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Once bone metastasis occurs in lung cancer, the efficiency of treatment can be greatly reduced. Current mainstream treatments are focused on inhibiting cancer cell growth and preventing bone destruction. Microwave ablation (MWA) has been used to treat bone tumors. However, MWA may damage the surrounding normal tissues. Therefore, it could be beneficial to develop a nanocarrier combined with microwave to treat bone metastasis. Herein, a microwave-responsive nanoplatform (MgFe2O4@ZOL) was constructed. MgFe2O4@ZOL NPs release the cargos of Fe3+, Mg2+ and zoledronic acid (ZOL) in the acidic tumor microenvironment (TME). Fe3+ can deplete intracellular glutathione (GSH) and catalyze H2O2 to generate •OH, resulting in chemodynamic therapy (CDT). In addition, the microwave can significantly enhance the production of reactive oxygen species (ROS), thereby enabling the effective implementation of microwave dynamic therapy (MDT). Moreover, Mg2+ and ZOL promote osteoblast differentiation. In addition, MgFe2O4@ZOL NPs could target and selectively heat tumor tissue and enhance the effect of microwave thermal therapy (MTT). Both in vitro and in vivo experiments revealed that synergistic targeting, GSH depletion-enhanced CDT, MDT, and selective MTT exhibited significant antitumor efficacy and bone repair. This multimodal combination therapy provides a promising strategy for the treatment of bone metastasis in lung cancer patients.

General practice in China has developed rapidly in recent years with remarkable progress, but the gap with developed countries in Europe and the United States is still large, and the training system of general practitioners still remains impefect. In Germany, the construction of the primary health care system and the training system of general practitioners have been well developed. Under the system of universal health insurance coverage and hierarchical diagnosis and treatment, a high level of health and patient satisfaction with primary healthcare services among residents have been achieved in Germany. Therefore, this study compares post-graduate education and continuing education of general practice in China and Germany, analyzes the challenges of general practice education reform in China, drawing on the conceptual framework of general practice education in Germany, and proposes targeted ideas and recommendations for solutions as follows: for the standardized residency training of general practice, increase the rotation flexibility as appropriate to facilitate the optimization of trainees' individualized competencies, incorporate the standardized curriculum of psychosomatic medicine and Balint group training to improve trainees' competence in psychosomatic medicine, establish standardized selection criteria and promote standardized training program for faculty of community hospital, and revisit the duration of general practice (including community) rotation after improving the qualifications of general practice faculty of community hospital; for the continuing education, incorporate the special interest and small specialties into the general practice continuing education system to strengthen the functional medical characteristics of general practice and promote the professional diversification of general practitioners, and establish a national unified platform for continuing education in general practice. More practical research and resources are needed to improve the training system of general practitioners in China in the future.

Dysfunction of the Nav1.5, Cav1.2, and Kv channels could interfere with the AP and result in arrhythmias and even heart failure. We herein present a novel library of nuciferine analogs that target ion channels for the treatment of arrhythmias. Patch clamp measurements of ventricular myocytes revealed that 6a dramatically blocked both the INa and ICa without altering the currentvoltage relationship (including the activation potential and peak potential), accelerated the inactivation of Nav and Cav channels and delayed the resurrection of these channels after inactivation. Additionally, 6a significantly decreased the APA and RMP without affecting the APD30 or APD50. The IC50 values of 6a against Nav1.5 and Cav1.2 were 4.98 μM and 4.62 μM, respectively. Furthermore, 6a (10 μM) blocked IKs, IK1, and Ito with values of 17.01 %±2.54 %, 9.09 %±2.78 %, and 11.15 %±3.52 %, respectively. Surprisingly, 6a weakly inhibited hERG channels, suggesting a low risk of proarrhythmia. The cytotoxicity evaluation of 6a with the H9c2 cell line indicated that this compound was noncytotoxic. In vivo studies suggested that these novel nuciferine analogs could shorten the time of arrhythmia continuum induced by BaCl2 and normalize the HR, QRS, QT and QTc interval and the R wave amplitude. Moreover, 6a dose-dependently affected aconitine-induced arrhythmias and notably improved the cumulative dosage of aconitine required to evoke VP, VT, VF and CA in rats with aconitine-induced arrhythmia. In conclusion, nuciferine analogs could be promising ion channel blockers that could be further developed into antiarrhythmic agents.

Abstract Carbapenem-resistant Enterobacterales (CRE) has emerged as a worldwide spread nosocomial superbug exhibiting antimicrobial resistance (AMR) to all current antibiotics, leaving limited options for treating its infection. To discovery novel antibiotics against CRE, we designed and synthesized a series of 14 isothiazol-3(2H)-one analogues subjected to antibacterial activity evaluation against Escherichia coli (E. coli) BL21 (NDM-1) and clinical strain E. coli HN88 for investigating their structure–activity relationships (SAR). The results suggested that 5-chloroisothiazolone core with an N-(4-chlorophenyl) substitution 5a was the most potent antibacterial activity against the E. coli BL21 (NDM-1) with MIC value of less than 0.032 μg/mL, which was at least 8000-fold higher than the positive control Meropenem (MRM). It also displayed 2048-fold potent than the positive control MRM against E. coli HN88. Additionally, SAR analysis supported the conclusion that compounds with a chloro-group substituted on the 5-position of the heterocyclic ring was much more potent than other positions. The board spectrum analysis suggested that compound 5a showed a promising antimicrobial activity on MRSA and CRE pathogens. Meanwhile, cytotoxicity study of compound 5a suggested that it had a therapeutic index value of 875, suggesting future therapeutic potential. In vivo efficacy study declared that compound 5a could also protect the BALB/c mice against American type culture collection (ATCC) 43,300. Further screening of our compounds against a collection of CRE strains isolated from patients indicated that compound 5 g displayed much stronger antibacterial activity compared with MRM. In conclusion, our studies indicated that isothiazolones analogues could be potent bactericidal agents against CRE and MRSA pathogens.

Abstract Objectives Innate immunity plays a significant role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA), which is characterized by synovial inflammation and condylar cartilage degradation. We are urged to investigate the impact of Resatorvid, a preventative drug that inhibits Toll-like receptor 4 (TLR4), on experimental inflammatory TMJOA pathology. Methods An intra-articular injection of complete Freund’s adjuvant (CFA) was used to induce an experimental inflammatory mouse TMJOA model, and TLR4 expression was identified by immunofluorescent labeling. Intraperitoneal injections of Resatorvid were administered to CFA-induced TMJOA mice, and the pathology of TMJOA animals with and without Resatorvid treatment was examined by H&E, Safranin-O/Fast Green, and TRAP staining, as well as micro-CT, immunohistochemistry, and immunofluorescence. The impact of Resatorvid on chondrocyte pyroptosis and macrophage inflammation was further investigated using ATDC5 chondrocytes and RAW264.7 macrophages pretreated with relevant antagonists. Results CFA-induced TMJOA mice revealed remarkable synovial inflammation, together with a time course of cartilage degradation and bone destruction, with TLR4 elevated in the synovium and condylar cartilage. Prophylactic treatment with Resatorvid mitigated synovial inflammation, cartilage degeneration, and bone destruction in CFA-induced TMJOA mice and downregulated MyD88/NF-κB expression. Ex vivo studies demonstrated that Resatorvid treatment alleviated NOD-like receptor protein 3 (NLRP3)-mediated chondrocyte pyroptosis and degeneration and relieved macrophage inflammation by preventing reactive oxygen species (ROS) production through NLRP3 signaling. Conclusion Prophylactic treatment with Resatorvid alleviates TMJOA pathology by inhibiting chondrocyte pyroptosis and degeneration, as well as ROS-induced macrophage inflammation, through TLR4/MyD88/NF-κB/NLRP3.

Objective: Recently, liquid platelet-rich fibrin (PRF), a rich source of concentrated platelets and growth factors, has emerged as a promising agent for stimulating tissue regeneration. However, its specific efficacy in chondrocyte proliferation and cartilage regeneration remains underexplored. To address this question, we investigated liquid PRF obtained through horizontal centrifugation and compared its effects with hyaluronic acid (HA), a high molecular weight glucosamine supplement widely used in clinical practice to safeguard against chondral damage.Materials and Methods: Liquid PRF, produced using horizontal centrifugation (liquid H-PRF) at 500 g for 8 min, served as our experimental agent. We conducted cell viability and proliferation assays using PRF-conditioned medium. We assessed the chondrocyte phenotype of ATDC5 cells through toluidine blue and alcian blue staining, real-time polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence staining. Furthermore, we examined the expression of genes involved in inflammation through RT-PCR and Western blot analysis.Results: Liquid H-PRF exerted notable effects on chondrocytes, influencing proliferation, inflammatory responses, and chondrogenic differentiation. The H-PRF group displayed significantly higher expression of chondrogenic markers, including Col2a1, compared to HA-treated cells, whereas aggrecan expression was significantly higher in the HA group. PRF also demonstrated the ability to reduce inflammatory levels in chondrogenic ATDC5 cells, and this effect was further enhanced when PRF from the buffy coat zone was added. In comparison, chondrocytes cultured in the HA group produced significantly fewer inflammatory factors than those in the PRF group, as confirmed qualitatively by Western blot analysis.Conclusion: Liquid H-PRF emerged as a potent stimulator for chondrogenesis and a regulator of the inflammatory response, achieving levels similar to HA. Moreover, liquid H-PRF exhibited strong potential for enhancing the production of cartilage extracellular matrix and promoting chondrogenic regeneration with notably increased Col2a1 levels. Future research should encompass animal studies and human trials to further evaluate the comparative effectiveness of liquid PRF versus HA, potentially as an alternative or complementary strategy for future clinical applications.

The aim of the present study is to evaluate the absolute content and accumulation patterns of flavonoid components; to give insight into the accumulation relationships among flavonoid components; to explore the correlation between the content of flavonoid components and the expression of flavonoid biosynthesis genes in Tartary buckwheat seeds; and to construct a biosynthetic pathway on the major flavonoid components in Tartary buckwheat seeds. In total, 61 flavonoid components were absolutely quantified in five Tartary buckwheat varieties, of which 41 existed in all varieties. The content of most flavonoids varied significantly among different varieties or within the same variety. Rutin, quercetin, nicotiflorin, and kaempferol were the dominant flavonoid components in the Tartary buckwheat seeds, accounting for 73.05–81.79% of the total flavonoids. Significantly positive or negative correlations with content accumulation were found between some flavonoid components. Thirty-six flavonoid components displayed four different accumulation patterns in the developing Tartary buckwheat seeds. Seventeen structural genes for flavonoid biosynthesis displayed a significantly positive correlation with the accumulation of most flavonoid components during the development of Tartary buckwheat seeds, and the F3′5′H-3 gene might be the most crucial contributor in determining the total flavonoid content in Tartary buckwheat seeds. A schematic of the biosynthesis pathways for 30 major flavonoids in Tartary buckwheat seeds was constructed. These findings provide an outlook of the flavonoid components and their biosynthesis in Tartary buckwheat seeds and have potential applications in breeding new cultivars with higher flavonoid contents.

Malignant cardiac arrhythmias with high morbidity and mortality have posed a significant threat to our human health. Scutellarein, a metabolite of Scutellarin which is isolated from Scutellaria altissima L., presents excellent therapeutic effects on cardiovascular diseases and could further be metabolized into methylated forms. A series of 22 new scutellarein derivatives with hydroxyl-substitution based on the scutellarin metabolite in vivo was designed, synthesized via the conjugation of the scutellarein scaffold with pharmacophores of FDA-approved antiarrhythmic medications and evaluated for their antiarrhythmic activity through the analyzation of the rat number of arrhythmia recovery, corresponding to the recovery time and maintenance time in the rat model of barium chloride-induced arrhythmia, as well as the cumulative dosage of aconitine required to induce VP, VT, VF and CA in the rat model of aconitine-induced arrhythmia. All designed compounds could shorten the time of the arrhythmia continuum induced by barium chloride, indicating that 4′-hydroxy substituents of scutellarein had rapid-onset antiarrhythmic effects. In addition, nearly all of the compounds could normalize the HR, RR, QRS, QT and QTc interval, as well as the P/T waves’ amplitude. The most promising compound 10e showed the best antiarrhythmic activity with long-term efficacy and extremely low cytotoxicity, better than the positive control scutellarein. This result was also approved by the computational docking simulation. Most importantly, patch clamp measurements on Nav1.5 and Cav1.2 channels indicated that compound 10e was able to reduce the INa and ICa in a concentration-dependent manner and left-shifted the inactivation curve of Nav1.5. Taken together, all compounds were considered to be antiarrhythmic. Compound 10e even showed no proarrhythmic effect and could be classified as Ib Vaughan Williams antiarrhythmic agents. What is more, compound 10e did not block the hERG potassium channel which highly associated with cardiotoxicity.

IntroductionThis paper examined the impact of public long-term care insurance (LTCI) pilots in China on the multidimensional poverty status of middle-aged and older adults.MethodsUsing panel data from the China Health and Retirement Longitudinal Survey, we utilized LTCI pilots conducted in different cities from 2012 to 2018 and assessed the impact of LTCI using a difference-in-differences strategy.ResultsWe found that the implementation of LTCI reduces the multidimensional poverty of middle-aged and older adults and their likelihood of future multidimensional poverty. LTCI coverage was also associated with a reduction in the likelihood that middle-aged and older adults in need of care fall into income poverty, living consumption poverty, health poverty, and social participation poverty.DiscussionFrom a policy perspective, the findings of this paper suggest that the establishment of an LTCI system can improve the poverty of middle-aged and older adults in several ways, which has important implications for the development of LTCI systems in China and other developing countries.

With the spread of distributed renewable energy, residents are shifting from being mere consumers to being energy producers and consumers. This role shift poses challenges to the electricity trading mechanism that connects distributed renewable energy sources to the grid. In this paper, a new efficient and secure blockchain-based distributed community energy trading mechanism is proposed, called CE-SDT. Our system is proved to be stable and scalable. It can also help shift loads and power peaks and reduce customer costs by 60%. As a result, our proposed blockchain-based trading mechanism, as compared to the centralized trading mechanism, is applied to microgrids formed by distributed renewable energy sources, not only obtaining greater economic benefits but also reducing the carbon footprint of residents, and furthermore, it promotes low or zero-carbon configurations of the power system, thereby achieving certain environmental benefits.

BackgroundAs an excellent nondestructive testing technology, cold neutron radiography is widely employed to image materials of interest in many basic and application research fields. One of key components of such device is the neutron sensitive scintillation screen. Normally, these screens are made up of scintillation or phosphor powder mixed with/without neutron sensing isotopes, such as 6LiF:ZnS(Ag) and Gd2O2S:Tb. Uniform scintillation screens are very difficult to make a trade-off between spatial resolution and neutron detection efficiency. Recently a new type of micro-structural scintillation screens has been proposed, which is expected to have higher spatial resolution while maintaining higher neutron detection efficiency. Following this idea, a scintillation screen has been proposed, developed, and studied by our group.PurposeThis study aims to develop a new type of scintillation screens based on a glass capillary array filled with scintillation powders to achieve high spatial resolution and neutron detection efficiency.MethodsFirst of all, a neutron sensing scintillation screen was made by filling very fine grinded Gd2O2S:Tb phosphor powder into glass capillary arrays. Three main steps, i.e. the phosphor powder grinding, the particle size screening, and the vacuum suction filtration process, were taken making such screens. Then, photographs of Gd2O2S:Tb phosphor before and after grinding were taken with a scanning electron microscope (SEM) to examine the filling efficiency of scintillation powder in the glass capillary arrays. Finally, experimental test of spatial resolution of such scintillation screens was carried out by using an optical system to read out the scintillation light emitted by the screen, and a Siemens Star neutron test target to characterize the screens' spatial resolution with cold neutrons.ResultsX-ray luminescence spectra show that the grinding process reduces the light yield of the phosphor. The filling efficiency of scintillation powder in the glass capillary arrays is up to 70%. The cold neutron imaging system with developed scintillation screen achieves spatial resolution of about 300 μm@CTF=3% by experimental test.ConclusionsAlthough the new neutron sensing scintillation screen is still under-developing and there are still some problems to be overcome, cold neutron imaging scintillation screen based on glass capillary array filled with Gd2O2S:Tb phosphor, proposed in this study, can be used to achieve high spatial resolution and neutron detection efficiency with advantages of low cost and simple fabrication process.

BackgroundOsteoid osteoma (OO) comprises approximately 11%-14% of benign bone tumors. The main symptom of OO is localized pain accompanied by nighttime aggravation. Surgical treatment is frequently used in clinic, including open surgery and percutaneous ablation, the latter including radiofrequency ablation, cryoablation, and microwave ablation, but there is no consensus on when and how to choose the best treatment for OO.PurposeWe did a systematic review of the literature on existing surgical treatments of OO to assess the safety and efficacy of surgical treatments of OO and to evaluate the surgical options for different locations of OO.MethodsThe inclusion criteria in the literature are 1. Patients diagnosed with osteoid osteoma and treated surgically; 2. Include at least five patients; 3. Perioperative visual analogue scale (VAS), postoperative complications, and recurrence were recorded; 4. Literature available in PubMed from January 2014 to December 2021.ResultsIn the cohort, 1565 patients (mainly adolescents) with OO received 1615 treatments. And there are 70 patients with postoperative recurrence and 93 patients with postoperative complications (minor: major=84:9). The results of Kruskal-Wallis examination of each experimental index in this experiment were clinical success rate H=14.818, p=0.002, postoperative short-term VAS score H=212.858, p

HMGB1 is a highly conserved nuclear protein that is rapidly released into the extracellular environment during infection or tissue damage. In osteoarthritis, HMGB1 acts as a pro-inflammatory cytokine inducing a positive feedback loop for synovial inflammation and cartilage degradation. The aim of this study was to explore the role of HMGB1 in inflammation and catabolism of temporomandibular joint osteoarthritis (TMJOA) and whether inhibition of HMGB1 affects TMJOA. Human synovial fibroblasts were incubated with HMGB1, the expression of pro-inflammatory cytokines and catabolic mediators were measured by Western blot and ELISA. NF-κB signaling pathway involvement was studied by the NF-κB inhibitor and detected by Western blotting and immunofluorescence staining. TMJOA was induced by an injection of Complete Freund’s adjuvant (CFA) into anterosuperior compartment of rat’s joint. An anti-HMGB1 antibody was used to assess the effect to HMGB1 in the synovium and cartilage of the CFA-induced TMJOA rats by H&E, Safranin O, Masson trichrome staining, immunohistochemistry and immunofluorescence. HMGB1 markedly increased the production of MMP13, ADAMTS5, IL-1β and IL-6 through activating NF-κB signaling pathway in human synovial fibroblasts. In vivo, application of the HMGB1 neutralizing antibody effectively ameliorated the detrimental extent of TMJOA. Furthermore, the HMGB1 neutralizing antibody reduced the expression of NF-κB, pro-inflammatory cytokines and catabolic mediators in the synovium and cartilage of CFA-induced TMJOA rats. HMGB1 inhibition alleviates TMJOA by reducing synovial inflammation and cartilage catabolism possibly through suppressing the NF-κB signaling pathway and may become a therapeutic method against TMJOA.

Introducing coherent precipitates is an important method to strengthen alloys. Recently, it is found that the introduction of coherent B2 phase in multi-principal element alloys with BCC structure can improve the mechanical properties significantly, developing a new class of important series alloys. The up-to-date knowledge of these alloys from the perspectives of composition, microstructure, phase stability, and mechanical properties was summarized. These alloys exhibit high yield strength over a wide temperature regime, but the ductility presents different characterization due to the compositional difference. At present, their engineering application is limited due to their weaker thermal stability at elevated temperature, especially above 500℃, and furthermore, the design of compositional content appears to be more easy method to resolve the problem. This paper aims at providing guidance to further design of multi-principal element alloys with coherent BCC/B2 dual-phases.

Objectives To evaluate the feasibility and safety of treating painful osseous metastases using image‐guided percutaneous thermal microwave ablation. Methods This is a retrospective study of patients treated from December 2016 to December 2019 in one institute. A total of 50 patients (35 men, 15 women; mean age 55.24 ± 11.03 years) with 56 osseous metastatic lesions underwent image‐guided percutaneous microwave ablation. There were 7 patients with multiple and 43 patients with single metastases. The numbers of patients with primary cancer were as follows: lung, 13; liver, 17; kidney, 10; prostate, 1; breast, 3; osteosarcoma, 1; and thyroid, 5. Seventeen patients had cancer combined with soft tissue masses. The radiological images for the ablative procedures were obtained by CT, fluoroscopy with ultrasound, and fluoroscopy alone in 16, 11, and 23 patients, respectively. Pain severity was estimated using the visual analogue scale before and after treatment (1 week, 1 month, and 3 months after treatment). Radiological evaluations were performed at baseline and 3 months after the procedure. Results In all patients, pain reduction occurred from the first day after treatment. Pain did not recur during the 3 months of follow up. The mean total ablation time per microwave electrode was 3.99 ± 2.48 min (range, 1–15 min). The mean power of the microwave electrode was 66.40 ± 12.08 W. The average volume of bone (load‐bearing bone, such as vertebra and acetabulum) cement after ablation was 2.82 ± 0.81 mL. There were no significant differences in visual analogue scale pain scores for different imaging techniques or ablation energies. No procedure‐related complications occurred. Conclusion Image‐guided percutaneous thermal microwave ablation of osseous metastases relieves pain and improves mobility. CT remains the first choice for percutaneous ablation. Fluoroscopy combined with ultrasound is effective for cases with soft tissue masses; fluoroscopy is also suitable for combination with vertebroplasty. However, further investigations are required.

Objectives To evaluate whether curettage with adjuvant microwave therapy was successful in the treatment of giant cell tumor of the bone (GCTB) in extremities, especially for GCTB with pathological fractures and GCTB of the distal radius. Methods This was a retrospective study of 54 cases of GCTB of the extremities treated by curettage with adjuvant microwave therapy between 2007 and 2019. Five patients were lost to follow up and excluded from the study. A total of 33 male and 21 female patients were included in this study. Patients were aged 15–57 years (mean 29.72 ± 10.48 years). Among these patients, there were 10 cases of GCTB with pathological fractures and eight cases of GCTB of the distal radius; one of these cases was combined with a pathological fracture. Comprehensive imaging examinations (X‐rays [including lesion site and chest], CT, MRI, emission computed tomography, and pathology examination) of all patients were reviewed. The clinical staging of these patients were evaluated radiologically using the Campanacci classification system based on the extent of spread of the tumor. All patients underwent curettage with adjuvant microwave therapy. Clinical and imaging evaluations were performed in all cases to check for recurrence or metastasis. Lower limb and upper limber function were assessed using the Musculoskeletal Tumor Society score (MSTS), and wrist function was assessed according to the disabilities of the arm, shoulder and hand (DASH) score. Data on surgical‐related complications were recorded. Results All cases were followed up for 24–126 months (mean 60.69 ± 29.61 months). There were 24 patients with a Campanacci grade of 3 and 30 with a Campanacci grade of 2. The 52 patients were continuously disease‐free. The local recurrence rate was 3.70% (2 patients). One patient had recurrence in the proximal femur, and the other developed in soft tissue of the calf muscle. No recurrence occurred for GCTB of the distal radius. One recurrence occurred in a GCTB with pathological fractures. The intervals were 9 and 28 months, respectively. The cases of recurrence all had a Campanacci grade of 3 (8.33%). The median MSTS among the 54 patients was 27.67 ± 3.81. The mean wrist function DASH score was 8.30 ± 2.53. The mean MSTS was 28.67 ± 1.63 and 26.71 ± 5.49 for patients with GCTB of the distal radius and for those with pathological fractures, respectively. In comparing patients with and without pathological fractures, there was no significant difference in the MSTS functional score. Five patients had complications after the surgery. Conclusion Curettage with adjuvant microwave ablation therapy provided favorable local control and satisfactory functional outcomes in the treatment of GCTB, especially for cases with pathological fractures and those with GCTB of the distal radius.

In order to enhance the wear property of TA2 alloy, ceramics reinforced composite coating was prepared on TA2 alloy by laser cladding with preplaced mixed WS2-TiC-Ti powders (mole ratio of 1:3:6). The micro-structure, phase compositions and micro-hardness of composite coating were analyzed in detail. The dry-sliding wear behaviors and corresponding wear mechanisms of TA2 alloy substrate and composite coating at different test temperatures (RT, 250 and 500 °C) were also studied systematically. The results showed that α-Ti, TiS, Ti2SC, (Ti, W)C1−x and TiC were in-situ synthesized in laser processing. The micro-hardness of the coating was improved significantly due to the formation of carbide ceramics Ti2SC, (Ti, W)C1−x and TiC. The coating exhibited excellent wear property at 500 °C, i.e. low friction coefficient (0.339) and wear rate (4.87 × 10−6 mm3/Nm). The predominant wear mechanism of the composite coating was formation and peeling off of lubricating transfer films, with incidental effect of adhesive wear and oxidation wear.

The regulation of glucose-stimulated insulin secretion and glucose excursion has a sensory component that operates in a sex-dependent manner. Objective: Here, we aim to dissect the basis of the sexually dimorphic interaction between sensory neurons and pancreatic β cells and its overall impact on insulin release and glucose homeostasis. Methods: We used viral retrograde tracing techniques, surgical and chemodenervation models, and primary cell-based co-culture systems to uncover the biology underlying sex differences in sensory modulation of pancreatic β-cell activity. Results: Retrograde transsynaptic labeling revealed a sex difference in the density of sensory innervation in the pancreas. The number of sensory neurons emanating from the dorsal root and nodose ganglia that project in the pancreas is higher in male than in female mice. Immunostaining and confocal laser scanning microscopy confirmed the higher abundance of peri-islet sensory axonal tracts in the male pancreas. Capsaicin-induced sensory chemodenervation concomitantly enhanced glucose-stimulated insulin secretion and glucose clearance in male mice. These metabolic benefits were blunted when mice were orchidectomized prior to the ablation of sensory nerves. Interestingly, orchidectomy also lowered the density of peri-islet sensory neurons. In female mice, capsaicin treatment did not affect glucose-induced insulin secretion nor glucose excursion and ovariectomy did not modify these outcomes. Interestingly, same- and opposite-sex sensory-islet co-culture paradigms unmasked the existence of potential gonadal hormone-independent mechanisms mediating the male-female difference in sensory modulation of islet β-cell activity. Conclusion: Taken together, these data suggest that the sex-biased nature of the sensory control of islet β-cell activity is a result of a combination of neurodevelopmental inputs, sex hormone-dependent mechanisms and the potential action of somatic molecules encoded by the sex chromosome complement.

Introduction: The avascular necrosis of the femoral head represents the death of bone tissue due to the lack of blood supply. The disease has a progressive evolution; it leads to femoral head collapse and severe arthritis when left untreated. The application of a pedicled bone flap graft is an effective treatment for femoral head necrosis. A pure Mg screw is a kind of degradable screw that can fix the grafted bone flap and prevent long-term stress occlusion and secondary dissection. Case presentation: The report shows the results of the treatment of traumatic femoral head necrosis with a pedicled bone flap with pure Mg screw. A patient had avascular necrosis of the femoral head after 2 years of internal fixation of the femoral neck fracture. We removed the patient's internal fixation hollow nail, cleaned the necrotic bone tissue and took part of the same ipsilateral pedicle iliac bone graft in the femoral head defect with biodegradable pure Mg screw fixation. Within 2 years after the surgery, the patients had no significant progressive necrosis of the femoral head. Postoperative Harris scores showed that the patient's left hip function was significantly improved compared with his preoperative state. The pure Mg screw in the body had gradually degraded. After 2 years, the screw's diameter had been significantly reduced compared with 3 days after the surgery. The postoperative Harris score showed that the patient's left hip function was significantly improved compared with the second preoperative examination. Discussion: The discussion includes the reasons for the choices of surgical approaches, the mode of pure Mg screw degradation and the postoperative functional assessment of the patient's left hip. Conclusion: Pure Mg screw fixation pedicled bone flap transplantation is an effective surgical treatment for femoral head necrosis in young patients. Pure Mg screw is a biodegradable internal fixation device with good biocompatibility, which has a good clinical application prospects. The translational potential of this article: Degradable pure Mg screw has the potential to preserve hip joint therapy for the treatment of femoral head necrosis.

Tumor cells rewire metabolism to meet their increased nutritional demands, allowing the maintenance of tumor survival, proliferation, and expansion. Enhancement of glycolysis and glutaminolysis is identified in most, if not all cancers, including multiple myeloma (MM), which interacts with a hypoxic, acidic, and nutritionally deficient tumor microenvironment (TME). In this review, we discuss the metabolic changes including generation, depletion or accumulation of metabolites and signaling pathways, as well as their relationship with the TME in MM cells. Moreover, we describe the crosstalk among metabolism, TME, and changing function of immune cells during cancer progression. The overlapping metabolic phenotype between MM and immune cells is discussed. In this sense, targeting metabolism of MM cells is a promising therapeutic approach. We propose that it is important to define the metabolic signatures that may regulate the function of immune cells in TME in order to improve the response to immunotherapy.