Long noncoding RNA small nucleolar RNA host gene 5 facilitates neuropathic pain in spinal nerve injury by promoting SCN9A expression via CDK9.

This study aims to explore the functions and mechanisms of long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) in chronic constriction injury (CCI)-induced neuropathic pain (NP). An NP rat model was established using the CCI method and the NP severity was evaluated by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The expression of SNHG5, CDK9, and SCN9A was quantified in rat dorsal root ganglion, in addition to the detections of apoptosis, pathological changes, neuron number, and the co-localization of Nav1.7 and cleaved caspase-3 with NeuN. In ND7/23 cells, the apoptosis and lactate dehydrogenase concentration were assessed, as well as the relationship between SNHG5, CDK9, and SCN9A. In the dorsal root ganglion of CCI-treated rats, SNHG5 and SCN9A were upregulated and downregulation of SNHG5 suppressed SCN9A expression, increased the PWT and PWL, blocked neuroinflammation and neuronal apoptosis, and alleviated NP. Mechanistically, SNHG5 recruited CDK9 to enhance SCN9A-encoded Nav1.7 expression and promoted peripheral neuronal apoptosis and injury. In addition, SCN9A overexpression nullified the alleviative effects of SNHG5 deficiency on NP and neuron loss in CCI rats. In conclusion, SNHG5 promotes SCN9A-encoded Nav1.7 expression by recruiting CDK9, thereby facilitating neuron loss and NP after spinal nerve injury, which may offer a promising target for the management of NP.

Biomechanical evaluation of different oblique lumbar interbody fusion constructs: a finite element analysis.

BACKGROUND: Finite element analysis (FEA) was performed to investigate the biomechanical differences between different adjunct fixation methods for oblique lumbar interbody fusion (OLIF) and to further analyze its effect on adjacent segmental degeneration. METHODS: We built a single-segment (Si-segment) finite element model (FEM) for L4-5 and a double-segment (Do-segment) FEM for L3-5. Each complete FEM was supplemented and modified, and both developed two surgical models of OLIF with assisted internal fixation. They were OLIF with posterior bilateral percutaneous pedicle screw (TINA system) fixation (OLIF + BPS) and OLIF with lateral plate system (OLIF + LPS). The range of motion (ROM) and displacement of the vertebral body, cage stress, adjacent segment disc stress, and spinal ligament tension were recorded for the four models during flexion/extension, right/left bending, and right/left rotation by applying follower load. RESULTS: For the BPS and LPS systems in the six postures of flexion, extension, right/left bending, and right/left rotation, the ROM of L4 in the Si-segment FEM were 0.32°/1.83°, 0.33°/1.34°, 0.23°/0.47°, 0.24°/0.45°, 0.33°/0.79°, and 0.34°/0.62°; the ROM of L4 in the Do-segment FEM were 0.39°/2.00°, 0.37°/1.38°, 0.23°/0.47°, 0.21°/0.44°, 0.33°/0.57°, and 0.31°/0.62°, and the ROM of L3 in the Do-segment FEM were 6.03°/7.31°, 2.52°/3.50°, 4.21°/4.38°, 4.21°/4.42°, 2.09°/2.32°, and 2.07°/2.43°. BPS system had less vertebral displacement, less cage maximum stress, and less spinal ligament tension in Si/Do-segment FEM relative to the LPS system. BPS system had a smaller upper adjacent vertebral ROM, greater intervertebral disc stress in terms of left and right bending as well as left and right rotation compared to the LPS system in the L3-4 of the Do-segment FEM. There was little biomechanical difference between the same fixation system in the Si/Do-segment FEM. CONCLUSIONS: Our finite element analysis showed that compared to OLIF + LPS, OLIF + BPS (TINA) is more effective in reducing interbody stress and spinal ligament tension, and it better maintains the stability of the target segment and provides a better fusion environment to resist cage subsidence. However, OLIF + BPS (TINA) may be more likely to cause adjacent segment degeneration than OLIF + LPS.

DOT1L decelerates the development of osteoporosis by inhibiting SRSF1 transcriptional activity via microRNA-181-mediated KAT2B inhibition.

OBJECTIVE: Our study explored the function of DOT1L in osteoporosis (OP) via the microRNA (miR)-181/KAT2B/SRSF1 axis. METHODS: Osteoclast (OC) number was evaluated via TRAP staining, and serum CTXI, PINP, and ALP contents were tested by ELISA. Following identification of bone marrow mesenchymal stem cells (BMSCs), OC differentiation was induced by M-CSF and RANKL, followed by the detection of OC differentiation and the expression of bone resorption-related genes, DOT1L, miR-181, KAT2B, and SRSF1. RESULTS: Overexpressed DOT1L or miR-181 stimulated calcified nodule formation and increased alkaline phosphatase activity and osteogenic marker gene expression. KAT2B knockdown enhanced the osteogenic differentiation of BMSCs by reducing SRSF1 acetylation. The enhancement of OC differentiation induced by overexpressed SRSF1 was inhibited by simultaneous DOT1L or miR-181 overexpression. DOT1L suppressed OP development in vivo via the miR-181/KAT2B/SRSF1 axis. CONCLUSION: DOT1L overexpression slowed down bone loss and promoted bone formation via the miR-181/KAT2B/SRSF1 axis, thereby alleviating OP development.

microRNA-143 targets SIRT2 to mediate the histone acetylation of PLAUR and modulates functions of astrocytes in spinal cord injury.

This study aimed to explore effects of microRNA (miR)-143 on the proliferation, apoptosis, and cytokine secretion in astrocytes after spinal cord injury (SCI). After gain- and loss-of-function assays and transforming growth factor (TGF)-ß stimulation in astrocytes, the cell viability, proliferation, and apoptosis were examined. The expression of miR-143, SIRT2, and PLAUR and levels of astrocyte-related glial fibrillary acidic protein (GFAP), Vimentin, chondroitin sulfate proteoglycan (CSPG), and connective tissue growth factor (CTGF) were also measured. The binding relationship between miR-143 and SIRT2 was assessed, as well as the correlation of PLAUR with SIRT2. In established SCI rat models, the locomotion function and astrocyte hyperplasia were detected. The TGF-ß stimulation decreased miR-143 but increased SIRT2 expression in astrocytes. Mechanistically, miR-143 negatively targeted SIRT2 and SIRT2 down-regulation inhibited the H3K27 deacetylation of PLAUR promoter to increase PLAUR expression. miR-143 up-regulation inhibited TGF-ß stimulated-proliferation, promoted cell apoptosis, and reduced GFAP, Vimentin, CSPG, and CTGF expression in astrocytes, which was counterweighed by SIRT2 overexpression. SIRT2 silencing reduced the proliferation and GFAP, Vimentin, CSPG, and CTGF expression while augmenting the apoptosis in TGF-ß stimulated astrocytes, which was abrogated by PLAUR silencing. The injection of miR-143 agomir improved the locomotion function and reduced the astrocyte hyperplasia in SCI rats, which was reversed by silencing PLAUR. miR-143 targeted SIRT2 to affect PLAUR expression via the regulation of histone acetylation, which repressed the astrocyte activation in vivo and in vitro to improve the locomotion function in SCI rats.

Yttrium-modified drinking water treatment residue for efficient phosphorus removal: efficacy, mechanism, and reproducibility.

The excessive presence of phosphate can cause eutrophication in water bodies. Yttrium has an extremely high affinity for phosphorus and is capable of forming stable complexes at low concentrations. Moreover, limitations in the resourcefulness of drinking water treatment residues were observed. In this study, a highly efficient phosphorus removal adsorbent (RJDWTR@Y) was prepared by calcination-alkali leaching-yttrium-loaded composite modification employing domestic drinking water treatment residue as raw material. And the effects of multiple factors on phosphate adsorption by RJDWTR@Y were examined. The results illustrated that the maximum adsorption capacity of the RJDWTR@Y for phosphate was 319.76 mg/g, with the chemical reaction of the multilayer as the predominant adsorption process. The adsorption mechanism is electrostatic gravitational force and the inner sphere complexation effect. RJDWTR@Y was effective against interference even at high concentrations of the coexisting anion. After five cycles, the desorption efficiency of phosphate was 75.11%. Filling the fixed bed with the material can efficiently remove phosphorus from the flowing liquid. The synthesis of RJDWTR@Y and the results of the study indicated that it has good application prospects. In addition to efficiently removing phosphorus, it can also recycle waste and achieve sustainability.

Effect of body mass index (BMI) on image contrast in the hepatobiliary phase of Gd-EOB-DTPA-enhanced-MRI and the feasibility of the application of half-dose Gd-EOB-DTPA to hepatobiliary phase imaging in patients with a BMI less than 24: a comparative study.

Background: Gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can detect more lesions through the image contrast of hepatobiliary phase. Body mass index (BMI) reflects the composition ratio of human tissue, which is an influencing factor of magnetic resonance image contrast. Meanwhile, Gd-EOB-DTPA is recommended to use the minimum dose when the diagnosis demands could be met. The aim of this paper was to investigate the effect of BMI on hepatobiliary phase image contrast and explore the feasibility of using low-dose Gd-EOB-DTPA to obtain good hepatobiliary phase image contrast in patients with normal and lean BMI. Methods: Eighty-two patients who had previously undergone Gd-EOB-DTPA-enhanced MRI (0.025 mmol/kg) were collected and divided into group A (BMI <24 kg/m2) and group B (BMI ≥24 kg/m2) according to Chinese BMI standards. Liver-to-portal vein contrast ratio (LPC20) and liver-to-spleen contrast ratio (LSC20) in hepatobiliary phase (20 min after injection) were calculated. Thirty patients with a BMI <24 kg/m2 who were about to receive Gd-EOB-DTPA-enhanced MRI were randomly divided into group C (0.0125 mmol/kg) and group D (0.025 mmol/kg). Image acquisition was performed at 10, 15, and 20 min after injection. LPC10, LPC15, LPC20 and LSC10, LSC15, LSC20 in corresponding phases were calculated. Results: In retrospective grouping study, compared with group B, group A's LPC20 was significantly higher [2.63 (2.42-3.00) vs. 2.22 (1.97-2.67); P<0.01]. In prospective grouping study, there were no differences in LPC15, LSC15, LPC20 and LSC20 between group C and group D. Intragroup comparison in each group showed that LPC15 (group C: 2.67±0.33; group D: 2.61±0.21) and LPC20 (group C: 2.74±0.37; group D: 2.72±0.27) were higher than LPC10 (group C: 2.19±0.18; group D: 1.94±0.17) (all P<0.01), while there were no changes between LPC15 and LPC20. Conclusions: Under conventional dose, hepatobiliary phase image contrast in patients with a BMI <24 was higher, which was mainly manifested in the high LPC. For patients with a BMI <24 kg/m2, using a half conventional dose (0.0125 mmol/kg), good hepatobiliary phase image contrast can still be obtained at 15-20 min after administration.

EGR1 mediates METTL3/m6A/CHI3L1 to promote osteoclastogenesis in osteoporosis.

OBJECTIVE: To investigate EGR1-mediated METTL3/m6A/CHI3L1 axis in osteoporosis. METHODS: Ovariectomy (OVX) was performed on mice to induce osteoporosis, followed by µ-CT scanning of femurs, histological staining, immunohistochemistry analysis of MMP9 and NFATc1, and ELISA of serum BGP, ALP, Ca, and CTXI. The isolated mouse bone marrow mononuclear macrophages (BMMs) were differentiated into osteoclasts under cytokine stimulation. TRAP staining was performed to quantify osteoclasts. The levels of Nfatc1, c-Fos, Acp5, and Ctsk in osteoclasts, m6A level, and the relationships among EGR1, METTL3, and CHI3L1 were analyzed. RESULTS: The EGR1/METTL3/CHI3L1 levels and m6A level were upregulated in osteoporotic mice and the derived BMMs. EGR1 was a transcription factor of METTL3. METTL3 promoted the post-transcriptional regulation of CHI3L1 by increasing m6A methylation. EGR1 downregulation reduced BMMs-differentiated osteoclasts and alleviated OVX-induced osteoporosis by regulating the METTL3/m6A/CHI3L1 axis. CONCLUSION: EGR1 promotes METTL3 transcription and increases m6A-modified CHI3L1 level, thereby stimulating osteoclast differentiation and osteoporosis development.

Continuous-Spectrum-Polarization Recombinant Optical Encryption with a Dielectric Metasurface.

The Jones matrix, with eight degrees of freedom (DoFs), provides a general mathematical framework for the multifunctional design of metasurfaces. Theoretically, the maximum eight DoFs can be further extended in the spectrum dimension to endow unique encryption capabilities. However, the topology and intrinsic spectral responses of meta-atoms constrains the continuous engineering of polarization evolution over wavelength dimension. In this work, a forward evolution strategy to quickly establish the mapping relationships between the solutions of the dispersion Jones matrix and the spectral responses of meta-atoms is reported. Based on the eigenvector transformation method, arbitrary conjugate polarization channels over the continuous-spectrum dimension are successfully reconstructed. As a proof-of-concept, a silicon metadevice is demonstrated for optical information encryption transmission. Remarkably, the arbitrary combination forms of polarization and wavelength dimension increase the information capacity (210 ), and the measured polarization contrasts of the conjugate polarization conversion are >94% in the entire wavelength range (3-4 µm). It is believed that the proposed approach will benefit secure optical and quantum information technologies.

Overexpression of SENP3 promotes PPAR-γ transcription through the increase of HIF-1α stability via SUMO2/3 and participates in molecular mechanisms of osteoporosis.

Patients with type II diabetes are exposed to a high risk of osteoporosis. The present study sought to exploit the detailed mechanisms of the SENP3/HIF-1α/PPAR-γ axis in osteoporosis. A rat model of type II diabetic osteoporosis was established, followed by the isolation of bone marrow mononuclear macrophages (BMMs). Gain- and loss-of-function assays were conducted in rat models and BMMs from rat models, followed by the evaluation of SENP3, HIF-1α, and PPAR-γ expression and detection of osteoclast differentiation-related indexes. Next, the SUMOylated modification of HIF-1α and the regulation of SENP3 on SUMOylated modification level of HIF-1α were assessed using immunoprecipitation, and the binding of HIF-1α to the PPARγ promoter was identified with ChIP and dual-luciferase reporter assays. SENP3 and HIF-1α expression was down-regulated in tissues of type II diabetes-induced osteoporotic rats and BMMs, with high SUMOylated modification levels of HIF-1α. Mechanically, HIF-1α was modified by SUMO2/3. SENP3 suppressed SUMOylated modification of HIF-1α and enhanced HIF-1α stability. HIF-1α bound to the PPAR-γ promoter and facilitated PPAR-γ transcription. SENP3 overexpression restrained osteoblast differentiation in type II diabetes-induced osteoporotic rats and BMMs from rat models. SENP3 knockdown facilitated osteoclast differentiation in type II diabetes-induced osteoporotic rats and BMMs from rat models, which was neutralized by further HIF-1α overexpression. To sum up, SENP3 overexpression restrained osteoclast differentiation in type II diabetic osteoporosis by increasing HIF-1α stability and expression and thus promoting PPAR-γ expression via de-SUMOylation, which might expand the understanding of the mechanisms of type II diabetes combined with osteoporosis.

The RNA Binding Protein HuR Promotes Neuronal Apoptosis in Rats with Spinal Cord Injury via the HDAC1/RAD21 Axis.

The current research aims to study the regulation of the RNA binding protein HuR on neuronal apoptosis during spinal cord injury (SCI) and its underlying mechanism. SCI rat models were injected with HuR shRNA and/or pcDNA3.1-RAD21, followed by the evaluation of motor function, the degree of SCI, the expression of HuR and RAD21, and neuronal-like apoptosis. The co-localization of HuR-RAD21, RAD21-NeuN, and NeuN-cleaved caspase 3 was measured by immunofluorescence. Additionally, targeting relationships among HuR, HDAC1, and RAD21 were verified by chromatin immunoprecipitation and RNA immunoprecipitation. After transfection, apoptosis of PC12 cells was tested by flow cytometry. Results showed that silencing HuR or up-regulating RAD21 could alleviate SCI and reduce neuronal apoptosis. HuR could combine HDAC1 mRNA, and HDAC1 combined the promoter of RAD21. Further experiments revealed that HuR enhanced HDAC1 expression and reduced RAD21 promoter region acetylation. Overexpression of RAD21 reversed the enhancement in apoptosis of PC12 cells caused by overexpression of HuR. The injection of HuR shRNA in tail vein of SCI rats increased basso, beattie, and bresnahan score, relieved SCI, reduced HuR and HDAC1 expression, elevated RAD21 expression, and decreased neuronal-like apoptosis. However, this result was reversed by co-injection of pcDNA3.1-HDAC1. In conclusion, down-regulation of HuR alleviated SCI and neuronal apoptosis in rats by suppressing HDAC1 expression and promoting RAD21 expression.

Polychromatic full-polarization control in mid-infrared light.

Objects with different shapes, materials and temperatures can emit distinct polarizations and spectral information in mid-infrared band, which provides a unique signature in the transparent window for object identification. However, the crosstalk among various polarization and wavelength channels prevents from accurate mid-infrared detections at high signal-to-noise ratio. Here, we report full-polarization metasurfaces to break the inherent eigen-polarization constraint over the wavelengths in mid-infrared. This recipe enables to select arbitrary orthogonal polarization basis at individual wavelength independently, therefore alleviating the crosstalk and efficiency degradation. A six-channel all-silicon metasurface is specifically presented to project focused mid-infrared light to distinct positions at three wavelengths, each with a pair of arbitrarily chosen orthogonal polarizations. An isolation ratio of 117 between neighboring polarization channels is experimentally recorded, exhibiting detection sensitivity one order of magnitude higher than existing infrared detectors. Remarkably, the high aspect ratio ~30 of our meta-structures manufactured by deep silicon etching technology at temperature -150 °C guarantees the large and precise phase dispersion control over a broadband from 3 to 4.5 µm. We believe our results would benefit the noise-immune mid-infrared detections in remote sensing and space-to-ground communications.

USP7 regulates HMOX-1 via deubiquitination to suppress ferroptosis and ameliorate spinal cord injury in rats.

Heme oxygenase 1 (HMOX-1) is overexpressed in spinal cord injury (SCI) and relevant to ferroptosis. Ubiquitin-specific-processing protease 7 (USP7) has unveiled its role in regulating HMOX-1 stabilization while its function in SCI remains unknown. This study is to explore the potential molecular mechanism of the USP7-HMOX-1 axis in ferroptosis in a SCI rat model. SCI was assessed with Basso, Beattie, Bresnahan locomotion evaluation, hematoxylin-eosin histological staining, and immunofluorescence detection of NeuN. Ferroptosis was assessed by detections of the iron content, malondialdehyde and glutathione levels, mitochondrial damage, and glutathione peroxidase 4, 4-hydroxynonenal, USP7, and HMOX-1 expression in spinal cord. Co-immunoprecipitation was used to detect the binding of USP7 to HMOX-1. The ubiquitination level of HMOX-1 was measured after USP7 overexpression. USP7 expression was downregulated and HMOX-1 expression was upregulated in SCI rat models. HMOX-1 or USP7 overexpression promoted motor function recovery, ameliorated spinal cord damage, increased NeuN expression, and blocked the occurrence of ferroptosis in SCI rat models. In SCI rats, USP7 directly bound to HMOX-1 and its overexpression promoted HMOX-1 expression via deubiquitination. To sum up, USP7 overexpression facilitated the expression of HMOX-1 through deubiquitination, thereby reducing ferroptosis and alleviating SCI.

Upregulation of UBR1 m6A Methylation by METTL14 Inhibits Autophagy in Spinal Cord Injury.

Gene Expression Omnibus database shows significantly downregulated expression of ubiquitin protein ligase E3 component N-recognin 1 (UBR1) in spinal cord injury (SCI). In this study, we investigated the mechanism of action of UBR1 in SCI. Following the establishment of SCI models in rats and PC12 cells, Basso-Beattie-Bresnahan (BBB) score and hematoxylin-eosin (H&E) and Nissl staining were used to evaluate SCI. The localization of NeuN/LC3 and the expression of LC3II/I, Beclin-1, and p62 were detected to assess autophagy. The expression of Bax, Bcl-2, and cleaved caspase-3 was detected and TdT-mediated dUTP-biotin nick end-labeling staining was employed to determine the changes in apoptosis. The N(6)-methyladenosine (m6A) modification level of UBR1 was analyzed by methylated RNA immunoprecipitation, and the binding of METTL14 and UBR1 mRNA was analyzed by photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation. UBR1 was poorly expressed, and METTL14 was highly expressed in rat and cell models of SCI. UBR1 overexpression or METTL14 knock-down enhanced motor function in rats with SCI. Moreover, this modification increased Nissl bodies and autophagy and inhibited apoptosis in the spinal cord of SCI rats. METTL14 silencing reduced the m6A modification level of UBR1 and enhanced UBR1 expression. Importantly, UBR1 knock-down nullified METTL14 knock-down-induced autophagy promotion and apoptosis reduction. The METTL14-catalyzed m6A methylation of UBR1 promoted apoptosis and inhibited autophagy in SCI.

Suberoylanilide Hydroxamic Acid Ameliorates Pain Sensitization in Central Neuropathic Pain After Spinal Cord Injury via the HDAC5/NEDD4/SCN9A Axis.

Pain sensitization in spinal cord injury (SCI)-induced central neuropathic pain has been a research target. Additionally, suberoylanilide hydroxamic acid (SAHA) has been reported to protect against pain hypersensitivity in central neuropathic pain. Hence, this research probed the impact of SAHA on pain sensitization in central neuropathic pain after SCI via the HDAC5/NEDD4/SCN9A axis. After SAHA treatment, SCI modeling, and gain- and loss-of-function assays, behavioral analysis was performed in mice to evaluate pain hypersensitivity and anxiety/depression-like behaviors. The enrichment of H3K27Ac in the NEDD4 promoter and the ubiquitination of SCN9A were measured with ChIP and Co-IP assays, respectively. The treatment of SAHA regained paw withdrawal threshold and paw withdrawal latency values, entry time and numbers in the center area, and entry proportion in the open arm for SCI mice, accompanied by decreases in immobility time, eating latency, thermal hyperalgesia, and mechanical ectopic pain. However, SAHA treatment did not affect the motor function of mice. SAHA treatment lowered HDAC5 expression and SCN9A protein expression in SCI mice, as well as enhanced SCN9A ubiquitination and NEDD4 expression. HDAC5 knockdown greatly increased H3K27Ac enrichment in the NEDD4 promoter. NEDD4 upregulation or HDAC5 knockdown elevated SCN9A ubiquitination but diminished SCN9A protein expression in dorsal root ganglions of SCI mice. NEDD4 silencing mitigated the improving effects of SAHA treatment on the pain hypersensitivity and anxiety/depression-like behaviors of SCI mice. SAHA suppressed HDAC5 to augment NEDD4 expression and SCN9A degradation, thereby ameliorating the pain hypersensitivity and anxiety/depression-like behaviors of SCI mice.

Electroconvulsive therapy-induced neuroimaging alterations measured by cerebral blood flow in adolescents with major depressive disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is a novel treatment strategy for adolescents with major depressive disorder (MDD). However, its related neurobiological changes associated with ECT remain undetermined. OBJECTIVE: To elucidate the impact of ECT on the regional cerebral blood flow (CBF), and to identify alterations in the CBF associated with clinical outcomes in adolescents with MDD. METHODS: Fifty-two treatment-naive adolescents who had experienced their first episode of MDD and 36 healthy controls (HCs) were recruited. To assess baseline parameters, all subjects were scanned with arterial spin labeling resting-state functional magnetic resonance imaging (ASL-fMRI) at the beginning of the study. Subsequently, 27 MDD adolescents were re-scanned after 2 weeks after ECT. CBF imaging was used for the prediction of specific clinical outcomes. Lastly, the associations between alterations seen on brain imaging alterations after ECT and ECT clinical efficacy (ΔHAMD scores) were determined. RESULTS: Relative to HCs, adolescents with MDD exhibited reduced CBF in the left medial superior frontal gyrus (SFGmed) (cluster = 243, peak t = -3.9373, and P < 0.001) and augmented CBF in the right percental gyrus (PerCG) (cluster = 321, peak t = 4.3332, and P < 0.001) at baseline. Following ECT, MDD adolescents exhibited reduced CBF in the right fusiform gyrus (FFG) (cluster = 309, peak t = -4.346, and P < 0.001) and left hippocampus (HIP) (cluster = 290, peak t = -4.706, and P < 0.001), and enhanced CBF in the left orbital part of the inferior frontal gyrus (ORBinf) (cluster = 214, peak t = 4.073, and P < 0.001). Correlation analysis suggested an inverse association between ΔHAMD scores and CBF values in the left ORBinf (R2 = 0.196, P = 0.021). CONCLUSIONS: It was found that ECT resulted in alterations in CBF in specific brain areas, highlighting the significance of ORBinf in ECT pathophysiology in MDD adolescents.

Myricetin alleviated hydrogen peroxide-induced cellular senescence of nucleus pulposus cell through regulating SERPINE1.

BACKGROUND: Myricetin (MYR) is a common plant flavonoid with antioxidant and anticancer properties. However, the anti-aging effect of MYR on nucleus pulposus cells (NPCs) is still unknown. The study aimed to explore the effect of MYR on the senescence of NPCs. METHODS: Methyl-thiazolyl tetrazolium assay was used to detect NPCs viability. Senescence level was evaluated by senescence-associated ß-galactosidase (SA-ß-Gal) staining and the expression levels of P21, P16, IL-6 and IL-8. RNA-Sequencing (RNA-seq) technology was used to identify differentially expressed genes (DEGs) between hydrogen peroxide + MYR (HO + MYR) group and HO group, and Gene Ontology (GO) functional was performed to analyze DEGs. A Venn diagram was generated to screen overlapping DEGs related to aging and inflammation, and the role of the promising validated DEG was selected for further investigation by gene functional assays. RESULTS: HO inhibited NPCs viability and stimulated the senescent phenotype of NPCs, whereas MYR treatment significantly reversed SA-ß-gal activity in NPCs. MYR also reduced the expression of p21 and p16 and the secretion of IL-6 and IL-8 induced by HO. RNA-seq screened 421 DEGs. The GO enrichment results showed DEGs were mainly enriched in terms such as "sterol biosynthetic process". We also found SERPINE1 has the highest log2FC abs. Silence of SERPINE1 inhibited HO-induced NPCs senescence, and overexpression of SERPINE1 could limit the anti-aging effect of MYR. CONCLUSIONS: MYR alleviated HO-induced senescence of NPCs by regulating SERPINE1 in vitro.

METTL14 alleviates the development of osteoporosis in ovariectomized mice by upregulating m6A level of SIRT1 mRNA.

The purpose of this study was to investigate whether METTL14 participated in ovariectomized (OVX)-induced osteoporosis (OP) in mice by regulating the m6A level of SIRT1 mRNA. OVX was performed on mice to induce OP, and mouse bone marrow stromal cells (BMSCs) and bone marrow mononuclear macrophages (BMMs) were isolated to induce osteoblast differentiation and osteoclast differentiation, respectively. The morphology of bone trabeculae was evaluated under a micro-CT scanner. The changes in pathology of bone tissues were observed through staining using hematoxylin-eosin. The number of osteoclasts was measured by tartrate-resistant acid phosphatase staining, and the content of serum calcium, PINP, and CTX-I was tested by enzyme-linked immunosorbent assay, accompanied by the measurement of the expression of SIRT1, METTL14, osteogenic marker genes, and osteoclast marker genes. The m6A modification level of SIRT1 and the binding between METTL14 and SIRT1 were verified. In OVX mice, SIRT1 and METTL14 were downregulated. Overexpression of SIRT1 or METTL14 increased the expression of osteogenic marker genes but decreased the expression of osteoclast marker genes. Additionally, METTL14 overexpression increased m6A level of SIRT1 mRNA. Furthermore, overexpression of METTL14 promoted osteoblast differentiation and suppressed osteoclast differentiation, which were reversed by knockdown of SIRT1. METTL14 promoted osteoblast differentiation and repressed osteoclast differentiation by m6A-dependent upregulation of SIRT1 mRNA, thereby alleviating OP development.

Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy.

This study aimed to explore the effects of long non-coding RNAs LINC00689 (LINC00689) in human nucleus pulposus cells (NPCs). NPCs were isolated and their morphology was observed. The proliferation and apoptosis of NPCs, and the levels of LINC00689, miR-3127-5p, Bax, Bcl-2, Cleaved caspase-3, ATG5, ATG7, p62, and LC3Ⅱ/LC3I were detected. Interrelations of LINC00689, miR-3127-5p, and ATG7 were analyzed. LINC00689 was down-regulated yet miR-3127-5p was up-regulated in NPCs. LINC00689 could competitively bind with miR-3127-5p, and ATG7 was targeted by miR-3127-5p in NPCs. Overexpressed LINC00689 promoted proliferation yet inhibited apoptosis of NPCs, whereas LINC00689 silencing did the opposite. Overexpressed LINC00689 raised ATG7 level and LC3Ⅱ/LC3I value yet reduced that of p62 level, but the depletion of LINC00689 did the contrary. ATG7 silencing abolished the effects of overexpressed LINC00689 in NPCs, and likewise, up-regulation of miR-3127-5p overturned the effects of overexpressed LINC00689 in NPCs. Collectively, the up-regulation of LINC00689 inhibits the apoptosis of NPCs via miR-3127-5p/ATG7 axis-mediated autophagy.

Polarization-controlled varifocal metalens with a phase change material GSST in mid-infrared.

Detection of aldehyde carbonyl radiation plays an essential role in guaranteeing the safety of fried food. However, the radiation of low-content aldehyde carbonyl is always weak and includes polarized light. Focusing the weak radiation with polarization-sensitive configurations provides an efficient way to improve the signal-to-noise ratio of detection. The advent of dynamic metasurfaces based on phase-change materials (PCMs) have demonstrated superiorities over their traditional counterparts in tunability and miniaturization. In this paper, we propose two reflected varifocal metasurfaces, which combine Ge2Sb2Se4Te1 (GSST) with two materials that have close optical constants with amorphous and crystalline GSST. The first one realizes a four-spot focal system with linearly-polarized incidence based on polarization multiplexing. It adds a new polarization degree of freedom compared with traditional varifocal metasurfaces. Compared with traditional spatial-multiplexing method, our second metasurface enables the independent control of the polarization and phase profiles of circularly-polarized light. Remarkably, it reduces energy loss and crosstalk. We believe the novel scenarios of combing GSST with similar materials provide a new direction for tunable metasurfaces based on PCMs.

NBR2/miR-561-5p/DLC1 axis inhibited the development of multiple myeloma by activating the AMPK/mTOR pathway to repress glycolysis.

Long non-coding RNA NBR2 exerts a tumor-suppressive effect in a variety of cancers, but its role in multiple myeloma (MM) is unclear. This article will elucidate the role of NBR2 in MM. The expressions of NBR2, miR-561-5p, and deleted in liver cancer 1 (DLC1) in MM cell lines were determined by quantitative real time polymerase chain reaction (qRT-PCR). The regulatory relationship of the NBR2/miR-561-5p/DLC1 axis was predicted by bioinformatics and confirmed via a dual-luciferase reporter assay. The effect of NBR2 on the biological behavior of MM cells was verified by loss- and gain-of-function experiments (cell counting kit-8, colony formation, flow cytometry, extracellular acidification rate, and lactate production measurement). The effects of the NBR2/miR-561-5p axis on the biological behavior of MM cells, the activation of the AMPK/mTOR signaling pathway (western blot), and DLC1 expression (western blot) were verified by rescue experiments. The upregulation of NBR2 in MM cell lines induced a decrease in the viability, proliferation capacity, glycolysis, and lactic acid production, and an increase in apoptosis of MM cells. NBR2 regulated the biological behavior of MM cells and the activation of the AMPK/mTOR signaling pathway by targeting miR-561-5p. DLC1 was the target gene of miR-561-5p and the protein expression of DLC1 was regulated by the NBR2/miR-561-5p axis. Collectively, NBR2/miR-561-5p/DLC1 axis inhibits the development of MM by activating the AMPK/mTOR pathway to repress glycolysis.