, but the rate of clinically significant (grade B and C) fistula, as defined by the International Study Group on Pancreatic Fistula, 30 was only 17.1% (28 grade B and 2 grade C fistula). The results from univariate and multivariate logistic regression analysis showed that drain fluid volume on the first postoperative day (OR = 0.95, P = 0.03), drainage fluid amylase level on POD1 (OR = 0.99, P = 0.01) and the preoperative ALT level (OR = 0.73, P = 0.02) were independent risk factors associated with CR-POPF. Receiver operating characteristic (ROC) curve analysis revealed that a drainage volume of 156 mL within 24 h and an amylase greater than 3219.2 U/L on the first postoperative day were the optimal thresholds associated with complications. Conclusion After distal pancreatectomy, the drainage volume on the first postoperative day can predict the presence of a clinically relevant pancreatic fistula.

Pilea danxiaensis L.F.Fu, A.K.Monro & Y.G.Wei, a new species of Urticaceae from Danxia landform, Guangdong, China, is described and photographed. Phylogenetic analyses based on three DNA regions (ITS, trnL-F and rbcL) suggest that the new species belongs to P. sect. Pilea. Within the section, the new species is morphologically most similar to P. sinocrassifolia and P. peploides. Plastid genome and ribosomal DNA (rDNA) sequences of the new species are assembled and annotated. The plastid genome is 151,857 bp in length and comprises two inverted repeats (IRs) of 25,307 bp separated by a large single-copy of 82,836 bp and a small single-copy of 18,407 bp. A total of 113 functional genes are recovered, comprising 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. A global conservation assessment suggests that P. danxiaensis should be classified as of Least Concern (LC).

Paraphlomis jinggangshanensis (Lamiaceae), a new species from Jiangxi Province, China, is described and illustrated. The new species is morphologically similar to P. intermedia, but can be easily distinguished from the latter by its cordate leaf base (vs. cuneate, decurrent), stem and calyx tube with glandular hairs (vs. short pubescent), and glabrous anthers (vs. ciliate anthers). A phylogenetic analysis, based on ITS regions, suggests that P. jinggangshanensis represents a separate branch in Paraphlomis and is closely related to Clade II. It is currently known only from Jinggangshan National Natural Reserve. Because of its limited distribution and small population size, the species was assessed as Near Threatened (NT) according to the IUCN Red List Categories and Criteria.

Abstract Arterial calcification is highly prevalent, particularly in patients with end-stage renal disease (ESRD). The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is the critical process for the development of arterial calcification. However, the detailed mechanism of VSMCs calcification remains to be elucidated. Here, we investigated the role of exosomes (Exos) derived from endothelial cells (ECs) in arterial calcification and its potential mechanisms in ESRD. Accelerated VSMCs calcification was observed when VSMCs were exposed to ECs culture media stimulated by uremic serum or high concentration of inorganic phosphate (3.5 mM Pi). and the pro-calcification effect of the ECs culture media was attenuated by exosome depletion. Exosomes derived from high concentrations of inorganic phosphate-induced ECs (ECsHPi-Exos) could be uptaken by VSMCs and promoted VSMCs calcification. Microarray analysis showed that miR-670-3p was dramatically increased in ECsHPi-Exos compared with exosomes derived from normal concentrations of inorganic phosphate (0.9 mM Pi) induced ECs (ECsNPi-Exos). Mechanistically, insulin-like growth factor 1 (IGF-1) was identified as the downstream target of miR-670-3p in regulating VSMCs calcification. Notably, ECs-specific knock-in of miR-670-3p of the 5/6 nephrectomy with a high-phosphate diet (miR-670-3pEC-KI + NTP) mice that upregulated the level of miR-670-3p in artery tissues and significantly increased artery calcification. Finally, we validated that the level of circulation of plasma exosomal miR-670-3p was much higher in patients with ESRD compared with healthy controls. Elevated levels of plasma exosomal miR-670-3p were associated with a decline in IGF-1 and more severe artery calcification in patients with ESRD. Collectively, these findings suggested that ECs-derived exosomal miR-670-3p could promote arterial calcification by targeting IGF-1, which may serve as a potential therapeutic target for arterial calcification in ESRD patients.

Abstract The pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that regulate the physiological and pathological states of recipient cells. In the present study, significant up-regulation of miR-126-5p was observed in sEVs isolated from human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (A-EC/sEVs). Intriguingly, these sEVs suppressed the osteogenic differentiation of vascular smooth muscle cells (VSMCs) by targeting BMPR1B, which encodes the receptor for BMP, thereby blocking the smad1/5/9 signalling pathway. In addition, knocking down miR-126-5p in HUVECs significantly diminished the anti-calcification effect of A-EC/sEVs in a mouse model of type 2 diabetes. Overall, miR-126-5p is highly enriched in sEVs derived from AGEs stimulated HUVECs and can target BMPR1B to negatively regulate the trans-differentiation of VSMCs both in vitro and in vivo. Graphical Abstract

Although the expression of Mex3 RNA-binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HNECs) predominately in the eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) subtype, its functions as an RNA binding protein in airway epithelial cells remain unknown. Here, we revealed the role of MEX3B based on different subtypes of CRS and demonstrated that MEX3B decreased the TGF-β receptor III (TGFBR3) mRNA level by binding to its 3′ UTR and reducing its stability in HNECs. TGF-βR3 was found to be a TGF-β2–specific coreceptor in HNECs. Knocking down or overexpressing MEX3B promoted or inhibited TGF-β2–induced phosphorylation of SMAD2 in HNECs, respectively. TGF-βR3 and phosphorylated SMAD2 levels were downregulated in CRSwNP compared with controls and CRS without nasal polyps with a more prominent downregulation in the eosinophilic CRSwNP. TGF-β2 promoted collagen production in HNECs. Collagen abundance decreased and edema scores increased in CRSwNP compared with control, again more prominently in the eosinophilic type. Collagen expression in eosinophilic CRSwNP was negatively correlated with MEX3B but positively correlated with TGF-βR3. These results suggest that MEX3B inhibits tissue fibrosis in eosinophilic CRSwNP by downregulating epithelial cell TGFBR3 expression; consequently, MEX3B might be a valuable therapeutic target against eosinophilic CRSwNP.