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Articular cartilage is a tissue with relatively poor self‐regeneration capacity due to insufficient blood vessels and chondrocytes in the region. Biomaterial‐assisted tissue engineering has shown great potential in cartilage regeneration. However, there are still many worries over the uses of exogenous growth factors, stem cells and scaffolds. To address these concerns, here a dynamic proteinaceous hydrogel with a self‐recruiting ability of cartilage‐inducing factor for in situ cartilage regeneration is reported. The dynamic hydrogel (Pep‐GelSH) is prepared by using thiol‐modified gelatin and thiol‐capped TGF‐β1‐affinity peptide through the Au‐S coordination. The injectability and self‐recovery of Pep‐GelSH hydrogel enabled not only minimally invasive implantation but also the adaptability of the scaffold to irregular defect shapes. Meanwhile, the dynamic hydrogel showed improved adherence to the host tissue and allowed quick infiltration of host cells. More importantly, the hydrogel significantly enhanced local enrichment of endogenous TGF‐β1 and led to the recruitment of stem cells in vivo. After implantation, the hydrogel scaffold triggered the innate repair capacity of cartilage defects by successively promoting stem cells recruitment, infiltration and differentiation, resulting in significantly enhanced chondrogenesis and improved cartilage repair. Therefore, the study in this work may provide a feasible and promising approach for in situ cartilage regeneration. [ABSTRACT FROM AUTHOR]

Piezoelectric cantilever beams are broadly implemented in energy harvesting. However, simple cantilever‐shaped harvesters are mostly unimodal. Herein, a T‐shaped cantilever beam harvester that can have a bimodal amplitude–frequency curve is developed. The modal of the system is designed in COMSOL finite‐element software and the dynamic behavior is carried out using the finite element simulation. Then, validation experiments are used to estimate the results of finite‐element analysis and it is concluded that the simulation results are in good agreement with the experimental data. Furthermore, the frequency response curves are plotted for various system parameters so as to discuss the influence of these parameters on the bandwidth of the harvester. It is found that there is an optimal resistance that can obtain the P = 2.87 mW maximum power. Finally, theoretical modeling is established and exact analytical solutions are derived, and the comparisons of theoretical, numerical, and experimental results are implemented. It is found that the results of these three methods are consistent. In addition, all of these predictions show that the bidirectional coupling induces the bandwidth increases. [ABSTRACT FROM AUTHOR]

Maintaining high conversion under the premise of high oxygenates selectivity in syngas conversion is important but a formidable challenge in Rh catalysis. Monometallic Rh catalysts provide poor oxygenate conversion efficiency, and efforts have been focused on constructing adjacent polymetallic sites; however, the one‐pass yields of C2+ oxygenates over the reported Rh‐based catalysts were mostly <20 %. In this study, we constructed a monometallic Rh catalyst encapsulated in UiO‐67 (Rh/UiO‐67) with enhanced proximity to dual‐site Rh1,2‐Rhn ensembles. Unexpectedly, this catalyst exhibited high efficacy for oxygenate synthesis from syngas, giving a high oxygenate selectivity of 72.0 % with a remarkable CO conversion of 50.4 %, and the one‐pass yield of C2+ oxygenates exceeded 25 %. The state‐of‐the‐art characterizations further revealed the spontaneous formation of an ensemble of Rh single atoms/dimers (Rh1,2) in the proximity of ultrasmall Rh clusters (Rhn) confined within the nanocavity of UiO‐67, providing adjacent Rh+‐Rh0 dual sites dynamically during the reaction that promote the relay of the undissociated CHO species to the CHx species. Thus, our results open a new route for designing highly efficient Rh catalysts for the conversion of syngas to oxygenates by precisely tuning the ensemble and proximity of the dual active sites in a confined space. [ABSTRACT FROM AUTHOR]

Bronchoscopic lung volume reduction (BLVR) is a feasible, safe, effective and minimally invasive technique to significantly improve the quality of life of advanced severe chronic obstructive pulmonary disease (COPD). In this study, three‐dimensional computed tomography (3D‐CT) automatic analysis software combined with pulmonary function test (PFT) was used to retrospectively evaluate the postoperative efficacy of BLVR patients. The purpose is to evaluate the improvement of lung function of local lung tissue after operation, maximize the benefits of patients, and facilitate BLVR in the treatment of patients with advanced COPD. All the reported cases of advanced COPD patients treated with BLVR with one‐way valve were collected and analysed from 2017 to 2020. Three‐dimensional‐CT image analysis software system was used to analyse the distribution of low‐density areas <950 Hounsfield units in both lungs pre‐ and post‐ BLVR. Meanwhile, all patients performed standard PFT pre‐ and post‐operation for retrospective analysis. We reported six patients that underwent unilateral BLVR with 1 to 3 valves according to the range of emphysema. All patients showed a median increase in forced expiratory volume in 1 second (FEV1) of 34%, compared with baseline values. Hyperinflation was reduced by 16.6% (range, 4.9%‐47.2%). The volumetric measurements showed a significant reduction in the treated lobe volume among these patients. Meanwhile, the targeted lobe volume changes were inversely correlated with change in FEV1/FEV1% in patients with heterogeneous emphysematous. We confirm that 3D‐CT analysis can quantify the changes of lung volume, ventilation and perfusion, to accurately evaluate the distribution and improvement of emphysema and rely less on the observer. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Data on safety and immunogenicity of coronavirus disease 2019 (COVID‐19) vaccinations in hepatocellular carcinoma (HCC) patients are limited. In this multicenter prospective study, HCC patients received two doses of inactivated whole‐virion COVID‐19 vaccines. The safety and neutralizing antibody were monitored. Totally, 74 patients were enrolled from 10 centers in China, and 37 (50.0%), 25 (33.8%), and 12 (16.2%) received the CoronaVac, BBIBP‐CorV, and WIBP‐CorV, respectively. The vaccines were well tolerated, where pain at the injection site (6.8% [5/74]) and anorexia (2.7% [2/74]) were the most frequent local and systemic adverse events. The median level of neutralizing antibody was 13.5 (interquartile range [IQR]: 6.9–23.2) AU/ml at 45 (IQR: 19–72) days after the second dose of vaccinations, and 60.8% (45/74) of patients had positive neutralizing antibody. Additionally, lower γ‐glutamyl transpeptidase level was related to positive neutralizing antibody (odds ratio = 1.022 [1.003–1.049], p = 0.049). In conclusion, this study found that inactivated COVID‐19 vaccinations are safe and the immunogenicity is acceptable or hyporesponsive in patients with HCC. Given that the potential benefits may outweigh the risks and the continuing emergences of novel severe acute respiratory syndrome coronavirus 2 variants, we suggest HCC patients to be vaccinated against COVID‐19. Future validation studies are warranted. [ABSTRACT FROM AUTHOR]

Blocking the mevalonate pathway for cholesterol reduction by using statin may have adverse effects including statin‐induced colitis. Moreover, one of the predisposing factors for colitis is an imbalanced CD4+ T cell, which can be observed on the complete deletion of HMG‐CoA reductase (HMGCR), a target of statins. In this study, we inquired geranylgeranyl pyrophosphate (GGPP) is responsible for maintaining the T‐cell homeostasis. Following dextran sulfate sodium (DSS)‐induced colitis, simvastatin increased the severity of disease, while cotreatment with GGPP, but not with cholesterol, reversed the disease magnitude. GGPP ameliorated DSS‐induced colitis by increasing Treg cells. GGPP amplified Treg differentiation through increased IL‐2/STAT 5 signaling. GGPP prenylated Ras protein, a prerequisite for extracellular signal‐regulated kinase (ERK) pathway activation, leading to increased IL‐2 production. Higher simvastatin dose increased the severity of colitis. GGPP ameliorated simvastatin‐increased colitis by increasing Treg cells. Treg cells, which have the capacity to suppress inflammatory T cells and were generated through IL‐2/STAT5 signaling, increased IL‐2 production through prenylation and activation of the Ras/ERK pathway. [ABSTRACT FROM AUTHOR]

The impact of casein on atherosclerotic lesion progression remains controversial. In this study, we tested the effect of casein on atherosclerotic development and its potential mechanisms in male apolipoprotein E knockout (apoE‐/‐) mice fed with high‐fat diet (HFD). Male apoE‐/‐ mice fed with HFD were randomized into HFD group (subcutaneous injection with 0.5 ml of 0.9% sodium chloride daily, n = 6) and HFD + Casein group (subcutaneous injection with 0.5 ml of 10% casein daily, n = 6). Body weight was recorded at baseline and once a week thereafter. After 12 weeks of treatment, plasma lipid and inflammatory markers, and histological characterization of atherosclerotic plaques in the aortic arch and aortic sinus were analyzed. There was no significant difference in weight gain between the two groups after 12 weeks of treatment. Plasma levels of total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL‐C) were significantly lower, while high‐density lipoprotein cholesterol (HDL‐C) level tended to be higher in the HFD + Casein group compared with the HFD group. The positive percentages of atherosclerotic lesions in aortic arch and aortic sinus as well as collagen deposition in aortic sinus plaques were significantly lower in the HFD + Casein group compared with the HFD group. Plasma levels of interleukin (IL)‐1β and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were also significantly lower in the HFD + Casein group compared with the HFD group. In conclusion, subcutaneous administration of casein attenuates atherosclerotic lesion progression, possibly through decreasing fibrosis and inflammatory responses in male apoE‐/‐ mice fed with HFD. [ABSTRACT FROM AUTHOR]

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 was considered significant. Results: A total of 88 lymph nodes were punctured by the two needles separately. The diagnostic accuracy for each puncture between the two needles did not show any significant difference (P > 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 FROM AUTHOR]

Introduction: Peripheral pulmonary lesions (PPL) are difficult to diagnose. We analysed the diagnostic values and risks of endobronchial ultrasonography with a guide sheath (EBUS‐GS) and computed tomography‐guided transthoracic needle aspiration (CT‐TTNA) in diagnosing PPL. Methods: We collected 250 cases received EBUS‐GS examination, and 279 cases received CT‐TTNA examination. We analysed the diagnosis results and the complications of each operation and determined the relevant indications. Results: Biopsy was successful in 239 cases (95.6%) using EBUS‐GS and in 279 cases (100%) using CT‐TTNA. Lesions were smaller than or equal to 30 mm for biopsy using EBUS‐GS in 60.7% of the cases. The distances of lesions from the chest wall were greater than 80 mm for EBUS‐GS examination in 89.1% of the cases. The diagnostic rate of EBUS‐GS was 78.2%, including 41.8% (100 cases) malignant diseases. EBUS‐GS is a highly safe method. The distances of lesions from the chest wall were no greater than 80 mm for CT‐TTNA examination in 90.0% of the cases. The diagnosis rate using CT‐TTNA was 94.6%, including 90.0% (251 cases) malignant diseases. For CT‐TTNA, there is a high chance of complications such as pneumothorax and intrapulmonary hemorrhage. Conclusion: EBUS‐GS and CT‐TTNA each have their own limitations. EBUS‐GS has a slightly lower diagnostic rate but higher safety, while CT‐TTNA has a higher diagnostic rate but requires attention to complications. For lesions 80 mm more from the chest wall, we recommend EBUS‐GS. For lesions 80 mm from or closer to the chest wall, we recommend CT‐TTNA. [ABSTRACT FROM AUTHOR]

Reducing sympathetic neurohormone expression is a key therapeutic option in attenuating cardiac remodelling. Present study tested the feasibility of attenuating cardiac remodelling through reducing sympathetic neurohormone level by partial cardiac sympathetic denervation in a rat model of chronic volume overload. Male Sprague‐Dawley rats were randomized into sham group (S, n = 7), aortocaval fistula group (AV, n = 7), and aortocaval fistula with bilateral sympathetic stellate ganglionectomy group (AD, n = 8). After 12 weeks, myocardial protein expression of sympathetic neurohormones, including tyrosine hydroxylase, neuropeptide Y, growth associated protein 43, and protein gene product 9.5, were significantly up‐regulated in AV group compared to S group, and down‐regulated in AD group. Cardiac remodelling was aggravated in AV group compared to S group and attenuated in AD group. The myocardial deposition of extracellular matrix, including collagen I and III, was enhanced in AV group, which was reduced in AD group. Myocardial angiotensin II and aldosterone expressions were significantly up‐regulated in AV group and down‐regulated in AD group. Our results show that bilateral sympathetic stellate ganglionectomy could attenuate cardiac remodelling and fibrosis by down‐regulating sympathetic neurohormones expression in this rat model of chronic volume overload. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Few studies have reported the association between nonalcoholic fatty liver disease (NAFLD) and immunoglobulins. In this study, we aimed to investigate the relationship between serum immunoglobulin levels and NAFLD in a Chinese adult population. METHODS: We performed a cross‐sectional study including 11 261 Chinese adults. NAFLD was diagnosed based on the Chinese Guidelines for the diagnosis and treatment of fatty liver diseases and an alcohol intake of <70 g/week in women and <140 g/week in men, and serum immunoglobulin (Ig) levels were determined using immune nephelometry. Multiple logistic regression analysis was done to assess relationships between concentrations of serum immunoglobulins and NAFLD. RESULTS: Of the 11 261 adults recruited from January 2010 to December 2015, the prevalence of NAFLD was 40.8% (n = 4598). The geometric mean levels of IgG, IgM, IgE and IgA were 1177.49 mg/dL (95% confidence interval [CI] 1173.07–1181.93), 93.56 mg/dL (95% CI 92.70–94.42), 30.70 IU/mL (95% CI 29.92–31.49) and 216.64 mg/dL (95% CI 214.95–218.34), respectively. Compared with the lowest quintile, the multivariable adjusted odds ratio (95% CI) of NAFLD for the highest quintile of IgG, IgM, IgE, and IgA were 0.78 (0.66–0.92), 0.71 (0.60–0.84), 0.98 (0.84–1.15) and 1.41 (1.21–1.66), respectively. CONCLUSION: Increased IgA and decreased IgG and IgM levels are independently associated with NAFLD prevalence. Further research is needed to explore the causal association between serum immunoglobulins and NAFLD. [ABSTRACT FROM AUTHOR]

Aims: The full benefits of myocardial revascularization strategies applied to acute myocardial infarction patients might be reduced by myocardial ischaemia and reperfusion (I/R) injury. It is known that inflammation plays an important role in the pathogenesis of I/R injury and galectin‐3, a known inflammatory factor, is actively involved in ischaemia‐induced inflammation and fibrosis of various organs. Previous studies demonstrated that anti‐platelets therapy with ticagrelor, a new P2Y12 receptor antagonist, could effectively attenuate myocardial I/R injury and I/R injury‐related inflammatory responses. It remains unknown whether the cardioprotective effects of ticagrelor are also mediated by modulating myocardial galectin‐3 expression. Methods: We determined the ratio of infarct area (IA)/area at risk (AAR), expression of galectin‐3, TNF‐α and IL‐6 in infarct area of rats treated with placebo (equal volume saline per gastric gavage immediately after LAD ligation, then once daily till study end) or ticagrelor (150 mg kg−1 dissolved in saline per gastric gavage immediately after LAD ligation, then once daily till study end) at 24 h, 3 and 7 days post I (45 min)/R injury. Sham‐operated rats served as control. Results: Our results showed that ticagrelor treatment significantly reduced IA/AAR ratio at 3 and 7 days post I/R, downregulated mRNA and protein expression of galectin‐3, as well as mRNA expression of TNF‐α and IL‐6 in infarct area at 24 h, 3 and 7 days post I/R. Conclusions: Our results suggest that the cardioprotective effects of ticagrelor might partly be mediated by downregulating galectin‐3 expression in infarct area in this rat model of myocardial I/R injury. [ABSTRACT FROM AUTHOR]

Objective Endobronchial ultrasound-guided transbronchial needle aspiration ( EBUS-TBNA) is commonly used for clinical diagnosis of mediastinal lymphadenectasis. This study aimed to evaluate the diagnostic significance of EBUS-TBNA for mediastinal lymphadenectasis in a large single center. Methods A total of 846 patients who were not definitively diagnosed with mediastinal lymphadenectasis underwent EBUS-TBNA were retrospectively analyzed in this study. Results In total, 842 patients underwent EBUS-TBNA successfully. There were 589 patients with malignancy, including squamous carcinoma (118 cases; 20.6%), adenocarcinoma (187 cases; 32.7%) and small cell carcinoma (88 cases; 15.4%). A total of 253 patients were diagnosed with benign disease, including tuberculosis (111 cases; 43.9%) and sarcoidosis (93 cases; 36.7%). The diagnostic sensitivity of lung cancer, tuberculosis and sarcoidosis were 94.4%, 81.1% and 51.6%, respectively. The overall sensitivity of EBUS-TBNA was 92.0%. N2 stage in lung cancer patients who were diagnosed by EBUS-TBNA was significantly higher than other stages. The positive rate of targeted puncture is high for the lymph nodes whose short-axis diameters were larger than 1 cm. Conclusion The operation risk of EBUS-TBNA is relatively small. In diseases complicated by mediastinal lymphadenectasis, malignant diseases are most, and benign diseases mainly are granulomatous. EBUS-TBNA is a valuable diagnostic technique in patients with mediastinal lymphadenectasis whose diagnosis have not been determined. [ABSTRACT FROM AUTHOR]

Background and objective Although massive bleeding is the most life-threatening complication caused by flexible bronchoscopy, data on flexible bronchoscopy-induced massive bleeding are scarce, and the associated clinical characteristics and prognostic factors are unknown. Methods This was a multicentre retrospective cohort study of all patients who underwent flexible bronchoscopy in 33 tertiary hospitals from January 2001 to June 2013. The clinical characteristics and outcomes were collected and analysed. Results A total of 194 patients with massive bleeding were identified among 520 343 patients who underwent flexible bronchoscopy. The average blood loss reached up to 378 mL. The overall incidence and mortality were 0.037% and 0.004%, respectively, and the overall fatality was 10.8%. The risk of massive bleeding induced by therapeutic bronchoscopies was significantly higher than that induced by diagnostic bronchoscopies (incidence: 0.059% vs 0.031%, P < 0.001; mortality: 0.012% vs 0.003%, P < 0.001; fatality: 20% vs 8.4%, P = 0.068). Multivariate analysis showed that age ≥65 years, tracheal bleeding, blood loss ≥500 mL and occurrence of shock were independent factors predicting poor outcome, while emergency surgery was an independent protective factor. Re-bleeding occurred in six patients, resulting in three deaths within a month. Conclusion Flexible bronchoscopy-induced massive bleeding is rare but life-threatening. Age, bleeding location, bleeding volume, circulation condition and emergency surgery were independent prognostic factors. [ABSTRACT FROM AUTHOR]

Colorectal cancer ( CRC) is one of the most common malignancies and is the second leading cause of cancer death in humans. Tumour suppressor candidate 3 ( TUSC3) plays an important role in embryogenesis and metabolism. Deletion of TUSC3 often causes non-syndromic mental retardation. Even though TUSC3 deregulation is frequently observed in epithelial cancers, the function of TUSC3 in CRC has remained unknown. In this study, we observed greater expression of TUSC3 at the mRNA and protein level in clinical colorectal tumour samples compared with paired normal tissues. Gain- and loss-of-function analyses were performed to evaluate the functional significance of TUSC3 in CRC initiation and progression. Immunoblotting, immunofluorescence, and co-immunoprecipitation analyses were used to identify potential pathways with which TUSC3 might be involved. Overexpression of TUSC3 in CRC cells induced epithelial-mesenchymal transition ( EMT) in CRC cells, accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation, migration, and invasion, as well as accelerated xenograft tumour growth, were observed in TUSC3-overexpressing CRC cells, while opposite effects were achieved in TUSC3-silenced cells. In conclusion, our study demonstrated the oncogenic role of TUSC3 in CRC and showed that TUSC3 may be responsible for alternations in the proliferation ability, aggressiveness, and invasive/metastatic potential of CRC through regulating the MAPK, PI3K/Akt, and Wnt/β-catenin signalling pathways. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]