Research progress in the pathogenesis of hormone-induced femoral head necrosis based on microvessels: a systematic review.

Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral head, resulting in bone trabecular fracture, bone tissue necrosis collapse, and hip dysfunction. It is the most common type of non-traumatic necrosis of the femoral head, and its pathogenesis is complex, while impaired blood circulation is considered to be the key to its occurrence. There are a large number of microvessels in the femoral head, among which H-type vessels play a decisive role in the "angiogenesis and osteogenesis coupling", and thus have an important impact on the occurrence and development of femoral head necrosis. Glucocorticoids can cause blood flow injury of the femoral head mainly through coagulation dysfunction, endothelial dysfunction and impaired angiogenesis. Glucocorticoids may inhibit the formation of H-type vessels by reducing the expression of HIF-1α, PDGF-BB, VGEF and other factors, thus causing damage to the "angiogenesis-osteogenesis coupling" and reducing the ability of necrosis reconstruction and repair of the femoral head. Leads to the occurrence of hormonal femoral head necrosis. Therefore, this paper reviewed the progress in the study of the mechanism of hormone-induced femoral head necrosis based on microvascular blood flow at home and abroad, hoping to provide new ideas for the study of the mechanism of femoral head necrosis and provide references for clinical treatment of femoral head necrosis.

Advances in exosome modulation of ferroptosis for the treatment of orthopedic diseases.

Current treatments for orthopaedic illnesses frequently result in poor prognosis, treatment failure, numerous relapses, and other unpleasant outcomes that have a significant impact on patients' quality of life. Cell-free therapy has emerged as one of the most promising options in recent decades for improving the status quo. As a result, using exosomes produced from various cells to modulate ferroptosis has been proposed as a therapeutic method for the condition. Exosomes are extracellular vesicles that secrete various bioactive chemicals that influence disease treatment and play a role in the genesis and progression of orthopaedic illnesses. Ferroptosis is a recently defined kind of controlled cell death typified by large iron ion buildup and lipid peroxidation. An increasing number of studies indicate that ferroptosis plays a significant role in orthopaedic illnesses. Exosomes, as intercellular information transfer channels, have been found to play a significant role in the regulation of ferroptosis processes. Furthermore, accumulating research suggests that exosomes can influence the course of many diseases by regulating ferroptosis in injured cells. In order to better understand the processes by which exosomes govern ferroptosis in the therapy of orthopaedic illnesses. This review discusses the biogenesis, secretion, and uptake of exosomes, as well as the mechanisms of ferroptosis and exosomes in the therapy of orthopaedic illnesses. It focuses on recent research advances and exosome mechanisms in regulating iron death for the therapy of orthopaedic illnesses. The present state of review conducted both domestically and internationally is elucidated and anticipated as a viable avenue for future therapy in the field of orthopaedics.

Triphenylphosphonium-linked derivative of hecogenin with enhanced antiproliferative activity: Design, synthesis, and biological evaluation.

Hecogenin (HCG), a steroidal sapogenin, possesses good antitumor properties. However, the application of HCG for cancer treatment has been hindered primarily by its moderate potency. In this study, we incorporated triphenylphosphonium cation (TPP+) at the C-3 and C-12 positions through different lengths of alkyl chains to target mitochondria and enhance the efficacy and selectivity of the parent compound. Cytotoxicity screening revealed that most of the target compounds exhibited potent antiproliferative activity against five human cancer cell lines (MKN45, A549, HCT-116, MCF-7, and HepG2). Structure-activity relationship studies indicated that the TPP+ group significantly enhanced the antiproliferative potency of HCG. Among these compounds, 3c demonstrated remarkable potency against MKN45 cells with an IC50 value of 0.48 µM, significantly more effective than its parent compound HCG (IC50 > 100 µM). Further investigations into the mechanism of action revealed that 3c induced apoptosis of MKN45 cells through the mitochondrial pathway. In a zebrafish xenograft model, 3c inhibited the proliferation of MKN45 cells. Overall, these results suggest that 3c, with potent antiproliferative activity, may serve as a valuable scaffold for developing new antitumor agents.

Data-Driven Contact-Based Thermosensation for Enhanced Tactile Recognition.

Thermal feedback plays an important role in tactile perception, greatly influencing fields such as autonomous robot systems and virtual reality. The further development of intelligent systems demands enhanced thermosensation, such as the measurement of thermal properties of objects to aid in more accurate system perception. However, this continues to present certain challenges in contact-based scenarios. For this reason, this study innovates by using the concept of semi-infinite equivalence to design a thermosensation system. A discrete transient heat transfer model was established. Subsequently, a data-driven method was introduced, integrating the developed model with a back propagation (BP) neural network containing dual hidden layers, to facilitate accurate calculation for contact materials. The network was trained using the thermophysical data of 67 types of materials generated by the heat transfer model. An experimental setup, employing flexible thin-film devices, was constructed to measure three solid materials under various heating conditions. Results indicated that measurement errors stayed within 10% for thermal conductivity and 20% for thermal diffusion. This approach not only enables quick, quantitative calculation and identification of contact materials but also simplifies the measurement process by eliminating the need for initial temperature adjustments, and minimizing errors due to model complexity.

Cordymin alleviates osteoporosis induced by hindlimb unloading via regulating the gut - microelements -bone axis --for non-clinical studies.

INTRODUCTION: The purpose of this study was to evaluate the protective effects of cordymin on osteoporosis induced by hindlimb unloading(HLU) in rats and whether cordymin can prevent bone loss from HLU. MATERIALS AND METHODS: We employed the hindlimb suspension rats model to mimic physiological changes concomitant with space travel.The mechanical strength in the femoral neck,cancellous bone volume, gut microbiota structure,serum calcium and phosphorus contents, bone mineral content and bone mineral content can be changed after hindlimb unloading. Oral cordymin was administered for 4 weeks,cordymin treatment significantly increased the mechanical strength through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp). RESULTS: Importantly, 16 S rRNA sequencing showed cordymin treatment regulated the various genera that were imbalanced in hindlimb unloading rats. At the same time,The plasma total calcium and inorganic phosphate concentrations in hindlimb unloading rats decreased and bone mineral content in the lumbar vertebrae and femur increased after treatment with cordymin. CONCLUSION: These data indicate that the cordymin might exert bone protective effects indirectly via modulating the complex relationship between gut microbiota, microelements and bone loss.

Diabetes-related Screw Loosening: The Distinction of Surgical Sites and the Relationship among Diabetes, Implant Stabilization and Clinical Outcomes.

OBJECTIVES: Diabetes mellitus (DM) is correlated with poor clinical outcomes in spinal surgery. However, the effect of it on screw stabilization has not been investigated. The aim of this study was to evaluate the screw loosening rate and postoperative outcomes in diabetic patients and to identify potential risk factors associated with loosening. METHODS: This was a retrospective study. Two hundred and forty-three patients who received cervical or lumbar internal fixation between 2015 and 2019 were enrolled. Screw loosening was assessed on radiography, and clinical outcomes were evaluated by the improvement of visual analogue scale (VAS), Oswestry disability index (ODI) or Japanese Orthopaedic Association (JOA) scores. The relationship of DM, screw loosening and clinical outcomes were analyzed with chi-square tests and regression analyses. RESULTS: One hundred and twenty-two patients (50.2%) with diabetes were included in this study. Diabetes led to the increase of the rate of screw loosening in the lumbar spine, while the loosening rate did not vary significantly in the cervical spine. The occurrence of screw loosening in the lumbar spine was more likely to be associated with clinical outcomes for motor performance including walking and sitting. However, no significant effect on JOA and VAS scores in the cervical spine of screw loosening was found. Moreover, the history of DM affected the outcomes of the patients who underwent spinal surgery. CONCLUSION: DM had an adverse effect on screw stabilization. The impaired improvement of clinical outcomes in diabetics after spinal surgery was related to screw loosening. In addition to the direct effects on operative wounds and neural function, the impact on the screws due to DM was also worth noting.

A New Dual-Mass MEMS Gyroscope Fault Diagnosis Platform.

MEMS gyroscopes are one of the core components of inertial navigation systems. The maintenance of high reliability is critical for ensuring the stable operation of the gyroscope. Considering the production cost of gyroscopes and the inconvenience of obtaining a fault dataset, in this study, a self-feedback development framework is proposed, in which a dualmass MEMS gyroscope fault diagnosis platform is designed based on MATLAB/Simulink simulation, data feature extraction, and classification prediction algorithm and real data feedback verification. The platform integrates the dualmass MEMS gyroscope Simulink structure model and the measurement and control system, and reserves various algorithm interfaces for users to independently program, which can effectively identify and classify seven kinds of signals of the gyroscope: normal, bias, blocking, drift, multiplicity, cycle and internal fault. After feature extraction, six algorithms, ELM, SVM, KNN, NB, NN, and DTA, were respectively used for classification prediction. The ELM and SVM algorithms had the best effect, and the accuracy of the test set was up to 92.86%. Finally, the ELM algorithm is used to verify the actual drift fault dataset, and all of them are successfully identified.

Clinical efficacy of different open approaches in the surgical treatment of thoracolumbar tuberculosis: a single-center retrospective comparative study.

OBJECTIVE: To assess the clinical efficacy of three different surgical approaches in the treatment of thoracolumbar tuberculosis. METHODS: A total of 138 patients with thoracolumbar tuberculosis treated by open surgery were retrospectively analyzed. The surgical methods were divided into anterior, posterior and anterior-posterior combined. The hospital stays, amount of bleeding, operative time, preoperative, postoperative and last follow-up ESR, CRP, Frankel score, ODI, VAS, correction and loss rate of kyphosis, fusion rate and complications were recorded and analyzed. RESULTS: The average follow-up was 66 months. The average hospital stay, operative time and amount of bleeding of the anterior-posterior combined group were higher than other groups (P < 0.05). ESR and CRP of all patients were reduced postoperatively (P < 0.05). No significant difference among the three groups was found in the postoperative correction angle of kyphosis (P < 0.05), while the pre- and postoperative Cobb angle as well as correction rate had significant differences. The posterior approach could achieve better correction, and the loss of correction was more in the anterior group, 40.9 percent of patients performed correction loss. The Frankel score, VAS and ODI were significantly reduced among the three groups, and the incidence rate of complications of the anterior approach was lower than the other groups, with a significant difference (P < 0.05). CONCLUSION: The anterior approach has more advantages and fewer complications, which is supposed to give preference to and could not be replaced by the posterior and anterior-posterior combined approach.

Wei-Tong-Xin exerts anti-inflammatory effects through TLR4-mediated macrophages M1/M2 polarization and affects GLP-1 secretion.

OBJECTIVES: The present study was undertaken to explore the effects and mechanisms of Wei-Tong-Xin (WTX) in inhibiting lipopolysaccharide (LPS)-induced inflammatory response of macrophages, in turn, to study the influences on GLP-1 secretion of GLUTag cells. METHODS: We first evaluated the activation of Raw 264.7 cells and measured the intracellular ROS, CD86 and CD206 levels by flow cytometry. The expressions of proteins were detected by western blot and immunofluorescence. GLP-1 levels were detected by ELISA kits. TLR4 siRNA was used to investigate the role of TLR4 in the regulation of macrophage polarization by WTX. KEY FINDINGS: The results showed that WTX inhibited LPS-induced polarization of macrophages toward the M1 phenotype, but promoted the M2 phenotype. Meanwhile, WTX inhibited the TLR4/MyD88 pathway. The polarization of M1 phenotype promoted GLP-1 secretion by GLUTag cells, which was inhibited by WTX. The results of siRNA showed that WTX exhibited anti-inflammatory effects through targeting TLR4. CONCLUSIONS: Overall, WTX inhibited polarization of macrophages towards M1 phenotype but promoted the amounts of M2 phenotype, further the macrophages regulated by WTX alleviated GLP-1 content secreted by GLUTag cells. The aforementioned results were produced by WTX-mediated TLR4.

Pressure-induced high-temperature superconductivity in ternary Y-Zr-H compounds.

Compressed hydrogen-rich compounds have received extensive attention as appealing contenders for superconductors. Here, we found several stable hydrides YZrH6, YZrH8, YZr3H16 and YZrH18, and a series of metastable clathrate hexahydrides in the systematic investigation of Y-Zr-H ternary hydrides under pressure. Electron-phonon coupling calculations indicate that they all exhibit high temperature superconductivity and perform better than the binary Zr-H system. YZrH6 can maintain dynamic stability down to ambient pressure and keep a critical temperature (Tc) of 16 K. The stable YZrH18 and metastable Y3ZrH24 with high hydrogen content exhibit high Tc of 156 K and 185 K at 200 GPa, respectively. Further analysis shows that the phonon modes associated with H atoms contribute significantly to the electron-phonon coupling. The hydrogen content and the stoichiometric ratio of Y and Zr closely affect the density of states at the Fermi level, thereby affecting the superconductivity. Our work presents an important step toward understanding the superconductivity and stability of transition metal ternary hydrides.

A unique hyperdynamic dimer interface permits small molecule perturbation of the melanoma oncoprotein MITF for melanoma therapy.

Microphthalmia transcription factor (MITF) regulates melanocyte development and is the "lineage-specific survival" oncogene of melanoma. MITF is essential for melanoma initiation, progression, and relapse and has been considered an important therapeutic target; however, direct inhibition of MITF through small molecules is considered impossible, due to the absence of a ligand-binding pocket for drug design. Here, our structural analyses show that the structure of MITF is hyperdynamic because of its out-of-register leucine zipper with a 3-residue insertion. The dynamic MITF is highly vulnerable to dimer-disrupting mutations, as we observed that MITF loss-of-function mutations in human Waardenburg syndrome type 2 A are frequently located on the dimer interface and disrupt the dimer forming ability accordingly. These observations suggest a unique opportunity to inhibit MITF with small molecules capable of disrupting the MITF dimer. From a high throughput screening against 654,650 compounds, we discovered compound TT-012, which specifically binds to dynamic MITF and destroys the latter's dimer formation and DNA-binding ability. Using chromatin immunoprecipitation assay and RNA sequencing, we showed that TT-012 inhibits the transcriptional activity of MITF in B16F10 melanoma cells. In addition, TT-012 inhibits the growth of high-MITF melanoma cells, and inhibits the tumor growth and metastasis with tolerable toxicity to liver and immune cells in animal models. Together, this study demonstrates a unique hyperdynamic dimer interface in melanoma oncoprotein MITF, and reveals a novel approach to therapeutically suppress MITF activity.

The moderating role of authenticity between experience economy and memory? The evidence from Qiong Opera.

Scholars have used the experience economy to analyze the behavior of tourists. However, in the field of intangible cultural heritage (ICH) tourism, the relationship between the experience economy and the behavior intention of tourists has not been studied. Scholars also point out that the relationship between the four dimensions of the experience economy is not static, and that aesthetic experience may be predictive of other dimensions. This study uses aesthetic experience as the starting point and constructs a theoretical model that includes the experience economy, the memories of ICH tourists, the perception of authenticity, and behavioral intentions. Qiong Opera, part of China's national intangible cultural heritage, is used as a scenario in which to conduct empirical research. The results show that education, entertainment, and escape play a mediator role in the relationship between aesthetics and memory; memory plays a complete mediator role in the relationship between education, entertainment, escape, and behavioral intention; and authenticity plays a moderator role in the relationship between education, entertainment, escape, and memory. This study introduces the experience economy into ICH tourism. While expanding the application field of experience economy theory, it also provides theoretical and management inspiration for ICH tourism development.

Discovery of a Novel Potent Antitumor Molecule, P19G1, by Erlotinib Derivative Libraries Synthesized by Modular Click-Chemistry.

Objective:Traditional chemical synthesis methods are cumbersome and inefficient. In this study, a novel antitumor molecule, 4-(4-(3-((6,7-bis(2-methoxyethoxy)quinazolin-4-yl)amino)phenyl)-1H-1,2,3-triazol-1-yl)phenyl sulfurofluoridate (P19G1), was identified by screening a library of Erlotinib derivatives synthesized by modular click chemistry, and the antitumor activity and underlying mechanism of P19G1 were further revealed. Methods: A series of Erlotinib derivatives (840 compounds) were synthesized using a modular click-chemistry method, and then the thiazolyl blue (MTT) method was used to screen and evaluate the inhibitory effect of these compounds on the growth and metastasis of A549 lung adenocarcinoma cells. Among them, the compound P19G1 showed the best inhibitory activity. Furthermore, the antitumor activity and mechanism of P19G1 were investigated with in vitro cell biology and in vivo assays in an animal model. Results: In vitro pharmacological studies showed that P19G1 had inhibitory effects on a variety of tumor cell lines with IC50 values in the range of 1 to 5 µM. Moreover, P19G1 significantly inhibited the proliferation and migration of the human lung adenocarcinoma cell line A549 and human colorectal cancer cell line RKO and promoted cell apoptosis. In vivo tumor-bearing mouse model experiments revealed that 50 mg/kg P19G1 effectively inhibited the growth and metastasis of A549 tumors without obvious toxicity to the host. Conclusions: The rapid structural modification of lead compounds using novel modular click-chemistry reactions holds great potential for use in obtaining diverse derivatives for tumor drug screening and development. P19G1 was discovered because of the application of click chemistry in this study, and it is an antitumor candidate molecule worthy of development.

An Investigation of the Anti-Depressive Properties of Phenylpropanoids and Flavonoids in Hemerocallis citrina Baroni.

The World Health Organization predicts that over the next several years, depression will become the most important mental health issue globally. Growing evidence shows that the flower buds of Hemerocallis citrina Baroni (H. citrina) possess antidepressant properties. In the search for new anti-depression drugs, a total of 15 phenylpropanoids and 22 flavonoids were isolated and identified based on spectral data (1D and 2D NMR, HR-ESI-MS, UV) from H. citrina. Among them, compound 8 was a novel compound, while compounds 1-4, 6, 9, 10, 15, 17, 24-26, 28, and 37 were isolated for the first time from Hemerocallis genus. To study the antidepressant activity of phenylpropanoids and flavonoids fractions from H. citrina, macroporous resin was used to enrich them under the guidance of UV characteristics. UHPLC-MS/MS was applied to identify the constituents of the enriched fractions. According to behavioral tests and biochemical analyses, it showed that phenylpropanoid and flavonoid fractions from H. citrina can improve the depressive-like mental state of chronic unpredictable mild stress (CUMS) rats. This might be accomplished by controlling the amounts of the inflammatory proteins IL-6, IL-1ß, and TNF-α in the hippocampus as well as corticosterone in the serum. Thus, the monomer compounds were tested for their anti-neuroinflammatory activity and their structure-activity relationship was discussed in further detail.

Influencing factors and trend prediction of PM2.5 concentration based on STRIPAT-Scenario analysis in Zhejiang Province, China.

The government's development of eco-environmental policies can have a scientific foundation thanks to the fine particulate matter (PM2.5) medium- and long-term change forecast. This study develops a STRIPAT-Scenario analysis framework employing panel data from 11 cities in Zhejiang Province between 2006 and 2020 to predict the changing trend of PM2.5 concentrations under five alternative scenarios. The results reveal that: (1) urbanization development (P), economic development (A), technological innovation investment (T) and environmental regulation intensity have a significant inhibitory effect on PM2.5 concentration in Zhejiang Province, while industrial structure, industrial energy consumption and the number of motor vehicles (TR) have a significant increase on PM2.5 concentration. (2) Under any scenario, the PM2.5 concentration of 11 cities in Zhejiang Province can reach the constraint target set in the 14th Five-Year plan. The improvement in urban PM2.5 quality is most obviously impacted by the high-quality development scenario (S4). (3) Toward 2035, PM2.5 concentrations of 11 cities in Zhejiang Province can reach the National Class I level standard in most scenario models, among which Hangzhou, Jiaxing and Shaoxing are under high pressure to reduce emissions and are the key areas for PM2.5 management in Zhejiang Province. However, most cities cannot reach the 10 µg/m3 limit of WHO's AQG2005 version. Finally, this study makes recommendations for reducing PM2.5 in terms of enhancing industrial structure and funding science and technology innovation.

Chemical Composition, Anti-Breast Cancer Activity and Extraction Techniques of Ent-Abietane Diterpenoids from Euphorbia fischeriana Steud.

Ent-abietane diterpenoids are the main active constituents of Euphorbia fischeriana. In the continuing search for new anti-breast cancer drugs, 11 ent-abietane diterpenoids (1-11) were isolated from E. fischeriana. The structures of these compounds were clearly elucidated on the basis of 1D and 2D NMR spectra as well as HRESIMS data. Among them, compound 1 was a novel compound, compound 10 was isolated from Euphorbia genus for the first time, compound 11 was firstly discovered from E. fischeriana. These compounds exhibited varying degrees of growth inhibition against the MCF-10A, MCF-7, ZR-75-1 and MDA-MB-231 cell lines in vitro. The experimental data obtained permit us to identify the roles of the epoxy group, hydroxyl group and acetoxyl group on their cytotoxic activities. Extraction is an important means for the isolation, identification, and application of valuable compounds from natural plants. To maximize yields of ent-abietane diterpenoids of E. fischeriana, 17-hydroxyjolkinolide B, jolkinolide B, 17-hydroxyjolkinolide A and jolkinolide A were selected as quality controls to optimize the salting-out-assisted liquid-liquid extraction (SALLE) by response surface methodology (RSM). The optimized conditions for SALLE were 0.47 g sodium dihydrogen phosphate, 5.5 mL acetonitrile and 4.5 mL water at pH 7.5. The experimental values of 17-hydroxyjolkinolide B, jolkinolide B, 17-hydroxyjolkinolide A and jolkinolide A (2.134, 0.529, 0.396, and 0.148 mg/g, respectively) were in agreement with the predicted values, thus demonstrating the appropriateness of the model.

A pair of novel phenylethanol glycosides from Cistanche tubulosa (Schenk) Wight.

A pair of differential epimers with opposite C-7 configurations, crenatosides A and B (1 and 2), and 10 known phenylethanoid glycosides (PhGs) (3-12) were obtained from the succulent stem of Cistanche tubulosa. The structures were elucidated based on extensive spectral data (UV, IR, 1D and 2D NMR, HR-ESIMS), which are first reported natural products with unique glycoside structures. After acid hydrolysis, the configuration of the sugar was determined by comparing it with the normative sugar by HPLC. The absolute configurations of both compounds were determined by ECD spectrum analysis. All the obtained compounds were examined for their inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse microglial cells (BV-2 cells), and compounds 1 and 2 showed potent inhibition on NO production with IC50 values of 5.62 µM and 6.30 µM, respectively.

Deficit Irrigation at Pre-Anthesis Can Balance Wheat Yield and Water Use Efficiency under Future Climate Change in North China Plain.

BACKGROUND: Deficit irrigation (DI) is a feasible strategy to enhance crop WUE and also has significant compensation effects on yield. Previous studies have found that DI has great potential to maintain crop production as full irrigation (FI) does. Therefore, adopting DI to improve crop production and safeguard groundwater resources is of great importance in water scarce regions, e.g., the North China Plain (NCP). Under the background of global warming, it is worth investigating whether DI continues to play such a key role under future climate scenarios. METHODS: We studied the response of winter wheat yield and WUE to different DI levels at pre-anthesis under two Shared Socioeconomic Pathways (SSPs) scenarios (SSP245 and SSP585) using the Agricultural Production Systems Simulator (APSIM) model driven by 21 general circulation models (GCMs) from the Coupled Model Inter-Comparison Project phase 6 (CMIP6). Additionally, we explored the effects of different nitrogen (N) fertilizer application rates on DI. RESULTS: We found that simulated wheat yield would increase by 3.5-45.0%, with WUE increasing by 8.8-46.4% across all treatments under future climate change. Moderate deficit irrigation (DI3, ≤0.4 PAWC at the sowing to flowering stage) under the N3 (150 kg N ha-1) condition was identified as the optimum irrigation schedule for the study site under future climate change. However, compensation effects of DI3 on yield and WUE became weak in the future, which was mainly due to increased growing season rainfall projected by GCMs. In addition, we found that N fertilizer application could mitigate the effect of DI3. CONCLUSIONS: We highlight that in water scarce regions of NCP, DI remains an effective strategy to maintain higher yield and enhance water use under future climate scenarios. Results strongly suggest that moderate deficit irrigation under a 150 kg N ha-1 condition could mitigate the contradiction between production and water consumption and ensure food safety in the NCP.