The Spermine Oxidase/Spermine Axis Coordinates ATG5-Mediated Autophagy to Orchestrate Renal Senescence and Fibrosis.

Decreased plasma spermine levels are associated with kidney dysfunction. However, the role of spermine in kidney disease remains largely unknown. Herein, it is demonstrated that spermine oxidase (SMOX), a key enzyme governing polyamine metabolism, is predominantly induced in tubular epithelium of human and mouse fibrotic kidneys, alongside a reduction in renal spermine content in mice. Moreover, renal SMOX expression is positively correlated with kidney fibrosis and function decline in patients with chronic kidney disease. Importantly, supplementation with exogenous spermine or genetically deficient SMOX markedly improves autophagy, reduces senescence, and attenuates fibrosis in mouse kidneys. Further, downregulation of ATG5, a critical component of autophagy, in tubular epithelial cells enhances SMOX expression and reduces spermine in TGF-ß1-induced fibrogenesis in vitro and kidney fibrosis in vivo. Mechanically, ATG5 readily interacts with SMOX under physiological conditions and in TGF-ß1-induced fibrogenic responses to preserve cellular spermine levels. Collectively, the findings suggest SMOX/spermine axis is a potential novel therapy to antagonize renal fibrosis, possibly by coordinating autophagy and suppressing senescence.

Excited-state dynamics of 4-hydroxyisoindoline-1,3-dione and its derivative as fluorescent probes.

Fluorescent probes have become promising tools for monitoring the concentration of peroxynitrite, which is linked to many diseases. However, despite focusing on developing numerous peroxynitrite based fluorescent probes, limited emphasis is placed on their sensing mechanism. Here, we investigated the sensing mechanism of a peroxynitrite fluorescent probe, named BHID-Bpin, with a focus on the relevant excited state dynamics. The photoexcited BHID-Bpin relaxes to its ground state via an efficient nonradiative process (∼300 ps) due to the presence of a minimum energy conical intersection between its first excited state and ground state. However, upon reacting with peroxynitrite, the Bpin moiety is cleaved from BHID-Bpin and BHID is formed. The formed BHID exhibits strong dual band fluorescence which is caused by an ultrafast excited-state intramolecular proton transfer process (∼1 ps).

Screening and early warning system for chronic obstructive pulmonary disease with obstructive sleep apnoea based on the medical Internet of Things in three levels of healthcare: protocol for a prospective, multicentre, observational cohort study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory diseases in China and impose significant burdens on the healthcare system. Moreover, the co-occurrence of COPD and OSA exacerbates clinical outcomes significantly. However, comprehensive epidemiological investigations in China remain scarce, and the defining characteristics of the population affected by COPD and OSA, alongside their intrinsic relationship, remain ambiguous. METHODS AND ANALYSIS: We present a protocol for a prospective, multicentre, observational cohort study based on a digital health management platform across three different healthcare tiers in five sites among Chinese patients with COPD. The study aims to establish predicative models to identify OSA among patients with COPD and to predict the prognosis of overlap syndrome (OS) and acute exacerbations of COPD through the Internet of Things (IoT). Moreover, it aims to evaluate the feasibility, effectiveness and cost-effectiveness of IoT in managing chronic diseases within clinical settings. Participants will undergo baseline assessment, physical examination and nocturnal oxygen saturation measuring. Specific questionnaires screening for OSA will also be administered. Diagnostic lung function tests and polysomnography will be performed to confirm COPD and OSA, respectively. All patients will undergo scheduled follow-ups for 12 months to record the changes in symptoms, lung functions and quality of life. Primary outcomes include the prevalence and characteristics of OS, while secondary outcomes encompass OS prognosis and the feasibility of the management model in clinical contexts. A total of 682 patients with COPD will be recruited over 12-24 months. ETHICS AND DISSEMINATION: The study has been approved by Peking University Third Hospital, and all study participants will provide written informed consent. Study results will be published in an appropriate journal and presented at national and international conferences, as well as relevant social media and various stakeholder engagement activities. TRIAL REGISTRATION NUMBER: NCT04833725.

Ecological transformation is the key to improve ecosystem health for resource-exhausted cities: A case study in China based on future development scenarios.

Numerous cities are currently grappling with the challenge of ecological transformation, especially those categorized as resource-exhausted cities. In these urban areas, land use change is a highly scrutinized issue, as different land use strategies can lead to varied outcomes, impacting the ecological environment in multiple dimensions. Assessing ecosystem health reflects the quality of the regional ecological environment and serves as a comprehensive indicator for evaluating the sustainability and stability of urban ecosystems. To this end, a multi-objective optimization model was constructed to predict land use changes under four future development scenarios (four ecological transformation modes), using Shizuishan City (China), a resource-exhausted city situated in an ecologically fragile area, as an example. The "vigor-organization-resilience" assessment framework was employed to evaluate the ecosystem health conditions in each scenario from three dimensions. The study results showed: (1) The ranking of the average ecological health levels in Shizuishan City for 2022 and different future development scenarios is as follows: Low-Carbon Economic Development Scenario (0.302) > Ecological-Economic Coordinated Development Scenario (0.291) > Baseline Scenario (0.290) > Economic Development Scenario (0.281) > 2022 (0.248). (2) Compared to 2022, the ecosystem health levels under the four ecological transformation modes had all improved, with improvement areas accounting for over 60 %, highlighting the urgent necessity of ecological transformation in Shizuishan City. Among them, the Low-Carbon Economic Development Scenario exhibited the largest improvement area, reaching 75.81 %. (3) Ecological system vitality was identified as the dominant dimension influencing the ecological health in this region. This study emphasized multi-objective development needs and provided an integrated ecosystem health assessment method for assessing the comprehensive ecological effects of future ecological transformation modes in resource-exhausted cities.

Gasotransmitter Research Advances in Respiratory Diseases.

Significance: Gasotransmitters are small gas molecules that are endogenously generated and have well-defined physiological functions. The most well-defined gasotransmitters currently are nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), while other potent gasotransmitters include ammonia, methane, cyanide, hydrogen gas, and sulfur dioxide. Gasotransmitters play a role in various respiratory diseases such as asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, lung infection, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, and COVID-19. Recent Advances: Gasotransmitters can act as biomarkers that facilitate disease diagnosis, indicate disease severity, predict disease exacerbation, and evaluate disease outcomes. They also have cell-protective properties, and many studies have been conducted to explore their pharmacological applications. Innovative drug donors and drug delivery methods have been invented to amplify their therapeutic effects. Critical Issues: In this article, we briefly reviewed the physiological and pathophysiological functions of some gasotransmitters in the respiratory system, the progress in detecting exhaled gasotransmitters, as well as innovative drugs derived from these molecules. Future Directions: The current challenge for gasotransmitter research includes further exploring their physiological and pathological functions, clarifying their complicated interactions, exploring suitable drug donors and delivery devices, and characterizing new members of gasotransmitters. Antioxid. Redox Signal. 40, 168-185.

Sensing Mechanism and Excited-State Dynamics of a Widely Used Intracellular Fluorescent pH Probe: pHrodo.

The pHrodo with an "off-on" response to the changes of pH has been widely used as a fluorescent pH probe for bioimaging. The fluorescence off-on mechanism is fundamentally important for its application and further development. Herein, the sensing mechanism, especially the relevant excited-state dynamics, of pHrodo is investigated by steady-state and time-resolved spectroscopy as well as quantum chemical calculations, showing that pHrodo is best understood using the bichromophore model. Its first excited state (S1) is a charge transfer state between two chromophores. From S1, pHrodo relaxes to its ground state (S0) via an ultrafast nonradiative process (∼0.5 ps), which causes its fluorescence to be "off". After protonation, S1 becomes a localized excited state, which accounts for the fluorescence being turned "on". Our work provides photophysical insight into the sensing mechanism of pHrodo and indicates the bichromophore model might be relevant to a wide range of fluorescent probes.

Systemic Immune-Inflammation Index Was Significantly Associated with All-Cause and Cardiovascular-Specific Mortalities in Patients Receiving Peritoneal Dialysis.

Purpose: The prognosis of patients receiving peritoneal dialysis (PD) is associated with inflammation. Systemic immune-inflammation index (SII) is one of inflammatory markers, and the role in predicting clinical outcomes in PD patients is unclear. We aimed to investigate the relationship between the SII and all-cause and cardiovascular-specific mortalities in patients undergoing PD. Patients and Methods: A total of 1419 PD patients from the First Affiliated Hospital of Sun Yat-sen University between January 1, 2007 and December 31, 2019 were retrospectively included at baseline, and the patients were followed up until November 31, 2021. SII was calculated as platelet count×neutrophil count/lymphocyte count. Kaplan-Meier curves and Cox proportional hazards regression models were used to determine the relationship between SII levels and all-cause and cardiovascular-specific mortalities. Results: During follow-up (median period was 42 months), 321 patients died (171 died of cardiovascular disease). With adjustment for the potential confounding factors, each 1-SD increase in the SII was associated with 20.2% increase in all-cause mortality (hazard ratio [HR]: 1.202, 95% confidence interval [CI]: 1.088-1.327, P<0.001) and 28.0% increase in cardiovascular-specific mortality (HR: 1.280, 95% CI: 1.126-1.456, P<0.001). High SII (vs low SII) was significantly associated with increased risks of all-cause mortality (HR: 1.391, 95% CI: 1.066-1.815, P-value: 0.015) and cardiovascular-specific mortality (HR: 1.637, 95% CI: 1.185-2.261, P-value: 0.003). Subgroups analyses showed similar results for those younger than 65-year-old only. Conclusion: Elevated SII level was independently associated with increased risks of all-cause and cardiovascular-specific mortalities in PD patients, especially for those younger than 65-year-old.

Therapeutic mechanism of baicalein in peritoneal dialysis-associated peritoneal fibrosis based on network pharmacology and experimental validation.

Baicalein (5,6,7-trihydroxyflavone) is a traditional Chinese medicine with multiple pharmacological and biological activities including anti-inflammatory and anti-fibrotic effects. However, whether baicalein has a therapeutic impact on peritoneal fibrosis has not been reported yet. In the present study, network pharmacology and molecular docking approaches were performed to evaluate the role and the potential mechanisms of baicalein in attenuating peritoneal dialysis-associated peritoneal fibrosis. The results were validated in both animal models and the cultured human mesothelial cell line. Nine intersection genes among baicalein targets and the human peritoneum RNA-seq dataset including four encapsulating peritoneal sclerosis samples and four controls were predicted by network analysis. Among them, MMP2, BAX, ADORA3, HIF1A, PIM1, CA12, and ALOX5 exhibited higher expression in the peritoneum with encapsulating peritoneal sclerosis compared with those in the control, which might be crucial targets of baicalein against peritoneal fibrosis. Furthermore, KEGG and GO enrichment analyses suggested that baicalein played an anti-peritoneal fibrosis role through the regulating cell proliferation, inflammatory response, and AGE-RAGE signaling pathway. Moreover, molecular docking analysis revealed a strong potential binding between baicalein and MMP2, which was consistent with the predictive results. Importantly, using a mouse model of peritoneal fibrosis by intraperitoneally injecting 4.25% glucose dialysate, we found that baicalein treatment significantly attenuated peritoneal fibrosis, as evident by decreased collagen deposition, protein expression of α-SMA and fibronectin, and peritoneal thickness, at least, by reducing the expression of MMP2, suggesting that baicalein may have therapeutic potential in suppressing peritoneal dialysis-related fibrosis.

Association of multiple air pollutants with oxygen saturation during sleep in COPD patients: Effect modification by smoking status and airway inflammatory phenotypes.

Air pollution contributes substantially to the development of chronic obstructive pulmonary disease (COPD). To date, the effect of air pollution on oxygen saturation (SpO2) during sleep and potential susceptibility factors remain unknown. In this longitudinal panel study, real-time SpO2 was monitored in 132 COPD patients, with 270 nights (1615 h) of sleep SpO2 recorded. Exhaled nitric oxide (NO), hydrogen sulfide (H2S) and carbon monoxide (CO) were measured to assess airway inflammatory characteristics. Exposure levels of air pollutants were estimated by infiltration factor method. Generalized estimating equation was used to investigate the effect of air pollutants on sleep SpO2. Ozone, even at low levels (<60 µg/m3), was significantly associated with decreased SpO2 and extended time of oxygen desaturation (SpO2 < 90%), especially in the warm season. The associations of other pollutants with SpO2 were weak, but significant adverse effects of PM10 and SO2 were observed in the cold season. Notably, stronger effects of ozone were observed in current smokers. Consistently, smoking-related airway inflammation, characterized by higher levels of exhaled CO and H2S but lower NO, significantly augmented the effect of ozone on SpO2 during sleep. This study highlights the importance of ozone control in protecting sleep health in COPD patients.

Sulfone-Embedded Heterocyclic Narrowband Emitters with Strengthened Molecular Rigidity and Suppressed High-Frequency Vibronic Coupling.

Sulfone-embedded heterocyclics are of great interest in organic light-emitting diodes (OLEDs), however, exploring highly efficient narrowband emitters based on sulfone-embedded heterocyclics remains challenging. Herein, five emitters with different sulfur valence state and molecular rigidity, namely tP, tCPD, 2tCPD, tPD and tPT, are thoroughly analysed. With restricted twisting of flexible peripheral phenyl by strengthening molecular rigidity, molecular emission spectra can be enormously narrowed. Further, introducing the sulfone group with bending vibration in low-frequency region that suppresses high-frequency vibration, sharp narrow full-widths at half-maximum of 28 and 25 nm are achieved for 2tCPD and tPD, respectively. Maximum external quantum efficiencies of 22.0 % and 27.1 % are successfully realized for 2tCPD- and tPD-based OLED devices. These results offer a novel design strategy for constructing narrowband emitters by introducing sulfone group into a rigid molecular framework.

Serum SALL4 as a predictive biomarker for the prognosis of patients with hepatocellular carcinoma who underwent nonsurgical treatment.

To investigate the role of serum spalt like transcription factor 4 (SALL4) in the hepatocellular carcinoma (HCC) patients with nonsurgical treatment. Serum samples were collected from 101 patients with HCC without surgical treatment, then the SALL4 was detected by enzyme linked immunosorbent assay. According to subsequent treatment, patients were divided into 2 groups, best supportive care (BSC) (58 cases) and nonsurgical anticancer treatment (NSAT) (48 cases). Kaplan-Meier survival analysis and Cox multivariate regression analysis were applied to evaluate the relationship between SALL4 and survival time of 2 groups. In BSC group, there was no significant difference of the survival time between 2 groups (SALL4 < 800 ng/mL or SALL4 ≥ 800 ng/mL) (P = .339). In NSAT group, the survival time of patients with low SALL4 concentration was significantly longer than patients with high SALL4 concentration (P = .005). SALL4 have no predictive effect in BSC patients with HCC. But for patients received NSAT, low SALL4 concentration in serum may indicate longer survival.

The role of sulfur compounds in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that brings about great social and economic burden, with oxidative stress and inflammation affecting the whole disease progress. Sulfur compounds such as hydrogen sulfide (H2S), thiols, and persulfides/polysulfides have intrinsic antioxidant and anti-inflammatory ability, which is engaged in the pathophysiological process of COPD. Hydrogen sulfide mainly exhibits its function by S-sulfidation of the cysteine residue of the targeted proteins. It also interacts with nitric oxide and acts as a potential biomarker for the COPD phenotype. Thiols' redox buffer such as the glutathione redox couple is a major non-enzymatic redox buffer reflecting the oxidative stress in the organism. The disturbance of redox buffers was often detected in patients with COPD, and redressing the balance could delay COPD exacerbation. Sulfane sulfur refers to a divalent sulfur atom bonded with another sulfur atom. Among them, persulfides and polysulfides have an evolutionarily conserved modification with antiaging effects. Sulfur compounds and their relative signaling pathways are also associated with the development of comorbidities in COPD. Synthetic compounds which can release H2S and persulfides in the organism have gradually been developed. Naturally extracted sulfur compounds with pharmacological effects also aroused great interest. This study discussed the biological functions and mechanisms of sulfur compounds in regulating COPD and its comorbidities.

Novel Polycyclic Fused Amide Derivatives: Properties and Applications for Sky-blue Electroluminescent Devices.

Aromatic imide derivatives play a critical role in boosting the electroluminescent (EL) performance of organic light-emitting diodes (OLEDs). However, the majority of aromatic imide-based materials are limited to long wavelength emission OLEDs rather than blue emissions due to their strong electron-withdrawing characteristics. Herein, two novel polycyclic fused amide units were reported as electron acceptor to be combined with either a tetramethylcarbazole or acridine donor via a phenyl linker to generate four conventional fluorescence blue emitters of BBI-4MeCz, BBI-DMAC, BSQ-4MeCz and BSQ-DMAC for the first time. BSQ-4MeCz and BSQ-DMAC based on a BSQ unit exhibited higher thermal stability and photoluminescence quantum yields than BBI-4MeCz and BBI-DMAC based on a BBI unit due to their more planar acceptor structure. The intermolecular interactions that exist in the BSQ series materials effectively inhibit the molecular rotation and configuration relaxation, and thus allow for blue-shifted emissions. Blue OLED devices were constructed with the developed materials as emitters, and the effects of both the structure of the polycyclic fused amide acceptor and the electron donor on the EL performance were clarified. Consequently, a sky-blue OLED device based on BSQ-DMAC was created, with a high maximum external quantum efficiency of 4.94% and a maximum luminance of 7761 cd m-2.

Hydrogen sulfide alleviates particulate matter-induced emphysema and airway inflammation by suppressing ferroptosis.

BACKGROUND: Redox imbalance is an vital mechanism for COPD. At present, insufficient researches have been conducted on the protective effect of hydrogen sulfide (H2S) on PM-induced COPD. However, whether H2S exerts the anti-injury role by blocking ferroptosis and restoring redox equilibrium remain to be investigated. METHODS: Human lung tissue samples were collected for IHC staining, and the expressions of Nrf2, ferritinophagy- and ferroptosis-related proteins were observed. The WT C57BL/6 and Nrf2 knockout mice models were established with PM(200 µg per mouse). NaHS(Exogenous H2S) was injected intraperitoneally 30 min in advance. Twenty-nine days later, mice lung tissues were evaluated by HE's and PERLS-DAB's staining. Meanwhile, inflammation and oxidative stress indicators and iron levels were assessed by corresponding ELISA kit. Related protein expressions were detected through Western blot. BEAS-2B cells with or without H2S were exposed to PM2.5 for 36 h. Cell viability, mitochondrial morphology, inflammatory cytokines, antioxidant factors, iron levels, autophagic flux and the levels of ROS, LIP ROS, MitoROS, MMP, as well as related protein expressions were detected by specific methods, respectively. In addition, V5-Nrf2, Nrf2 siRNA, Nrf2 inhibitor ML385, PPAR-γ inhibitor GW9662, autophagy inhibitor CQ, iron chelator DFO and ferroptosis inhibitor Fer-1 were used to verify the target signaling pathways. RESULTS: We found that the expressions of LIP ROS, ROS, COX2, MDA and other oxidative factors increased, while the antioxidant markers GPX4, GSH and GSH-Px significantly decreased, as well as active iron accumulation in COPD patients, PM-exposured WT and Nrf2-KO mice models and PM2.5-mediated cell models. NaHS pretreatment markedly inhibited PM-induced emphysema and airway inflammation by alleviating ferroptotic changes in vivo and vitro. With the use of V5-Nrf2 overexpression plasmid, Nrf2 siRNA and pathway inhibitors, we found NaHS activates the expressions of Nrf2 and PPAR-γ, and inhibites ferritinophagy makers LC3B, NCOA4 and FTH1 in BEAS-2B cells. Moreover, the anti-ferroptotic effect of NaHS was further verified to be related to the activation of Nrf2 signal in MEF cells. CONCLUSION: This research suggested that H2S alleviated PM-induced emphysema and airway inflammation via restoring redox balance and inhibiting ferroptosis through regulating Nrf2-PPAR-ferritinophagy signaling pathway.

Simultaneous identification of contaminant sources and hydraulic conductivity field by combining geostatistics method with self-organizing maps algorithm.

In the contaminant remediation of groundwater, the release history of contaminant sources and hydraulic conductivity field are two key parameters that need to know, but their actual values are difficult to obtain and can only be inversely identified by limited measured data. However, the process of solving the inverse problem needs to repeatedly call the forward model of contaminant transport, which is very time-consuming, especially for the high-dimensional inverse problems. In this study, based on the training data generated from a prior range of parameters (the release strength of contaminant sources and hydraulic conductivity at pilot points), the self-organizing maps (SOM) algorithm was employed to construct the surrogate model for the numerical model of contaminant transport in a simplified hypothetical aquifer, then the surrogate model was used to retrieve jointly the contaminant strength of sources and the hydraulic conductivity at pilot points, and the Kriging method of geostatistics was further used to process the estimated K-values at pilot points to obtain the hydraulic conductivity field. Also, to investigate the ability of the SOM-based surrogate model for retrieving both contaminant source strengths and hydraulic conductivity, we gradually expanded the prior range and increased the number of inversion terms in each prior range. Moreover, the robustness of the SOM-based surrogate model for inversion was illustrated by proposing the scarcity of data and different degrees of measurement error in the limited actual observation data. When the actual observation data is reduced by 2/3, the Root Mean Square Error (RMSE) of retrieving source strengths and hydraulic conductivity at pilot points are 1.07 and 0.09, respectively. The results indicated the SOM-based surrogate model shows remarkable inversion precision and robustness, and an accurate estimation of the actual hydraulic conductivity field could be obtained by the Kriging method based on that.

A pilot study of the ultrathin cryoprobe in the diagnosis of peripheral pulmonary ground-glass opacity lesions.

BACKGROUND: It is very difficult to obtain samples of peripheral pulmonary ground-glass opacity lesions (GGOs) by traditional transbronchial biopsy. This study was conducted to evaluate the diagnostic efficacy and safety of transbronchial cryobiopsy (TBCB) of GGOs using a newly developed ultrathin cryoprobe with an outer diameter of 1.1 mm. METHODS: We retrospectively analyzed 20 patients with 23 GGOs who underwent TBCB using the ultrathin cryoprobe from October 2018 to November 2019 in the Shanghai Chest Hospital. The TBCB procedure was performed under the guidance of virtual bronchoscopic navigation (VBN), electromagnetic navigation bronchoscopy (ENB), endobronchial ultrasound, and fluoroscopy. We collected the baseline information of participants, reported diagnostic yield and complications, and analyzed factors may have affected the diagnostic yield. RESULTS: A total of 23 GGOs (12 pure GGOs, 11 mixed GGOs), with an average diameter of 21.58±11.88 mm, underwent TBCB, and the diagnostic yield was 82.61% (19/23). Of the 19 GGOs diagnosed by TBCB, 12 were adenocarcinomas, 5 were inflammation, 1 was occupational interstitial lung disease, and 1 was a pulmonary meningothelial-like nodule. The remaining 4 undiagnosed lesions were confirmed to be adenocarcinomas by further analysis. The diagnostic yield was unchanged by factors including size (GGOs ≥20 mm, GGOs <20 mm), navigation (VBN, ENB), fluoroscopic visibility (visible, invisible), GGO-component (pure GGOs, mixed GGOs), and guide sheath (K-201, K203). There was no presentation of pneumothorax or severe hemorrhage. CONCLUSIONS: The ultrathin cryoprobe is feasible, safe, and has a high diagnostic yield in the diagnosis of pulmonary GGOs. There is vast potential for the ultrathin cryoprobe as a tool for the diagnosis of GGOs, especially for cases suspicious of early-stage lung cancer. TRIAL REGISTRATION: ClinicalTrials.gov. No: NCT03716284. Registered: 20 October, 2018. URL: ClinicalTrials.gov.

The value of navigation bronchoscopy in the diagnosis of peripheral pulmonary lesions: A meta-analysis.

BACKGROUND: To compare the diagnostic yield of peripheral pulmonary lesions (PPLs) with and without navigation system. METHODS: Studies dating from January 1990 to October 2019 were collected from databases. Diagnostic yield of navigation bronchoscopy and non-navigation bronchoscopy was extracted from comparative studies. Subgroup analysis was adopted to test diagnostic yield variation by lesion size, lobe location of the lesion, distance from the hilum, bronchus sign and nature of the lesion. RESULTS: In total, 2131 patients from 10 studies were enrolled into the study. Diagnostic yield of navigation bronchoscopy was statistically higher than non-navigation bronchoscopy for PPLs (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.32, 2.18, P < 0.001), particularly for PPLs in the peripheral third lung (OR 2.26, 95% CI 1.48, 3.44, P < 0.001) and for bronchus sign positive PPLs (OR 2.26, 95% CI 1.21, 4.26, P = 0.011). Navigation bronchoscopy had better performance than non-navigation bronchoscopy when PPLs were ≤ 20 mm (OR 2.09, 95% CI 1.44, 3.03, P < 0.001). It also elevated diagnostic yield of malignant PPLs (OR 1.67, 95% CI 1.26, 2.22, P < 0.001) and PPLs in the bilateral upper lobes (OR 1.50, 95% CI 1.09, 2.08, P = 0.014). CONCLUSIONS: Navigation bronchoscopy enhanced diagnostic yield when compared to non-navigation bronchoscopy, particularly for PPLs in the peripheral third lung, PPLs being bronchus sign positive, PPLs ≤ 20 mm, malignant PPLs and PPLs in the bilateral upper lobes. KEY POINTS: The current study provided systematic evaluation on the diagnostic value of navigation bronchoscopy by comparing it with non-navigation bronchoscopy, and exploring the factors affecting the diagnostic yield.

Degradation of 4-chlorophenol by BM Fe/Cu-O2 system: The symbiosis of · O 2 - and ·OH radicals.

In this study, Fe/Cu bimetal composite was prepared by high-energy ball milling (BM) method for the removal of refractory organics. The BM Fe/Cu bimetal was characterized by SEM-EDS, XRD, and XPS. Evenly distributed Fe and Cu was observed in the EDS mapping. In contrasting experiments, the removal rate of 4-chlorophenol (4-CP) by BM Fe/Cu materials was about 10-fold faster than that by chemical substitution deposition (CSD) of Fe/Cu material. Complete 4-CP removal and 66.7% of total organic carbon (TOC) mineralization in the BM Fe/Cu-O2 system were achieved. Dissolved oxygen plays a crucial role for 4-CP degradation through the in situ generation of reactive oxygen species (ROS) such as H2 O2 , ·OH, and · O 2 - via oxygen activation reactions. The predominant reactive radicals were identified to be · O 2 - and ·OH through ESR technique and inhibition experiments. The coexistence of oxidation and reduction of 4-CP in the BM Fe/Cu-O2 system was proposed. PRACTITIONER POINTS: 4-CP removal rate by BM Fe/Cu is 10-fold faster than that by CSD Fe/Cu at the same conditions. Complete 4-CP removal and 66.7% of TOC reduction were achieved. All three ROS including ·OH, · O 2 - , and H2 O2 coexisted in the BM Fe/Cu-O2 system. A harmonious coexistence of oxidation and reduction mechanism was proposed.

Foxk2 inhibits non-small cell lung cancer epithelial-mesenchymal transition and proliferation through the repression of different key target genes.

Increasing evidence suggests that numerous fork-head transcription factors are required to repress the mammalian cells phenotype. Among them, Foxk2 is a ubiquitously expressed family member, but the role of Foxk2 in mediating tumor metastasis in non-small cell lung cancer has not been explored. In this investigation reduced Foxk2 expression was found in lung adenocarcinoma tissues compared with the adjacent non-tumor tissues, and was associated with better overall survival. Low expression was also found in the NSCLC cell lines such as A549, NCI-H520, H1299, H358 and H460 cells. Recombinant lentivirus expressing Foxk2 constructs or ShFoxk2 were developed and transfected into A549 cells or NCI-H520 cells, immunofluorescence assay, qRT-PCR, and western blot analysis were used to measure the change of the epithelial markers, E-cadherin and α-catenin, and mesenchymal markers N-cadherin and vimentin. Wound healing assay and Transwell assay were used to measure the relative cell invasion ability. MTT assay, Edu assay, and cell cycle distribution analysis were used to confirm the effect of Foxk2 on cell proliferation. ChIP-seq, qChIP, as well as luciferase reporter gene assays were used to detect the target genes regulated by Foxk2, Bioinformatics predicated the potential miRNAs that could target Foxk2. Our study demonstrated that Foxk2 played major roles in NSCLC EMT by directly targeting N-cadherin and Snail, we found that Foxk2 regulated NSCLC cell growth by suppressing the expression of cyclin D1 and CDK4, which suggested that Foxk2 might be a multifunctional regulator in NSCLC. The expression of Foxk2 may be regulated by miR-1271, which could serve as a promising therapeutic target for NSCLC.

Identification of gene markers in the development of smoking-induced lung cancer.

Lung cancer is a malignant tumor with high mortality in both women and men. To study the mechanisms of smoking-induced lung cancer, we analyzed microarray of GSE4115. GSE4115 was downloaded from Gene Expression Omnibus including 78 and 85 bronchial epithelium tissue samples separately from smokers with and without lung cancer. Limma package in R was used to screen differentially expressed genes (DEGs). Hierarchical cluster analysis for DEGs was conducted using orange software and visualized by distance map. Using DAVID software, functional and pathway enrichment analyses separately were conducted for the DEGs. And protein-protein interaction (PPI) network was constructed using Cytoscape software. Then, the pathscores of enriched pathways were calculated. Besides, functional features were screened and optimized using the recursive feature elimination (RFE) method. Additionally, the support vector machine (SVM) method was used to train model. Total 1923 DEGs were identified between the two groups. Hierarchical cluster analysis indicated that there were differences in gene level between the two groups. And SVM analysis indicated that the five features had potential diagnostic value. Importantly, MAPK1 (degree=30), SRC (degree=29), SMAD4 (degree=23), EEF1A1 (degree=21), TRAF2 (degree=21) and PLCG1 (degree=20) had higher degrees in the PPI network of the DEGs. They might be involved in smoking-induced lung cancer by interacting with each other (e.g. MAPK1-SMAD4, SMAD4-EEF1A1 and SRC-PLCG1). MAPK1, SRC, SMAD4, EEF1A1, TRAF2 and PLCG1 might be responsible for the development of smoking-induced lung cancer.