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Abstract Baduanjin has been shown to be an effective method of exercise for promoting body function in patients with chronic obstructive pulmonary disease (COPD). However, this method is rarely used by rural doctors in rural communities. The aim of this study was to compare the therapeutic effects of Baduanjin exercise with those of conventional pulmonary rehabilitation (CPR) implemented by rural doctors in patients with COPD. A total of 472 COPD patients from 18 village clinics were randomly allocated to the Baduanjin group (n = 158), CPR group (n = 154), or control group (n = 160). The Baduanjin group received six months of Baduanjin training, the CPR group received six months of rehabilitation training, and the control group received usual care. The primary outcomes were changes in health status, as measured by the COPD Assessment Test (CAT), and dyspnoea, as assessed via the modified Medical Research Council (mMRC) dyspnoea scale. The secondary outcomes included six-minute walking distance (6MWD) performance and anxiety and depression scores on the Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively). Baseline data were collected before randomization, and outcomes were ascertained at the six-month follow-up by blinded assessors. After six months of training, compared with the control group, the Baduanjin group presented significant improvements in CAT scores (t = 5.121, P

Abstract Background The prediction of coronavirus disease in 2019 (COVID-19) in broader regions has been widely researched, but for specific areas such as urban areas the predictive models were rarely studied. It may be inaccurate to apply predictive models from a broad region directly to a small area. This paper builds a prediction approach for small size COVID-19 time series in a city. Methods Numbers of COVID-19 daily confirmed cases were collected from November 1, 2022 to November 16, 2023 in Xuzhou city of China. Classical deep learning models including recurrent neural network (RNN), long and short-term memory (LSTM), gated recurrent unit (GRU) and temporal convolutional network (TCN) are initially trained, then RNN, LSTM and GRU are integrated with a new attention mechanism and transfer learning to improve the performance. Ten times ablation experiments are conducted to show the robustness of the performance in prediction. The performances among the models are compared by the mean absolute error, root mean square error and coefficient of determination. Results LSTM outperforms than others, and TCN has the worst generalization ability. Thus, LSTM is integrated with the new attention mechanism to construct an LSTMATT model, which improves the performance. LSTMATT is trained on the smoothed time series curve through frequency domain convolution augmentation, then transfer learning is adopted to transfer the learned features back to the original time series resulting in a TLLA model that further improves the performance. RNN and GRU are also integrated with the attention mechanism and transfer learning and their performances are also improved, but TLLA still performs best. Conclusions The TLLA model has the best prediction performance for the time series of COVID-19 daily confirmed cases, and the new attention mechanism and transfer learning contribute to improve the prediction performance in the flatten part and the jagged part, respectively.

Abstract Background Idiopathic pulmonary fibrosis (IPF) stands as a significant contributor to global mortality rates. Presently, there exists a dearth of effective anti-fibrotic treatments for this condition. While itraconazole (ITR) has exhibited potential in mitigating pulmonary fibrosis, its oral administration is hampered by unfavorable pharmacokinetics, which elevate the risk of adverse reactions, thus limiting its clinical utility. Methods An inhalable formulation of ITR were engineered which aimed at enhancing its pulmonary dispersion. First, pharmacokinetics were conducted to investigate the blood concentration and tissue residue of ITR after inhalation administration. In addition, bleomycin induced mouse pulmonary fibrosis model was used to compare the therapeutic effects of ITR administered by inhalation and intragastric administration. Finally, single-cell RNA sequencing (scRNAseq) was used to explore the mechanism of ITR inhalation administration. Results We found that a large amount of drugs accumulated in the lung tissue for a long time after inhalation administration, thus maximizing the therapeutic effect of drugs. Inhalation of ITR daily at for 21 days significantly attenuated bleomycin-induced lung fibrosis and inflammation in murine models. Additionally, our findings revealed that ITR inhalation diminished the proportion of diseased fibroblasts while promoting reparative fibroblast populations in the murine model. Furthermore, it effectively reversed the proportion of activated phagocytic macrophages. Mechanistically, ITR inhalation exerted its effects by regulating SPP1 and C3 signaling pathway pivotal in the interaction between phagocytic macrophages and diseased fibroblasts. Conclusions These insights into the molecular mechanisms underlying ITR’s therapeutic effects on IPF underscore the favorable pharmacokinetic profile conferred by inhalation, thus presenting a promising formulation poised for clinical translation.

Abstract The increasing amount of coal gasification fine slag (CGFS) necessitates its resource utilization. CGFS, mainly composed of porous carbonaceous particles and partially fused spherical or agglomerated ash particles, is an inexpensive and high-quality raw material for preparing adsorbent materials. However, the challenge remains in developing a simple, low-cost, and environmentally friendly method to produce high-performance porous materials from CGFS. In this study, a one-step treatment method using 2 mol/L nitric acid under hydrothermal conditions was proposed for CGFS. The adsorbent material (CGFS-2 M) prepared under a solid–liquid ratio of 2:5 and an initial concentration of 200 mg/L methylene blue (MB) exhibited an equilibrium adsorption capacity as high as 210.20 mg/g. The excellent adsorption performance of CGFS-2 M can be attributed to several factors: acid leaching for mineral removal and pore formation, resulting in a specific surface area and total pore volume 2.2 and 1.6 times that of untreated CGFS, respectively, and an optimized mesoporous pore size distribution favorable for MB adsorption; optimal mineral removal and a well-defined carbon microcrystal structure providing more space for MB adsorption; nitric acid treatment increasing the surface oxygen content and hydrophilicity, enhancing its ability to remove MB. The synergistic effect of pore structure improvement and surface modification indicates a feasible research direction for enhancing the performance of CGFS-based adsorbent materials. These results provide theoretical support for the development of efficient CGFS-based adsorbents.

Abstract Waste activated sludge (WAS) is attracting attention for its energy and resource potential. Anaerobic digestion (AD) can be used to efficiently recover energy resources and stabilize pollutants in WAS, with biochar emerging as an ideal additive to boost this process. However, the low abundance of surface functional groups and small pore structure of raw biochar may limit its performance in the AD of WAS. These limitations can be overcome by using functional biochar. In this review, the preparation and modification methods for functional biochar and its role in the AD of WAS are systematically summarized and discussed. Notably, the role of functional biochar in electron transfer, buffering effects, microbial immobilization, alleviation of inhibitory effects, and functional microbial modulation are analyzed. Additionally, the impacts of biochar on digestate utilization, pollutant removal, and carbon fixation are discussed. Special attention is given to functional biochar for its ability to promote circular economy and carbon neutrality. Finally, future perspectives on the use of functional biochar in the AD of WAS are presented. The aim of this review is to provide insights into the application of functional biochar in the AD of WAS from the perspective of performance improvement, resource utilization, and circular economy. Graphical Abstract

In this work, dense CdCu3(Al[Formula: see text]Ta[Formula: see text]Ti[Formula: see text]O[Formula: see text] ceramics were prepared by a conventional solid phase method. The effect of Al[Formula: see text]/Ta[Formula: see text] dopants on the dielectric properties of CdCu3Ti4O[Formula: see text] ceramics was systematically investigated. Upon Al[Formula: see text]/Ta[Formula: see text] co-doping, the dielectric properties of CdCu3(Al[Formula: see text]Ta[Formula: see text]Ti[Formula: see text]O[Formula: see text] were significantly enhanced. Particularly, the CdCu3(Al[Formula: see text]Ta[Formula: see text]Ti[Formula: see text]O[Formula: see text] material displays a decent dielectric property, where dielectric constants ([Formula: see text]), loss tangent (tan [Formula: see text]) at a test frequency of 1[Formula: see text]kHz are able to satisfy the application temperature requirement of the Y6R capacitor. Surprisingly, the refined grains resulting from Al[Formula: see text]/Ta[Formula: see text] co-doping lead to heightened resistance at grain boundaries, which is closely associated with enhanced dielectric properties. Meanwhile, the giant dielectric property of the materials can be attributed to the effect of the internal barrier layer capacitance. The obtained results are expected to provide a new idea for obtaining high dielectric constant and low loss tangent in CdCTO-based materials and promote the practical application of such materials.

Oxygen-enriched combustion could rise the hazard of unexpected fire and explosion in industry. This study experimentally and numerically analyzed the combustion characteristic of H2 and CH4 in oxygen-enriched environment (Ω = 21%–100 %). For H2 at Φ = 1 and Ω = 100 %, the maximum explosion pressure and maximum pressure rise rate were about 3.89 MPa and 1259.2 MPa/s. For CH4, these values were about 4.77 MPa and 6279.4 MPa/s. The upper flammability limit of gases increased sharply with the increase of Ω, however, the lower flammability limit was almost unchanged. Besides, the increasing of Ω also could result in the rising of aforementioned combustion parameters. The sensitivity of burning velocity was also analyzed. For H2 flame at Φ = 0.8, R35 could slow down burning velocity when Ω = 21 %, but promote it when Ω = 30 % and 70 %. For CH4 flame at Φ = 1.4, the sensitivity coefficients of R11, R35, R43 and R84 changed from negative to positive when Ω increased from 21 % - 30 %–70 % - 100 %. It was concluded that the oxygen concentration not only affect the inert gas but also affect the reaction kinetic of flame.

Chinese baijiu as one of the famous distilled liquor in which fermented in open environments, with various microorganisms (i.e., bacteria, fungi, and yeast) involved in their brewing process, and created corresponding unique flavor. However, the sources of environmentally enriched microbial communities associated with liquor fermentation are still being characterized yet. Given the dependence of microbial growth and reproduction on environmental ecology, it is important to understand the correlation between baijiu fermentation microbial community and surrounding environmental ecology (i.e., temperature, humidity, wind, and precipitation). This study systematically overviewed the sources of microorganisms in the Jiang-flavor-Baijiu fermentation system. The results showed that microorganisms in baijiu brewing (i.e., mold, lactic acid bacteria, and yeast) mainly originated from surrounding environmental matrices, including the air (i.e., Yeast, Streptomyces and Bacillus), soil (i.e., Xanthomonas, Methanococcus and Comamonas) and water (i.e., Flavobacterium, Acinetobacter, and Pseudomonas) via atmospheric transport, raw material transfer and surface runoff. In addition, the unique baijiu fermentation microbial community diversity depends on local geology and meteorological conditions, highlighting that the structural stability and diversity of the microorganisms in the Baijiu brewing process dominated by local environmental ecology. We also explored the regional environmental conditions on the microbial community and found that the unique Jiang-flavor-Baijiu fermentation microbial community diversity depends on local geology and meteorological conditions. The Jiang-flavor-Baijiu workshop is located in the basin of the middle-and low latitude mountainous areas, with sufficient solar irradiation and rainfall, high air humidity, and low wind speed that favor the growth and propagation of Baijiu fermentation microorganisms. Therefore, the obtained conclusions provide new insights unraveling the key factor controlling the unique flavor of Chinese Baijiu, where protecting the ecology of baijiu brewing-regions is fundamental for maintaining the long-term quality of baijiu.

In this work, a traditional solid-state method was adopted to prepare dense Ba[Formula: see text]Ca[Formula: see text][(Zr[Formula: see text]Ti[Formula: see text])[Formula: see text]–(Nb[Formula: see text]La[Formula: see text])x]O3(BCZT–xNL) lead-free relaxation ferroelectrics with excellent energy storage performance (ESP). Remarkably, a large breakdown field strength of BDS ([Formula: see text][Formula: see text]kV/cm) resulting from decreased grain size by double ions doping at the B-site was achieved in BCZT–xNL ceramics. Especially, the BCZT–0.12NL ceramic displays a good recoverable energy density ([Formula: see text]) of 3.1[Formula: see text]J/cm3, a high efficiency of 86.7% ([Formula: see text]) and a superior fatigue resistance, as well as a superior charge–discharge performance ([Formula: see text][Formula: see text]A/cm2, [Formula: see text][Formula: see text]MW/cm3, [Formula: see text][Formula: see text]J/cm3, [Formula: see text][Formula: see text]ns) and good thermal stability. Besides, upon NL doping, the FE to RFE phase transition results in a dielectric behavior traversing the relaxation phase ([Formula: see text]) accompanied by frequency dispersion, which is beneficial to improve ESP. The superior ESP in this work indicates that BCZT–0.12[Formula: see text]NL ceramics are a promising candidate used in energy storage capacitors.

Abstract Allelopathy is a process whereby a plant directly or indirectly promotes or inhibits growth of surrounding plants. Perennial sugarcane root extracts from various years significantly inhibited Bidens pilosa, Digitaria sanguinalis, sugarcane stem seedlings, and sugarcane tissue-cultured seedlings (P

Compressive sensing (CS) is a notable technique in signal processing, especially in multimedia, as it allows for simultaneous signal acquisition and dimensionality reduction. Recent advancements in deep learning (DL) have led to the creation of deep unfolding architectures, which overcome the inefficiency and subpar quality of traditional CS reconstruction methods. In this paper, we introduce a novel CS image reconstruction algorithm that leverages the strengths of the fast iterative shrinkage-thresholding algorithm (FISTA) and modern Transformer networks. To enhance computational efficiency, we employ a block-based sampling approach in the sampling module. By mapping FISTA’s iterative process onto neural networks in the reconstruction module, we address the hyperparameter challenges of traditional algorithms, thereby improving reconstruction efficiency. Moreover, the robust feature extraction capabilities of Transformer networks significantly enhance image reconstruction quality. Experimental results show that the FusionOpt-Net model surpasses other advanced methods on various public benchmark datasets.

Abstract Genomic MET amplification and exon 14 skipping are currently clinically recognized biomarkers for stratifying subsets of non-small cell lung cancer (NSCLC) patients according to the predicted response to c-Met inhibitors (c-Metis), yet the overall clinical benefit of this strategy is quite limited. Notably, c-Met protein overexpression, which occurs in approximately 20–25% of NSCLC patients, has not yet been clearly defined as a clinically useful biomarker. An optimized strategy for accurately classifying patients with c-Met overexpression for decision-making regarding c-Meti treatment is lacking. Herein, we found that SYK regulates the plasticity of cells in an epithelial state and is associated with their sensitivity to c-Metis both in vitro and in vivo in PDX models with c-Met overexpression regardless of MET gene status. Furthermore, TGF-β1 treatment resulted in SYK transcriptional downregulation, increased Sp1-mediated transcription of FRA1, and restored the mesenchymal state, which conferred resistance to c-Metis. Clinically, a subpopulation of NSCLC patients with c-Met overexpression coupled with SYK overexpression exhibited a high response rate of 73.3% and longer progression-free survival with c-Meti treatment than other patients. SYK negativity coupled with TGF-β1 positivity conferred de novo and acquired resistance. In summary, SYK regulates cell plasticity toward a therapy-sensitive epithelial cell state. Furthermore, our findings showed that SYK overexpression can aid in precisely stratifying NSCLC patients with c-Met overexpression regardless of MET alterations and expand the population predicted to benefit from c-Met-targeted therapy.

Abstract Background Alexithymia is a common psychological disorder. However, few studies have investigated its prevalence and predictors in patients with chronic obstructive pulmonary disease (COPD). Therefore, we aimed to determine the prevalence and predictors of alexithymia in Chinese patients. Methods This cross-sectional study included 842 COPD patients to assess the prevalence and predictors of alexithymia using the 20-item Toronto Alexithymia Scale (TAS-20). We used the Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression, the modified British Medical Research Council dyspnea Rating Scale (mMRC) to assess dyspnea, St. George's Respiratory Questionnaire (SGRQ) to assess quality of life, and the age-adjusted Charlson comorbidity index (ACCI) to assess comorbidities. Alexithymia-related predictors were identified using univariate and multivariate logistic regression analyses. Results The prevalence of alexithymia in COPD patients was 23.6% (199/842). Multivariate analysis showed that age [odds ratio (OR) 0.886; 95% confidence interval (CI) 0.794–0.998], body mass index (OR 0.879; 95% CI 0.781–0.989), HADS-anxiety (OR 1.238; 95% CI 1.097–1.396), HADS-depression (OR 1.178; 95% CI 1.034–1.340), mMRC (OR 1.297; 95% CI 1.274–1.320), SGRQ (OR 1.627; 95% CI 1.401–1.890), ACCI (OR 1.165; 95% CI 1.051–1.280), and GOLD grade (OR 1.296; 95% CI 1.256–1.337) were independent predictors for alexithymia in patients with COPD. Conclusions The prevalence of alexithymia was high in Chinese COPD patients. Anxiety, depression, dyspnea, quality of life, comorbidities, and disease severity are independent risk factors, and age and BMI are predictive factors for alexithymia in COPD patients.

Background and aims Hyperuricaemia can lead to gout and is associated with an increased risk of cardiometabolic disease. We aimed to investigate the prevalence of hyperuricaemia and its related factors in Chinese children and adolescents.Methods We pooled data from 11 population-based studies comprising 54,580 participants aged 3–19 years. The sex- and age-standardized prevalence of hyperuricaemia was estimated overall and by sex, age, weight status, geographic region and survey year.Results Serum uric acid (SUA) increased gradually from 3 to 11 years with no significant sex difference, and then increased dramatically during 11–15 years. The estimated overall prevalence of hyperuricaemia was 23.3% (26.6% in boys and 19.8% in girls, p 50,000 children and adolescents aged 3–19 years, we found that the prevalence of hyperuricaemia was high in overall population and subgroups of sex, age, obesity, region and survey year.Meaning: Our findings indicate that hyperuricaemia is an important health problem in Chinese children and adolescents, and effective intervention strategies are needed to reduce its burden.

The Chishui River Valley is a microscale ecology-preservation area with industrial clusters. The significance of evaluating vehicular emissions has been gradually highlighted with the rapid development of the local transportation and tourism sectors. This study provides the first estimates based on both bottom-up and top-down approaches. The annual total emissions of CO, NOx, hydrocarbons (HC), PM10, and PM2.5 in 2019 were 347.8, 189.6, 46.3, 6.9, and 6.3 Mg, respectively. Trucks contributed the most (55%) to the NOx emissions, followed by heavy-duty passenger vehicles (26%). In contrast, light-duty passenger vehicles and motorcycles generated 75% of the HC emissions. The superior accuracy of highly spatial and temporal bottom-up estimates versus top-down estimates is validated by the similar variation trends of hourly emission intensities and enhanced concentrations relative to background observations for both NOx and CO, with Pearson correlation coefficients between the intensities and concentrations ranging from 0.79 to 0.85. Historical HC emissions peaked in 2013, followed by a sharp decline in 2014 and a continuous rise since then, whereas NOx emissions have kept increasing since 2010. These indicated the necessity and urgency of effective vehicular emission mitigations. Based on scenario analysis, traffic restrictions combined with upgrading the emission standards of admitted vehicles will possess huge emission reduction potentials. Future recommendations about establishing a low emission zone in the valley and supporting policies were introduced.

Curcumenol, an effective ingredient of Wenyujin, has been reported that exerted its antitumor potential in a few cancer types. However, the effect and molecular mechanism of curcumenol in lung cancer are largely unknown. Here, we found that curcumenol induced cell death and suppressed cell proliferation in lung cancer cells. Next, we demonstrated that ferroptosis was the predominant method that contributed to curcumenol-induced cell death of lung cancer in vitro and vivo for the first time. Subsequently, using RNA sequencing, we found that the long non-coding RNA H19 (lncRNA H19) was significantly downregulated in lung cancer cells treated with curcumenol, when compared to untreated controls. Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol, while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. In conclusion, our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Therefore, our findings will hopefully provide a valuable drug for treating lung cancer patients.

BackgroundThe suppressor of cytokine signaling 3 (SOCS3) is the negative feedback regulator of the JAK-STAT signaling pathway. The purpose of our study was to investigate the SOCS3 status in colon primary tumor and lung metastasis and its relationship with macrophages.MethodsThe SOCS3 expression pattern and its relationship with the immune response in pan-cancer was investigated using multiple methods. Samples and corresponding clinical information of 32 colon cancer patients with lung metastasis were collected, and the CD68, CD163, and SOCS3 status were conducted using immunohistochemistry (IHC). The relationship between SOCS3 status and macrophage markers was analyzed. Besides, we explored the molecular mechanisms of SOCS3 in lung metastasis via the TCGA database.ResultsHigh SOCS3 expression was more inclined to poor prognosis and was positively correlated with main immune cell infiltration in almost each cancer type, especially in colon cancer. Compared with the colon primary tumor, lung metastasis harbored higher CD163 and SOCS3 expression, and high SOCS3 expression was more likely to be associated with high CD163 expression in lung metastasis. Besides, the exceptional differentially expressed genes in lung metastasis significantly enriched in immune responses and regulations.ConclusionsSOCS3 possessed value as a prognostic marker and target for immunotherapeutic intervention in different tumors and might be a potential target of tumor progression and tumor immunotherapy in colon cancer.

Abstract Background “Overlap syndrome” refers to obstructive sleep apnea (OSA) combined with chronic obstructive pulmonary disease (COPD), and has poorer outcomes than either condition alone. We aimed to evaluate the prevalence and possible predictors of overlap syndrome and its association with clinical outcomes in patients with COPD. Methods We assessed the modified Medical Research Council dyspnea scale (mMRC), Epworth sleepiness scale (ESS), COPD assessment test (CAT), Hospital Anxiety and Depression Scale (HADS), Charlson Comorbidity Index (CCI), and STOP-Bang questionnaire (SBQ) and performed spirometry and full overnight polysomnography in all patients. An apnea–hypopnea index (AHI) ≥ 5 events per hour was considered to indicate OSA. Risk factors for OSA in COPD patients were identified by univariate and multivariate logistic regression analyses. Results A total of 556 patients (66%) had an AHI ≥ 5 events per hour. There were no significant differences in age, sex ratio, mMRC score, smoking index, number of acute exacerbations and hospitalizations in the last year, and prevalence of cor pulmonale between the two groups (all p > 0.05). Body mass index (BMI), neck circumference, CAT score, CCI, ESS, HADS, and SBQ scores, forced expiratory volume (FEV)1, FEV1% pred, FEV1/forced vital capacity ratio, and prevalence of hypertension, coronary heart disease, and diabetes were all significantly higher and the prevalence of severe COPD was significantly lower in the COPD-OSA group compared with the COPD group (p

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types; however, the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown. In the study, we investigated the effect of baicalin on bladder cancer cells 5637 and KU-19-19. As a result, we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells. Subsequently, we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo, accompanied by reactive oxygen species (ROS) accumulation and intracellular chelate iron enrichment. The ferroptosis inhibitor deferoxamine but not necrostatin-1, chloroquine (CQ), N-acetyl-l-cysteine, l-glutathione reduced, or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK) rescued baicalin-induced cell death, indicating ferroptosis contributed to baicalin-induced cell death. Mechanistically, we show that ferritin heavy chain 1 (FTH1) was a key determinant for baicalin-induced ferroptosis. Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells. Taken together, our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis, which will hopefully provide a prospective compound for bladder cancer treatment.

Accumulating evidence suggests that chronic inflammation may play a critical role in various malignancies, including bladder cancer. This hypothesis stems in part from inflammatory cells observed in the urethral microenvironment. Chronic inflammation may drive neoplastic transformation and the progression of bladder cancer by activating a series of inflammatory molecules and signals. Recently, it has been shown that the microbiome also plays an important role in the development and progression of bladder cancer, which can be mediated through the stimulation of chronic inflammation. In effect, the urinary microbiome can play a role in establishing the inflammatory urethral microenvironment that may facilitate the development and progression of bladder cancer. In other words, chronic inflammation caused by the urinary microbiome may promote the initiation and progression of bladder cancer. Here, we provide a detailed and comprehensive account of the link between chronic inflammation, the microbiome and bladder cancer. Finally, we highlight that targeting the urinary microbiome might enable the development of strategies for bladder cancer prevention and personalized treatment.

Abstract Background There are many studies on neoadjuvant immunotherapy for locally advanced non‐small cell lung cancer (NSCLC) patients. Expert consensus recommends neoadjuvant immunotherapy for patients with resectable stage IB–IIIA NSCLC. However, there are few clinical studies or cases to verify this. Methods Data were collected from all NSCLC patients who underwent surgical resection after neoadjuvant chemoimmunotherapy admitted to the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital between September 2020 and April 2021. Data collected included patient information, relevant examination results, intraoperative parameters, postoperative complications, pathological changes, and 90‐day mortality. Results In total, 25 patients achieved R0 resection. Eleven (44%) patients completed surgery by thoracotomy, and three (12%) procedures were changed from minimally invasive procedures due to dense adhesions of hilar lymph nodes, which rendered it difficult to dissect the blood vessels. Thirteen (52%) patients achieved a major pathological response (MPR) with eight (32%) of these patients having a pathological complete response (pCR). Twenty‐two (88%) patients showed radiological regression, and three (12%) patients had stable disease. The median drainage time was 8.50 (3–27) days. Thirteen (52%) postoperative complications were observed, but none were above grade 3. Conclusions In this study, neoadjuvant chemoimmunotherapy was found to reduce tumor volume, cause pathological downstaging, and raise the surgical resection rate of patients with locally advanced NSCLC, and achieve a 100% R0 resection rate. There was an acceptable rate of postoperative complications. Thus, neoadjuvant chemoimmunotherapy is safe and practical.

Obesity is characterized by excessive lipid accumulation, hypertrophy, and hyperplasia of adipose cells. Hulless barley (Hordeum vulgare L. var. nudum Hook. f.) is the principal crop grown in the Qinghai-Tibet plateau. Polyphenols, the major bioactive compound in hulless barley, possess antioxidant, anti-inflammatory, and antibacterial properties. However, the anti-obesity effect of hulless barley polyphenol (HBP) extract has not been explored. Therefore, the current study assessed the impact of HBP extract on preventing obesity. For this purpose, we evaluated the inhibitory effect of HBP extract against obesity-related enzymes. Moreover, we investigated the effect of HBP extract on adipocyte differentiation and adipogenesis through 3T3-L1 adipocytes. Our results demonstrated that HBP extract could inhibit α-amylase, α-glucosidase (α-GLU), and lipase in a dose-dependent manner. In addition, HBP extract inhibited the differentiation of 3T3-L1 preadipocytes by arresting the cell cycle at the G0/G1 phase. Furthermore, the extract suppressed the expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), regulating fatty acid synthase (FAS), fatty acid-binding protein 4 (FABP4), and adipose triglyceride lipase (ATGL). It was also observed that HBP extract alleviated intracellular lipid accumulation by attenuating oxidative stress. These findings specify that HBP extract could inhibit obesity-related enzymes, adipocyte differentiation, and adipogenesis. Therefore, it is potentially beneficial in preventing obesity.

Abstract Background Advances in regenerative medicine technologies have been strongly proposed in the management of thyroid diseases. Mechanistically, the adoption of thyroid bioengineering requires a scaffold that shares a similar three-dimensional (3D) space structure, biomechanical properties, protein component, and cytokines to the native extracellular matrix (ECM). Methods 24 male New Zealand white rabbits were used in this experimental study. The rabbit thyroid glands were decellularized by immersion/agitation decellularization protocol. The 3D thyroid decellularization scaffolds were tested with histological and immunostaining analyses, scanning electron microscopy, DNA quantification, mechanical properties test, cytokine assay and cytotoxicity assays. Meanwhile, the decellularization scaffold were seeded with human thyroid follicular cells, cell proliferation and thyroid peroxidase were determined to explore the biocompatibility in vitro. Results Notably, through the imaging studies, it was distinctly evident that our protocol intervention minimized cellular materials and maintained the 3D spatial structure, biomechanical properties, ECM composition, and biologic cytokine. Consequently, the decellularization scaffold was seeded with human thyroid follicular cells, thus strongly revealing its potential in reinforcing cell adhesion, proliferation, and preserve important protein expression. Conclusions The adoption of our protocol to generate a decellularized thyroid scaffold can potentially be utilized in transplantation to manage thyroid diseases through thyroid bioengineering.

Background and objective: This study was performed to investigate the effect of expressive art therapy (EAT) on the health status of patients with chronic obstructive pulmonary disease (COPD). Methods: This community-based cluster randomized controlled trial involved patients with COPD from 16 communities in China. Participants received either EAT plus usual care (UC) or UC only. General practitioners were trained in EAT before the intervention. The primary outcomes were depression and anxiety symptoms, measured with the Hospital Anxiety and Depression Scale (HADS) and expressed as the HADS score for depression or anxiety (HADS-D or HADS-A, respectively). The secondary outcomes were the quality of life and dyspnoea, measured with the COPD assessment test (CAT). Dyspnoea was assessed using the modified Medical Research Council (mMRC) dyspnoea scale. Lung function was expressed as the forced expiratory volume in 1 s as a percentage of the predicted value [FEV 1 (% pred)]. Outcome data were collected from all participants at baseline, 2 and 6 months. Results: In total, 360 participants with COPD and comorbid depression were included in the analysis with the control group of 181 receiving UC only and the intervention group of 179 receiving EAT plus UC. The EAT group showed significantly greater improvement in the HADS-D and HADS-A scores than the UC group at 2 months ( p

Encouraging enterprises to adopt green and low-carbon technological innovation is an important measure to cope with climate change and achieve low-carbon economic development. As the main stakeholders of green and low-carbon technological innovation of enterprises, what measures should the government and the public take to encourage green and low-carbon technological innovation of enterprises has become one of the focuses of research. This study constructs a tripartite evolutionary game model among the government, the public, and enterprises and then obtains the evolutionary stability strategy by analyzing the replication dynamic equation of each subject. Numerical simulation is made on the evolution path of the game under different enforcement intensities of environmental regulation means. The result shows that pollution tax, low-carbon technology innovation subsidy, and environmental protection publicity and guidance are three environmental regulation means to effectively stimulate enterprises’ green and low-carbon technology innovation. And moderate pollution tax, low-intensity publicity of public environmental protection, and high innovation incentive compensation have the highest incentive efficiency for enterprises’ green and low-carbon technological innovation. Targeted suggestions for promoting green and low-carbon technological innovation of enterprises are put forward in the end.

It may be very difficult to receive the signals from satellite positioning systems due to the existing obstacles in indoor environment. Arising from the popularity of smart phones, Wi-Fi based indoor positioning technology has the advantages with convenient deployment and low hardware cost. In this study, we focused on indoor positioning using Wi-Fi fingerprint data that were collected in shopping malls. Due to the volatility of Wi-Fi signals and the high-dimensional sparseness of fingerprint data, we proposed a feature extraction algorithm, called joint multi-task stacked denoising auto-encoder (JMT-SDAE), aiming at reducing the dimensionality of the original fingerprint data and improving the indoor positioning performance in shopping malls. Furthermore, the features extracted by JMT-SDAE and gradient boosting decision tree (GBDT) were merged to construct a hybrid model, named as JMT-SDAE+GBDT. The experimental results based on 13 location datasets showed that the proposed feature fusion model had better positioning accuracy when compared with other existing positioners, and thus confirmed the effectiveness of our proposed feature extraction algorithm through multi-task learning.

Abstract Background Angiogenesis, as an endogenous repair mechanism, plays crucial roles in wound healing and tissue regeneration. However, this process is impaired in the elderly due to aging-related vascular endothelial dysfunction. This study was aimed to explore the pro-angiogenic effects of exosomes from human embryonic stem cells (ESC-Exos) in aged mice of pressure-induced ulcer model and the underlying mechanism. Methods Pressure ulcer wounds were created on the back of d-galactose-induced aging mice. ESC-Exos were locally applied onto the wound beds, with PBS as control. The effects of ESC-Exos on wound healing were analyzed by measuring wound closure rates, histological and immunofluorescence analyses. Then, the anti-aging effect of ESC-Exos on vascular endothelial cells was tested in an in vitro d-galactose-induced HUVEC senescence model. Results ESC-Exos could accelerate wound closure and enhance angiogenesis, and the senescence of vascular endothelial cells was significantly ameliorated after ESC-Exos treatment. In vitro, ESC-Exos could rejuvenate the senescence of endothelial cells and recover compromised proliferation, migratory capacity, and tube formation. This recovery was Nrf2-activation-dependent, since cotreatment with Nrf2 inhibitor Brusatol could abolish the rejuvenative effects of ESC-Exos. Further study revealed that miR-200a was highly enriched in ESC-Exos and played a crucial role in ESC-Exos-mediated rejuvenation through downregulating Keap1, which negatively regulates Nrf2 expression. Conclusions ESC-Exos ameliorate endothelial senescence by activating Nrf2 and recover aging-related angiogenic dysfunction, thereby accelerating wound healing in aged mice. ESC-Exos might be a natural nano-biomaterial for aging-related diseases therapy.

Bamboo is a widely distributed graminaceous plant in China and is a potential source of bioactive substances. Incidentally, bamboo’s fruit is rich in phytochemicals such as polyphenols and flavonoids, which are significant to human health. In this study, we identified the phenolic compounds of the fruit and investigated the antioxidant activities of Cephalostachyum fuchsianum Gamble (CFG) fruit polyphenols with in vitro and in vivo tests for the first time. UPLC–Q–TOF–MS/MS analysis results showed that the fruit contained 43 phenolic compounds, including 7 hydroxybenzoic acids, 12 flavonoids, 7 coumarins, 10 hydroxycinnamic acids, 1 terpenoid, and 5 lignans. The TPC of SP extracts was higher than that of IBPs extracts in FP and FF. The SP extracts in FP showed better antioxidant activities in vitro compared to those in FF. In addition, polyphenols from CFG fruits protected against H2O2-induced oxidative damage in HepG2 cells, and the protective effect of polyphenols in FP was superior to that in FF. The analysis results showed that CFG fruit has great potential in exploiting natural chemical substances, which can provide valuable pieces of information for the further development and utilization of CFG.

Baicalin, as a natural active ingredient extracted and isolated from the traditional Chinese medicine Scutellaria baicalensis Georgi., has been potentially used in various areas for its antioxidative, antitumor, anti-inflammatory, and anti-proliferative activities. Although several studies have reported the antitumor effects of baicalin against various cancer types, its beneficial effects on lung cancer have not yet been elucidated. Therefore, the therapeutic effects and molecular mechanisms of baicalin on lung cancer cell lines H1299 and H1650 were investigated. Here, the results of its antitumor activity were shown. We found that Akt/mTOR pathway inhibition was the essential determinant in baicalin-induced cell cycle arrest. Furthermore, when the Akt Agonist SC79 or Akt plasmid transfection was performed, the antitumor effect of baicalin was significantly abrogated in both H1299 and H1650 cells. In conclusion, we found that baicalin exerted its antitumor activity mainly by inducing Akt-dependent cell cycle arrest and promoting apoptosis, which show great potential for developing a new drug for lung cancer treatment.

Estrogen and progesterone regulate the growth and development of human tissues, including the reproductive system and breasts, through estrogen and progesterone receptors, respectively. These receptors are also important indicators for the clinical prognosis of breast cancer and various reproductive cancers. Many studies have reported that cancer stem cells (CSCs) play a key role in tumor initiation, progression, metastasis, and recurrence. Although the role of estrogen and progesterone in human organs and various cancers has been studied, the molecular mechanisms underlying the action of these hormones on CSCs remain unclear. Therefore, further elucidation of the effects of estrogen and progesterone on CSCs should provide a new direction for developing pertinent therapies. In this review, we summarize the current knowledge on the estrogen and progesterone axis involved in cancer stemness and discuss potential therapeutic strategies to inhibit CSCs by targeting relevant pathways.

ObjectiveColorectal cancer is a malignant tumor of the digestive system with high morbidity and mortality. 5-fluorouracil remains a widely used chemotherapeutic drug in the treatment of advanced colorectal cancer, but chemotherapy drugs are prone to develop drug resistance, p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to 5-fluorouracil. β-elemene has been proved to have the potential of reverse chemotherapy drug resistance, but the mechanism is unknown. This study aimed to investigate the effect of β-elemene to 5-fluorouracil in drug-resistant p53-deficient colorectal cancer cells HCT116p53–/–, and determine the possible molecular mechanism of β-elemene to reverse 5-fluorouracil resistance.MethodsThe effect of β-elemene on HCT116p53–/– cell activity was detected by Cell counting Kit-8. Cell proliferation was detected by monoclonal plate. The apoptosis was detected by flow cytometry and western blot. The autophagy was detected by western blot, immunofluorescence and transmission electron microscope. Determine the role of Cyclin-related protein Cyclin D3 in β-elemene reversing the resistance of HCT116p53–/– to 5-fluorouracil was detected by overexpression of Cyclin D3. The effect of β-elemene on the tumorigenic ability of p53-deficient colorectal cancer cells was detected establishing HCT116p53–/– all line xenograft model.ResultsFor p53 wildtype colorectal cancer cells, β-elemene could augment the sensitivity of 5-fluorouracil, for p53-deficient colorectal cancer cells, β-elemene significantly inhibited cell proliferation in a concentration-dependent manner, and reversed the resistance of HCT116p53–/– to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest.Conclusionβ-elemene enhances the sensitivity of p53 wild-type cells to 5-fluorouracil, β-elemene can reverse the resistance of HCT116p53–/– to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest in p53-deficient colorectal cancer, which will provide a new method for the treatment of p53 deletion colorectal cancer patients.

Abstract Farnesoid X receptor (FXR), a nuclear receptor for maintaining bile acid homeostasis, has been recognized as a tumor suppressor in enterohepatic tissues. However, its expression and functional role in non-small cell lung cancer (NSCLC) remain unclear. We report that FXR is significantly increased in NSCLC and that it predicts poor clinical outcomes in NSCLC patients. FXR knockdown in NSCLC cells inhibited in vitro cell proliferation, blocked xenograft growth in nude mice, and delayed the G1/S transition of the cell cycle, whereas ectopic overexpression of FXR promoted NSCLC cell proliferation. Mechanistic analysis demonstrated that FXR could directly bind to an inverted repeat-0 sequence in the CCND1 promoter and activate its transcription. Cyclin D1 overexpression rescued NSCLC cells from the delayed G1/S transition and the impaired cell proliferation induced by FXR knockdown. Importantly, a positive correlation between the expression of FXR and cyclin D1 was confirmed in NSCLC samples, and patients with high expression of both FXR and cyclin D1 had the worst prognosis. In summary, our results suggest that FXR has oncogenic potential in NSCLC development, providing mechanistic insights that could be exploited for both prognostic and therapeutic purposes.

Tissue-resident stem cell senescence leads to stem cell exhaustion, which is a major cause of physiological and pathological ageing. Stem cell-derived extracellular vesicles (SC-EVs) have been reported in preclinical studies to possess therapeutic potential for diverse diseases. However, whether SC-EVs can rejuvenate senescent tissue stem cells to prevent age-related disorders still remains unknown. Here, we show that chronic application of human embryonic stem cell-derived small extracellular vesicles (hESC-sEVs) rescues the function of senescent bone marrow mesenchymal stem cells (BM-MSCs) and prevents age-related bone loss in ageing mice. Transcriptome analysis revealed that hESC-sEVs treatment upregulated the expression of genes involved in antiaging, stem cell proliferation and osteogenic differentiation in BM-MSCs. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified 4122 proteins encapsulated in hESC-sEVs. Bioinformatics analysis predicted that the protein components in the hESCs-sEVs function in a synergistic way to induce the activation of several canonical signalling pathways, including Wnt, Sirtuin, AMPK, PTEN signalling, which results in the upregulation of antiaging genes in BM-MSCs and then the recovery of senescent BM-MSCs function. Collectively, our findings reveal the effect of hESC-sEVs in reversing BM-MSCs senescence and age-related osteogenic dysfunction, thereby preventing age-related bone loss. Because hESC-sEVs could alleviate senescence of tissue-resident stem cells, they might be promising therapeutic candidates for age-related diseases.

Liver aging is associated with age-related histopathological and functional changes that significantly enhance the risk of numerous diseases or disorders developing in elderly populations. 6-Bromoindirubin-3′-oxime (6BIO), a potent inhibitor of glycogen synthase kinase-3 (GSK-3), has been implicated in various age-related diseases and processes, such as tumorigenesis, neurodegeneration, and diabetes. Recent studies have also revealed that 6BIO increases autophagy in yeast, mammalian cell lines, and dopaminergic neurons, which is one of the classical mechanisms strongly associated with liver aging. However, the impact or the mechanism of action of 6BIO in liver remains entirely unknown. Here, we find that 6BIO reduces oxidative stress, improves lipid metabolism, enhances autophagy, and significantly retards liver aging via modulating the GSK-3β pathway and mTOR pathway. Our findings suggest that 6BIO could be a potential agent to protect the liver in the field of anti-aging pharmacology.

Software stability means the resistance to the amplification of changes in software. It has become one of the most important attributes that affect maintenance cost. To control the maintenance cost, many approaches have been proposed to measure software stability. However, it is still a very difficult task to evaluate the software stability especially when software becomes very large and complex. In this paper, we propose to characterize software stability via change propagation simulation. First, we propose a class coupling network (CCN) to model software structure at the class level. Then, we analyze the change propagation process in the CCN by using a simulation way, and by doing so, we develop a novel metric, SS (software stability), to measure software stability. Our SS metric is validated theoretically using the widely accepted Weyuker’s properties and empirically using a set of open source Java software systems. The theoretical results show that our SS metric satisfies most of Weyuker’s properties with only two exceptions, and the empirical results show that our metric is an effective indicator for software quality improvement and class importance. Empirical results also show that our approach has the ability to be applied to large software systems.