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The performance and operation stability of proton exchange membrane fuel cells (PEMFCs) are closely related to the transportation of reactants and water management in the membrane electrode assembly (MEA) and flow field. In this paper, a new three-dimensional wave parallel flow field (WPFF) in cathode was designed and analyzed throughout simulation studies and an experimental method. The experimental results show that the performance of PEMFC with WPFF outperforms that of PEMFC with straight parallel flow field (SPFF). Specifically, the peak power density increased by 13.45% for the PEMFC with WPFF as opposed to PEMFC with SPFF. In addition, the flow field with area of 11.56 cm2 was formed by the assembly of transparent end plate used for cathode and the traditional graphite plate used for anode. To understand the mechanism of the novel flow field improving the performance of PEMFC, a model of PEMFC was proposed based on the geometry, operating conditions and MEA parameters. The thickness of gas diffusion layers (GDL), catalytic layers (CL) and proton exchange membrane were measured by scanning electron microscope. The simulation result shows that compared with SPFF, the WPFF based PEMFC promote the oxygen transfer from flow channel to the surface of CL through GDL, and it was beneficial to remove the liquid water in the flow channel and the MEA.

Exploring the production and application of clean energy has always been the core of sustainable development. As a clean and sustainable technology, electrocatalysis has been receiving widespread attention. It is crucial to achieve efficient, stable and cheap electrocatalysts. However, the traditional “trial and error” method is time-consuming, laborious and costly. In recent years, with the significant increase in computing power, computations have played an important role in electrocatalyst design. Nevertheless, it is still difficult to search for advanced electrocatalysts in the vast chemical space through traditional density functional theory (DFT) computations. Fortunately, the development of machine learning and interdisciplinary integration will inject new impetus into targeted design of electrocatalysts. Machine learning is able to predict electrochemical performances with an accuracy close to DFT. Here we provide an overview of the application of machine learning in electrocatalyst design, including the prediction of structure, thermodynamic properties and kinetic barriers. We also discuss the potential of explicit solvent model combined with machine learning molecular dynamics in this field. Finally, the favorable circumstances and challenges are outlined for the future development of machine learning in electrocatalysis. The studies on electrochemical processes by machine learning will further realize targeted design of high-efficiency electrocatalysts.

Huihao Zhang,1,* Sai Yao,1,* Zhiguo Zhang,1,* Chengcong Zhou,1 Fangda Fu,1 Yishan Bian,1 Huan Luo,2 Yan Li,1 Shuxin Yan,1 Yuying Ge,1 Yuying Chen,3 Kunyu Zhan,4 Yanzhi Ge,1 Zuxiang Chen,1 Ming Yue,5 Xiaofeng Li,6 Weibin Du,1,7 Hongting Jin,1 Peijian Tong,1 Hongfeng Ruan,1,8 Chengliang Wu1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Physiology, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Orthopedics and Traumatology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 7Research Institute of Orthopedics, The Affiliated JiangNan Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 8Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Peijian TongInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaEmail rhf@zcmu.edu.cn; peijiantongzjtcm@163.comPurpose: To explore the pharmacological mechanisms of Liuwei Dihuang Decoction (LWDHD) against intervertebral disc (IVD) degeneration (IVDD) via network pharmacology analysis combined with experimental validation.Methods: First, active ingredients and related targets of LWDHD, as well as related genes of IVDD, were collected from public databases. The protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed to predict the core targets and pathways of LWDHD against IVDD. Secondly, the IVDD model of mice treated with LWDHD was selected to validate the major targets predicted by network pharmacology.Results: By searching the intersection of the active ingredient targets and IVDD targets, a total of 110 targets matched the related targets of 30 active ingredients in LWDHD and IVDD were retrieved. PPI network analysis indicated that 17 targets, including Caspase-3, IL-1β, P53, etc., were hub targets. GO and KEGG enrichment analyses showed that the apoptosis pathway was enriched by multiple targets and served as the target for in vivo experimental study validation. The results of animal experiments revealed that LWDHD administration not only restored the decrease in disc height and abnormal degradation of matrix metabolism in IVDD mice but also reversed the high expression of Bax, Caspase-3, IL-1β, P53, and low expression of Bcl-2, thereby inhibiting the apoptosis of IVD tissue and ameliorating the progression of IVDD.Conclusion: Using a comprehensive network pharmacology approach, our findings predicted the active ingredients and potential targets of LWDHD intervention for IVDD, and some major target proteins involved in the predictive signaling pathway were validated experimentally, which gave us a new understanding of the pharmacological mechanism of LWDHD in treating IVDD at the comprehensive level.Keywords: intervertebral disc degeneration, Liuwei Dihuang decoction, network pharmacology, pharmacological mechanisms, apoptosis

Zhiguo Zhang,1,2,* Fangda Fu,1,2,* Yishan Bian,1,2,* Huihao Zhang,1,2 Sai Yao,1,2 Chengcong Zhou,1,2 Yuying Ge,2 Huan Luo,3 Yuying Chen,4 Weifeng Ji,1 Kun Tian,1 Ming Yue,5 Weibin Du,6 Hongting Jin,1 Peijian Tong,1 Chengliang Wu,1,2 Hongfeng Ruan1,2 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People’s Republic of China; 2The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 5Department of Physiology, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 6Research Institute of Orthopedics, The Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongfeng Ruan; Chengliang Wu, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Fax +86 571 86613684, Email rhf@zcmu.edu.cn; wcl@zcmu.edu.cnBackground: With the rapid growth of the elderly population, the incidence of osteoarthritis (OA) increases annually, which has attracted extensive attention in public health. The roles of dietary intake in controlling joint disorders are perhaps one of the most frequently posed questions by OA patients, while the information about the interaction between dietary intake and OA based on scientific research is limited. α-Chaconine is the richest glycoalkaloid in eggplants such as potatoes. Previous evidence suggests that α-Chaconine is a toxic compound to nervous and digestive systems with potentially severe and fatal consequences for humans and farm animals, but its effect on OA development remains obscure.Objective: To determine whether α-Chaconine deteriorates OA progression through sensory innervation and chondrocyte pyroptosis via regulating nuclear factor-κB (NF-κB) signaling, providing evidence for a possible linkage between α-Chaconine and OA progression.Methods: We established a mouse OA model by destabilization of medial meniscus (DMM) surgery and then intra-articular injection of 20 or 100 μM α-Chaconine into the OA mice for 8 and 12 weeks. The severity of OA progression was evaluated by histological staining and radiographic analyses. The expressions of matrix metabolic indicators, Col2, Mmp3, and Mmp13, as well as pyroptosis-related proteins, Nlrp3, Caspase-1, Gsdmd, IL-1β, IL-18, were determined by immunohistochemistry. And the changes in sensory nerve ingrowth and activity of NF-κB signaling were determined by immunofluorescence.Results: We found that α-Chaconine could exacerbate mouse OA progression, resulting in subchondral sclerosis, osteophyte formation, and higher OARSI scores. Specifically, α-Chaconine could augment cartilage matrix degradation and induce chondrocyte pyroptosis and nerve ingrowth. Mechanistical analysis revealed that α-Chaconine stimulated NF-κB signaling by promoting I-κB α phosphorylation and p65 nuclear translocation.Conclusion: Collectively, our findings raise the possibility that α-Chaconine intake can boost chondrocyte pyroptosis and nerve ingrowth to potentiate OA progression by activating NF-κB signaling.Graphical Abstract: Keywords: α-Chaconine, osteoarthritis, pyroptosis, nerve ingrowth, NF-κB signaling

The stirred ball mill (SBM) method is a common method applied in large-scale sludge disintegration. Many reports focus on the disintegration results of sludge or the influence of parameters on the anaerobic process of treated sludge, but there have been few studies on the mechanism of sludge disintegration by SBM. This study focused on the mechanism of sludge disintegration by the SBM method. The results show that the flocs and bacterial cell wall were well disrupted and that the cytoplasm flowed remarkably out of the cell. Although the size with the largest volume distribution was expected to decrease with increasing treatment time, the volume of particles with a size of 34.56–44.04 μm increased in the sample treated for 60 min. We observed a temperature increase in the reflocculation of the biomacromolecules. The maximal value of DDCOD was 18.6%, and the concentrations of proteins and nucleic acids reached peaks at 691.80 mg/L and 281.05 mg/L, respectively. The peptidoglycan concentration showed that only 25.4% of the cell wall was broken and dissolved into liquid. From the results, we show that SBM can effectively break flocs and bacterial cell walls, but the method has a low efficiency for breaking biomacromolecule fragments into the liquid phase.

Cadmium (Cd) is a ubiquitous toxic metal and environmental pollutant. Increasing studies have shown that Cd exposure increases the incidence of various endocrine system diseases, including thyrotoxicity reflected by thyroid structural damage and endocrine toxicity. However, the observed outcomes are complex and conflicting, leading to the mechanism of Cd-induced thyrotoxicity remaining obscure. In this study, 4-week-old male C57BL/6 mice were given 2 or 7 mg/kg Cadmium Chloride (CdCl

Electrochemical CO2 reduction reaction (CO2RR) is a very important approach to realize sustainable development. Single-atom catalysts show advantages in both homogeneous and heterogeneous catalysis, and considerable progress has been made in optimizing the performance of catalysts by controlling local coordination environment, especially through out-of-plane methods. In this work, we used an explicit solvent model combined with the “slow-growth” method and thermodynamic integration to investigate the influence of an axial oxygen atom on graphene-supported NiN4 moiety catalysts on CO2RR. The axial oxygen significantly promotes CO2 activation, computationally disclosed by simulations in realistic electrochemical environment. Our results provide a new perspective for CO2RR catalyzed by single-atom catalysts.

To efficiently produce green energy and to overcome energy crises and environmental issues, photocatalytic water splitting has become the core heart of recent research. Fabricating heterostructures with type-II band alignment can enhance the photocatalytic activity. By first-principles computations, we study Mo(W)Te2–As van der Waals (vdW) heterostructures as promising photocatalysts for overall water splitting. The bandgap, band edge position and optical properties can be modified by biaxial strain. With appropriate compressive strain of 2% and 3%, the WTe2–As heterostructures show transition from type-I to type-II band alignment, which could slow down electron-hole pair recombination. Compared with Mo(W)Te2 and As monolayers, the band edge of Mo(W)Te2–As heterostructures is on favorable positions for straddling the water redox potentials. Moreover, Mo(W)Te2–As heterostructures fascinatingly show strong absorption peaks in both visible and near ultra-violet region, making them promising candidates for overall water splitting photocatalysts.

Electroreduction of CO2 is one of the most potential ways to realize CO2 recycle and energy regeneration. The key to promoting this technology is the development of high-performance electrocatalyst...

Summary Purpose The purpose of our study was to introduce and validate a metal-free, reproducible and reliable mouse model of anterior cruciate ligament (ACL) reconstruction (ACLR) surgery as an effective tool for a better understanding of molecular mechanisms of graft-tunnel healing after ACLR. Methods A total of 150 C57BL/6 mice were randomly allocated into five Groups: Group 1 (mice with intact ACL), Group 2–4 (mice underwent modified ACLR surgery and sacrificed 1-, 2-, and 4-weeks after surgery), and Group 5 (mice underwent unmodified ACLR surgery and sacrificed 4 weeks after surgery). Micro-computed tomography (CT), biomechanical histological as well as immunohistochemical (IHC) analyses were performed to characterize the modified ACLR. Results Micro-CT analysis demonstrated there is a non-significant increase in BV/TV and BMD of the bone tunnel during the tendon-to-bone healing following ACLR. Biomechanical tests showed that the mean load-to-failure forces of Group 3 and 4 are equal to 31.7% and 46.0% of that in Group 1, while the stiffness was 33.1% and 57.2% of that of Group 1, respectively. And no obvious difference in biomechanical parameters was found between Group 4 and 5. Histological analysis demonstrated that formation of fibrovascular tissue in the tibial tunnel and aperture in Groups 4 and 5 and direct junction appeared between tendon graft and tunnel both in Groups 4 and 5. IHC results showed that there are gradually enhanced expression of Patched1, Smoothened and Gli2 concomitant with decreased Gli3 protein in the tendon-bone interface during the tendon-bone healing process. Conclusion We introduced a metal-free, reproducible and reliable mouse model of ACLR compared to the unmodified ACLR procedure, and characterized the expression pattern of key molecules in Ihh signaling during the graft healing process. The translational potential of this article In the present study we introduced and validated, for the first time, a metal-free, reproducible and reliable ACLR mouse model, which could be used to investigate the detailed molecular mechanisms of graft-tunnel healing after ACLR. We also explored new strategies to promote the healing of tendon-to-bone integration.

Both the elemental sulfur-based autotrophic denitrification (ESAD) and the biomass‑sulfur-based mixotrophic (simultaneous autotrophic and heterotrophic) denitrification processes (BSMD) are efficient methods for removing nitrate from wastewater. However, a comparative analysis of the denitrification capacity of the BSMD and ESAD in the packed bed reactors is still lacking. In this paper, corncob powder was selected as the biomass source to prepare biomass‑sulfur-based composite filter (BSCF) for the BSMD process. The denitrification performances of the three identical lab-scale bioreactors packed with varying elemental sulfur-based composite filters (ESCFs) were compared under varying loading conditions, and the optimal ESCF of the ESAD system was 2:1 by weight ratio of sulfur powder to shell powder. In pilot-scale experiments, the results showed that BSCF could decrease the sulfate productivity and gave better denitrification performance than the ESCF with the optimal nitrate removal rate (NRR) of 504 ± 12.3 mg NO

Zn–air batteries are promising devices for electrochemical energy storage and conversion. Bifunctional oxygen electrocatalysts with low cost are urgently needed to realize practical application. Herein, metal-free porous S and N co-doped carbon nanosheets (SNCs) were prepared through facile two-step thermal treatment. Owing to the synergistic effect of S and N, superior bifunctional electrocatalytic activity toward both oxygen reduction and evolution reactions was achieved, much better than that of singly doped carbon nanosheets. Computations further confirm that the introduction of S into N-doped carbon nanosheets can effectively increase their OER catalytic activity and even the overall catalytic performance. Additionally, Zn–air batteries fabricated with SNCs showed high power density and excellent rechargeability, outperforming most reported metal-free and even metal-based electrocatalysts, and fully demonstrating good prospects for practical application.

Primary hypertension is an important risk factor for the development of cardiovascular disease, cerebrovascular disease and renal disease, and its prevalence is increasing...

In the new era of Air Force equipment upgrading with times, in view of the air crew safety quality growing impact on the aviation flight safety, this paper, based on a large number of data, investigates the basic situation of the safety quality of the maintenance personnel by using the questionnaire survey method, analyzes the reliability of the questionnaire content by using SPSSAU system, summarizes the components of the safety quality of the maintenance personnel according to the feedback results of the questionnaire, and divides the training indicators; then the Delphi method and analytic hierarchy process are used to calculate the weight of each training index of the safety quality of the maintenance personnel. Finally, the training index system of the safety quality of the maintenance personnel is established, and some suggestions are given for the assessment and improvement of the safety quality of the maintenance personnel.

Aberrant mechanical factor is one of the etiologies of the intervertebral disc (IVD) degeneration (IVDD). However, the exact molecular mechanism of spinal mechanical loading stress-induced IVDD has yet to be elucidated due to a lack of an ideal and stable IVDD animal model. The present study aimed to establish a stable IVDD mouse model and evaluated the effect of aberrant spinal mechanical loading on the pathogenesis of IVDD. Eight-week-old male mice were treated with lumbar spine instability (LSI) surgery to induce IVDD. The progression of IVDD was evaluated by μCT and Safranin O/Fast green staining analysis. The metabolism of extracellular matrix, ingrowth of sensory nerves, pyroptosis in IVDs tissues were determined by immunohistological or real-time PCR analysis. The apoptosis of IVD cells was tested by TUNEL assay. IVDD modeling was successfully produced by LSI surgery, with substantial reductions in IVD height, BS/TV, Tb.N. and lower IVD score. LSI administration led to the histologic change of disc degeneration, disruption of the matrix metabolism, promotion of apoptosis of IVD cells and invasion of sensory nerves into annulus fibrosus, as well as induction of pyroptosis. Moreover, LSI surgery activated Wnt signaling in IVD tissues. Mechanical instability caused by LSI surgery accelerates the disc matrix degradation, nerve invasion, pyroptosis, and eventually lead to IVDD, which provided an alternative mouse IVDD model.

Two-dimensional (2D) triphosphides, as an important family of 2D materials, have attracted more attention. Here, by using density functional theory (DFT) computations, we explored the remaining XP3 monolayers (X = the metal of group IIIA-VA), and then proposed two novel 2D triphosphides, antimony triphosphide (SbP3) and gallium triphosphide (GaP3) monolayer. SbP3 and GaP3 monolayer are structurally stable semiconductors with indirect bandgaps of 2.36 eV and 1.45 eV, respectively. They not only show strong light absorption coefficients (up to 105 cm−1) in the visible and ultraviolet regions, but also their band edge positions straddle the redox potentials of water, making them promising catalysts for water splitting. Under strain, SbP3 monolayer can effectively reduce the bandgap and GaP3 monolayer can achieve the transition from indirect to direct bandgap, which can improve the photocatalytic efficiency accordingly. Our work would stimulate the fabrication of SbP3 and GaP3 monolayer and explore their potential applications in electronic and optoelectronic devices.

Perovskite materials have been attracting much attention in recent years, especially in the field of energy conversion. However, the inherent disadvantages constrict the development of perovskites. Though many modification strategies have been proposed, the fundamental connection between those modifications and electronic properties is not clear. In this work, we investigated a series of Ruddlesden–Popper (RP) perovskites to explore the relationship between chemical components and their electronic properties. We revealed the influence of the components at A and B sites on band gaps and band edge positions by first-principles computations. After summarizing the design rules for RP perovskites, we proposed three new ones, MgSrMnO4, Mg2SrMn2O7 and MgSr2Mn2O7. Computed electronic properties demonstrate that Mg2SrMn2O7 has the suitable band gap and optimal light absorption, while MgSrMnO4 also has the optimal band edge position at the same time. These two new perovskites have desirable potential for application in the field of luminous energy conversion. Therefore, the rules of band engineering can provide guidance for further development of RP perovskites for photovoltaic or photocatalytic applications.

Hydrogen production by electrocatalytic water splitting is currently the most attractive route, but the development of electrocatalysts with high activity, long durability and low cost is still a big challenge. Here, by combining algorithm screening and density functional theory (DFT) computations, we developed a method to predict two-dimensional (2D) metal-free materials with metallicity as efficient electrocatalysts for the hydrogen evolution reaction (HER). From all metal-free compounds in the Materials Project database, we obtained 18 layered materials without band gaps as candidates for the HER. After being exfoliated into monolayers, a stable metal-free material, a C3N monolayer, proved to be an efficient HER electrocatalyst according to computations. With this strategy, we can adjust the screening conditions with the target to find promising materials, which overcomes the obstacles of traditional trial-and-error methods and greatly saves computational resource. We hope that this work would inspire the development of a new research paradigm and promote the discovery of more functional materials.

Both the vibration and backwashing methods are efficient pathway to improve the denitrification ability in reactors. However, the comparison of the effects of vibration and backwashing on the sulfur-based autotrophic denitrification (SAD) reactor is still lacking. In this study, two SAD reactors were compared under various conditions, and the results showed that the use of the oyster shell powder could lower the sulfate productivity with better denitrification ability, and the denitrifiers could be more enriched due to the use of the oyster shell powder. In addition, vibration method performs better than backwashing in improving SAD denitrification ability, reasonable vibration intensity can not only help to reduce energy consumption, but also improve the ability of denitrification of the SAD reactors to a greater extent. Overall, the results of the experiments in this study are helpful for improving the ability of SAD reactors at low temperature and could provide the possibility for wider application of SAD technology.

This study explored the denitrification performance of solid-phase denitrification reactors packed with elemental sulfur/wheat straw/shell powder composites to treat nitrate-contaminated wastewater under different conditions. The sulfur-based autotrophic denitrification integrated natural-carbon-source (NCS)-based heterotrophic denitrification system was formed (SND). The fast start-up and intensified nitrogen removal performance were obtained in SND systems. The optimum denitrification performance was achieved by the SND15 reactor, with a maximum denitrification rate of 530 mg N·L-1·d-1 over 180 days operation. The co-existence of autotrophs and heterotrophs were observed in all reactors, this may contribute to better control of nitrogen in SND system. The outcomes provide a potential strategy of cost reduction to improve nitrogen removal of wastewater treatment plants (WWTPs) effluent.

The sulfur-based autotrophic denitrification (SAD) and the solid organic carbon-based denitrification processes are both efficient techniques to remove nitrate from wastewater, and the hydrogen ions generated by the SAD process would be consumed in the heterotrophic denitrification process. Therefore, it is possible to improve the denitrification capacity when the solid organic carbon was added into a SAD reactor. In this study, corncob powder and sawdust powder were selected as solid organic carbon sources, and the sulfur-based autotrophic denitrification integrated biomass-based heterotrophic denitrification system was formed (SBD). The laboratory and field experiments showed that SBD could shorten the start-up period, decrease the sulfate productivity, and maintain a good denitrification performance when treated wastewater. According to the field experiment results, when the HRT was 1 h, the effluent total nitrogen (TN) concentration was always lower than 15 mg L−1. In addition, nitrite inhibition was observed when the concentration of nitrite in the reactors reached above 30 mg L−1. The mixture of elemental sulfur powder, shell powder, corncob powder, and sawdust powder with a mass ratio of 6:2:1:1 was the optimal filter for the SBD system, with an average nitrate reduction rate (NAR) of 420 mg NO3–N·L−1·d−1 obtained at the end of the study. During the whole operation, the major autotrophs in the SBD systems were Thermomonas, Ferritrophicum, and Thiobacillus, while the major heterotrophs were Saprospiraceae, Ferruginibacter, Dokdonella, and Simplicispira. Overall, the SBD system was a feasible and practically favorable way to remove nitrate from wastewater.

Breast cancer (BC) is the most commonly diagnosed cancer in females globally and is more aggressive at later stages. Chromosome region maintenance 1 (CRM1) is involved in the nuclear export of proteins and RNAs and has been associated with a number of malignancies. However, the clinicopathological significance of its expression in BC remains to be elucidated therefore this was investigated in the present study. CRM1 expression in 280 breast cancer tissues and 60 normal tissues was retrospectively analyzed using immunohistochemistry (IHC) and western blotting. IHC investigation demonstrated that CRM1 expression was significantly increased in BC compared with the normal breast epithelium (P

Background Whole body vibration (WBV) is a non-pharmaceutical therapy that has been widely incorporated into clinical practice for musculoskeletal disorders, including low back pain (LBP). Intervertebral disc (IVD) degeneration (IVDD) is clinically associated with LBP and is known as the main cause for LBP. However, cumulative evidence also suggested WBV might have an adverse impact on IVDs. Moreover, previous studies have been focusing on the effects of WBV on healthy mice, rather than those suffering from IVDD. Thus, uncertainties still exist concerning the effects of WBV on IVDs undergoing IVDD. This study was aiming to evaluate the effects of WBV intervention on the development and progression of IVDD mouse model induced by lumbar spine instability (LSI) surgery. Methods LSI surgery, by resecting the lumbar 3 rd -5 th spinous processes along with the supraspinous and interspinous ligaments, was conducted in 10-week-old male mice which then received WBV treatment (1 h per day, 5 days per week, at 3 Hz with peak acceleration at 0.4 g) or sham treatment. The progression of IVDD was evaluated by MRI, μCT and histological analyses after WBV treatment. The matrix metabolism, distribution of sensory nerves, pyroptosis in IVDs tissues were determined by immunohistological analysis or real-time PCR. The apoptosis of IVD cells was detected by TUNEL assay. Results LSI surgery was successful in producing IVDD modeling. WBV caused decreases in IVD height and annulus fibrosus (AF) score, as well as increased numbers of apoptotic cells in IVD tissues. WBV contributed to sensory innervation into AF and upregulation of Adamts5 and MMP3 expression in IVDD mice received LSI surgery. In addition, WBV treatment triggered earlier activation of Wnt/β-catenin signaling in IVDD mice with WBV treatment compared with those without WBV treatment. Unexpectedly, WBV significantly attenuated Caspase-1 and IL-1β expression in AF. Conclusions Collectively, our findings demonstrate that WBV treatment may worsen the development of ongoing IVDD. Decrease of IL-1β expression after WBV intervention may partially account for patient self-reported pain relief after WBV treatment in some previous trials. This study may help us better understand the effects of WBV intervention on patients experiencing LBP resulting from the degeneration of lumbar IVDs.

Osteoarthritis (OA) is the most common arthropathy, characterized by progressive degeneration of the articular cartilage. Currently, there are no disease-modifying approaches for OA treatment. Adeno-associated virus (AAV)-mediated gene therapy has recently become a potential treatment for OA due to its exceptional characteristics; however, the tropism and transduction efficiency of different AAV serotypes to articular joints and the safety profile of AAV applications are still unknown. The present study aims to screen an ideal AAV serotype to efficiently transfer genes to arthritic cartilage. AAV vectors of different serotypes expressing eGFP protein were injected into the knee joint cavities of mice, with all joint tissues collected 30 days after AAV injection. The transduction efficiency of AAVs was quantified by assessing the fluorescent intensities of eGFP in the cartilage of knee joints. Structural and morphological changes were analyzed by toluidine blue staining. Changes to ECM metabolism and pyroptosis of chondrocytes were determined by immunohistochemical staining. Fluorescence analysis of eGFP showed that eGFP was expressed in the cartilage of knee joints injected with each AAV vector. Quantification of eGFP intensity indicated that AAV2, 7 and 8 had the highest transduction efficiencies. Both toluidine blue staining and Mankin score showed that AAV6 aggravated cartilage degeneration. The analysis of key molecules in ECM metabolism suggested that AAV5 and 7 significantly reduced collagen type II, while AAV9 increased ADAMTS-4 but decreased MMP-19. In addition, transduction with AAV2, 5, 7 and 8 had no obvious effect on pyroptosis of chondrocytes. Comprehensive score analysis also showed that AAV2 had the highest score in intra-articular gene transfer. Collectively, our findings point to AAV2 as the best AAV serotype candidate for gene transfer on arthritic cartilage, resulting in minimal impact to ECM metabolism and pyroptosis of chondrocytes.

In this study, a novel coupling process with partial nitritation-anaerobic ammonium oxidation (anammox) (PNA) and sulfur autotrophic denitrification (SAD) was studied using an upflow biofilm reactor with mechanical vibration. At a lower dissolved oxygen (DO) concentration (0.40 ± 0.20 mg L−1), ammonia could be efficiently removed from synthetic wastewater by the coupling system with a total nitrogen removal efficiency (NRE) of 98% and an influent NH4+-N concentration of 600 mg L−1. In this system, the nitrate, which was produced during the anammox reaction, could be timely reduced by the SAD reaction. Compared with the conventional PNA and SAD processes, coupling the PNA and SAD processes in a single reactor prevented nitrite accumulation in the SAD reaction and reduced the total sulfate production by 59%. The high-throughput sequencing analysis supported that the SAD bacteria (Thiobacillus) and anammox bacteria (Candidatus Kuenenia) could coexist on the elemental sulfur stone. Additionally, sulfur consumption and sulfate production were increased under a high DO concentration. The sulfate production/nitrate reduction ratio and changing profile of the substrate suggested that the short-cut SAD process mainly occurred in this coupling system. Otherwise, batch experiments also suggested that the nitrite removal rate in the anammox process was 34.5 times higher than that in the SAD process. The outcomes of these experiments revealed that most of the nitrite, as an intermediate product in the SAD reaction, served as an electron acceptor for the anammox reaction. A stoichiometric calculation of this coupling process indicated that the novel reaction scheme with a high NRE was successfully achieved. Under an ideal short-cut SAD process, almost 55% of the sulfur consumption could be reduced in this coupling system. The coupling system provides a new perspective for nitrogen removal in a single reactor and further promotes anammox and SAD performance in wastewater treatment processes.

Ethnopharmacological relevance Corni Fructus (CF), the red fruit of Cornus officinalis Siebold & Zucc, has been used both as food and medicinal herb in traditional Chinese medicine (TCM). Loganin is a major iridoid glycoside and one of the quality control indexes of CF. In TCM clinical practice, prescription containing CF is commonly used to treat osteoarthritis (OA), but the underlying mechanisms of loganin are not yet utterly understood. Aim of the study The aims of the present study are to confirm the therapeutic effects of loganin in an OA mouse model and to determine the mechanisms involved in the OA protective effects. Materials and methods The destabilization of the medial meniscus (DMM) procedure was performed on the right knee of 8-week-old C57BL/6 male mice. 30 or 100 μg/ml of loganin was then injected into articular space twice a week for 8 and 12-week. Safranin O/Fast green staining, H&E staining, micro-CT analysis were performed to analyze structural and morphological changes. The protein expression of collagen type II (Col2), metalloproteinase-3 (Mmp3), matrix metalloproteinase 13 (Mmp13) collagen type X (Col10), cryopyrin and caspase-1 were detected by immunochemistry staining. Immuno-fluorescence assay was performed to assess changes in expression of CD31, endomucin, p65 and p-I-κB. Results Results of histomorphometry showed that loganin delays the progression of OA in the DMM model. In cartilage, loganin decreased the OARSI score, increasing hyaline cartilage (HC) thickness and decreasing calcified cartilage (CC) thickness. Moreover, loganin inhibited osteophyte formation, reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th) and increased trabecular separation (Tb.Sp) in subchondral bone. Mechanistically, loganin increased the expressions of Col2, decreases the expression of Mmp3, Mmp13, Col10, cryopyrin and caspase-1 in cartilage. In parallel, loganin inhibited the expression of CD31 and endomucin in subchondral bone. Furthermore, loganin suppressed nuclear translocation of p65 protein, and decreased the amount of p-I-κB in chondrocytes. Conclusions In summary, these results uncovered that loganin inhibits NF-κB signaling and attenuates cartilage matrix catabolism and pyroptosis of chondrocytes in articular cartilage. Loganin may serve as a potential therapeutic agent for OA treatment.

An upflow biofilm reactor was operated for 211 days to investigate the effects of vibration on anammox treatment performance. With vibration, the highest nitrogen removal rates (20 kg-N·m−3·d−1) were obtained on day 180. Since the vibration could directly applied on the biofilm, it could release the dinitrogen gas accumulated in the biofilm timely and reduce the internal mass transfer resistance sharply. The specific anammox activity increased by more than 3 times with a higher vibration intensity. Meanwhile, the unique random motion caused by mechanical vibration promotes the production of extracellular proteins. Moreover, the VSS reached 20.97 g·L−1 which was 1.6 times higher than the control reactor. Such enrichment method resulted in a hard and thick anammox biofilm with a special granular morphology, and the nitrite tolerance concentration could reach 500 mg-N·L−1. Operated with an adequate vibration intensity could maintain the biofilm thickness and conducive to improve the stability of the reactor. In addition, this technique also allowed the microorganisms inside the biofilm and those on the surface to reach the same culture conditions. Base on the batch experiments, intermittent vibration caused a decrease in energy consumption from about 7.757 (kW·h)·(kg-N)−1 in group 0-Lv7(60-60) to 0.912 (kW·h)·(kg-N)−1 in group 0-Lv7(5-60). Compared to the internal recycle without vibration, the energy consumption fell by a slice over 65%. Furthermore, the high-throughput sequencing results showed that the relative abundance of Candidatus Kuenenia in reactor 1 increased from 13.2% to 43.9%.