High-precision and lightweight small-target detection algorithm for low-cost edge intelligence.

The proliferation of edge devices driven by advancements in Internet of Things (IoT) technology has intensified the challenge of achieving high-precision small target detection, as it demands extensive computational resources. This amplifies the conflict between the need for precise detection and the requirement for cost-efficiency across numerous edge devices. To solve this problem, this paper introduces an enhanced target detection algorithm, MSGD-YOLO, built upon YOLOv8. The Faster Implementation of CSP Bottleneck with 2 convolutions (C2f) module is enhanced through the integration of the Ghost module and dynamic convolution, resulting in a more lightweight architecture while enhancing feature generation. Additionally, Spatial Pyramid Pooling with Enhanced Local Attention Network (SPPELAN) replaces Spatial Pyramid Pooling Fast (SPPF) to expand the receptive field, optimizing multi-level feature aggregation for improved performance. Furthermore, a novel Multi-Scale Ghost Convolution (MSGConv) and Multi-Scale Generalized Feature Pyramid Network (MSGPFN) are introduced to enhance feature fusion and integrate multi-scale information. Finally, four optimized dynamic convolutional detection heads are employed to capture target features more accurately and improve small target detection precision. Evaluation on the VisDrone2019 dataset shows that compared with YOLOv8-n, MSGD-YOLO improves mAP@50 and mAP@50-95 by 14.1% and 11.2%, respectively. In addition, the model not only achieves a 16.1% reduction in parameters but also attains a processing speed of 24.6 Frames Per Second (FPS) on embedded devices, thereby fulfilling real-time detection requirements.

Cytochrome P450 CYP81A104 in Eleusine indica confers resistance to multiherbicide with different modes of action.

BACKGROUND: Developing herbicide-resistant (HR) crop cultivars is an efficient way to control weeds and minimize crop yield losses. However, widespread and long-term herbicide application has led to the evolution of resistant weeds. Here, we established a resistant (R) E. indica population, collected from imidazolinone-resistant rice cultivar fields. RESULTS: The R population evolved 4.5-fold resistance to imazamox. Acetolactate synthase (ALS) gene sequencing and ALS activity assays excluded the effect of target-site resistance in this population. P450 inhibitor malathion pretreatment significantly reversed resistance to imazamox. RNA sequencing showed that a P450 gene CYP81A104 was expressed higher in R versus susceptible (S) plants. Arabidopsis overexpressing CYP81A104 showed resistance to ALS inhibitors (imazamox, tribenuron-methyl, penoxsulam and flucarbazone-sodium), PSII inhibitor (bentazone), hydroxyphenyl pyruvate dioxygenase inhibitor (mesotrione) and auxin mimics (MCPA), which was generally consistent with the results presented in the R population. CONCLUSION: This study confirmed that the CYP81A104 gene endowed resistance to multiherbicides with different modes-of-action. Our findings provide an insight into the molecular characteristics of resistance and contribute to formulating an appropriate strategy for weed management in HR crops. © 2024 Society of Chemical Industry.

A novel coupling process to replace the traditional multi-stage anammox process-sulfur autotrophic denitrification coupled anammox system.

A novel coupling process to replace the traditional multi-stage anammox process-sulfur autotrophic denitrification (SAD) coupled anaerobic ammonium oxidation (anammox) system was designed, which solved problems of nitrate produced in anammox process and low nitrate conversion rate caused by nitrite accumulation in SAD process. Different filter structures (SAD filter and anammox granular sludge) were investigated to further explore the excellent performance of the novel integrated reactor. The results of sequential batch experiments indicated that nitrite accumulation occurred during SAD, which inhibited the conversion of nitrate to dinitrogen gas. When SAD filter and anammox granular sludge were added to packed bed reactor simultaneously, the nitrate removal rate increased by 37.21% and effluent nitrite concentration decreased by 100% compared to that achieved using SAD. The stratified filter structure solved groove flow. Different proportion influence of SAD filter and anammox granular sludge on the stratified filter structure was evaluated. More suitable ratio of SAD filter to anammox granular sludge was 2:1. Proteobacteria (57.26%), Bacteroidetes (20.12%) and Chloroflexi (9.95%) were the main phyla. The dominant genera of denitrification functional bacteria were Thiobacillus (39.80%), Chlorobaculum (3.99%), norank_f_PHOs-HE36 (2.90%) and Ignavibacterium (2.64%). The dominant genus of anammox bacterium was Candidatus_Kuenenia (3.05%).

MINK1 deficiency stimulates nucleus pulposus cell pyroptosis and exacerbates intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration, induced by aging and irregular mechanical strain, is highly prevalent in the elderly population, serving as a leading cause of chronic low back pain and disability. Evolving evidence has revealed the involvement of nucleus pulposus (NP) pyroptosis in the pathogenesis of IVD degeneration, while the precise regulatory mechanisms of NP pyroptosis remain obscure. Misshapen/Nck-interacting kinase (NIK)-related kinase 1 (MINK1), a serine-threonine protein kinase, has the potential to modulate the activation of NLRP3 inflammasome, indicating its pivotal role in governing pyroptosis. In this study, to assess the significance of MINK1 in NP pyroptosis and IVD degeneration, NP tissues from patients with varying degrees of IVD degeneration, and IVD tissues from both aging-induced and lumbar spine instability (LSI) surgery-induced IVD degeneration mouse models, with or without MINK1 ablation, were meticulously evaluated. Our findings indicated a notable decline in MINK1 expression in NP tissues of patients with IVD degeneration and both mouse models as degeneration progresses, accompanied by heightened matrix degradation and increased NP pyroptosis. Moreover, MINK1 ablation led to substantial activation of NP pyroptosis in both mouse models, and accelerating ECM degradation and intensifying the degeneration phenotype in mechanically stress-induced mice. Mechanistically, MINK1 deficiency triggered NF-κB signaling in NP tissues. Overall, our data illustrate an inverse correlation between MINK1 expression and severity of IVD degeneration, and the absence of MINK1 stimulates NP pyroptosis, exacerbating IVD degeneration by activating NF-κB signaling, highlighting a potential innovative therapeutic target in treating IVD degeneration.

An Asp376Glu substitution and P450s-involved metabolism endow resistance to ALS inhibitors in an Ammannia auriculata Willd. Population.

Ammannia auriculata Willd. is a noxious broadleaf weed, commonly infesting rice ecosystems across southern China. A putative resistant A. auriculata population (AHSC-5) was sampled from a rice field of Anhui Province, where bensulfuron-methyl (BM) was unable to control its occurrence. This study aimed to determine the sensitivities of the AHSC-5 population to common-use herbicides, and to investigate the underlying resistance mechanisms. The bioassays showed that the AHSC-5 population was 138.1-fold resistant to BM, compared with the susceptible population (JSGL-1). Pretreatment of malathion reduced the resistance index to 19.5. ALS sequencing revealed an Asp376Glu substitution in the AHSC-5 population, and in vitro ALS activity assays found that 50% activity inhibition (I50) of BM in AHSC-5 was 75.4 times higher than that of JSGL-1. Moreover, the AHSC-5 population displayed cross-resistance to pyrazosulfuron-ethyl (10.6-fold), bispyribac­sodium (3.6-fold), and imazethapyr (2.2-fold), and was in the process of evolving multiple resistance to synthetic auxin herbicides fluroxypyr (2.3-fold) and florpyrauxifen-benzyl (3.1-fold). This study proved the BM resistance in A. auriculata caused by the Asp376Glu mutation and P450-regulated metabolism. This multi-resistant population can still be controlled by penoxsulam, MCPA, bentazone, and carfentrazone-ethyl, which aids in developing targeted and effective weed management strategies.

α-Solanine attenuates chondrocyte pyroptosis to improve osteoarthritis via suppressing NF-κB pathway.

α-Solanine has been shown to exhibit anti-inflammatory and anti-tumour properties; however, its efficacy in treating osteoarthritis (OA) remains ambiguous. The study aimed to evaluate the therapeutic effects of α-solanine on OA development in a mouse OA model. The OA mice were subjected to varying concentrations of α-solanine, and various assessments were implemented to assess OA progression. We found that α-solanine significantly reduced osteophyte formation, subchondral sclerosis and OARSI score. And it decreased proteoglycan loss and calcification in articular cartilage. Specifically, α-solanine inhibited extracellular matrix degradation by downregulating collagen 10, matrix metalloproteinase 3 and 13, and upregulating collagen 2. Importantly, α-solanine reversed chondrocyte pyroptosis phenotype in articular cartilage of OA mice by inhibiting the elevated expressions of Caspase-1, Gsdmd and IL-1ß, while also mitigating aberrant angiogenesis and sensory innervation in subchondral bone. Mechanistically, α-solanine notably hindered the early stages of OA progression by reducing I-κB phosphorylation and nuclear translocation of p65, thereby inactivating NF-κB signalling. Our findings demonstrate the capability of α-solanine to disrupt chondrocyte pyroptosis and sensory innervation, thereby improving osteoarthritic pathological progress by inhibiting NF-κB signalling. These results suggest that α-solanine could serve as a promising therapeutic agent for OA treatment.

Atrazine exposure promotes cardiomyocyte pyroptosis to exacerbate cardiotoxicity by activating NF-κB pathway.

Atrazine is a ubiquitous herbicide with persistent environmental presence and accumulation in the food chain, posing potential health hazards to organisms. Increasing evidence suggests that atrazine may have detrimental effects on various organ systems, including the nervous, digestive, and immune systems. However, the specific toxicity and underlying mechanism of atrazine-induced cardiac injury remain obscure. In this study, 4-week-old male C57BL/6 mice were administered atrazine via intragastric administration at doses of 50 and 200 mg/kg for 4 and 8 weeks, respectively. Our findings showed that atrazine exposure led to cardiac fibrosis, as evidenced by elevated heart index and histopathological scores, extensive myofiber damage, and interstitial collagen deposition. Moreover, atrazine induced cardiomyocyte apoptosis, macrophage infiltration, and excessive production of inflammatory factors. Importantly, atrazine upregulated the expressions of crucial pyroptosis proteins, including NLRP3, ASC, CASPASE1, and GSDMD, via the activation of NF-κB pathway, thus promoting cardiomyocyte pyroptosis. Collectively, our findings provide novel evidence demonstrating that atrazine may exacerbate myocardial fibrosis by inducing cardiomyocyte pyroptosis, highlighting its potential role in the development of cardiac fibrosis.

Current status of cyhalofop-butyl and metamifop resistance and diversity of the ACCase gene mutations in Chinese sprangletop (Leptochloa chinensis) from China.

Leptochloa chinensis populations in China have evolved widespread resistance to acetyl coenzyme A carboxylase (ACCase)-inhibiting herbicides cyhalofop-butyl (CyB) and metamifop (Met). 124 L. chinensis populations, randomly collected from rice fields in Jiangsu Province, were surveyed for CyB and Met resistance status, and all potential ACCase gene resistance-conferring mutations and effective pre-emergence herbicides for its control were investigated. Single-dose tests confirmed that 82 (66.1%) and 70 (56.4%) populations evolved resistance to CyB and Met, respectively. ACCase sequencing revealed that 56.4% of the populations contain plants with diverse target-site ACCase mutations (Ile1781Leu, Trp1999Cys, Trp2027Cys, Trp2027Ser, Ile2041Asn, Gly2096Ala, and in particular, a Leu1818Phe mutation). Notably, the Leu1818Phe mutation had been detected in 8 resistant populations, indicating this mutation was prone to occur in L. chinensis. Additionally, 9.7% of the populations may have single metabolic resistance to CyB, as these populations was susceptible to Met, and no any ACCase mutations were found. Moreover, the resistant populations with different ACCase mutations showed 6.5 to 33.6-fold resistance to CyB, and 4.4 to 82.6-fold resistance to Met. Importantly, five pre-emergence herbicides, including pretilachlor, pendimethalin, clomazone, pyraclonil, and mefenacet, all exhibited good control effect on resistant L. chinensis populations. This work confirmed the prevalence and distribution of CyB and Met resistance in L. chinensis. Target-site ACCase mutations made a major contribution to CyB and Met resistance. Pre-emergence herbicides could be valuable tools for management of resistant L. chinensis populations.

Inhibition of Caspase-1-mediated pyroptosis promotes osteogenic differentiation, offering a therapeutic target for osteoporosis.

BACKGROUND: Pyroptosis, an emerging inflammatory form of cell death, has been previously demonstrated to stimulate a massive inflammatory response, thus hindering the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Nevertheless, the impact of pyroptosis in thwarting osteogenic differentiation and exacerbating the advancement of osteoporosis (OP) remains enigmatic. METHODS: We evaluated the expression levels of pyroptosis-associated indicators, including NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), CASPASE-1, IL-1ß, and IL-18, in specimens obtained from femoral heads of OP patients, as well as in an ovariectomy-induced mouse model of OP. Subsequently, the precise roles of pyroptosis in osteogenic differentiation were investigated using bioinformatics analysis, alongside morphological and biochemical assessments. RESULTS: The pivotal pyroptotic proteins, including NLRP3, Caspase-1, IL-1ß, and IL-18, exhibited significant upregulation within the bone tissue samples of clinical OP cases, as well as in the femoral tissues of ovariectomy (OVX)-induced mouse OP model, displaying a negatively associated with compromised osteogenic capacity, as represented by lessened bone mass, suppressed expression of osteogenic proteins such as Runt-related transcription factor 2 (RUNX2), Alkaline phosphatase (ALP), Osterix (OSX), and Osteopontin (OPN), and increased lipid droplets. Moreover, bioinformatics analysis substantiated shared gene expression patterns between pyroptosis and OP pathology, encompassing NLRP3, Caspase-1, IL-1ß, IL-18, etc. Furthermore, our in vitro investigation using ST2 cells revealed that dexamethasone treatment prominently induced pyroptosis while impeding osteogenic differentiation. Notably, gene silencing of Caspase-1 effectively counteracted the inhibitory effects of dexamethasone on osteogenic differentiation, as manifested by increased ALP activity and enhanced expression of RUNX2, ALP, OSX, and OPN. CONCLUSION: Our findings unequivocally underscore that inhibition of Caspase-1-mediated pyroptosis promotes osteogenic differentiation, providing a promising therapeutic target for managing OP.

ACCase gene mutations and P450-mediated metabolism contribute to cyhalofop-butyl resistance in Eleusine indica biotypes from direct-seeding paddy fields.

Eleusine indica causes problems in direct-seeding rice fields across Jiangsu Province in China. Long-term application of chemical herbicides has led to the widespread evolution of resistance in E. indica. In this study, we surveyed the resistance level of cyhalofop-butyl (CyB) in 19 field-collected E. indica biotypes, and characterized its underlying resistance mechanisms. All 19 biotypes evolved moderate- to high-level resistance to CyB (from 5.8- to 171.1-fold). 18 biotypes had a target-site mechanism with Trp-1999-Ser, Trp-2027-Cys, or Asp-2078-Gly mutations, respectively. One biotype (JSSQ-1) was identified to have metabolic resistance, in which malathion pretreatment significantly reduced the CyB resistance, and cyhalofop acid was degraded 1.7- to 2.5-times faster in this biotype compared with a susceptible control. Furthermore, the JSSQ-1 biotype showed multiple resistance to acetyl-CoA carboxylase (ACCase) inhibitor metamifop (RI = 4.6) and fenoxaprop-p-ethyl (RI = 5.1), acetolactate synthase (ALS) inhibitor imazethapyr (RI = 4.1), and hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor mesotrione (RI = 3.5). In addition, 11 out of 19 E. indica biotypes exhibited multiple resistance to glyphosate. This research has identified the widespread occurrence of CyB resistance in E. indica, attributed to target-site mutations or enhanced metabolism. Moreover, certain biotypes have exhibited resistance to multiple herbicides or even cross-resistance. Consequently, there is an urgent need to implement diverse weed management practices to effectively combat the proliferation of this weed in rice fields.

Hu'po Anshen decoction promotes fracture healing in mice with traumatic brain injury through BMP2-COX2-ATF4 signaling pathway.

Hu'po Anshen decoction (HPASD), a traditional Chinese medicine used to treat concussion and fracture, could regulate the expression of bone morphogenetic protein 2 (BMP2). However, whether HPASD affects the fracture healing of traumatic brain injury (TBI) combined with a fracture through BMP2 and its downstream signals remains obscure. The chondrocyte-specific BMP2 conditional knockout mice and chondrocyte-specific cyclooxygenase-2 (COX2) overexpression mice were generated. BMP2 conditional knockout mice were treated with fracture surgery, fracture combined with TBI, or fracture combined with TBI followed by different doses of HPASD (2.4, 4.8, and 9.6 g/kg), respectively. TBI was induced by Feeney's weight-drop technique. The fracture callus formation and fracture sites were determined by X-ray, micro-CT, and histological analyses. The expressions of chondrocyte-, osteoblast-, and BMP2/COX2 signal-related targets were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot assays. The specific absence of BMP2 in chondrocytes led to the prolonged formation of cartilage callus, a delay in the osteogenesis initiation and the downregulation of RUNX2, Smad1/5/9, EP4, ERK1/2, RSK2, ATF4. Overexpression of COX2 partially reverses the effects of chondrocyte-specific BMP2 knockout mice. HPASD promoted cartilage callus formation and osteogenesis initiation, as accompanied by upregulated expression levels of RUNX2, Smad1/5/9, EP4, ERK1/2, RSK2, and ATF4 in a time-dependent and concentration-dependent manner in chondrocyte-specific BMP2 knockout mice. Overall, our findings demonstrated that HPASD induced COX2 transcription through the BMP2-Smad1/5/9-RUNX2 axis, and then affected fracture healing through the COX2-mediated EP4-ERK1/2-RSK2-ATF4 axis.

Effects of recycling hyper-thermal inoculum by repeated batch cultivation into co-composting of sludge and livestock-poultry manure.

The enrichment and adaptation of hyper-thermal compost-derived thermophilic inoculum by repeated batch cultivation (RBC) was conducted by investigating bacterial community. The effects of recycling hyper-thermal inoculum by RBC into co-composting were investigated through evaluating the influences of temperature, pH, moisture, C/N ratio, transformation of nitrogen, composting maturity, humification levels and scanning electron microscopy (SEM). The results showed that RBC enriched the thermophilic bacterial community and nitrogen fixation bacteria of the compost-derived thermophilic inoculum. Simultaneously, recycling the inoculum into co-composting increased the temperature, nitrate nitrogen (NO3--N) and Germination index (GI), and improved the transformation of nitrogen and humification levels. Conclusively, recycling hyper-thermal inoculum by RBC into co-composting can improve the degradation process.

Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling.

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 (CdCl2) intragastrically for 4 and 8 weeks, and the Cd-mediated thyrotoxicity was evaluated by determining alterations in thyroid structure and endocrine function, and alterations of oxidant stress, apoptosis, and pyroptosis. Our data showed that Cd exposure could reduce body weight and induce thyrotoxicity by impairing thyroid follicular morphology and endocrine function, accompanied by elevated oxidative stress and apoptosis, macrophage infiltration, and inflammatory cytokine secretion. Importantly, Cd significantly promoted thyroid follicular cell pyroptosis by increasing Nlrp3, Asc, Caspase-1, Gsdmd, IL-1ß, and IL-18 expression. Mechanistical analysis suggested that Cd treatment could inhibit antioxidant pathway by downregulating antioxidant response protein, Nrf2, and upregulating its negative feedback regulator, Keap1. Collectively, our in vivo findings suggest that Cd exposure could facilitate thyroid follicular cell pyroptosis by inhibiting Nrf2/Keap1 signaling, thereby disrupting thyroid tissue structure and endocrine function, which offers novel insights into the Cd-mediated detrimental consequences on thyroid homeostasis.

Direct Anterior Approach Provides Superior Prosthesis Adaptability in the Early Postoperative Period of Total Hip Arthroplasty.

OBJECTIVES: Prosthesis awareness is the perception of foreign bodies, which has a critical effect on the function of the prosthetic joint. In total hip arthroplasty (THA), the direct anterior approach (DAA) has more advantages than the posterior approach (PA), including superior rehabilitation outcomes. This study was to evaluate the recovery of "prosthesis awareness" through these two approaches. METHODS: Three hundred and seventy-six patients who received THA with either DAA (n = 41) or PA (n = 335) from January 2016 to December 2017 were retrospectively analyzed. The Forgotten Joint Score-12 (FJS-12), Harris hip score (HHS), and visual analog scale (VAS) analyses were used to evaluate the recovery of "prosthesis awareness" in these patients 2 weeks, 1, 3, 6, and 12 months after surgery. The student t-test, Wilcoxon rank sum test, chi-square test, and MANOVA were used to compare the differences among groups. RESULTS: We found that DAA patients had higher FJS-12 scores than PA patients at 2 weeks (42.15 ± 3.36 vs. 38.09 ± 3.28, p = 0.042), 1 month (49.06 ± 5.14 vs. 41.11 ± 5.21, p = 0.038), and 3 months (53.23 ± 4.07 vs. 48.09 ± 3.71, t = 3.152, p = 0.045). And the recovery rates of FJS-12 scores in DAA and PA groups at 2 weeks, 1 month, and 3 months after surgery were 75.46% ± 6.04%, 84.05% ± 6.57%, 91.37% ± 7.13%, and 74.14% ± 5.54%, 78.16% ± 6.01%, 88.23% ± 6.42%, respectively. To compare the recovery effects of the two procedures in more detail, we classified the 12 items in FJS-12 that evaluate different types of gravity center motions into three categories: low-movement group (LG), middle-movement group (MG), and high-movement group (HG). Interestingly, DAA patients had significantly higher HG than PA patients at 2 weeks, 1 month, and 3 months after operation (t = 3.225, p = 0.022 at 2 weeks, t = 3.081, p = 0.041 at 1 month and t = 2.783, p = 0.046 at 3 months), whereas no significant differences were observed in LG- and MG-related items. In addition, there were no significant differences in HHS and VAS scores between DAA and PA patients at 2 weeks (p = 0.102, p = 0.093), or from 1 month to 12 months (each p > 0.05). CONCLUSIONS: DAA-mediated THA is superior to PA in terms of prosthesis adaptability and recovery of hip joint motion in the first 3 months after surgery, especially concerning high-movement gravity center motions.

Study on the mechanism of cadmium chloride pollution accelerating skin tissue metabolism disorder, aging and inhibiting hair regeneration.

Drinking water contaminated by Cd2+ is one of the main pathways for Cd to enter the body. The skin barrier is destroyed when the skin is contaminated by environmental Cd2+, however, the detailed mechanism by which Cd2+ induces skin metabolic disorder, and senescence and affects hair regeneration is not completely understood. In this study, 18 C57BL/6 mice were randomly divided into a Control group, a Low-dose group, and a High-dose group with 6 mice in each group, and intragastrically administered with different concentrations of cadmium chloride once a day, respectively. After 1 month of intervention, the skin tissues on the back of mice were collected for non-targeted metabolomics analysis, and the related proteins were detected by immunofluorescence assay. Non-targeted metabolomics analysis result showed that compared with the Control group, there were 29 different metabolites, mainly including lysophospholipids, fatty acids, and bile acids, in the Low-dose group, and 39 differential metabolites in the High-dose group, in addition to the above compounds, there were more amino acid compounds, and most of the metabolites had a reduced response after administration. Immunofluorescence assay result showed that the higher the concentration of cadmium chloride led to the more obvious the proliferation inhibition and apoptosis promotion effects of skin cells, and the more significant damage to hair follicle stem cells. Thus, our findings demonstrate that cadmium chloride pollution can accelerate skin metabolism disorder, and aging and impair hair regeneration.

Morroniside attenuates nucleus pulposus cell senescence to alleviate intervertebral disc degeneration via inhibiting ROS-Hippo-p53 pathway.

Intervertebral disc (IVD) degeneration (IVDD) which is highly prevalent within the elderly population, is a leading cause of chronic low back pain and disability. Nucleus pulposus (NP) cell senescence plays an indispensable role in the pathogenesis of IVDD. Morroniside is a major iridoid glycoside and one of the quality control metrics of Cornus officinalis Siebold & Zucc (CO). An increasing body of evidence suggests that morroniside and CO-containing formulae share many similar biological effects, including anti-inflammatory, anti-oxidative, and anti-apoptotic properties. In a previous study, we reported that Liuwei Dihuang Decoction, a CO-containing formula, is effective for treating IVDD by targeting p53 expression; however, the therapeutic role of morroniside on IVDD remains obscure. In this study, we assessed the pharmacological effects of morroniside on NP cell senescence and IVDD pathogenesis using a lumbar spine instability surgery-induced mouse IVDD model and an in vitro H2O2-induced NP cell senescence model. Our results demonstrated that morroniside administration could significantly ameliorate mouse IVDD progression, concomitant with substantial improvement in extracellular matrix metabolism and histological grading score. Importantly, in vivo and in vitro experiments revealed that morroniside could significantly reduce the increase in SA-ß-gal activities and the expression of p53 and p21, which are the most widely used indicators of senescence. Mechanistically, morroniside suppressed ROS-induced aberrant activation of Hippo signaling by inhibiting Mst1/2 and Lats1/2 phosphorylation and reversing Yap/Taz reduction, whereas blockade of Hippo signaling by Yap/Taz inhibitor-1 or Yap/Taz siRNAs could antagonize the anti-senescence effect of morroniside on H2O2-induced NP cell senescence model by increasing p53 expression and activity. Moreover, the inhibition of Hippo signaling in the IVD tissues by morroniside was further verified in mouse IVDD model. Taken together, our findings suggest that morroniside protects against NP cell senescence to alleviate IVDD progression by inhibiting the ROS-Hippo-p53 pathway, providing a potential novel therapeutic approach for IVDD.

α-Chaconine Facilitates Chondrocyte Pyroptosis and Nerve Ingrowth to Aggravate Osteoarthritis Progression by Activating NF-κB Signaling.

Background: 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-1ß, 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.

What is the Real Origin of the Activity of Fe-N-C Electrocatalysts in the O2 Reduction Reaction? Critical Roles of Coordinating Pyrrolic N and Axially Adsorbing Species.

Fe-N-C electrocatalysts have emerged as promising substitutes for Pt-based catalysts for the oxygen reduction reaction (ORR). However, their real catalytic active site is still under debate. The underlying roles of different types of coordinating N including pyridinic and pyrrolic N in catalytic performance require thorough clarification. In addition, how to understand the pH-dependent activity of Fe-N-C catalysts is another urgent issue. Herein, we comprehensively studied 13 different N-coordinated FeNxC configurations and their corresponding ORR activity through simulations which mimic the realistic electrocatalytic environment on the basis of constant-potential implicit solvent models. We demonstrate that coordinating pyrrolic N contributes to a higher activity than pyridinic N, and pyrrolic FeN4C exhibits the highest activity in acidic media. Meanwhile, the in situ active site transformation to *O-FeN4C and *OH-FeN4C clarifies the origin of the higher activity of Fe-N-C in alkaline media. These findings can provide indispensable guidelines for rational design of better durable Fe-N-C catalysts.

Hu'po Anshen Decoction Accelerated Fracture-Healing in a Rat Model of Traumatic Brain Injury Through Activation of PI3K/AKT Pathway.

Hu'po Anshen decoction (HPASD) is a traditional Chinese medicine formula comprising five herbal medicines for the treatment of concussion and fracture healing, but its pharmacological mechanism is still unclear. Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS) was used to analyze the main active components of HPASD. Rats were randomly assigned to fracture group, fracture combined with traumatic brain injury (TBI) group (FBI) and FBI combined with HPASD treatment group (FBIH). Rats in the FBIH group were given oral doses of HPASD (2.4 g/kg, 4.8 g/kg and 9.6 g/kg) for 14 or 21 consecutive days. The fracture callus formation and fracture sites were determined by radiographic analysis and micron-scale computed tomography (micro-CT) analysis. Hematoxylin and eosin (H&E) staining and a three-point bending test were applied to assess histological lesions and biomechanical properties, respectively. The levels of cytokines-/protein-related to bone formation and differentiation as well as PI3K/AKT pathway-related proteins were determined by Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), or western blot assays, respectively. UPLC-Q/TOF-MS-based serum metabolomic analysis was also performed to investigate the therapeutic effects of HPASD in the treatment of FBI. UPLC/Q-TOF MS analysis showed the chemical components in HPASD, including flavonoids, amino acids, saponins, and phenylpropanoid constituents, etc. HPASD dose-dependently promoted callus formation, increased bone density, improved mechanical parameters and morphological scores, and facilitated the expressions of VEGF, PDGF, bFGF, VEGFA, CoL1A1, RUNX2, BMP2, and Aggrecan, inhibited the expression of MMP13, and activated PI3K/AKT pathway. Metabolomics analysis revealed abnormalities of malate-aspartate shuttle and glucose-alanine. HPASD accelerates fracture healing by promoting bone formation and regulating the malate-aspartate shuttle and glucose-alanine cycle, which might be associated with the activation of the PI3K/AKT pathway.

Corrective Osteotomy with Volar and Dorsal Fixation for Malunion of Intra-Articular Fracture of the Distal Radius: A Retrospective Study.

OBJECTIVES: Although corrective osteotomy with volar or dorsal plate fixation can treat malunion of distal radius fractures, each has its own disadvantages. Little is currently known on whether dorsal fixation combined with volar fixation may further improve recovery. This study aimed to evaluate the clinical value of corrective osteotomy combined with volar and dorsal plate fixation in patients with malunion of intra-articular fractures of the distal radius. METHODS: Seventeen patients with malunion of intra-articular fractures of the distal radius treated with corrective osteotomy with volar and dorsal plate fixation from 1 January 2016 to 31 November 2018 were retrospectively analyzed. The enrolled patients included seven males and 10 females with an average age of 54.9 years (range: 36-70 years). The radiographic parameters, including the radial length, the radial inclination angle, the ulnar variance, and the volar tilt, as well as clinical outcomes, including wrist and forearm range of motion (ROM), grip strength, the Mayo Modified Wrist Score (MMWS), and the disabilities of the Arm, Shoulder, and Hand (DASH) score, were examined at 3 months and 18 months after operation and compared with the preoperative state. The paired t-test was used for statistical analysis. RESULTS: After corrective osteotomy combined with volar and dorsal plate fixation, all included patients were followed up for 18 months, and there was no surgical site infection. Patients reported postoperative pain due to the irritation of extensor tendon (two cases) and wrist arthritis (two cases). The radial length increased from 1.34 ± 2.34 mm to 9.25 ± 2.65 mm and 9.03 ± 2.47 mm at 3 months and 18 months postoperatively (t = 8.257, 7.954, all p < 0.05). The radial inclination angle increased from 6.45° ± 0.76° to 19.35° ± 3.43° and 19.03° ± 3.63° at 3 and 18 months (t = 12.517, 12.122, all p < 0.05). The ulnar variance decreased from 5.11 ± 0.23 mm to 1.32 ± 0.31 mm and 1.54 ± 0.62 mm at 3 and 18 months (t = 4.214, 4.895, all p < 0.05). The volar tilt was corrected from 4.47° ± 3.46° to 15.51° ± 2.72° and 14.12° ± 2.41°, respectively (t = 11.247, 10.432, all p < 0.05). Moreover, wrist ROM increased from 42.53° ± 8.99° to 98.70° ± 7.61° and 101.24° ± 7.66° (t = 41.433, 46.627, all p < 0.05), while forearm ROM was increased from 94.82° ± 6.54° to 134.47° ± 5.06° and 137.24° ± 5.52°, respectively (t = 31.507, 32.584, all p < 0.05). Similarly, grip strength, MMWS, and DASH were also remarkably improved. There were no significant differences in the wrist and forearm ROM, grip strength, MMWS, and DASH scores between follow-up at 3 and 18 months (all p > 0.05). CONCLUSIONS: Corrective osteotomy with volar and dorsal fixation can improve recovery of volar tilt, relieve wrist pain, restore wrist and forearm function, and increase grip strength of patients with malunion of intra-articular fractures of the distal radius.