Activation of BMP4/SMAD pathway by HIF-1α in hypoxic environment promotes osteogenic differentiation of BMSCs and leads to ectopic bone formation.

OBJECTIVE: Heterotopic ossification (HO), also known as ossifying myositis, is a condition that produces abnormal bone and cartilage tissue in the soft tissues. Hypoxia inducible factor lα (HIF-lα) regulates the expression of various genes, which is closely related to the promotion of bone formation, and Drosophila mothers against decapentaplegic protein (SMAD) mediates the signal transduction in the Bone morphogenetic protein (BMP) signaling pathway, which affects the function of osteoblasts and osteoclasts, and thus plays a key role in the regulation of bone remodeling. We aimed to investigate the mechanism by which HIF-1α induces osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in a hypoxic environment. METHODS: A cellular hypoxia model was constructed to verify the expression of HIF-1α, while alizarin red staining was performed to observe the osteogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs). Alizarin red staining was used to analyze the late mineralization ability of the cells. Western blot analysis was performed to analyze the expression levels of osteogenesis-related factors OCN, OPN proteins as well as the pathway proteins BMP4, p-Smad1/5/8, and Smad1. We also constructed a rat model of ectopic bone formation, observed ectopic ossification by X-ray, and verified the success of the rat model by ELISA of HIF-1α. HE staining was used to observe the matrix and trabecular structure of bone, and Masson staining was used to observe the collagen and trabecular structure of bone. Immunohistochemistry analyzed the expression of OCN and OPN in ectopic bone tissues, and WB analyzed the expression of pathway proteins BMP4, p-Smad1/5/8 and Smad1 in ectopic bone tissues to verify the signaling pathway of ectopic bone formation. RESULTS: Our results indicate that hypoxic environment upregulates HIF-1a expression and activates BMP4/SMAD signaling pathway. This led to an increase in ALP content and enhanced expression of the osteogenesis-related factors OCN and OPN, resulting in enhanced osteogenic differentiation of BMSCs. The results of our in vivo experiments showed that rats inoculated with BMSCs overexpressing HIF-1α showed bony structures in tendon tissues, enhanced expression of the bone signaling pathways BMP4 and p-Smad1/5/8, and enhanced expression levels of the osteogenic-related factors OCN and OPN, resulting in the formation of ectopic bone. CONCLUSIONS: These data further suggest a novel mechanistic view that hypoxic bone marrow BMSCs activate the BMP4/SMAD pathway by up-regulating the expression level of HIF-1α, thereby promoting the secretion of osteogenic factors leading to ectopic bone formation.

Perfluoroalkyl sulfonate induces cardiomyocyte apoptosis via endoplasmic reticulum stress activation and autophagy flux inhibition.

Perfluoroalkyl sulfonate (PFOS) is a commonly used chemical compound that often found in materials such as waterproofing agents, food packaging, and fire retardants. Known for its stability and persistence in the environment, PFOS can enter the human body through various pathways, including water and the food chain, raising concerns about its potential harm to human health. Previous studies have suggested a cardiac toxicity of PFOS, but the specific cellular mechanisms remained unclear. Here, by using AC16 cardiomyocyte as a model to investigate the molecular mechanisms potential the cardiac toxicity of PFOS. Our findings revealed that PFOS exposure reduced cell viability and induces apoptosis in human cardiomyocyte. Proteomic analysis and molecular biological techniques showed that the Endoplasmic Reticulum (ER) stress-related pathways were activated, while the cellular autophagy flux was inhibited in PFOS-exposed cells. Subsequently, we employed strategies such as autophagy activation and ER stress inhibition to alleviate the PFOS-induced apoptosis in AC16 cells. These results collectively suggest that PFOS-induced ER stress activation and autophagy flux inhibition contribute to cardiomyocyte apoptosis, providing new insights into the mechanisms of PFOS-induced cardiomyocyte toxicity.

Exosome MiR-21-5p Upregulated by HIF-1α Induces Adipose Stem Cell Differentiation to Promote Ectopic Bone Formation.

Heterotopic bone occurs after burns, trauma and major orthopedic surgery, which cannot be completely cured by current treatments. The development of new treatments requires more in-depth research into the mechanism of HO. Available evidence suggests that miR-21-5p plays an important role in bone formation. However, its mechanism in traumatic HO is still unclear. First, we identified exosomes extracted from L6 cells using TEM observation of the structure and western blotting detection of the surface marker CD63. Regulation effect of HIF-1α to miR-21-5p was confirmed by q-PCR assay. Then we co-cultured L6 cells with ASCs and performed alizarin red staining and ALP detection. Overexpression of miR-21-5p upregulated BMP4, p-smad1/5/8, OCN and OPN, which suggests the BMP4-smad signaling pathway may be involved in miR-21-5p regulation of osteogenic differentiation of ASCs. Finally in vivo experiments showed that miR-21-5p exosomes promoted ectopic formation in traumatized mice. This study confirms that HIF-1α could modulate miR-21-5p exosomes to promote post-traumatic ectopic bone formation by inducing ASCs cell differentiation. Our study reveals the mechanisms of miR-21-5p in ectopic ossification formation after trauma.

TBC1D23 mediates Golgi-specific LKB1 signaling.

Liver kinase B1 (LKB1), an evolutionarily conserved serine/threonine kinase, is a master regulator of the AMPK subfamily and controls cellular events such as polarity, proliferation, and energy homeostasis. Functions and mechanisms of the LKB1-AMPK axis at specific subcellular compartments, such as lysosome and mitochondria, have been established. AMPK is known to be activated at the Golgi; however, functions and regulatory mechanisms of the LKB1-AMPK axis at the Golgi apparatus remain elusive. Here, we show that TBC1D23, a Golgi-localized protein that is frequently mutated in the neurodevelopment disorder pontocerebellar hypoplasia (PCH), is specifically required for the LKB1 signaling at the Golgi. TBC1D23 directly interacts with LKB1 and recruits LKB1 to Golgi, promoting Golgi-specific activation of AMPK upon energy stress. Notably, Golgi-targeted expression of LKB1 rescues TBC1D23 deficiency in zebrafish models. Furthermore, the loss of LKB1 causes neurodevelopmental abnormalities in zebrafish, which partially recapitulates defects in TBC1D23-deficient zebrafish, and LKB1 sustains normal neuronal development via TBC1D23 interaction. Our study uncovers a regulatory mechanism of the LKB1 signaling, and reveals that a disrupted Golgi-LKB1 signaling underlies the pathogenesis of PCH.

DNAJA1 positively regulates amino acid-stimulated milk protein and fat synthesis in bovine mammary epithelial cells.

Several cellular processes, including the recovery of misfolded proteins, the folding of polypeptide chains, transit of polypeptides across the membrane, construction and disassembly of protein complexes, and modulation of protein control, are carried out by DnaJ homolog subfamily A member 1 (DNAJA1), which belongs to the DnaJ heat-shock protein family. It is unknown if DNAJA1 regulates the production of milk in bovine mammary epithelium cells (BMECs). Methionine and leucine increased DNAJA1 expression and nuclear location, as seen by us. In contrast to DNAJA1 knockdown, overexpression of DNAJA1 boosted the production of milk proteins and fats as well as mammalian target of rapamycin (mTOR) and sterol regulatory element binding protein-1c (SREBP-1c). As a result of amino acids, mTOR and SREBP-1c gene expression are stimulated, and DNAJA1 is a positive regulator of BMECs' amino acid-induced controlled milk protein and fat production.

Bidirectional enhancement of Li2S redox reaction by NiSe2/CoSe2-rGO heterostructured bi-functional catalysts.

The high activity barriers of Li2S nucleation and deposition limit the redox reaction kinetics of lithium polysulfides (LiPSs), meanwhile, the significant shuttle effect of LiPSs hampers the advancement of Li-S batteries (LSBs). In this work, a NiSe2/CoSe2-rGO (NiSe2/CoSe2-G) sulfur host with bifunctional catalytic activity was prepared through a hard template method. Electrochemical experiment results confirm that the combination of NiSe2 and CoSe2 not only facilitates the bidirectional catalytic function during charge and discharge processes, but also increases the active sites toward LiPSs adsorption. Simultaneously, the highly conductive rGO network enhances the electronic conductivity of NiSe2/CoSe2-G/S and provides convenience for loading NiSe2/CoSe2 catalysts. Benefitting from the exceptional catalytic-adsorption capability of NiSe2/CoSe2 and the presence of rGO, the NiSe2/CoSe2-G/S electrode exhibits excellent electrochemical properties. At 1C, it demonstrates a low capacity attenuation of 0.087 % per cycle during 500 cycles. The electrode can maintain a discharge capacity of 927 mAh/g at a sulfur loading of 3.3 mg cm-2. The bidirectional catalytic activity of NiSe2/CoSe2-G offers a prospective approach to expedite the redox reactions of active S, meanwhile, this work also offers an ideal approach for designing efficient S hosts for LSBs.

Regulation of pDC fate determination by histone deacetylase 3.

Dendritic cells (DCs), the key antigen-presenting cells, are primary regulators of immune responses. Transcriptional regulation of DC development had been one of the major research interests in DC biology; however, the epigenetic regulatory mechanisms during DC development remains unclear. Here, we report that Histone deacetylase 3 (Hdac3), an important epigenetic regulator, is highly expressed in pDCs, and its deficiency profoundly impaired the development of pDCs. Significant disturbance of homeostasis of hematopoietic progenitors was also observed in HDAC3-deficient mice, manifested by altered cell numbers of these progenitors and defective differentiation potentials for pDCs. Using the in vitro Flt3L supplemented DC culture system, we further demonstrated that HDAC3 was required for the differentiation of pDCs from progenitors at all developmental stages. Mechanistically, HDAC3 deficiency resulted in enhanced expression of cDC1-associated genes, owing to markedly elevated H3K27 acetylation (H3K27ac) at these gene sites in BM pDCs. In contrast, the expression of pDC-associated genes was significantly downregulated, leading to defective pDC differentiation.

Adaptive differentiable grids for cryo-electron tomography reconstruction and denoising.

Motivation: Tilt-series cryo-electron tomography is a powerful tool widely used in structural biology to study 3D structures of micro-organisms, macromolecular complexes, etc. Still, the reconstruction process remains an arduous task due to several challenges: The missing-wedge acquisition, sample misalignment and motion, the need to process large data, and, especially, a low signal-to-noise ratio. Results: Inspired by the recently introduced neural representations, we propose an adaptive learning-based representation of the density field of the captured sample. This representation consists of an octree structure, where each node represents a 3D density grid optimized from the captured projections during the training process. This optimization is performed using a loss that combines a differentiable image formation model with different regularization terms: total variation, boundary consistency, and a cross-nodes non-local constraint. The final reconstruction is obtained by interpolating the learned density grid at the desired voxel positions. The evaluation of our approach using captured data of viruses and cells shows that our proposed representation is well adapted to handle missing wedges, and improves the signal-to-noise ratio of the reconstructed tomogram. The reconstruction quality is highly improved in comparison to the state-of-the-art methods, while using the lowest computing time footprint. Availability and implementation: The code is available on Github at https://github.com/yuanhaowang1213/adaptivediffgrid_ex.

Critical review on modified floating photocatalysts for emerging contaminants removal from landscape water: problems, methods and mechanism.

Due to the disorderly discharge in modern production and daily life of people, emerging contaminants(ECs) began to appear in landscape water, and have become a key public concern. Because of the unique characteristics of landscape water, it is difficult to efficiently remove ECs either by natural purification or by traditional large-scale sewage treatment facilities. The ideal purification method is to remove them while maintaining a beautiful environment. Possessing the feature of low-density, floating photocatalysts could harvest sufficient light on the surface of the water for photocatalytic degradation, which may be an important supplement for ECs treatment in landscape water. This paper gave a review related to floating photocatalysts and proposed an idea of combining floating photocatalysts to construct bionic photocatalytic materials for contaminative landscape water treatment. Six types of common floating substrates and corresponding applications for floating photocatalysts were concluded in this paper, and the main problem leading to the low efficiency of photocatalysts and three corresponding three improvement strategies were discussed. Besides, the modification mechanisms of photocatalysts were discussed thoroughly. On this basis, the engineering application prospects of bionic photocatalytic materials were proposed to remove ECs in landscape water.

Mechanically Interlocked [2]Rotaxane Aerogels with Tunable Morphologies and Mechanical Properties.

Mechanical bonds have been utilized as promising motifs to construct mechanically interlocked aerogels (MIAs) with mechanical adaptivity and multifunctionality. However, fabricating such aerogels with not only precise chemical structures but also dynamic features remains challenging. Herein, we present MIAs carrying dense [2]rotaxane units, which bestow both the stability and flexibility of the aerogel network. Owing to the stable chemical structure of a [2]rotaxane, MIAs possessing a precise and full-scale mechanically interlocked network could be fabricated with the aid of diverse solvents. In addition, the dynamic nature of the [2]rotaxane resulted in morphologies and mechanical performances of the MIAs that can be dramatically modulated under chemical stimuli. We hope that the structure-property relationship in MIAs will facilitate the development of mechanically interlocked materials and provide novel opportunities toward constructing smart materials with multifunctionalities.

Fluoroscopy guided transpedicular abscess infusion and drainage in thoracic-lumbar spondylitis with prevertebral abscess.

PURPOSE: To evaluate the effectiveness of fluoroscopy guided transpedicular abscess infusion and drainage in thoracic-lumbar spondylitis with prevertebral abscess. METHODS: We retrospectively reviewed 14 patients with infectious spondylitis with prevertebral abscesses from January 2019 to December 2022. All patients underwent fluoroscopy guided transpedicular abscess infusion and drainage. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), visual analog scale (VAS), Macnab criteria, and magnetic resonance imaging (MRI) were compared before and after the operation to evaluate clinical outcomes. RESULTS: Among the 14 patients with prevertebral abscesses, 64.29% (9/14) involved the lumbar spine and 35.71% (5/14) involved the thoracic spine. The ESR, CRP, and VAS scores decreased from 87.34 ± 9.21, 93.01 ± 11.17, and 8.38 ± 0.97 preoperatively to 12.35 ± 1.61, 8.52 ± 1.19, and 2.02 ± 0.64 at the final follow-up, respectively. MRI at the final follow-up showed the disappearance of the prevertebral abscess compared with that in the preoperative group (66.95 ± 12.63 mm in diameter). Ten patients achieved an "excellent" outcome, while the remaining four patients obtained a "good" outcome according to the Macnab criteria. CONCLUSION: Fluoroscopy guided transpedicular abscess infusion and drainage is a safe and minimally invasive procedure for the management of thoracic-lumbar spondylitis with a prevertebral abscess.

Flexible BaTiO3 Thin Film-Based Coupled Nanogenerator for Simultaneously Scavenging Light and Vibration Energies.

Ferroelectric materials have a variety of properties, such as piezoelectricity, pyroelectricity, and the ferroelectric photovoltaic effect, which enable them to obtain electrical energy from various external stimuli. Here, we report a coupled nanogenerator based on flexible BTO ferroelectric films with a cantilevered beam structure. It combines the photovoltaic and flexoelectric effects in a ferroelectric materials-based coupled nanogenerator for simultaneously scavenging vibration energy and light energy, thus improving energy scavenging performance. As compared with the photovoltaic effect individually, simultaneous vibration and light illumination under a light intensity of 57 mW/cm2 at 405 nm can produce a photo-flexoelectric coupling current of 85 nA, where the current peak has been enhanced by 121%. Due to the photo-flexoelectric coupling effect, the device has outstanding charging performance, where a 4.7 µF capacitor can be charged to 60 mV in 150 s. These devices have potential applications in multi-energy scavenging and self-powered sensors.

Pulsed Laser Spot Welding Thermal-Shock-Induced Microcracking of Inconel 718 Thin Sheet Alloy.

This paper investigates the change in solidification microcrack susceptibility under the influence of thermal-shock-induced effects for pulsed laser spot welding molten pools with different waveforms, powers, frequencies, and pulse widths. During the welding process, the temperature of the molten pool under the effect of thermal shock changes sharply, triggering pressure waves, creating cavities in the molten pool paste area, and forming crack sources during solidification. The microstructure near the cracks was analyzed using a SEM (scanning electron microscope) and EDS (electronic differential system), and it was found that bias precipitation occurred during the rapid solidification of the melt pool, and a large amount of Nb elements were enriched in the interdendritic and grain boundaries, which eventually formed a liquid film with a low melting point, known as a Laves phase. When cavities appear in the liquid film, the chance of crack source formation is further increased. Using a slow rise and slow fall waveform is good for reducing cracks; reducing the peak laser power to 1000 w is good for reducing cracks in the solder joint; increasing the pulse width to 20 ms reduces the degree of crack damage; reducing the pulse frequency to 10 hz reduces the degree of crack damage.

Research Progress of α-Synuclein Aggregation Inhibitors for Potential Parkinson's Disease Treatment.

INTRODUCTION: Parkinson's disease (PD) is characterized by fibrillation of disordered proteins known as Lewy bodies in the substantia nigra that also undergo progressive neurodegeneration. The aggregation of α-synuclein (α-syn) is a hallmark and potentially a critical step in the development of Parkinson's disease and other synucleinopathies. The synaptic vesicle protein α-syn is a small, abundant, highly conserved disordered protein and the causative agent of neurodegenerative diseases. Several novel pharmacologically active compounds are used to treat PD and other neurodegenerative disorders. Though, the mechanism through which these molecules inhibit the α-syn aggregation is still not fully understood. OBJECTIVE: This review article is focused on the recent advancements in compounds that can inhibit the development of α-syn fibrillation and oligomerization. METHODS: The current review article is based on the most recent and frequently cited papers from Google Scholar, SciFinder, and Researchgate sources. DESCRIPTION: In the progression of PD, the mechanism of α-syn aggregation involves the structural transformation from monomers into amyloid fibrils. As the accumulation of α-syn in the brain has been linked to many disorders, the recent search for disease-modifying medications mainly focused on modifying the α-syn aggregation. This review contains a detailed report of literature findings and illustrates the unique structural features, structure-activity relationship, and therapeutic potential of the natural flavonoids in the inhibition of α-syn are also discussed. CONCLUSION: Recently, many naturally occurring molecules such as curcumin, polyphenols, nicotine, EGCG, and stilbene have been recognized to inhibit the fibrillation and toxicity of α-syn. Therefore, knowing the α-synuclein filament's structure and how they originate will help invent particular biomarkers for synucleinopathies and develop reliable and effective mechanism-based therapeutics. We hope the information this review provides may help evaluate novel chemical compounds, such as α- syn aggregation inhibitors, and will contribute to developing novel drugs for treating Parkinson's disease.

In Situ Synthesis of Ni-BTC Metal-Organic Framework@Graphene Oxide Composites for High-Performance Supercapacitor Electrodes.

In response to serious ecological and environmental problems worldwide, a novel graphene oxide (GO) induction method for the in situ synthesis of GO/metal organic framework (MOF) composites (Ni-BTC@GO) for supercapacitors with excellent performance is presented in this study. For the synthesis of the composites, 1,3,5-benzenetricarboxylic acid (BTC) is used as an organic ligand due to its economic advantages. The optimum amount of GO is determined by a comprehensive analysis of morphological characteristics and electrochemical tests. 3D Ni-BTC@GO composites show a similar spatial structure to that of Ni-BTC, revealing that Ni-BTC could provide an effective framework and avoid GO aggregation. The Ni-BTC@GO composites have a more stable electrolyte-electrode interface and an improved electron transfer route than pristine GO and Ni-BTC. The synergistic effects of GO dispersion and Ni-BTC framework on electrochemical behavior are determined, where Ni-BTC@GO 2 achieves the best performance in energy storage performance. Based on the results, the maximum specific capacitance is 1199 F/g at 1 A/g. Ni-BTC@GO 2 has an excellent cycling stability of 84.47% after 5000 cycles at 10 A/g. Moreover, the assembled asymmetric capacitor exhibits an energy density of 40.89 Wh/kg at 800 W/kg, and it still remains at 24.44 Wh/kg at 7998 W/kg. This material is expected to contribute to the design of excellent GO-based supercapacitor electrodes.

Study of Phase Evolution Behavior of Ti6Al4V/Inconel 718 by Pulsed Laser Melting Deposition.

In this study, a pulsed laser was used as the heat source for the additive work. The Ti6Al4V/Inconel 718 alloy wire was deposited on the substrate by melting using a pulsed laser. Using the above method, single-layer and double-layer samples were printed. The sample material printed in this way is highly utilized. Compared to the complicated pre-preparation work of metal powder pre-mixing, this printing method is simple to prepare and only requires changing the wire feeding speed. The study of this paper provides a theoretical guide for the subsequent fusion deposition of heterogeneous wire materials. The samples were analyzed after molding using SEM, EDS and XRD to characterize the microstructure of the samples. The samples can be divided into three zones depending on the microstructure, the bottom columnar crystal zone, the middle mixed phase zone, and the bottom equiaxed crystal zone. From the bottom to the top of the sample, the phase microstructure changes as γ + Laves → α + ß + Ti2Ni + TiNi + Ni3Ti → α + ß. The hardness data show that the highest value in the transition zone is 951.4 HV. The hardness of the top part is second only to the transition zone due to a large number of equiaxed crystals. The bottom region is dominated by columnar crystals and is the softest of the three regions with the lowest hardness value of 701.4 HV.

Solvent-Responsive Reversible and Controllable Conversion between a Polyimine Membrane and an Organic Molecule Cage.

Adaptive bionic self-correcting behavior offers an attractive property for chemical systems. Here, based on the dynamic feature of imine formation, we propose a solvent-responsive strategy for smart switching between an amorphous ionic polyimine membrane and a crystalline organic molecule cage without the addition of other building blocks. To adapt to solvent environmental constraints, the aldehyde and amine components undergo self-correction to form a polymer network or a molecular cage. Studies have shown that the amorphous film can be switched in acetonitrile to generate a discrete cage with bright birefringence under polarized light. Conversely, the membrane from the cage crystal conversion can be regained in ethanol. Such a membrane-cage interconversion can be cycled continuously at least 5 times by switching the two solvents. This work builds a bridge between the polymer network and crystalline molecules and offers prospects for smart dynamic materials.

Progress in semiconductor materials for photocathodic protection: Design strategies and applications in marine corrosion protection.

Metal protection of offshore equipment is very complicated owing to the complex marine environment. Photocathodic protection (PCP) is one of the popular research topics in marine metal protection. The protection efficiency of photoanode depends largely on the photoelectric properties of semiconductor materials, viz. the process of charge separation, charge migration, and light absorption. In this article, the enhancement strategies, photoelectrochemical properties, and electron transfer mechanisms of different composites for PCP were reviewed and highlighted. Some photoanodes with unusual and striking properties were emphasized. In addition, the outlooks and challenges of the application of PCP and the design of photoanodes materials are proposed.

Light-Driven Conversion of Silicon Nitride Nanopore to Nanonet for Single-Protein Trapping Analysis.

The single-molecule technique for investigation of an unlabeled protein in solution is very attractive but with great challenges. Nanopore sensing as a label-free tool can be used for collecting the structural information of individual proteins, but currently offers only limited capabilities due to the fast translocation of the target. Here, a reliable and facile method is developed to convert the silicon nitride nanopore to a stable nanonet platform for single-entity sensing by electrophoretic or electroosmotic trapping. A nanonet is fabricated based on a material reorganization process caused by electron-beam and light-irradiation treatment. Using protein molecules as a model, it is revealed that the solid-state nanonet can produce collision and trapping flipping signals of the protein, which provides more structural information than traditional nanopore sensing. More importantly, thanks to the excellent stability of the solid-state silicon nitride nanonet, it is demonstrated that the ultraviolet-light-irradiation-induced structural-change process of an individual protein can be captured. The developed nanonet supplies a robust platform for single-entity studies but is not limited to proteins.

New natural furfural derivatives from the leaves and stems of Pogostemon cablin.

A new furfural derivative, pogoscafuran A (1), a new natural product, HMF levulinate (2), together with four known compounds (3-6) were isolated from an extract of the leaves and stems of Pogostemon cablin (Blanco) Benth. Their structures were elucidated on the basis of extensive spectroscopic analyses and single-crystal X-ray crystallography. Compound 1 was the first example of natural furfural derivative with a unique C5-C1' linkage between a molecule of furfural and 3-methyl-2-cyclopentenone moiety. The plausible biogenetic pathway for the new compound 1 was proposed. All these isolated compounds were tested for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells, and only compound 1 exhibited weak inhibitory activity.