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Objective: To investigate the differences in metabolites of Chinese nectarine, peento, yellow peach, Yangshan honey peach and Xinyi honey peach by using non-target metabolomics. Methods: 250 Fresh peaches of comparable maturity were used as test materials, and the fresh peach pulp was determined by high performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry (UPLC-QTOF-MS), and the metabolites of different varieties of fresh peaches were investigated by principal component analysis and metabolite variability analysis. Results: A total of 74 metabolites were detected, mainly phenolic acids, flavanols, flavonols, anthocyanins, amino acids, glycosides, iridoid glycosides, B vitamins, etc. PCA analysis revealed that compared with the other 4 fresh peaches, Yangshan honey peach had higher contents of 7-hydroxycoumarin, pinocembrin, chlorogenic acid, neochlorogenic acid, epicatechin, procyanidin A2, cryptochlorogenic acid, plantagoside, procyanidin B2, and lower levels of vitamin B2, kaempferol, rutin. Based on OPLS-DA analysis, 4 fresh peaches were screened for differential metabolites with Yangshan honey peach respectively. Nectarine had 18 species of procyanidin B3 and other metabolites, peento had 12 species of procyanidin B2 and other metabolites, yellow peach had 18 species of procyanidin A2 and other metabolites, and Xinyi honey peach had 15 species of procyanidin C1 and other metabolites, which could be used as a potential biomarker to differentiate between Yangshan honey peach and the other 4 fresh peaches. In this study, the differential metabolites of the 5 fresh peaches were mainly plant polyphenolic compounds, and chlorogenic acid and procyanidin metabolites were high in Yangshan honey peach, which were the key differential metabolites. Conclusion: The non-target metabolomics technology can effectively distinguish the five fresh peaches, which is feasible for the identification of fresh peaches, and can be used to assist the qualitative identification of fresh peaches and deep-processed fresh peaches as an important basis for the identification of true and false Yangshan honey peaches, and it is of great significance to protect the development of Yangshan honey peach speciality industry.

Abstract Background Kaposiform hemangioendothelioma (KHE) is a rare neoplasm of vascular origin. It may involve skin, bone, connective tissue, and parenchymal organs, and it is difficult to make a definite diagnosis in the early stage because Kasabach-Merritt phenomenon may occur in some cases. Case presentation On June 12, 2022, a 19-month boy was admitted to our department with the chief complaint of flexion of the right hip joint for over 1 year. An exploratory laparotomy and pelvic lesion resection were conducted and the resection of the iliopsoas muscle mass was performed. The intraoperative resection of the neoplasm confirmed the pathological diagnosis of kaposiform hemangioendothelioma. The vital signs of the child were stable and recovered well after surgery, and the platelet and coagulation indices were normal. Conclusion KHE is a rare disease in clinics, the number of confirmed cases in the world is still relatively few, and the etiology and mechanism of the disease are still unknown, which could result in misdiagnose and delayed treatment in the disease early stages. It is necessary to continue to collect relevant cases, to unify the standard treatment guidelines as soon as possible, to reduce the mortality rate, and to improve the quality of life of the cases.

Abstract Background Estrogen deficiency-mediated hyperactive osteoclast represents the leading role during the onset of postmenopausal osteoporosis. The activation of a series of signaling cascades triggered by RANKL-RANK interaction is crucial mechanism underlying osteoclastogenesis. Vorinostat (SAHA) is a broad-spectrum pan-histone deacetylase inhibitor (HDACi) and its effect on osteoporosis remains elusive. Methods The effects of SAHA on osteoclast maturation and bone resorptive activity were evaluated using in vitro osteoclastogenesis assay. To investigate the effect of SAHA on the osteoclast gene networks during osteoclast differentiation, we performed high-throughput transcriptome sequencing. Molecular docking and the assessment of RANKL-induced signaling cascades were conducted to confirm the underlying regulatory mechanism of SAHA on the action of RANKL-activated osteoclasts. Finally, we took advantage of a mouse model of estrogen-deficient osteoporosis to explore the clinical potential of SAHA. Results We showed here that SAHA suppressed RANKL-induced osteoclast differentiation concentration-dependently and disrupted osteoclastic bone resorption in vitro. Mechanistically, SAHA specifically bound to the predicted binding site of RANKL and blunt the interaction between RANKL and RANK. Then, by interfering with downstream NF-κB and MAPK signaling pathway activation, SAHA negatively regulated the activity of NFATc1, thus resulting in a significant reduction of osteoclast-specific gene transcripts and functional osteoclast-related protein expression. Moreover, we found a significant anti-osteoporotic role of SAHA in ovariectomized mice, which was probably realized through the inhibition of osteoclast formation and hyperactivation. Conclusion These data reveal a high affinity between SAHA and RANKL, which results in blockade of RANKL-RANK interaction and thereby interferes with RANKL-induced signaling cascades and osteoclastic bone resorption, supporting a novel strategy for SAHA application as a promising therapeutic agent for osteoporosis.

Acute pancreatitis (AP) is an inflammatory disease characterized by localized pancreatic injury and a systemic inflammatory response. Fatty acids (FAs), produced during the breakdown of triglycerides (TGs) in blood and peripancreatic fat, escalate local pancreatic inflammation to a systemic level by damaging pancreatic acinar cells (PACs) and triggering M1 macrophage polarization. This paper provides a comprehensive analysis of lipases' roles in the onset and progression of AP, as well as the effects of long-chain fatty acids (LCFAs) on the function of pancreatic acinar cells (PACs). Abnormalities in the function of PACs include Ca2+ overload, premature trypsinogen activation, protein kinase C (PKC) expression, endoplasmic reticulum (ER) stress, and mitochondrial and autophagic dysfunction. The study highlights the contribution of long-chain saturated fatty acids (LC-SFAs), especially palmitic acid (PA), to M1 macrophage polarization through the activation of the NLRP3 inflammasome and the NF-κB pathway. Furthermore, we investigated lipid lowering therapy for AP. This review establishes a theoretical foundation for pro-inflammatory mechanisms associated with FAs in AP and facilitating drug development.

Summary: For a long time, myeloid-derived suppressor cells (MDSCs) dilated in circulation system of colorectal cancer (CRC) patients have been puzzling clinicians. Various evidence shows that MDSCs constitute the bulk of immunosuppression in CRC, which is related to tumor growth, adhesion, invasion, metastasis, and immune escape. However, the mechanisms underlying these cells formation remain incompletely understood. In this study, we reported that CRC cell-derived LC3-dependent extracellular vesicles (LDEVs)-mediated M-MDSCs formation via TLR2-MYD88 pathway. Furthermore Hsp60 was the LDEVs surface ligand that triggered these MDSCs induction. In clinical studies, we reported that accumulation of circulating M-MDSCs as well as IL-10 and arginase1 secretion were reliant upon the levels of tumor cell-derived LDEVs in CRC patients. These findings indicated how local tumor cell-derived extracellular vesicles influence distal hematopoiesis and provided novel justification for therapeutic targeting of LDEVs in patients with CRC.

Abstract Periprosthetic osteolysis (PPO) induced by wear particles at the interface between the prosthesis and bone is a crucial issue of periprosthetic bone loss and implant failure. After wear and tear, granular material accumulates around the joint prosthesis, causing a chronic inflammatory response, progressive osteoclast activation and eventual loosening of the prosthesis. Although many studies have been conducted to address bone loss after joint replacement surgeries, they have not fully addressed these issues. Focusing on osteoclast activation induced by particles has important theoretical implications. Cannabinoid type II receptor (CB2) is a seven-transmembrane receptor that is predominantly distributed in the human immune system and has been revealed to be highly expressed in bone-associated cells. Previous studies have shown that modulation of CB2 has a positive effect on bone metabolism. However, the exact mechanism has not yet been elucidated. In our experiments, we found that NOX1-mediated ROS accumulation was involved in titanium particle-stimulated osteoclast differentiation. Furthermore, we confirmed that CB2 blockade alleviated titanium particle-stimulated osteoclast activation by inhibiting the NOX1-mediated oxidative stress pathway. In animal experiments, downregulation of CB2 alleviated the occurrence of titanium particle-induced cranial osteolysis by inhibiting osteoclasts and scavenging intracellular ROS. Collectively, our results suggest that CB2 blockade may be an attractive and promising therapeutic scheme for particle-stimulated osteoclast differentiation and preventing PPO.

Background: Growing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies. Methods: This study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer’s disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses. Results: Each 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00–2.02), ADHD (1.51, 1.15–1.98), schizophrenia (1.47, 1.15–1.87), and AD (1.57, 1.16–2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%. Conclusions: This study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.

Abstract Objective Investigate the use of endobronchial ultrasonography with a guide sheath (EBUS-GS) combined with Gene Xpert MTB/RIF (Xpert) for diagnosis of Mycobacterium tuberculosis (MTB) infection in isolated pulmonary nodules. Methods Patients who had isolated pulmonary nodules and unknown diagnoses at our institution from October 2020 to December 2021 were prospectively examined using EBUS-GS and Xpert. The diagnostic values of using EBUS-GS or bronchoalveolar lavage fluid (BALF) with acid-fast staining, MGIT 960 culture, pathological examination, and Xpert for isolated pulmonary nodules caused by MTB infection were compared using receiver operating characteristic (ROC) analysis. Results There were 135 patients, 64 with isolated pulmonary tuberculomas and 71 with non-tuberculous lesions. The sensitivity of EBUS-GS with Xpert was significantly higher than BALF with Xpert (57.81% vs. 34.78%, P = 0.017). Use of EBUS-GS with Xpert and MGIT 960 culture further increased the sensitivity to 62.50% (95%CI 50.64–74.36) and increased the specificity to 100%. The AUC values of BALF with MGIT 960 culture was 0.663(95%CI 0.543–0.783) and BALF with Xpert was 0.674 (95%CI 0.556–0.792). The AUC values of EBUS-GS with MGIT 960 culture was 0.680 (95%CI 0.554–0.743), with pathological examination was 0.713 (95%CI 0.573–0.760), and with Xpert was 0.789 (95%CI 0.655–0.829). Conclusion Use of EBUS-GS with Xpert had high sensitivity and specificity in the diagnosis of isolated pulmonary tuberculoma. This method has significant potential for use in clinical practice.

Abstract Background Many studies have shown that circular RNAs (circRNAs) are abnormally expressed in various tumor tissues and served as a key regulator in the occurrence and development of cancer. However, in hepatocellular carcinoma (HCC), the molecular mechanism of circRNAs in body fluids remains to be further explored. Methods The expression levels of genes and proteins were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting, respectively. Cell counting Kit‐8 (CCK‐8), 5‐Ethynyl‐2'‐deoxyuridine (EdU), wound healing assay, Transwell assays, flow cytometry, and tumor formation models in nude mice were conducted to investigate the effects of circFAM114A2 on HCC cells both in vitro and in vivo. RNA antisense purification (RAP), dual luciferase reporter assays and rescue assays were carried out to verify the interaction between circFAM114A2, miR‐630 and HHIP. Results CircFAM114A2 was significantly downregulated in HCC tissues and was associated with microvascular invasion and lymph node metastasis of HCC patients. We also observed that circFAM114A2 was lowly expressed in HCC plasma, which may serve as an effective biomarker to screen HCC patients from healthy controls (area under curve (AUC)=0.922). In vitro, circFAM114A2 overexpression significantly blunted HCC cell proliferation, migration, invasion, and promoted apoptosis, whereas circFAM114A2 silencing posed opposite effects. In vivo, circFAM114A2 overexpression inhibited the growth of HCC cells. Mechanistically, circFAM114A2 could increase the expression of the tumor suppressor HHIP via acting as a sponge for miR‐630. Conclusions CircFAM114A2 exerts a tumor suppressor role in HCC through miR‐630/HHIP axis, and may be served as a potential diagnostic and therapeutic biomarker for HCC patients.

Abstract Programmed cell death protein 1 (PD-1), expressed on tumor-infiltrating T cells, is a T cell exhaustion marker. The mechanisms underlying PD-1 upregulation in CD4 T cells remain unknown. Here we develop nutrient-deprived media and a conditional knockout female mouse model to study the mechanism underlying PD-1 upregulation. Reduced methionine increases PD-1 expression on CD4 T cells. The genetic ablation of SLC43A2 in cancer cells restores methionine metabolism in CD4 T cells, increasing the intracellular levels of S-adenosylmethionine and yielding H3K79me2. Reduced H3K79me2 due to methionine deprivation downregulates AMPK, upregulates PD-1 expression and impairs antitumor immunity in CD4 T cells. Methionine supplementation restores H3K79 methylation and AMPK expression, lowering PD-1 levels. AMPK-deficient CD4 T cells exhibit increased endoplasmic reticulum stress and Xbp1s transcript levels. Our results demonstrate that AMPK is a methionine-dependent regulator of the epigenetic control of PD-1 expression in CD4 T cells, a metabolic checkpoint for CD4 T cell exhaustion.

Abstract Chronic liver disease (CLD) has become a major health problem worldwide owing to its increased morbidity and mortality. Evaluation of the degree of liver injury is crucial for the clinical management and treatment of CLD patients. In the current clinical practice, liver biopsy with histological analysis is the clinical standard for assessing the degree of CLD injury. However, liver biopsy is an invasive procedure that is limited by sampling errors and interobserver variability and is insufficient for screening and monitoring. Advanced three‐dimensional magnetic resonance elastography (3D MRE) is a simple, fast, safe, and noninvasive technology. This offers comprehensive insight into increased liver stiffness beyond stage‐specific fibrosis. This technology exhibits considerable potential for comprehensively and simultaneously assessing early necroinflammation, discriminating necroinflammation from fibrosis, detecting nonalcoholic steatohepatitis severity, predicting cirrhosis complications, and identifying tumor recurrence. Nevertheless, the clinical application and promotion of this technology are currently required in China. 3D MRE should evolve towards better clinical convenience and satisfaction to provide an imaging basis to improve treatment selection in CLD patients and facilitate its widespread use.

Abstract Objective This study investigated the diagnostic performance of endobronchial ultrasound with Xpert MTB/RIF Ultra (Ultra) for detecting smear-negative pulmonary tuberculosis (TB). Methods 143 patients suspected of sputum smear-negative pulmonary tuberculosis were enrolled in this study in Shanghai Pulmonary Hospital, China. These patients underwent endobronchial ultrasound with a guide sheath (EBUS-GS) or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) based on their chest CT manifestations. We assessed the sensitivity and specificity of tissue specimens with Ultra in the TB group and non-TB group. Culture and clinical diagnosis were used as gold-standard for TB. Results Among these 143 patients, 11 patients were culture-positive TB, 85 patients were diagnosed with culture-negative TB and 47 were with the non-TB diseases. Direct testing with microscopy (Acid-Fast Bacilli smear, AFB), liquid culture, pathology, Xpert MTB/RIF(Xpert) test and Ultra had a sensitivity of 8.3%, 11.5%, 42.7%, 64.6%, and 78.1% individually among all the TB patients. Ultra had a higher sensitivity than Xpert (P = 0.011). But Ultra had a specificity of 59.6% (95% CI 44.3–73.3), lower than that of Xpert (89.4%, 95% CI 76.1–96.0, P = 0.001). Ultra had the same sensitivity on specimens from EBUS-TBNA and EBUS-GS (P = 0.975). Ultra’s positive predictive value and negative predictive value were 79.8% and 57.1% respectively. Conclusions Tissue specimens from interventional bronchoscopy combined with Ultra provide a sensitive method for diagnosing smear-negative pulmonary tuberculosis, but its specificity was lower than Xpert.

Dimethyl ether (DME) was a carbon neutral alternative fuel for engines.The combustion and emission characteristics of a DME/gasoline Dual Fuel Spark Ignition (DFSI) engine with various excess air coefficients (λs) at different DME ratios (ΦDME) were investigated experimentally in this study.The in-cylinder pressures along with their relevant crank angle were used for the combustion characteristics calculation. The light five component exhaust gas analyzer and particle analyzer were employed for the gaseous and particulate matter emission measurement, respectively. Results showed that the DME/gasoline dual fuel combustion strategy can enhance the Brake Mean Effective Pressure (BMEP) by up to 12.6% because the high diffusivity, superior LTR and fast LFS of DME. Although adding DME was beneficial for the reduction of gaseous emissions (HC, CO and NOx) from DME/gasoline DFSI engines, the gaseous emissions were mainly determined by the variation of λ s. Particularly, up to 93.4% of the CO emissions at stoichiometric condition can be reduced after increasing λ to 1.3. The fast evaporation rate and superior LTR of DME helped to suppress PN emissions, but larger DME ratio (ΦDME > 5%) was needed for λ >1.2.

Breakthrough infection of SARS-CoV-2 is a serious challenge, as increased infections were documented in fully-vaccinated individuals. Recipients with poor antibody response are highly vulnerable to reinfection, whereas those with strong antibody responses achieve sterilizing immunity. Thus far, biomarkers associated with levels of vaccine-elicited antibody response are still lacking. Here, we studied the antibody response of age- and gender-controlled healthy cohort, who received inactivated SARS-CoV-2 vaccines and profiled the B cell receptor repertoires in longitudinally consecutive samples. Upon vaccination, all vaccinated individuals displayed a convergent antibody response with shared common antibody clones and public neutralizing antibodies. Strikingly, poor vaccine-responders are distinguishable from strong vaccine-responders by a biased V-usage before vaccination and IgG to IgM mRNA ratio. These findings reveal molecular signatures associated with the different levels of vaccine-induced antibody response, which could be further developed into biomarkers for the design of vaccination strategies.

Abstract Background To observe the effect and mechanism of alpha-adrenergic receptor inhibitor phentolamine (PTL) in a rabbit model of acute pulmonary embolism (APE) combined with shock. Methods Twenty-four New Zealand rabbits were randomly divided into sham operation group (S group, n = 8), model group (M group, n = 8) and PTL group (n = 8), the model of APE combined with shock was established. Mean pulmonary arterial pressure (MPAP), peripheral mean arterial pressure (MAP) and pulmonary circulation time were evaluated. The expression levels of α1 receptor, α2 receptor and their downstream molecules in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions lung tissues were detected and compared, respectively. Results In M group, α receptor-related signaling pathways were significantly activated in both PE and non-PE areas as expressed by up-regulated α1, α2 receptor and phospholipase C (PLC); the expression level of phosphorylated protein kinase A (p-PKA) was significantly down-regulated; myosin light chain kinase (MLCK) and α-smooth muscle actin (α-SMA) levels were up-regulated. PTL treatment significantly improved pulmonary as well as systemic circulation failure: decreased MPAP, restored blood flow in non-PE area, shortened pulmonary circulation time, increased MAP, and restored the circulation failure. PTL induced significantly down-regulated expression of α1 receptor and its downstream molecule PLC in both PE and non-PE area, the expression level of α2 receptor was also down-regulated, the expression level of p-PKA was significantly up-regulated. PTL treatment can inhibit both α1 and α2 receptor-related signaling pathways in whole lung tissues, and inhibit Ca2+ signaling pathways. The expression level of MLCK and α-SMA were significantly down-regulated. Compared with PE area, the changes of expression levels of α receptor and its downstream molecules were more significant in the non-PE region. Conclusion In this model of APE combined with shock, the sympathetic nerve activity was enhanced in the whole lung, α1 and α2 receptor and their downstream signaling activation might mediate blood flow failure in the whole lung. PTL treatment can effectively restore pulmonary blood flow in non-PE area and improve pulmonary as well as systemic circulation failure possibly through down-regulating α1 and α2 receptor and their downstream signaling pathways.

Background: Few studies have investigated traditional Chinese medicine (TCM) utilization patterns for irritable bowel syndrome (IBS), despite the potential benefits of exploring TCM utilization patterns in optimizing TCM management. This study aimed to evaluate TCM utilization patterns and clinical features for IBS patterns in Taiwan.Methods: This was a population-based cross-sectional study using claim data from the National Health Insurance Research Database between 2012 and 2018. Patients newly diagnosed with IBS and aged over 20 years were included. The TCM utilization patterns and characteristics, including Chinese herbal medicine (CHM) treatment types and prescription patterns, were evaluated.Results: A total of 73,306 patients newly diagnosed with IBS used TCM for IBS at least once. Females used TCM for IBS more than males (female-to-male ratio = 1.89: 1). The age distribution showed a peak at 30–39 years (27.29%), followed by 40–49 years (20.74%) and 20–29 years (20.71%). Patients who received Western medications for IBS had a lower tendency to seek TCM. CHM was the most commonly used TCM modality (98.22%), with Jia-wei-xiao-yao-san being the most commonly prescribed Chinese herbal formula and Bai-zhu being the most frequently prescribed single Chinese herb.Conclusion: This study enhances our understanding of TCM usage patterns for IBS, particularly CHM prescriptions. Further research is needed to investigate commonly used TCM formulas and individual herbs.

The efficient design optimization of electric machines for electric power steering (EPS) applications poses challenges in meeting demanding performance criteria, including high power density, efficiency, and low vibration. Traditional optimization approaches often fail to find a global solution or suffer from excessive computation time. In response to the limitations of traditional approaches, this paper introduces a novel methodology by incorporating a Gaussian process-based adaptive sampling technique into a surrogate-assisted optimization process using a metaheuristic algorithm. Validation on a 72-slot/8-pole interior permanent magnet (IPM) machine demonstrates the superiority of the proposed approach, showcasing improved exploitation–exploration balance, faster convergence, and enhanced repeatability compared to conventional optimization methods. The proposed design process is then applied to two surface PM (SPM) machine configurations with 9-slot/6-pole and 12-slot/10-pole combinations for EPS applications. The results indicate that the 12-slot/10-pole SPM design surpasses the alternative design in torque density, efficiency, cogging torque, torque ripple, and manufacturability.

Abstract Periprosthetic osteolysis (PPO) triggered by wear particles is the most severe complication of total joint replacement (TJR) surgeries, representing the major cause of implant failure, which is public health concern worldwide. Previous studies have confirmed the specialized role of osteoclast-induced progressive bone destruction in the progression of PPO. Additionally, the reactive oxygen species (ROS) induced by wear particles can promote excessive osteoclastogenesis and bone resorption. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), a cellular enzyme, is considered to be responsible for the production of ROS and the formation of mature osteoclasts. However, NOX4 involvement in PPO has not yet been elucidated. Therefore, we investigated the mechanism by which NOX4 regulates osteoclast differentiation and the therapeutic effects on titanium nanoparticle-induced bone destruction. We found that NOX4 blockade suppressed osteoclastogenesis and enhanced the scavenging of intracellular ROS. Our rescue experiment revealed that nuclear factor-erythroid 2-related factor 2 (Nrf2) silencing reversed the effects of NOX4 blockade on ROS production and osteoclast differentiation. In addition, we found increased expression levels of NOX4 in PPO tissues, while NOX4 inhibition in vivo exerted protective effects on titanium nanoparticle-induced osteolysis through antiosteoclastic and antioxidant effects. Collectively, these findings suggested that NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway and that NOX4 blockade may be an attractive therapeutic approach for preventing PPO. Graphical Abstract

Tracheobronchopathia osteoplastica (TO), is an underreported affliction characterized by squamous metaplasia and heterotopic bone formation in trachea and bronchi. Here the authors apply functional, as well as genome-wide transcriptional and epigenetic profiling to identify airway basal cells dysfunction underlying TO.

Abstract Wear particle-induced periprosthetic osteolysis (PPO) have become a major reason of joint arthroplasty failure and secondary surgery following joint arthroplasty and thus pose a severe threat to global public health. Therefore, determining how to effectively suppress particle-induced PPO has become an urgent problem. The pathological mechanism involved in the PPO signaling cascade is still unclear. Recently, the interaction between osteogenic inhibition and wear particles at the implant biological interface, which has received increasing attention, has been revealed as an important factor in pathological process. Additionally, Hedgehog (Hh)-Gli1 is a crucial signaling cascade which was regulated by multiple factors in numerous physiological and pathological process. It was revealed to exert a crucial part during embryonic bone development and metabolism. However, whether Hh-Gli1 is involved in wear particle-induced osteogenic inhibition in PPO remains unknown. Our present study explored the mechanism by which the Hh-Gli1 signaling cascade regulates titanium (Ti) nanoparticle-induced osteolysis. We found that Hh-Gli1 signaling was dramatically downregulated upon Ti particle treatment. Mechanistically, glycogen synthesis kinase 3β (GSK-3β) activation was significantly increased in Ti particle-induced osteogenic inhibition via changes in GSK-3β phosphorylation level and was found to participate in the posttranslational modification and degradation of the key transcription factor Gli1, thus decreasing the accumulation of Gli1 and its translocation from the cytoplasm to the nucleus. Collectively, these findings suggest that the Hh-Gli1 signaling cascade utilizes a GSK3β-mediated mechanism and may serve as a rational new therapeutic target against nanoparticle-induced PPO. Graphical Abstract

Background. To explore the prognostic risk factors of 30-day death in patients with traumatic lower limb fracture (TLLF) complicated with acute pulmonary embolism (APE). Methods. 295 consecutive TLLF patients diagnosed as APE according to pulmonary artery CT angiography, hospitalized in our hospital from January 2017 to December 2021, were included in this study. Patients were divided into nonsurvival group and survival group according to 30-day follow-up results. After adjusting age, sex, and all the clinical variables with P values of

IntroductionAcute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear.MethodsAn integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of Tlr2 in vivo.ResultsThe numbers of anti-inflammatory response-related cells, such as M2 macrophages (P = 3.2 × 10–3), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils (P = 3.0 × 10–8), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation.DiscussionIn summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, TLR2might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression.

Abstract Background AMP-activated protein kinase (AMPK) is a metabolic sensor that maintains energy homeostasis. AMPK functions as a tumor suppressor in different cancers; however, its role in regulating antitumor immunity, particularly the function of regulatory T cells (Tregs), is poorly defined. Methods AMPKα1 fl/fl Foxp3 YFP-Cre, Foxp3 YFP-Cre, Rag1 −/− , and C57BL/6 J mice were used for our research. Flow cytometry and cell sorting, western blotting, immuno-precipitation, immuno-fluorescence, glycolysis assay, and qRT-PCR were used to investigate the role of AMPK in suppressing programmed cell death 1 (PD-1) expression and for mechanistic investigation. Results The deletion of the AMPKα1 subunit in Tregs accelerates tumor growth by increasing the expression of PD-1. Metabolically, loss of AMPK in Tregs promotes glycolysis and the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme of the mevalonate pathway. Mechanistically, AMPK activates the p38 mitogen-activated protein kinase (MAPK) that phosphorylates glycogen synthase kinase-3β (GSK-3β), inhibiting the expression of PD-1 in Tregs. Conclusion Our study identified an AMPK regulatory mechanism of PD-1 expression via the HMGCR/p38 MAPK/GSK3β signaling pathway. We propose that the AMPK activator can display synergic antitumor effect in murine tumor models, supporting their potential clinical use when combined with anti-PD-1 antibody, anti-CTLA-4 antibody, or a HMGCR inhibitor.

Objective To undertake a meta-analysis to investigate if there is an association between the glutathione S-transferase mu 1 ( GSTM1 ) gene polymorphism, coronary artery disease (CAD) susceptibility and smoking. Methods Electronic databases, including PubMed®, Web of Science and Embase®, were searched for relevant case–control studies. Data were extracted and the odds ratio (OR) was calculated and appropriate statistical methods were used for the meta-analysis. Results The analysis included eight studies with a total of 1880 cases with CAD and 1758 control subjects. The results of this meta-analysis demonstrated that there is no association between the GSTM1 null and CAD (OR 1.24, 95% confidence interval [CI] 1.00, 1.55). An increased risk of CAD was observed in the smoking population with the GSTM1 null genotype (OR 1.48, 95% CI 1.02, 2.15). Subgroup analyses of geographical region, genotyping method and publication language category demonstrated potential relationships among gene polymorphism, smoking and CAD. Conclusions Based on the current literature, the GSTM1 null genotype was associated to CAD in the smoking population. The interaction between smoking and GSTM1 polymorphism may contribute to the susceptibility of CAD.

Primary osteoporosis has long been underdiagnosed and undertreated. Currently, ferroptosis may be a promising research direction in the prevention and treatment of primary osteoporosis. However, the specific mechanism of ferroptosis in primary osteoporosis remains a mystery. Differentially expressed genes (DEGs) were identified in bone mesenchymal stromal cells (BMSCs) of primary osteoporosis and heathy patients from the GEO databases with the help of bioinformatics analysis. Then, we intersected these DEGs with the ferroptosis dataset and obtained 80 Ferr-DEGs. Several bioinformatics algorithms (PCA, RLE, Limma, BC, MCC, etc.) were adopted to integrate the results. Additionally, we explored the potential functional roles of the Ferr-DEGs via GO and KEGG. Protein–protein interactions (PPI) were used to predict potential interactive networks. Finally, 80 Ferr-DEGs and 5 key Ferr-DEGs were calculated. The 5 key Ferr-DEGs were further verified in the OVX mouse model. In conclusion, through a variety of bioinformatics methods, our research successfully identified 5 key Ferr-DEGs associated with primary osteoporosis and ferroptosis, namely, sirtuin 1(SIRT1), heat shock protein family A (Hsp70) member 5 (HSPA5), mechanistic target of rapamycin kinase (MTOR), hypoxia inducible factor 1 subunit alpha (HIF1A) and beclin 1 (BECN1), which were verified in an animal model.

HypothesisPatients with cancer have different impedances or conductances than patients with benign normal tissue; thus, we can apply electrical impedance analysis (EIA) to identify patients with cancer.MethodTo evaluate EIA’s efficacy and safety profile in diagnosing pulmonary lesions, we conducted a prospective, multicenter study among patients with pulmonary lesions recruited from 4 clinical centers (Zhongshan Hospital Ethics Committee, Approval No. 2015-16R and 2017-035(3). They underwent EIA to obtain an Algorithm Composite Score or ‘Prolung Index,’ PI. The classification threshold of 29 was first tested in an analytical validation set of 144 patients and independently validated in a clinical validation set of 418 patients. The subject’s final diagnosis depended on histology and a 2-year follow-up.ResultsIn total, 418 patients completed the entire protocol for clinical validation, with 186 true positives, 145 true negatives, 52 false positives, and 35 false negatives. The sensitivity, specificity, and diagnostic yield were 84% (95% CI 79.3%-89.0%), 74% (95% CI 67.4%-79.8%), and 79% (95%CI 75.3%-83.1%), respectively, and did not differ according to age, sex, smoking history, body mass index, or lesion types. The sensitivity of small lesions was comparable to that of large lesions (p = 0.13). Four hundred eighty-four patients who underwent the analysis received a safety evaluation. No adverse events were considered to be related to the test.ConclusionElectrical impedance analysis is a safe and efficient tool for risk stratification of pulmonary lesions, especially for patients with a suspicious lung lesion.

To take full advantage of the lightweight and high strength characteristics of aluminium alloy honeycomb panels and to overcome the shortcoming of the low elastic modulus of the aluminium alloy lattice shell, the present study proposes a new aluminium alloy combined lattice shell (AACLS) structure, which consists of aluminium honeycomb panels and an aluminium alloy lattice shell that jointly resist the load. In the present study, a cylindrical combined lattice shell with a span of 4.4 m was designed and fabricated to carry out the bearing capacity test, and on this basis, the load bearing characteristics and the failure mechanism of this new type of spatial structure are described. The test results show that because the honeycomb panels acted as an integral part of the structure, the overall stiffness and stable bearing capacity of this new type of combined lattice shell were significantly improved compared to those of a panel-free single-layer aluminium alloy lattice shell with the same span. Using the connection performance simulation method proposed in the present study, the load bearing performance of the combined cylindrical lattice shell was well simulated, with an error of only 2% between the calculated and tested ultimate bearing capacities. Parametric analysis was carried out to investigate the effects of the boundary conditions, rise-to-span ratio, and geometric imperfections on the performance of the combined lattice shell. Based on the finite element analysis results of 552 numerical examples and using the probability-based partial factor design method, a simplified method for calculating the stable bearing capacity of the combined lattice shell is proposed, which provides a theoretical basis for the engineering design and specification development of this new type of combined structure in the future.

Objective: Preliminary clinical studies have confirmed that Shexiang Tongxin dropping pills (STDPs) could improve angina pectoris and attenuate vascular endothelial dysfunction in patients with slow coronary flow, but the underlying mechanism is not fully unclear. We aimed to investigate the impact of STDP in a swine model of coronary slow flow (SF) and related mechanisms.Methods: SF was induced by coronary injection of 40μm microspheres, and pigs were randomly divided into the SF group and SF plus STDP group. Pigs in the STDP group received sublingual STDP for 10 min, followed by 1 g STDP oral administration daily for 6 days. Coronary angiography was performed, the TIMI frame count (TFC) was determined, and hemodynamic measurements were performed before, at 30 min, and 7 days post-SF. Serum levels of total NO, NOS, ET-1, C-TNI, and BNP were measured. Myocardial expressions of TNF and IL-6, eNOS, VEGF, CD31, and α-SMA were analyzed by immunohistochemistry and Western blotting.Results: Compared to the SF group, LVEF and TFC were significantly improved at 7 days post-SF in the STDP group. The serum ET-1 level was significantly reduced at 7 days, and NO and NOS levels were significantly higher in the STDP group. Seven days post-SF, myocardial TNF and IL-6 expressions were significantly downregulated, while the expressions of eNOS and VEGF, CD31, and ɑ-SMA were significantly upregulated in the STDP group.Conclusion: Our results showed that STDP improved cardiac function and coronary flow, possibly through reducing inflammatory responses and upregulating myocardial eNOS and VEGF, CD31, and the ɑ-SMA expression.

Graphical AbstractUro-A, which is a metabolite of intestinal flora and mainly produced from pomegranates and some nuts, suppresses osteoclast formation and bone resorption by activating autophagy. Uro-A upregulated the expression of Beclin 1 and LC3 and modulated bone homeostasis 4 in BMMs, thus resulting in decreased osteoclast-related markers and bone loss.

We propose a method for rapid prototyping of a three-phase AC drive system for educational purposes. The proposed method allows college students to design and manufacture a drive system comprising three-phase inverters, a permanent-magnet (PM) machine, a controller, and sensors within a semester. The rapid prototyping process, which requires less than a day, enables efficient iteration and testing during the development process. In addition to addressing the electrical design considerations, this study also addresses the mechanical aspects of the drive system, including the use of coreless PM machines fabricated, using additive manufacturing technology, and the inverter manufacturing process, utilizing an auto-milling machine. Finally, we provide details of the rapid prototyping of closed-loop control, based on sensor feedback to regulate the rotating magnetic fields and output torque.

Requirement conversion (RC) is an important activity in product customized design. Nowadays, the RC process is mostly driven by designers’ knowledge, the RC model is passive to dynamic customer requirements, and the RC behavior is a black box to customers. Digital twin (DT) is characterized as a self-reinforcing mechanism driven by mirroring between the physical and virtual spaces, which is powerful in addressing these challenges for RC. This paper proposes a digital twin driven requirement conversion (DTRC) architecture and a tri-model-based approach integrated by digital model, behavior model, and evolution model for DTRC development. Firstly, the digital model based on the artificial neural network can simulate the virtual twin data to compensate for the absence of real-world data. Then, driven by the virtual-reality integration data, the behavior model mirrors and visualizes the RC behavior in real world based on the decision tree. Finally, a genetic algorithm based evolution model optimizes the RC rules via physical data throughout the whole product life cycle. A case study of DTRC for elevator customized design is further conducted to validate feasibility and effectiveness of the proposed approach. Experimental results show that DTRC outperforms other RC approaches in terms of conversion accuracy. Meanwhile, DTRC can visualize and optimize the conversion path through the tree topology, which is beneficial to the customer participation and proactive to the dynamic environment.

The second-order generalized integrator based orthogonal signal generator (SOGI-OSG) is commonly used to produce direct and quadrature axis ( $dq$ -axes) signals in stationary reference frame for single-phase systems. Fast and robust OSG with harmonic rejection capability is required for parallel operation of power generation systems. The frequency response function (FRF) of classical OSG does not show robustness towards DC offset and grid harmonic disturbances compared to the direct signal of SOGI. This paper presents OSGs based on $n^{th}$ order bandpass filter with a phase shifter using a scaled $Q$ factor as a design variable. The frequency and time-domain performance analysis will be performed based on the scaled $Q$ factor to simplify the design process of the proposed OSGs. The −3dB frequency and settling step time will be matched in higher order OSGs selecting a scaled $Q$ factor. The proposed method will show enhanced harmonic rejection ratio of an additional −20dB with increasing OSG order with tradeoff in computational burden.

Background and AimsEmergency endoscopy is recommended for patients with acute esophageal variceal bleeding (EVB) and their prognosis has improved markedly over past decades due to the increased specialization of endoscopic practice. The study aimed to compare outcomes following emergency endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) in cirrhotic patients with acute EVB.MethodsCirrhotic patients with acute EVB who underwent emergency endoscopy were retrospectively enrolled from 2013 to 2020 across 34 university hospitals from 30 cities. The primary outcome was the incidence of 5-day rebleeding after emergency endoscopy. Subgroup analysis was stratified by Child-Pugh class and bleeding history. A 1:1 propensity score matching (PSM) analysis was performed.ResultsA total of 1,017 and 382 patients were included in EIS group and EVL group, respectively. The 5-day rebleeding incidence was similar between EIS group and EVL group (4% vs. 5%, P = 0.45). The result remained the same after PSM (P = 1.00). Among Child-Pugh class A, B and C patients, there were no differences in the 5-day rebleeding incidence between the two groups after PSM (P = 0.25, 0.82, and 0.21, respectively). As for the patients with or without bleeding history, the differences between EIS group and EVL group were not significant after PSM (P = 1.00 and 0.26, respectively).ConclusionThe nationwide cohort study indicates that EIS and EVL are both efficient emergency endoscopic treatment strategies for acute EVB. EIS should not be dismissed as an economical and effective emergency endoscopic treatment strategy of acute EVB. ClincialTrials.gov number NCT04307264.

Abstract Background In the benefit of the large population and rapid economic growth, the interventional techniques and equipment for brain arteriovenous malformations (bAVMs) in mainland China have been rapidly improved. Chinese neurosurgical cerebrovascular physicians have accumulated rich experience and made pioneering explorations. This study aims to summarize the experience and treatment progress of bAVMs in mainland China. Methods We performed a web-based nationwide questionnaire survey among 67 tertiary neurosurgical institutions that had acknowledged treating bAVMs in the primary survey. Our questionnaire included clinical characteristics, radiological findings, intervention indications/contraindications, intervention timing, and intraoperative management of different treatment modalities. Results A total of 63 participants from 49 (73.1%) tertiary neurosurgical institutions responded to our questionnaire. Forty-two (66.7%) were neurosurgeons, 13 (20.6%) were neurointerventionists, and 8 (12.7%) were radiosurgeons. Approximately 3500 to 4000 cases of bAVMs were treated annually in these 49 departments. All participants agreed that the conclusions of ARUBA are debatable. Flow-related aneurysms, deep venous drainage, and arteriovenous fistula were considered as common hemorrhagic risk factors. Unruptured SM IV-V bAVMs, giant bAVMs, pediatric bAVMs, elderly bAVMs, and eloquent bAVMs were not absolute contraindications to intervention. Maximum lesion occlusion and minimal functional impairment were the principles of intervention management. Most of the neurosurgeons and neurointerventionists recommended early intervention (< 30 days) for ruptured bAVMs, and the radiosurgeons suggested intervention in the chronic phase or recovery phase (P < 0.01) and preferably 3 months after bleeding. Multi-modality strategies were thought effective for complex bAVMs, and more exploration of individualized intraoperative management was necessary. Conclusions Intervention was acceptable for specific selected unruptured bAVMs in mainland China, especially in patients with hemorrhagic risk factors. The application of multidisciplinary cerebrovascular team and multicenter large-sample international registry study might be the next work for Chinese neurosurgical cerebrovascular physicians.

Background The ProCore 25‐gauge needle is a novel specifically designed puncture needle for endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA), which may improve the puncture efficiency of the procedure while ensuring the diagnostic rate. The aim of the present study was to evaluate the diagnostic accuracy, mRNA yield, and complication rate of 25‐gauge needles compared to those of 22‐gauge needles in the evaluation of mediastinal and hilar lymphadenopathy. Methods A total of 39 patients undergoing EBUS‐TBNA at our institution were evaluated. All the procedures were performed by an experienced endoscopist formally trained in interventional pulmonology. Both the traditional 22‐gauge and ProCore 25‐gauge needles were used at each lymph node station. For all specimens obtained via EBUS‐TBNA, 50 μL was used to extract mRNA and detect the RNA concentration, whereas the other part was sent to the pathological evaluation. χ2 test and t‐test were performed to determine the differences between the two types of the needles. A P‐value of 0.05). No serious procedure‐related complications were reported. In addition, the mRNA concentration did not differ between the two types of needles (P > 0.05). Conclusion The ProCore 25‐gauge needle gained a similar diagnostic yield with less puncture time and frequency compared with the 22‐gauge needle.

Abstract Introduction Electronic bronchoscopy is invasive and may cause pain. This study aimed to explore the clinical value of virtual bronchoscopic navigation (VBN) in the diagnosis of benign central airway stenosis (CAS) secondary to tracheobronchial tuberculosis (TBT). Methods Sixty-eight patients with benign CAS caused by TBT were recruited between July 2015 and December 2017. The location, length and diameter of stenoses were independently determined by VBN and electronic bronchoscopy (EOB), and the sensitivity and specificity of VBN in identifying stenosis were assessed with EOB as the gold standard. Results In 68 patients with TBT, the overall coincidence between EOB and VBN in the identification of stenosis was 100%. A total of 188 sites were selected from the central airway, and the stenosis was graded into 0%, ≤ 25%, 26–50%, 51–75%, 76–90% and > 90%. The sensitivity of VBN in determining the degree of stenosis was 98.45%, 100.00%, 100.00%, 100.00%, 84.62% and 0.00%, respectively; the specificity was 91.53%, 96.07%, 97.09%, 97.08%, 97.14% and 97.30%, respectively; the accuracy rate was 96.28%, 96.28%, 97.34%, 97.34%, 96.28% and 95.7%, respectively. The length of airway stenosis on EOB was divided into 50 mm. There was no significant difference in the length of airway stenosis between VBN and EOB (t = 0.083, P = 0.936; t = 1.340, P = 0.199; t = 1.297, P = 0.216; t = 2.186, P = 0.081). In three patients who received stent placement, VBN was able to accurately assess the postoperative expansion. Conclusion VBN is helpful for the diagnosis of TBT-induced CBS and may provide important information on the location, length, diameter and cross-sectional area of stenosis for further EOB examination and interventional therapy. VBN is recommended for patients with TBT and those with contradictions to bronchoscopy, as well as for regular follow-up of stable TBT, because it reduces the incidence of injury, avoids repeat operations and shortens treatment time.

High-frequency injection (HFI) is widely used for zero-to-low speed self-sensing in machines with saliency. HFI algorithms use inductive saliency in the d- and q-axes to estimate the rotor position in permanent magnet synchronous machines (PMSMs). Generally speaking, surface PMSMs (SPMSMs), which are designed without inductive saliency, are not suitable for HFI inductive based self-sensing. In this article, a method to enhance HFI algorithms at zero-to-low speed for classically designed SPMSMs with low inductive saliency is presented. The proposed method is based on using intentional magnetic saturation under flux-intensifying (FI) operation, which will temporarily enable robust self-sensing operation in the zero-to-low speed region in machines that are not suitable for traditional HFI self-sensing.

Self-bearing machines do not contain physical bearings but magnetic bearings. Both rotor rotary and spatial positions displacement are required in these types of machines to control the rotor position while it is levitating. Self-bearing machines often use external sensors for x (horizontal) and y (vertical) spatial position measurement, which will result in additional cost, volume, complexity, and number of parts susceptible to failure. To overcome these issues, this paper proposes a xy-position estimation self-sensing technique based on both main- and cross-inductance variation. The proposed method estimates x and y position based on inductive saliency between two sets of three-phase coils. The proposed idea is applied on a combined winding self-bearing machine which does not require additional suspension force winding. No additional search coil placement for xy-position estimation is required. Therefore, the proposed algorithm can result in a compact size self-bearing machine that does not require external sensors for xy-position measurement and suspension force winding.

The gut-uterus axis plays a pivotal role in the pathogenesis of endometrial cancer (EC). However, the correlations between the endometrial microbiome and endometrial tumor transcriptome in patients with EC and the impact of the endometrial microbiota on hematological indicators have not been thoroughly clarified. In this prospective study, endometrial tissue samples collected from EC patients (n = 30) and healthy volunteers (n = 10) were subjected to 16S rRNA sequencing of the microbiome. The 30 paired tumor and adjacent nontumor endometrial tissues from the EC group were subjected to RNAseq. We found that Pelomonas and Prevotella were enriched in the EC group with a high tumor burden. By integrating the microbiome and hematological indicators, a correlation was observed between Prevotella and elevated serum D-dimer (DD) and fibrin degradation products (FDPs). Further transcriptome analysis identified 8 robust associations between Prevotella and fibrin degradation-related genes expressed within ECs. Finally, the microbial marker of Prevotella along with DD and FDPs showed a high potential to predict the onset of EC (AUC = 0.86). Our results suggest that the increasing abundance of Prevotella in endometrial tissue combined with high serum DD and FDP contents may be important factors associated with tumor burden. The microbe-associated transcripts of host tumors can partly explain how Prevotella promotes DD and FDPs.

Abstract Background We recently showed that intravenous sodium nitroprusside treatment (SNP) could relieve the pulmonary vasospasm of pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions in a rabbit massive pulmonary embolism (MPE) model associated with shock. The present study explored the potential role of cardiopulmonary sympathetic activity on the pathogenesis and the impact of vasodilators on cardiopulmonary sympathetic activity in this model. Methods Rabbits were randomly divided into sham operation group (S group, n = 8), model group (M, equal volume of saline intravenously, n = 11), SNP group (3.5 μg/kg/min intravenously, n = 10) and diltiazem group (DLZ, 6.0 μg/kg/min intravenously, n = 10). Results MPE resulted in reduced mean arterial pressure and increased mean pulmonary arterial pressure as well as reduced PaO2 in the M, SNP and DLZ groups. Tyrosine hydroxylase (TH), neuropeptide Y (NPY) and endothelin-1 (ET-1) expression levels were significantly increased, while nitric oxide (NO) levels were reduced in both PE and non-PE regions in the M group. Both SNP and DLZ decreased mean pulmonary arterial pressure, reversed shock status, downregulated the expression of TH, NPY and ET-1, and increased NO levels in PE and non-PE regions. Conclusion Present results indicate that upregulation of the sympathetic medium transmitters TH and NPY in whole lung tissues serves one of the pathological features of MPE. The vasodilators SNP and DLZ could relieve pulmonary vasospasm in both embolization and non-embolization regions and reverse circulatory shock, thereby indirectly downregulating the sympathetic activation of the whole lung tissues and breaking a vicious cycle related to sympathetic activation in this model.

Abstract Background Some studies have suggested that blood glucose fluctuation and C-peptide level were considered as predictive factors for carotid artery intima–media thickness (CIMT). However, the relationships of these variables are unclear. This research was aimed to identify the potential effects of blood glucose fluctuation, C-peptide level and conventional risk factors on CIMT. Methods A total of 280 type 2 diabetes mellitus (T2DM) patients were enrolled into this study. Population characteristics were obtained through medical history and clinical parameters. The patients were divided into two groups according to the critical value of CIMT (0.9). Research data were analyzed to identify risk factors of CIMT between the two groups. Results The comparison results of basic information showed that differences in age and illness years between the two groups were statistically significant (p = 0.0002 and p = 0.0063). Logistic regression analysis results indicated that smoking, uric acid (UA) levels, 2 h C-peptide and standard deviation of blood glucose (SDBG) were the influence factors for CIMT thickening (p = 0.032, p = 0.047, p = 0.049 and p = 0.042, respectively). Blood glucose fluctuation could affect the risk of some complications. In largest amplitude of glycemic excursions (LAGE) > 4.4 group, the CIMT abnormal rate was 27.10%, which was significantly higher than 12.12% in the LAGE ≤ 4.4 group (p = 0.012). The CIMT abnormal rate of SDBG > 2.0 group was 27.81%, which was significantly higher than that of the SDBG ≤ 2.0 group (p = 0.018). Conclusions Blood glucose fluctuation is an independent risk factor associated with CIMT in T2DM patients, in addition to conventional risk factors, such as smoking, high UA level and 2 h C-peptide. Therefore, more attention should be given to the change of CIMT and the complications.

The imbalance between the supply and demand of electricity is becoming expansive due to the increase in renewable energy penetration. Consequently, the time-varying electricity price is proposed as a tool to manage the mismatch. To cope with the electricity price difference across time and to extract the benefit to the limit, an energy storage system (ESS) can be a good tool to smooth out electricity usage. Nevertheless, ESS can be expensive due to the high installation cost and centrally managed system. In this paper, we propose a distributed ESS installed in each home appliance. Separately installed batteries can avoid sizeable initial investment costs. We calculated the benefit of the system that mainly stemmed from the electricity price difference and compared the benefits across various sizes of the battery system. In addition, the charging/discharging schedule depends on the power consumption profile and electricity price distribution. Decreasing battery prices and rising electricity price volatility can increase the system’s potential benefit.

Postmenopausal osteoporosis is a disease of bone mass reduction and structural changes due to estrogen deficiency, which can eventually lead to increased pain and fracture risk. Chronic inflammatory microenvironment leading to the decreased activation of osteoblasts and inhibition of bone formation is an important pathological factor that leads to osteoporosis. Theaflavin-3,3′-digallate (TFDG) is an extract of black tea, which has potential anti-inflammatory and antiviral effects. In our study, we found that TFDG significantly increased the bone mass of ovariectomized (OVX) mice by micro-CT analysis. Compared with OVX mice, TFDG reduced the release of proinflammatory cytokines and increased the expression of osteogenic markers in vivo. In vitro experiments demonstrated that TFDG could promote the formation of osteoblasts in inflammatory environment and enhance their mineralization ability. In this process, TFDG activated MAPK, Wnt/β-Catenin and BMP/Smad signaling pathways inhibited by TNF-α, and then promoted the transcription of osteogenic related factors including Runx2 and Osterix, promoting the differentiation and maturation of osteoblasts eventually. In general, our study confirmed that TFDG was able to promote osteoblast differentiation under inflammatory environment, enhance its mineralization ability, and ultimately increase bone mass in ovariectomized mice. These results suggested that TFDG might have the potential to be a more effective treatment of postmenopausal osteoporosis.

BackgroundThe pro-inflammatory cytokines were detected in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) tissues to explore the role of inflammation responses and their relationship with the pulmonary blood flow in a rabbit model of acute pulmonary embolism combined with shock.Methods and ResultsNineteen rabbits were randomly divided into sham operation group (S group, n = 8) and massive PE (MPE group, n = 11). The MPE model was established by injecting the autologous blood clots into the main pulmonary artery of rabbit. Pulmonary angiography showed that the pulmonary circulation time was significantly prolonged in the MPE group, and pulmonary blood flow was attenuated at 120 min post PE. Hematoxylin–eosin (HE) staining revealed enhanced inflammatory cell infiltration around the pulmonary vessels in PE and non-PE tissues, and obvious edema on the perivascular region. Meanwhile, the expressions of inducible nitric oxide synthase (iNOS) and arginase 1 (Arg-1) in pulmonary vascular and alveolar tissues were significantly upregulated and the iNOS/Arg-1 ratio was significantly higher in the MPE group than in the S group. Moreover, the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were also significantly increased in PE and non-PE tissues, and interleukin-6 (IL-6) level was significantly increased in non-PE tissues in the MPE group as compared to the S group. Thromboxane A2 (TXA2) and alpha smooth muscle actin (α-SMA) levels were significantly higher in both PE and non-PE tissues in the MPE group than in the S group.ConclusionActivation of inflammation mediators in PE and non-PE tissues might be one of the crucial factors responsible for pulmonary vasculature constriction and pulmonary blood flow attenuation in this MPE model.

Schwertmannite (sch), an iron oxyhydrosulfate mineral, can catalyse a Fenton-like reaction to degrade organic contaminants, but the reduction of Fe(III) to Fe(II) on the surface of schwertmannite is a limiting step for the Fenton-like process. In the present study, the sch/few-layer graphene (sch–FLG) composite was synthesized to promote the catalytic activity of sch in a Fenton-like reaction. It was found that sch can be successfully carried by FLG in sch–FLG composite, mainly via the chemical bond of Fe–O–C on the surface of sch–FLG. The sch–FLG exhibited a much higher catalytic activity than sch or FLG for the degradation of sulfamethazine (SMT) in the heterogeneous Fenton-like reaction, which resulted from the fact that the FLG can pass electrons efficiently. The degradation efficiency of SMT was around 100% under the reaction conditions of H2O2 200–500 mg l−1, sch–FLG dosage 1–2 g l−1, temperature 28–38°C, and initial solution pH 1–9. During the repeated uses of sch–FLG in the Fenton-like reaction, it maintained a certain catalytic activity for the degradation of SMT and the mineral structure was not changed. In addition, SMT may be finally mineralized in the Fenton-like reaction catalysed by sch–FLG, and the possible degradation pathways were proposed. Therefore, the sch–FLG is an excellent catalyst for SMT degradation in a heterogeneous Fenton-like reaction.

Postmenopausal osteoporosis is a worldwide disease characterized by reduced bone mineral density and increased fracture risk. Inflammatory bone loss due to excessive osteoclast bone resorption is significant in the pathogenesis and development of osteoporosis. Punicalagin (PUN) is a pomegranate fruit derivative and has potential anti-inflammatory effects. However, the effect of PUN on osteoporotic bone loss has yet to be clarified. In this study, we investigated the effect of PUN on RANKL-induced osteoclast formation and bone resorption in vitro, as well as its potential therapeutic effect on ovariectomized-induced bone loss in vivo. PUN was demonstrated to suppress osteoclast formation and bone resorptive function dose-dependently, while osteoclast-specific genes were also downregulated by PUN. In vivo micro-CT and histopathological staining showed that the OVX procedure led to significant bone loss characterized by decreased bone parameters and increased osteoclast numbers, while PUN treatment dramatically prevented these changes. Furthermore, PUN treatment effectively inhibited proinflammatory cytokine expression in vitro. Mechanistically, PUN maintained bone mass via suppressing nuclear factor κB (NF-κB) and mitogen‐activated protein kinase (MAPK) signaling pathway activation. Collectively, our observations provide evidence that PUN is a potential candidate for the treatment of osteoporosis.

Background: We previously reported that bilateral sympathetic stellate ganglionectomy attenuated cardiac remodeling and fibrosis in rats with chronic volume overload. Transforming growth factor beta 1 (TGF-β1) is a polypeptide member of the transforming growth factor beta superfamily of cytokines and actively involved in many pathological processes of cardiovascular diseases. The present study explored the impact of bilateral sympathetic stellate ganglionectomy on the TGF-β1 pathway in this model.Methods and Results: Male Sprague–Dawley rats were randomly divided into sham (S) group, abdominal aorta-cava fistula (AV) group, and bilateral sympathetic stellate ganglionectomy after abdominal aorta-cava fistula (AD) group. Twelve weeks after the abdominal aorta-cava fistula surgery, the myocardial expressions of norepinephrine (NE) and hydroxyproline were significantly higher, while acetylcholine was downregulated in the AV group compared to the S group; the above changes were partly reversed in the AD group. The myocardial expression of TGF-β1 and activity of Smad2/3 phosphorylation were also upregulated in the AV group compared to the S group, which could be reversed by bilateral sympathetic stellate ganglionectomy. In vitro, the TGF-β1 expression in cultured myocardial fibroblasts and the proliferation of myocardial fibroblasts were significantly increased post-stimulation with NE in a dose-dependent manner, and these effects could be blunted by co-treatment with a TGF-β1 inhibitor.Conclusion: Our study results indicate that stellate ganglionectomy decreases cardiac norepinephrine release, which leads to decreased TGF-β1 release and reduced fibrosis in rats with chronic volume overload.

Abstract It is reported that glutathione S-transferase mu (GSTM1) polymorphism is associated with non-viral hepatic cirrhosis (HC). However, some studies showed different views. Therefore, in this paper, a meta-analysis was conducted to get a more comprehensive understanding of GSTM1 polymorphisms in non-viral HC susceptibility. The results showed that GSTM1 null was associated with the increased risk of non-viral HC (OR = 1.337, 95% CI 1.112–1.804, p = 0.005). Subgroup analysis of cirrhosis type revealed that GSTM1 null was a prominent risk factor for alcoholic HC (OR = 1.416, 95% CI 1.112–1.804, p = 0.005). Meanwhile, subgroup analysis of population indicated that the significant differences only existed in Asian population (OR = 1.719, 95% CI 1.212–2.438, p = 0.002). In hospital-based studies, patients with GSTM1 null were more likely in risk of HC (OR = 1.426, 95% CI 1.092–1.863, p = 0.009). Subgroup analysis using genotyping method showed a significant association between GSTM1 null genotype and HC occurrence in the studies employing the multiple PCR genotyping method (OR = 1.559, 95% CI 1.171–2.076, p = 0.002). Based on the results of this analysis, it was concluded that GSTM1 null genotype could increase the susceptibility of non-viral hepatic cirrhosis. In addition, alcohol intake, Asian ethnicity, sample source from hospital and multiple PCR genotyping method may also influence the susceptibility of hepatic cirrhosis.