Nanoscale Ultrafine Zinc Metal Anodes for High Stability Aqueous Zinc Ion Batteries.

Aqueous Zn batteries (AZBs) are a promising energy storage technology, due to their high theoretical capacity, low redox potential, and safety. However, dendrite growth and parasitic reactions occurring at the surface of metallic Zn result in severe instability. Here we report a new method to achieve ultrafine Zn nanograin anodes by using ethylene glycol monomethyl ether (EGME) molecules to manipulate zinc nucleation and growth processes. It is demonstrated that EGME complexes with Zn2+ to moderately increase the driving force for nucleation, as well as adsorbs on the Zn surface to prevent H-corrosion and dendritic protuberances by refining the grains. As a result, the nanoscale anode delivers high Coulombic efficiency (ca. 99.5%), long-term cycle life (over 366 days and 8800 cycles), and outstanding compatibility with state-of-the-art cathodes (ZnVO and AC) in full cells. This work offers a new route for interfacial engineering in aqueous metal-ion batteries, with significant implications for the commercial future of AZBs.

Regulating reconstruction-engineered active sites for accelerated electrocatalytic conversion of urea.

Reconstruction-engineered electrocatalysts with enriched high active Ni species for urea oxidation reaction (UOR) have recently become promising candidates for energy conversion. However, to inhibit the over-oxidation of urea brought by the high valence state of Ni, tremendous efforts are devoted to obtaining low-value products of nitrogen gas to avoid toxic nitrite formation, undesirably causing inefficient utilization of the nitrogen cycle. Herein, we proposed a mediation engineering strategy to significantly boost high-value nitrite formation to help close a loop for the employment of a nitrogen economy. Specifically, platinum-loaded nickel phosphides (Pt-Ni2P) catalysts exhibit a promising nitrite production rate (0.82 mol kWh-1 cm-2), high stability over 66 h of Zn-urea-air battery operation, and 135 h of co-production of nitrite and hydrogen under 200 mA cm-2 in a zero-gap membrane electrode assembly (MEA) system. The in situ spectroscopic characterizations and computational calculations demonstrated that the urea oxidation kinetics is facilitated by enriched dynamic Ni3+ active sites, thus augmenting the "cyanate" UOR pathway. The *NOO desorption was further verified as the rate-determining step for nitrite generation.

Periostin promotes nucleus pulposus cells apoptosis by activating the Wnt/ß-catenin signaling pathway.

Intervertebral disc (IVD) degeneration (IVDD) is closely linked to degenerative spinal disease, resulting in disability, poor quality of life, and financial burden. Apoptosis of nucleus pulposus (NP) cells (NPCs) is a key pathological basis of IVDD. Periostin (POSTN), an extracellular matrix protein, is expressed in many tissues, whereas its abnormal expression is associated with IVDD. The conventional Wnt/ß-catenin pathway is also involved in IVDD and contributes to NPCs apoptosis. However, research on the mechanisms of POSTN in IVDD is lacking. This study investigated the relationship between POSTN and ß-catenin expression in degenerated IVDs. We detected the expression of POSTN, ß-catenin, and cleaved-caspase-3 (C-caspase3) in degenerated and non-degenerated IVD tissues of different grades (n = 8) using RT-qPCR, immunohistochemical staining, and western blotting analysis. Next, we explored the effects of recombinant periostin (rPOSTN) and isoquercitrin (Iso), an inhibitor of the Wnt/ß-catenin pathway, on NPCs apoptosis. Finally, we inhibited the expression of POSTN in degenerated NPCs in vivo and investigated the anti-apoptotic effect. The expression of ß-catenin, POSTN, and C-caspase3 in severe degenerative IVDs was significantly higher than that in mild degenerative IVDs. These findings were confirmed in rat and cell-based degenerative models. When treated with rPOSTN, the Wnt/ß-catenin pathway activity and cell apoptosis were time- and dose-dependent. However, rPOSTN-induced NPCs apoptosis decreased after iso-induced inhibition of the Wnt/ß-catenin pathway. POSTN inhibition reduced apoptosis but was restored by rPOSTN re-addition. Lastly, POSTN inhibition ameliorated puncture-induced IVDD in vivo. Overall, our study demonstrated that POSTN promotes NPCs apoptosis and aggravates degeneration by activating the Wnt/ß-catenin pathway.

Recent Progress and Applications of Thermal Lens Spectrometry and Photothermal Beam Deflection Techniques in Environmental Sensing.

This paper presents recent development and applications of thermal lens microscopy (TLM) and beam deflection spectrometry (BDS) for the analysis of water samples and sea ice. Coupling of TLM detection to a microfluidic system for flow injection analysis (µFIA) enables the detection of microcystin-LR in waters with a four samples/min throughput (in triplicate injections) and provides an LOD of 0.08 µg/L which is 12-times lower than the MCL for microcystin-LR in water. µFIA-TLM was also applied for the determination of total Fe and Fe(II) in 3 µL samples of synthetic cloudwater. The LODs were found to be 100 nM for Fe(II) and 70 nM for total Fe. The application of µFIA-TLM for the determination of ammonium in water resulted in an LOD of 2.3 µM for injection of a 5 µL sample and TLM detection in a 100 µm deep microfluidic channel. For the determination of iron species in sea ice, the BDS was coupled to a diffusive gradient in the thin film technique (DGT). The 2D distribution of Fe(II) and total Fe on DGT gels provided by the BDS (LOD of 50 nM) reflected the distribution of Fe species in sea ice put in contact with DGT gels.

Role of Nrf2 and HO-1 in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a common age-related disease with clinical manifestations of lumbar and leg pain and limited mobility. The pathogenesis of IDD is mainly mediated by the death of intervertebral disc (IVD) cells and the imbalance of extracellular matrix (ECM) synthesis and degradation. Oxidative stress and inflammatory reactions are the important factors causing this pathological change. Therefore, the regulation of reactive oxygen species and production of inflammatory factors may be an effective strategy to delay the progression of IDD. In recent years, nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream regulated protein heme oxygenase-1 (HO-1) have received special attention due to their antioxidant, anti-inflammatory and anti-apoptotic protective effects. Recent studies have elucidated the important role of these two proteins in the treatment of IDD disease. However, Nrf2 and HO-1 have not been systematically reported in IDD-related diseases. Therefore, this review describes the biological characteristics of Nrf2 and HO-1, the relationship between Nrf2- and HO-1-regulated oxidative stress and the inflammatory response and IDD, and the progress in research on some extracts targeting Nrf2 and HO-1 to improve IDD. Understanding the role and mechanism of Nrf2 and HO-1 in IDD may provide novel ideas for the clinical treatment and development of Nrf2- and HO-1-targeted drugs.

Proanthocyanidins inhibit the apoptosis and aging of nucleus pulposus cells through the PI3K/Akt pathway delaying intervertebral disc degeneration.

BACKGROUND: Low back pain is a common symptom of intervertebral disc degeneration (IDD), which seriously affects the quality of life of patients. The abnormal apoptosis and senescence of nucleus pulposus (NP) cells play important roles in the pathogenesis of IDD. Proanthocyanidins (PACs) are polyphenolic compounds with anti-apoptosis and anti-aging effects. However, their functions in NP cells are not yet clear. Therefore, this study was performed to explore the effects of PACs on NP cell apoptosis and aging and the underlying mechanisms of action. METHODS: Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. The apoptosis rate was determined TUNEL assays. Levels of apoptosis-associated molecules (Bcl-2, Bax, C-caspase-3 and Caspase-9) were evaluated via western blot. The senescence was observed through SA-ß-gal staining and western blotting analysis was performed to observe the expression of senescence-related molecules (p-P53, P53, P21 and P16). RESULTS: Pretreatment with PACs exhibited protective effects against IL-1ß-induced NP cell apoptosis including apoptosis rate, expressions of proapoptosis and antiapoptosis related genes and protein. PACs could also alleviate the increase of p-p53, P21, and P16 in IL-1ß-treated NP cells. SA-ß-gal staining showed that IL-1ß-induced senescence of NP cells was prevented by PACs pertreatment. In addition, PACs activated PI3K/Akt pathway in IL-1ß-stimulated NP cells. However, these protected effects were inhibited after LY294002 treatment. CONCLUSION: The results of the present study showed that PACs inhibit IL-1ß-induced apoptosis and aging of NP cells by activating the PI3K/Akt pathway, and suggested that PACs have therapeutic potential for IDD.

Controlled Growth of Large-Sized and Phase-Selectivity 2D GaTe Crystals.

GaTe has recently attracted significant interest due to its direct bandgap and unique phase structure, which makes it a good candidate for optoelectronics. However, the controllable growth of large-sized monolayer and few-layer GaTe with tunable phase structures remains a great challenge. Here the controlled growth of large-sized GaTe with high quality, chemical uniformity, and good reproducibility is achieved through liquid-metal-assisted chemical vapor deposition method. By using liquid Ga, the rapid growth of 2D GaTe flakes with high phase-selectivity can be obtained due to its reduced reaction temperature. In addition, the method is used to synthesize many Ga-based 2D materials and their alloys, showing good universality. Raman spectra suggest that the as-grown GaTe own a relatively weak van der Waals interaction, where monoclinic GaTe displays highly-anisotropic optical properties. Furthermore, a p-n junction photodetector is fabricated using GaTe as a p-type semiconductor and 2D MoSe2 as a typical n-type semiconductor. The GaTe/MoSe2 heterostructure photodetector exhibits large photoresponsivity of 671.52 A W-1 and high photo-detectivity of 1.48 × 1010 Jones under illumination, owing to the enhanced light absorption and good quality of as-grown GaTe. These results indicate that 2D GaTe is a promising candidate for electronic and photoelectronic devices.

Biodegradable Bi2 O2 Se Quantum Dots for Photoacoustic Imaging-Guided Cancer Photothermal Therapy.

As new 2D layered nanomaterials, Bi2 O2 Se nanoplates have unique semiconducting properties that can benefit biomedical applications. Herein, a facile top-down approach for the synthesis of Bi2 O2 Se quantum dots (QDs) in a solution is described. The Bi2 O2 Se QDs with a size of 3.8 nm and thickness of 1.9 nm exhibit a high photothermal conversion coefficient of 35.7% and good photothermal stability. In vitro and in vivo assessments demonstrate that the Bi2 O2 Se QDs possess excellent photoacoustic (PA) performance and photothermal therapy (PTT) efficiency. After systemic administration, the Bi2 O2 Se QDs accumulate passively in tumors enabling efficient PA imaging of the entire tumors to facilitate imaging-guided PTT without obvious toxicity. Furthermore, the Bi2 O2 Se QDs which exhibit degradability in aqueous media not only have sufficient stability during in vivo circulation to perform the designed therapeutic functions, but also can be discharged harmlessly from the body afterward. The results reveal the great potential of Bi2 O2 Se QDs as a biodegradable multifunctional agent in medical applications.

Determination of Trace Cr(VI) with Diphenylcarbazide by µFIA-Thermal Lens Microscopy.

The optimum reaction parameters for the interaction of hexavalent chromium [Cr(VI)] with diphenylcarbazide in microfluidic chips (µFIA) with thermal-lens microscopic detection were selected. The characteristic feature of the applied flow scheme is the injection of the reagent into the stream containing the test metal, which enables in-field and real-time monitoring of Cr(VI) simply by flowing the sample continuously through the microchip. The limit of detection of Cr(VI) under the selected conditions (signal generating wavelength, 514.5 nm; excitation power, 100 mW; detection position, 10 cm downstream from the mixing zone of the microchip; flow rate 10 µL min-1; injection volume, 1.4 µL) is 15 ng mL-1 (2.9 × 10-7 mol L-1). The linear range is 40 ng mL-1 - 10 µg mL-1 with a relative standard deviation no higher than 10% in the concentration range 0.1-1 µg mL-1. The online monitoring by this scheme provides the possibility of up to 360 analyses per hour.

A Case of Verruciform Xanthoma of Labia in a Child.

Purpose: Verruciform xanthoma (VX) is a rare, chronic, and benign lesion affecting the skin and mucous membranes. We reported a case of VX in the vulva of a female child. Patients and Methods: A 12-year-old female had vulvar lesions for over 10 years without any discomfort. Physical examination revealed red lobulated patches on the left labia majora with a few scales attached to the surface. Histopathological examination indicated excessive and incomplete keratinization, hypertrophic spinous layer hyperplasia, neutrophil infiltration in the epidermis, and foam-like tissue could be seen in the dermal papilla. Lymphocyte-dominated inflammatory cell infiltration was scattered around the blood vessels. Immunohistochemical results showed positive CD68. Results: The final diagnosis confirmed the presence of VX. Conclusion: Surgical intervention proved successful in achieving favorable outcomes for the patient.

Verruciform xanthoma (VX) is a rare and non-cancerous skin condition that usually appears in the mouth but can occur on the genitals. In this case, a 12-year-old girl had red, warty lesions on her left labia majora for over 10 years. The cause of VX is not well understood but may be linked to inflammation, trauma, or immune disorders rather than lipid metabolism. The girl's condition was confirmed through a biopsy, and she underwent surgical removal with no recurrence after a year. VX in the genital area is known as Vegas xanthomas. Though VX can look like other skin issues, a detailed examination of tissue samples is crucial for an accurate diagnosis. Treatment options include surgery, laser therapy, or topical creams. While VX is generally benign, seeking medical attention is important to rule out other concerns.

KRAS/PI3K axis driven GTF3C6 expression and promotes LUAD via FAK pathway.

INTRODUCTION: Effective targeting drugs for KRAS mutation-mediated Lung Adenocarcinoma (LUAD) are currently are limited. OBJECTIVES: Investigating and intervening in the downstream key target genes of KRAS is crucial for clinically managing KRAS mutant-driven LUAD. GTF3C6, a newly identified member of the general transcription factor III (GTF3) family, plays a role in the transcription of RNA polymerase III (pol III)-dependent genes. However, its involvement in cancer remains unexplored. METHODS: This study examined the expression, roles, and potential molecular mechanisms of GTF3C6 in LUAD tissues, LSL-KrasG12D/+;LSL-p53-/- LUAD mouse models, and LUAD patients-derived organoid using Western blot, qRT-PCR, immunofluorescence, immunohistochemistry, and gene manipulation assays. RESULTS: We present the first evidence that GTF3C6 is highly expressed in LUAD tissues, LSL-KrasG12D/+;LSL-p53-/- LUAD mouse models, and LUAD organoids, correlating with poor clinical prognosis. Furthermore, GTF3C6 was found to promote anchorage-independent proliferation, migration, and invasion of LUAD cells. Mechanistically, KRAS mutation drives GTF3C6 expression through the PI3K pathway, and GTF3C6 knockdown reverses the malignant phenotype of KRAS mutation-driven LUAD cells. Additionally, the FAK pathway emerged as a crucial downstream signaling pathway through which GTF3C6 mediates the malignant phenotype of LUAD. Finally, GTF3C6 knockdown suppresses LUAD organoid formation and inhibits tumor growth in vivo. CONCLUSION: Our findings demonstrate that GTF3C6, driven by KRAS mutation, promotes LUAD development by regulating FAK phosphorylation, suggesting its potential as a biomarker and therapeutic target in KRAS mutant-driven LUAD.

Prognostic effects of different malignant obstructive jaundice sites on percutaneous biliary intervention: A retrospective controlled study.

Purpose: To compare the survival prognosis of percutaneous transhepatic biliary stenting (PTBS) in the treatment of malignant obstructive jaundice (MOJ) at different horizontal sites. Methods: A total of 120 patients with MOJ who underwent biliary stenting were retrospectively included and analyzed and divided into the high-position group (36 patients), middle-position group (43 patients), and low-position group (41 patients) according to biliary obstruction plane by biliary anatomy. Kaplan-Meier curves were used to test for differences in the overall survival (OS), risk assessment of death and potential risk factors for 1-year survival were analyzed using multifactorial Cox regression. Results: The median survival of the high-, middle-, low-position groups were 16, 8.6, and 5.6 months, with a statistically significant difference (P = 0.017). The 1-year survival rate was 67.6%, 41.9%, and 41.5% in the high-, middle-, low-position groups (P < 0.05), and the 1-year risk of death was 2.35 and 2.93 times higher in the medium- and low-position groups, respectively. The incidences of the main complications were 25%, 48.8%, and 65.9% in the high-, middle-, and low-position groups, respectively, (P = 0.002). While the differences in median stent patency were not statistically significant (P > 0.05) in the groups, alanine transaminase, aspartate transaminase, and total bilirubin levels decreased gradually in each group at 1 month and 3 months after interventional therapy (P < 0.001), while there was no significant difference in the decrease between the groups. Conclusions: Different levels of biliary obstruction in patients with MOJ affect survival, especially at 1 year, where high obstruction treated with PTBS has a low incidence of complications and a low risk of death.

In situ BaSO4 coating enabled activation-free and ultra-stable δ-MnO2 for aqueous Zn-ion batteries.

In situ BaSO4 coating, generated in the first discharging of Ba2+ pre-intercalated δ-MnO2, shortens the activation process by inducing fast proton intercalation and stabilizes the MnO2 crystal by suppressing Mn dissolution. The cathode delivers a decent electrochemical performance of 210 mA h g-1 at 1C with a 98% retention after 200 cycles.

An Ultrafast, Energy-Efficient Electrochromic and Thermochromic Device for Smart Windows.

Smart windows nowadays undertake the esteemed obligation of reducing energy consumption as well as upgrading living experience. This project aims to devise a smart window that responds to both electricity and heat, with the intention of achieving energy efficiency, privacy preservation, and enhanced decorative attributes. Through the implementation of a novel electrochromic material design, coupled with the optimization of electrochromic devices (ECDs), a high-performance ECD is obtained, demonstrating coloring/bleaching time of 0.53/0.16 s, a transmittance modulation of 78% (from 99% to 21%), and superior performance in six dimensions. Furthermore, temperature-responsive units and an ionic liquid are incorporated into the electrolyte system to create a novel thermochromic gel electrolyte with transmittance modulation from 80% to 0%, and excellent thermal insulation (6.4 °C reduction). Ultimately, an electro- and thermochromic device is developed, featuring an ultrafast color-switching speed of 0.82/0.60 s and multiple working modes. Overall, this work showcases a prospective design pathway for the development of next-generation ultrafast-switching, and energy-efficient intelligent windows.

CUL3 induces mitochondrial dysfunction via MRPL12 ubiquitination in renal tubular epithelial cells.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease worldwide and the strongest predictor of mortality in patients with diabetes. Despite its significance, the pathological mechanism underlying the onset and progression of DKD remains incompletely understood. In this study, we have shown that mitochondrial ribosomal protein L12 (MRPL12) plays a significant role in DKD by modulating mitochondrial function. We demonstrated that MRPL12 was mainly ubiquitinated at K150 in renal tubular epithelial cells. We have found that Cullin3 (CUL3), an E3 ubiquitin ligase, directly interacts with MRPL12 and induces the K63-linked ubiquitination of MRPL12, resulting in mitochondrial biosynthesis dysfunction. Moreover, under high-glucose (HG) conditions in renal tubular epithelial cells, we observed up-regulation of CUL3 expression, significant increase in CUL3-mediated ubiquitination of MRPL12 and dysregulation of mitochondrial biosynthesis. Notably, CUL3 knockdown stabilised the MRPL12 protein and protected mitochondrial biosynthesis under HG conditions. Our findings provide novel insight into how CUL3 affects mitochondrial biosynthesis in renal tubular epithelial cells through MRPL12 ubiquitination and suggest a potential therapeutic strategy for DKD in the future.

Association of hepatitis B virus DNA levels with efficacy and safety outcomes in patients with hepatitis B virus-associated advanced hepatocellular carcinoma receiving tyrosine kinase inhibitor plus anti-PD-1 antibody: a multicenter propensity-matched study.

BACKGROUND: The efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with anti-PD-1 antibodies (α-PD-1) in advanced hepatocellular carcinoma (HCC) with high hepatitis B virus (HBV) DNA levels (>500 IU/mL) remain unclear. METHODS: We retrospectively assessed patients from seven medical institutions diagnosed with HBV-related HCC, undergoing treatment with TKIs and α-PD-1 in conjunction with antiviral therapies. Based on HBV-DNA levels, patients were categorized into either high (HHBV-DNA, >500 IU/mL) or low HBV-DNA (LHBV-DNA, ≤500 IU/mL) cohorts Propensity score matching (PSM) was used to minimize baseline imbalance between groups. RESULTS: 149 patients were included, with 66 patients exhibiting HBV-DNA > 500 IU/mL and 83 patients presenting HBV-DNA ≤ 500 IU/mL. Compared with the LHBV-DNA cohort, the HHBV-DNA cohort had a greater incidence of serum HBeAg positivity, tumor diameter ≥ 10 cm, and vascular invasion. Following PSM, 57 individuals were enrolled in each group. Oncological outcomes were comparable between HHBV-DNA and LHBV-DNA cohorts before and after PSM. Before PSM, the median PFS and OS were 6.1 months and 17.5 months in the HHBV-DNA cohort and 6.7 months and 19.3 months in the LHBV-DNA cohort (all P > 0.05). After PSM, the median PFS and OS were 6.0 months and 19.5 months in the HHBV-DNA cohort and 6.0 months and 17.1 months in the LHBV-DNA cohort, respectively (all P > 0.05). Safety profiles were equivalent across cohorts with no fatal incidents reported. Seven patients (4.7 %) had HBV reactivation. 1 (0.7 %) from HHBV-DNA and 6 (4.0 %) from LHBV-DNA (P = 0.134). Only one patient developed HBV-related hepatitis. CONCLUSIONS: The effectiveness and safety of TKIs plus α-PD-1 in advanced HCC with HBV-DNA > 500 IU/mL were not compromised in the context of concomitant antiviral therapy.

Nrf2 Signaling in the Oxidative Stress Response After Spinal Cord Injury.

Spinal cord injury (SCI) is a central nervous system trauma that can cause severe neurological impairment. A series of pathological and physiological changes after SCI (e.g., inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction) promotes further deterioration of the microenvironment at the site of injury, leading to aggravation of neurological function. The multifunctional transcription factor NF-E2 related factor 2 (Nrf2) has long been considered a key factor in antioxidant stress. Therefore, Nrf2 may be an ideal therapeutic target for SCI. A comprehensive understanding of the function and regulatory mechanism of Nrf2 in the pathophysiology of SCI will aid in the development of targeted therapeutic strategies for SCI. This review discusses the roles of Nrf2 in SCI, with the aim of aiding in further elucidation of SCI pathophysiology and in efforts to provide Nrf2-targeted strategies for the treatment of SCI.

Intervertebral Disc Degeneration Models for Pathophysiology and Regenerative Therapy -Benefits and Limitations.

Aim: This review summarized the recent intervertebral disc degeneration (IDD) models and described their advantages and potential disadvantages, aiming to provide an overview for the current condition of IDD model establishment and new ideas for new strategies development of the treatment and prevention of IDD. Methods: The database of PubMed was searched up to May 2021 with the following search terms: nucleus pulposus, annulus fibrosus, cartilage endplate, intervertebral disc(IVD), intervertebral disc degeneration, animal model, organ culture, bioreactor, inflammatory reaction, mechanical stress, pathophysiology, epidemiology. Any IDD model-related articles were collected and summarized.Results: The best IDD model should have the features of repeatability, measurability and controllability. There are a lot of aspects to be considered in the selection of animals. Mice, rats and rabbits are low-cost and easy to access. However, their IVD size and shape are more different from human anatomy than pigs, cattle, sheep and goats. Organ culture models and animal models are two options in model establishment for IDD. The IVD organ culture model can put the studying variables into the controllable system for transitional research. Unlike the animal model, the organ culture model can only be used to evaluate the short-term effects and it is not applicable in simulating the complex process of IDD. Similarly, the animal models induced by different methods also have their advantages and disadvantages. For studying the mechanism of IDD and the corresponding treatment and prevention strategies, the selection of model should be individualized based on the purpose of each study.Conclusions: Various models have different characteristics and scope of application due to their different rationales and methods of construction. Currently, there is no experimental model that can perfectly mimic the degenerative process of human IVD. Personalized selection of appropriate model based on study purpose and experimental designing can enhance the possibility to obtain reliable and real results.

BRD4 Inhibition Suppresses Senescence and Apoptosis of Nucleus Pulposus Cells by Inducing Autophagy during Intervertebral Disc Degeneration: An In Vitro and In Vivo Study.

Intervertebral disc degeneration (IDD) is the most common chronic skeletal muscle degeneration disease. Although the underlying mechanisms remain unclear, nucleus pulposus (NP) autophagy, senescence, and apoptosis are known to play a critical role in this process. Previous studies suggest that bromodomain-containing protein 4 (BRD4) promotes senescent and apoptotic effects in several age-related degenerative diseases. It is not known, however, if BRD4 inhibition is protective in IDD. In this study, we explored whether BRD4 influenced IDD. In human clinical specimens, the BRD4 level was markedly increased with the increasing Pfirrmann grade. At the cellular level, BRD4 inhibition prevented IL-1ß-induced senescence and apoptosis of NP cells and activated autophagy via the AMPK/mTOR/ULK1 signaling pathway. Inhibition of autophagy by 3-methyladenine (3-MA) partially reversed the antisenescence and antiapoptotic effects of BRD4. In vivo, BRD4 inhibition attenuated IDD. Taken together, the results of this study showed that BRD4 inhibition reduced NP cell senescence and apoptosis by induced autophagy, which ultimately alleviated IDD. Therefore, BRD4 may serve as a novel potential therapeutic target for the treatment of IDD.

A New Hope in Spinal Degenerative Diseases: Piezo1.

As a newly discovered mechanosensitive ion channel protein, the piezo1 protein participates in the transmission of mechanical signals on the cell membrane and plays a vital role in mammalian biomechanics. Piezo1 has attracted widespread attention since it was discovered in 2010. In recent years, studies on piezo1 have gradually increased and deepened. In addition to the discovery that piezo1 is expressed in the respiratory, cardiovascular, gastrointestinal, and urinary systems, it is also stably expressed in cells such as mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, chondrocytes, and nucleus pulposus cells that constitute vertebral bodies and intervertebral discs. They can all receive external mechanical stimulation through the piezo1 protein channel to affect cell proliferation, differentiation, migration, and apoptosis to promote the occurrence and development of lumbar degenerative diseases. Through reviewing the relevant literature of piezo1 in the abovementioned cells, this paper discusses the effect of piezo1 protein expression under mechanical stress stimuli on spinal degenerative disease, providing the molecular basis for the pathological mechanism of spinal degenerative disease and also a new basis, ideas, and methods for the prevention and treatment of this degenerative disease.