High glucose enhances fibrosis in human annulus fibrosus cells by activating mTOR, PKCδ, and NF-κB signaling pathways.

Low back pain stands as a significant factor in disability, largely resulting from intervertebral disc degeneration (IVDD). High glucose (HG) levels have been implicated in the pathogenesis of IVDD. However, the detailed mechanism of HG in IVDD is largely unknown. Our clinical results revealed that fibrosis markers such as CTGF, Col1a1, ATF4, and EIF2 are highly expressed in advanced-stage IVDD patients. Stimulation of human annulus fibrosus cells (HAFCs) with HG, but not mannitol, promotes fibrosis protein production. Ingenuity Pathway Analysis in the GSE database found that the mTOR, PKCδ, and NF-κB pathways were significantly changed during IVDD. The mTOR, PKCδ, and NF-κB inhibitors or siRNAs all abolished HG-induced fibrosis protein production. In addition, treatment of HAFCs with HG enhances the activation of mTOR, PKCδ, and NF-κB pathways. Thus, HG facilitates fibrosis in IVDD through mTOR, PKCδ, and NF-κB pathways. These results underscore the critical role of HG as a fibrotic factor in the progression of IVDD.

MCP-1 controls IL-17-promoted monocyte migration and M1 polarization in osteoarthritis.

Osteoarthritis (OA) is a low-grade inflammatory joint illness in which monocytes migrate and infiltrate synovial tissue, differentiating into the pro-inflammatory M1 macrophage phenotype. IL-17 is a proinflammatory mediator principally generated by Th17 cells, which is elevated in OA patients; nevertheless, investigators have yet to elucidate the function of IL-17 in M1 polarization during OA development. Our analysis of clinical tissues and results from the open online dataset discovered that the level of M1 macrophage markers is elevated in human OA tissue samples than in normal tissue. High-throughput screening demonstrated that MCP-1 is a potential candidate factor after IL-17 treatment in OA synovial fibroblasts (OASFs). Immunohistochemistry data revealed that the level of MCP-1 is higher in humans and mice with OA than in normal tissues. IL-17 stimulation facilitates MCP-1-dependent macrophage polarization to the M1 phenotype. It also appears that IL-17 enhances MCP-1 synthesis in human OASFs, enhancing monocyte migration via the JAK and STAT3 signaling cascades. Our findings indicate the IL-17/MCP-1 axis as a novel strategy for the remedy of OA.

Biotransformation of Patchouli Alcohol by Cladosporium cladosporioides and the Anti-Influenza Virus Activities of Biotransformation Products.

The biotransformation of patchouli alcohol by Cladosporium cladosporioides afforded 31 products, including 21 new ones (1-3, 5, 6, 8-14, and 17-25). Their structures were determined by extensive spectroscopic data analysis (1H and 13C NMR, HSQC, HMBC, 1H-1H COSY, ROESY, and HRESIMS), and the absolute configuration of compounds 1, 2, 8, 9, and 17 was determined by single-crystal X-ray diffraction using Cu Kα radiation. Structurally, compounds 21-24 were patchoulol-type norsesquiterpenoids without Me-12. Among them, a Δ3(4) double bond existed in compounds 21 and 22; a three-membered ring was formed between C-4, C-5, and C-6 in compound 23; an epoxy moiety appeared between C-3 and C-4 in compound 24. Furthermore, the biotransformation products 9, 10, 12, and 25 showed potent anti-influenza virus activity with EC50 values of 2.11, 7.94, 20.87, and 3.45 µM, respectively.

Tunable VO2 cavity enables multispectral manipulation from visible to microwave frequencies.

Optical materials capable of dynamically manipulating electromagnetic waves are an emerging field in memories, optical modulators, and thermal management. Recently, their multispectral design preliminarily attracts much attention, aiming to enhance their efficiency and integration of functionalities. However, the multispectral manipulation based on these materials is challenging due to their ubiquitous wavelength dependence restricting their capacity to narrow wavelengths. In this article, we cascade multiple tunable optical cavities with selective-transparent layers, enabling a universal approach to overcoming wavelength dependence and establishing a multispectral platform with highly integrated functions. Based on it, we demonstrate the multispectral (ranging from 400 nm to 3 cm), fast response speed (0.9 s), and reversible manipulation based on a typical phase change material, vanadium dioxide. Our platform involves tandem VO2-based Fabry-Pérot (F-P) cavities enabling the customization of optical responses at target bands independently. It can achieve broadband color-changing capacity in the visible region (a shift of ~60 nm in resonant wavelength) and is capable of freely switching between three typical optical models (transmittance, reflectance, and absorptance) in the infrared to microwave regions with drastic amplitude tunability exceeding 0.7. This work represents a state-of-art advance in multispectral optics and material science, providing a critical approach for expanding the multispectral manipulation ability of optical systems.

Sodium tanshinone IIA sulfonate inhibits tumor growth via miR-138 upregulation in intermittent hypoxia-induced xenograft mice.

PURPOSE: We studied the functions of sodium tanshinone IIA sulfonate (TSA) in inducing tumor growth in obstructive sleep apnea (OSA)-mimicking intermittent hypoxia (IH) xenograft mice and the underlying potential molecular mechanism. METHODS: RNA sequencing was conducted to screen the differentially expressed microRNAs in cell lines exposed to IH with or without TSA treatment. As part of the 5-week in vivo study, we treated xenograft mice with 8-h IH once daily. TSA and miR-138 inhibitors or mimics were administrated appropriately. In addition, we performed real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), microvessel density (MVD), and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. RESULTS: RNA sequencing and RT-PCR results demonstrated that TSA increased the levels of miR-138 under IH conditions in vitro. TSA reduced the IH-stimulated high levels of hypoxia-induced factor-1α and vascular endothelial growth factor. Furthermore, IH contributed to high tumor migration, invasion, MVD, and low apoptosis. TSA attenuated IH-mediated tumor proliferation, migration, invasion, MVD, and increased apoptosis, whereas miR-138 inhibitor interrupted the effect of TSA on treating IH-induced tumor behaviors. CONCLUSIONS: OSA mimicking IH facilitates tumor growth and reduces miR-138 levels. TSA inhibits IH-induced tumor growth by upregulating the expression of miR-138.

Association between oxidative balance score and frailty in chronic obstructive pulmonary disease.

Background: Oxidative stress is associated with frailty and adverse outcomes in chronic obstructive pulmonary disease (COPD). The oxidative balance score (OBS) assesses oxidative stress from diet and lifestyle, with higher OBS indicating more antioxidants than oxidants. A cross-sectional study was conducted to investigate the potential association between OBS and frailty in US adults with COPD. Methods: A total of 1201 COPD subjects from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were assessed for frailty using the Frailty Index. OBS, consisting of 20 dietary and lifestyle factors, was the exposure variable. Weighted multiple logistic regression, subgroup analysis, and restricted cubic spline curves were used to assess the association between OBS and frailty. Results: Compared with the lowest OBS reference group (Q1), the adjusted odds ratios (ORs) for the highest quartile group (Q4) for OBS, dietary OBS, and lifestyle OBS were 0.41 (95% CI: 0.19-0.92), 0.37 (95% CI: 0.20-0.71), and 0.41 (95% CI: 0.24-0.71), respectively. All trend p-values were less than 0.05. Subgroup and RCS analyses revealed a negative linear association between OBS and frailty, with a significant reduction in frailty risk observed in women compared to men. Conclusions: OBS was negatively associated with frailty in COPD. The higher the OBS, the lower the risk of frailty, especially in women. Identifying at-risk populations with OBS and through antioxidant diet and lifestyle are potential ways to reduce the prevalence of frailty.

IL-17 promotes IL-18 production via the MEK/ERK/miR-4492 axis in osteoarthritis synovial fibroblasts.

The concept of osteoarthritis (OA) as a low-grade inflammatory joint disorder has been widely accepted. Many inflammatory mediators are implicated in the pathogenesis of OA. Interleukin (IL)-18 is a pleiotropic cytokine with versatile cellular functions that are pathogenetically important in immune responses, as well as autoimmune, inflammatory, and infectious diseases. IL-17, a proinflammatory cytokine mainly secreted by Th17 cells, is upregulated in OA patients. However, the role of IL-17 in OA progression is unclear. The synovial tissues collected from healthy donors and OA patients were used to detect the expression level of IL-18 by IHC stain. The OA synovial fibroblasts (OASFs) were incubated with recombinant IL-17 and subjected to Western blot, qPCR, and ELISA to examine IL-18 expression level. The chemical inhibitors and siRNAs which targeted signal pathways were used to investigate signal pathways involved in IL-17-induced IL-18 expression. The microRNAs which participated IL-18 expression were surveyed with online databases miRWalk and miRDB, followed by validation with qPCR. This study revealed significantly higher levels of IL-18 expression in synovial tissue from OA patients compared with healthy controls, as well as increased IL-18 expression in OASFs from rats with severe OA. In vitro findings indicated that IL-17 dose-dependently promoted IL-18 production in OASFs. Molecular investigations revealed that the MEK/ERK/miR-4492 axis stimulated IL-18 production when OASFs were treated with IL-17. This study provides novel insights into the role of IL-17 in the pathogenesis of OA, which may help to inform OA treatment in the future.

Predicting adverse pregnancy outcomes of pregnant mothers with syphilis based on a logistic regression model: a retrospective study.

Objective: Maternal syphilis could cause serious consequences. The aim of this study was to identify risk factors for maternal syphilis in order to predict an individual's risk of developing adverse pregnancy outcomes (APOs). Methods: A retrospective study was conducted on 768 pregnant women with syphilis. A questionnaire was completed and data analyzed. The data was divided into a training set and a testing set. Using logistic regression to establish predictive models in the training set, and its predictive performance was evaluated in the testing set. The probability of APOs occurrence is presented through a nomogram. Results: Compared with the APOs group, pregnant women in the non-APOs group participated in a longer treatment course. Course, time of the first antenatal care, gestation week at syphilis diagnosis, and gestation age at delivery in weeks were independent predictors of APOs, and they were used to establish the nomogram. Conclusions: Our study investigated the impact of various characteristics of syphilis pregnant women on pregnancy outcomes and established a prediction model of APOs in Suzhou. The incidence of APOs can be reduced by controlling for these risk factors.

Broadband electromagnetic wave absorption using pure carbon aerogel by synergistically modulating propagation path and carbonization degree.

Carbon materials were widely used as electromagnetic (EM) wave absorption due to their advantages of light weight, environmental resistance and high electrical conductivity. However, conventional means were typically available by combining carbon and other materials to achieve effective absorption. Herein, a novel strategy using pure carbon aerogel with oriented structure was reported to enhance the EM wave absorption by synergistically modulating the wave propagation path and carbonization degree. The aerogel contained proposed modified carbon nanofibers (MCNF) derived from bacterial cellulose (BC), and core-shell carbon nanofibers @ reduced oxide graphene (CNF@RGO). The oriented structure was induced by the temperature field, which manifests anisotropic EM constitutive parameters (εx ≠ Îµz) at different directions of incident wave. The carbonization degree was adjusted by varying the carbonization temperature. At the carbonization temperature of 700 °C, the maximum reflection loss and effective absorption bandwidth reached -53.94 dB and 7.14 GHz, respectively, enabling the aerogel to outperform its previous counterparts. To clarify the EM wave mode-of-action in conjunction, physical models of the aerogel were established in addition to finite element simulation and theoretical analysis. Notably, the aerogel with a density of 3.6 mg/cm3 featured ultra-light weight, superhydrophobicity, superior compressibility, and thermal insulation. Our work offers an efficient strategy for designing broadband and multifunctional EM wave absorption materials (EWAMs), promising great potentials in complex stealth equipment.

Nesfatin-1 stimulates BMP5 expression and osteoclastogenesis in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease marked by immune cell activation and chronic inflammation in the synovium accompanied by osteoclast activation and local joint destruction. Increased levels of the adipokine nesfatin-1 in RA synovium are associated with proinflammatory cytokines. Our analysis of datasets from the Gene Expression Omnibus (GEO) database and synovial tissue samples from RA patients revealed that these had higher levels of nesfatin-1 and osteoclast markers compared with normal synovium. These findings were the same in tissue samples from mice with collagen-induced arthritis (CIA) and normal healthy controls. RNA sequencing analysis revealed that nesfatin-1 increased levels of bone morphogenetic protein-5 (BMP5) expression via JAK/STAT signaling in RA synovial fibroblasts. Finally, we found that nesfatin-1 short hairpin RNA reduced BMP5 and osteoclast formation in CIA mice. These findings provide new insights into the pathogenesis of RA.

Recent advances in metasurface design and quantum optics applications with machine learning, physics-informed neural networks, and topology optimization methods.

As a two-dimensional planar material with low depth profile, a metasurface can generate non-classical phase distributions for the transmitted and reflected electromagnetic waves at its interface. Thus, it offers more flexibility to control the wave front. A traditional metasurface design process mainly adopts the forward prediction algorithm, such as Finite Difference Time Domain, combined with manual parameter optimization. However, such methods are time-consuming, and it is difficult to keep the practical meta-atom spectrum being consistent with the ideal one. In addition, since the periodic boundary condition is used in the meta-atom design process, while the aperiodic condition is used in the array simulation, the coupling between neighboring meta-atoms leads to inevitable inaccuracy. In this review, representative intelligent methods for metasurface design are introduced and discussed, including machine learning, physics-information neural network, and topology optimization method. We elaborate on the principle of each approach, analyze their advantages and limitations, and discuss their potential applications. We also summarize recent advances in enabled metasurfaces for quantum optics applications. In short, this paper highlights a promising direction for intelligent metasurface designs and applications for future quantum optics research and serves as an up-to-date reference for researchers in the metasurface and metamaterial fields.

The Pathological Mechanism of Neuronal Autophagy-Lysosome Dysfunction After Ischemic Stroke.

The abnormal initiation of autophagy flux in neurons after ischemic stroke caused dysfunction of autophagy-lysosome, which not only led to autophagy flux blockage, but also resulted in autophagic death of neurons. However, the pathological mechanism of neuronal autophagy-lysosome dysfunction did not form a unified viewpoint until now. In this review, taking the autophagy lysosomal dysfunction of neurons as a starting point, we summarized the molecular mechanisms that led to neuronal autophagy lysosomal dysfunction after ischemic stroke, which would provide theoretical basis for the clinical treatment of ischemic stroke.

Interface engineering of the NiO/CeO2@NF heterostructure to boost the electro-oxidation of 5-hydroxymethylfurfural.

The synthesis of furan-based platform chemicals from abundant and renewable biomass-based hexoses plays an important role in the development and utilization of biomass energy. The electrochemical 5-hydroxymethylfurfural oxidation reaction (HMFOR) represents a promising route for synthesizing the 2,5-furandicarboxylic acid (FDCA) product which is a high value-added biomass-based monomer. Interface engineering is an effective strategy to adjust the electronic structure, optimize the adsorption of intermediates, and expose more active sites, thus attracting extensive attention for designing efficient HMFOR electrocatalysts. Herein, a NiO/CeO2@NF heterostructure with an abundant interface is designed for boosting the HMFOR performance under alkaline conditions. At 1.475 V vs. RHE, the conversion of HMF is nearly 100%, the selectivity of FDCA is 99.0%, and the faradaic efficiency is as high as 98.96%. The NiO/CeO2@NF electrocatalyst also exhibits robust stability for HMFOR for 10 cycles. When coupled with the cathode hydrogen evolution reaction (HER) in alkaline medium, the yields of FDCA and hydrogen production are 197.92 and 600 µmol cm-2 h-1, respectively. The NiO/CeO2@NF catalyst is also suitable for the electrocatalytic oxidation of other biomass-derived platform compounds. The abundant interface between NiO and CeO2, which can regulate the electronic properties of Ce and Ni atoms, improve the oxidation state of Ni species, regulate intermediate adsorption, and promote electron/charge transfer, makes the most contribution to high HMFOR performance. This work will provide a simple route for the design of heterostructured materials and reveal the application prospect of interface engineering for promoting the upgrading of biomass derivatives.

Hepatocyte ferroptosis contributes to anti-tuberculosis drug-induced liver injury: Involvement of the HIF-1α/SLC7A11/GPx4 axis.

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common serious adverse event observed during the clinical treatment of tuberculosis. However, the molecular mechanisms underlying ATB-DILI remain unclear. A recent study has indicated that ferroptosis and lipid peroxidation may be involved in liver injury. Therefore, this study aimed to investigate the role of ferroptosis in the molecular mechanisms underlying ATB-DILI. Our results showed that anti-TB drugs induced hepatocyte damage in vivo and in vitro and inhibited BRL-3A cell activity in a dose-dependent manner, accompanied by increased lipid peroxidation and reduced antioxidant levels. Moreover, ACSL4 expression and Fe2+ concentration significantly increased following anti-TB drug treatment. Interestingly, anti-TB drug-induced hepatocyte damage was reversed by ferrostatin-1 (Fer-1, a specific ferroptosis inhibitor). In contrast, treatment with erastin (a ferroptosis inducer) resulted in further elevation of ferroptosis indicators. Additionally, we also found that anti-TB drug treatment inhibited HIF-1α/SLC7A11/GPx4 signaling in vivo and in vitro. Notably, HIF-1α knockdown significantly enhanced anti-TB drug-induced ferroptotic events and the subsequent exacerbation of hepatocyte damage. In conclusion, our findings indicated that ferroptosis plays a crucial role in the development of ATB-DILI. Furthermore, anti-TB drug-induced hepatocyte ferroptosis was shown to be regulated by HIF-1α/SLC7A11/GPx4 signaling. These findings shed new light on the mechanisms underlying ATB-DILI and suggest novel therapeutic strategies for this disease.

Super-reflector enabled by non-interleaved spin-momentum-multiplexed metasurface.

Electromagnetic wave multiplexing, especially for that occurring at different incidences (spatial-frequency multiplexing), is pivotal for ultrathin multifunctional interfaces and high-capacity information processing and communication. It is yet extremely challenging based on passive and compact wave elements, since the wave excitation and scattering channels are exclusively coupled through gradient phases and hence momentum matching condition at the interface. Here, we propose a spin-momentum multiplexed paradigm called a super-reflector enabling on-demand control of both retroreflections and anomalous reflections using a non-interleaved single-celled metasurface. By multiplexing four channels connecting two spin states excited onto each input of three spatial frequencies, a total of twelve channels are engineered, among which three are retroreflected channels and the residual are anomalous reflection ones. Our compound multiplexed super-reflector allows five degrees of freedom in circular polarization Jones' matrix, approaching the intrinsic upper limit of such planar metasurface. The concept has been experimentally verified by a proof-of-concept super-reflector at microwave frequency, showcasing twelve reflected beams and a high efficiency exceeding 90.6% defined as the ratio of reflected power to incidence for each channel beam. Our strategy opens a new avenue for angle multiplexing and angle-resolved metadevices toward the capacity limit of 2D planar Jones' matrix.

Nesfatin-1 Stimulates CCL2-dependent Monocyte Migration And M1 Macrophage Polarization: Implications For Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a prototypic inflammatory disease, characterized by the infiltration of proinflammatory cytokines into the joint synovium and the migration of mononuclear cells into inflammatory sites. The adipokine nesfatin-1 is linked to inflammatory events in various diseases, although its role in RA pathology is uncertain. Analysis of the Gene Expression Omnibus GSE55235 dataset revealed high levels of expression of the adipokine nesfatin-1 in human RA synovial tissue. Similarly, our human synovial tissue samples exhibited increasing levels of nesfatin-1 expression and Ccl2 mRNA expression. Nesfatin-1-induced stimulation of CCL2 expression and monocyte migration involved the MEK/ERK, p38, and NF-κB signaling pathways. Notably, nesfatin-1-induced increases in CCL2 expression favored M1 macrophage polarization, which increased the expression of proinflammatory cytokines IL-1ß, IL-6, and TNF-α. Finally, nesfatin-1 shRNA ameliorated the severity of inflammatory disease and reduced levels of M1 macrophage expression in CIA mice. Our studies confirm that nesfatin-1 appears to be worth targeting in RA treatment.

Retracted: Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury.

This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study. Reference: Xiao-Bin Zhang, Gong-Ping Chen, Mao-Hong Huang, Xiang-Xing Chen, Feng-Fu Zhan, Xiu-Zhen He, Ling Cai, Hui-Qing Zeng Med. Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human Renal Tubular Epithelial Cell Injury. Med Sci Monit, 2022; 28: e936760. DOI: 10.12659/MSM.936760.

Circularly Polarized Antenna Array with Decoupled Quad Vortex Beams.

Achieving multiple vortex beams with different modes in a planar microstrip array is pivotal, yet still extremely challenging. Here, a hybrid method combining both Pancharatnam−Berry (PB) phase that is induced by the rotation phase and excitation phase of a feeding line has been proposed for decoupling two orthogonal circularly polarized vortex beams. Theoretical analysis is derived for array design to generate quad vortex beams with different directions and an arbitrary number of topological charges. On this basis, two 8 × 8 planar arrays were theoretically designed in an X band, which are with topological charges of l1 = −1, l2 = 1, l3 = −1, and l4 = 1 in Case I and topological charges of l1 = −1, l2 = 1, l3 = −1, and l4 = 1 in Case II. To further verify the above theory, the planar array in Case I is fabricated and analyzed experimentally. Dual-LP beams are realized by using rectangular patch elements with two orthogonally distributed feeding networks on different layers based on two types of feeding: proximity coupling and aperture coupling. Both the numerical simulation and experimental measurement results are in good agreement and showcase the corresponding quad-vortex-beam characteristics within 8~12 GHz. The array achieves a measured S11 < −10 dB and S22 < −10 dB bandwidth of more than 33.4% and 29.2%, respectively. In addition, the isolation between two ports is better than −28 dB. Our strategy provides a promising way to achieve large capacity and high integration, which is of great benefit to wireless and radar communication systems.

Dynamic livelihood impacts of COVID-19 on different rural households in mountainous areas of China.

BACKGROUND: The outbreak of COVID-19 pandemic has brought about severe negative livelihood consequences for rural households worldwide. However, the heterogeneity and dynamics of livelihood impacts have been under-researched. There is also lacking a livelihood assessment of the pandemic based on a whole pandemic cycle. This study aimed to investigate the dynamic and heterogeneous livelihood impacts of COVID-19 pandemic for rural households in 2020 based on a case study of Southeast China. METHODS: The pandemic in China had experienced a complete cycle from initial outbreak, to intermediate recovery and finally new normal stage in 2020. We conducted face-to-face interviews with 95 rural households randomly drawn from 2 rural villages in Xunwu County, Jiangxi Province, Southeast China. The sampled households are interviewed with a questionnaire through face-to-face surveys in February and March, 2021 to evaluate the overall livelihood impacts of the pandemic during 2020. The survey collected data on demographic and economic characteristics, governmental control measures, and effects of the COVID-19 on agricultural production, employment, income, education, and daily life. In-depth interviews are also conducted to clarify the livelihood impacts of COVID-19 on villages. RESULTS: Results showed that the pandemic tremendously caused substantially negative livelihood impacts, including decreasing household income, and disorders in daily lives. The average income loss of all survey households is 6,842 RMB, accounting for 13.01% of the total household income in 2020. Containment measures also resulted in a series of disturbances in daily lives, such as rising food price additional expenditures, travel restrictions, party restrictions, closure of schools and deceasing living standards. There is remarkable household heterogeneity in the livelihood impacts. Results also revealed that the livelihood strategies of rural households to cope with the threat of COVID-19 were different in various pandemic stages. CONCLUSION: Our findings have illustrated the severity and heterogeneity of livelihood impacts on rural households induced by COVID-19 pandemic. The dynamics of livelihood impacts is also highlighted in the study. Several policy suggestion was proposed to mitigate these negative consequences of the pandemic.