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Abstract: This paper examined the relationship between remotely sensed anthropogenic heat discharge and energy use from residential and commercial buildings across multiple scales in the city of Indianapolis, Indiana, USA. The anthropogenic heat discharge was estimated with a remote sensing-based surface energy balance model, which was parameterized using land cover, land surface temperature, albedo, and meteorological data. The building energy use was estimated using a GIS-based building energy simulation model in conjunction with Department of Energy/Energy Information Administration survey data, the Assessor’s parcel data, GIS floor areas data, and remote sensing-derived building height data. The spatial patterns of anthropogenic heat discharge and energy use from residential and commercial buildings were analyzed and compared. Quantitative relationships were evaluated across multiple scales from pixel aggregation to census block. The results indicate that anthropogenic heat discharge is consistent with building energy use in terms of the spatial pattern, and that building energy use accounts for a significant fraction of anthropogenic heat discharge. The research also implies that the relationship between anthropogenic heat discharge and building energy use is scale-dependent. The simultaneous estimation of anthropogenic heat discharge and building energy use via two independent methods improves the understanding of the surface energy balance in an urban landscape. The anthropogenic heat discharge derived from remote sensing and meteorological data may be able to serve as a spatial distribution proxy for spatially-resolved building energy use, and even for fossil-fuel CO2 emissions if additional factors are considered. [Copyright &y& Elsevier]

Inflammatory pain presents a significant clinical challenge. AMP-activated protein kinase (AMPK) is recognized for its capacity to alleviate inflammation by inhibiting transcription factors such as nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription (STAT). Our prior research demonstrated that AMPK reduces inflammatory pain by inhibiting NF-κB activation and interleukin-1 beta (IL-1β) expression. However, the role of AMPK in regulating reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) by modulating STAT3 phosphorylation in inflammatory pain remains inadequately understood. This study aims to investigate the role of AMPK in modulating STAT3 phosphorylation in the macrophages of inflamed tissues to mitigate inflammatory pain. A Complete Freund's Adjuvant (CFA)-induced inflammatory pain model was established by subcutaneous injection into the plantar surface of the left hindpaw of adult male mice. Behavioral tests of mechanical allodynia and thermal latency were used to determine nociceptive behavior. Immunoblotting quantified p-AMPK and iNOS expression levels. Nuclear translocation of p-STAT3(Ser727) and STAT3 in macrophages was assessed by western blot and immunofluorescence. ROS accumulation and mitochondrial damage in NR8383 macrophages were detected by flow cytometry. Lentivirus infection cells experiment was performed to transfect vectors encoding the STAT3 S727D mutants. Treatment with the AMPK activator AICAR alleviated CFA-induced inflammatory pain, enhanced AMPK phosphorylation, and reduced iNOS expression in inflamed skin tissues. AICAR effectively prevented STAT3 nuclear translocation while promoting the phosphorylation of STAT3 (Ser727) in the cytoplasm. In vitro studies with CFA-stimulated NR8383 macrophages revealed that AICAR increased STAT3(Ser727) phosphorylation, curtailed iNOS expression, and attenuated ROS accumulation and mitochondrial damage. Furthermore, the S727D mutation, which enhances STAT3 phosphorylation, replicated the protective effects of AICAR against CFA-induced oxidative stress and mitochondrial dysfunction. Our study shows that the AMPK acitvation downregulates iNOS expression by inhibiting the STAT3 nuclear translocation and promotes cytoplasmic STAT3(Ser727) phosphorylation, which reduces ROS expression and mitochondrial dysfunction, thereby alleviating inflammatory pain. These findings underscore the therapeutic potential of targeting AMPK and STAT3 pathways in inflammatory pain management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Accurately predicting response during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer remains clinically challenging. In this study, we investigated the effectiveness of blood-based tumor mutational burden (bTMB) and a deep learning (DL) model in predicting major pathologic response (MPR) and survival from a phase 2 trial., Methods: Blood samples were prospectively collected from 45 patients with stage IIIA (N2) non-small cell lung cancer undergoing neoadjuvant chemoimmunotherapy. An integrated model, combining the computed tomography-based DL score, bTMB, and clinical factors, was developed to predict tumor response to neoadjuvant chemoimmunotherapy., Results: At baseline, bTMB were detected in 77.8% (35 of 45) of patients. Baseline bTMB ≥11 mutations/megabase was associated with significantly greater MPR rates (77.8% vs 38.5%, P = .042), and longer disease-free survival (P = .043), but not overall survival (P = .131), compared with bTMB <11 mutations/megabase in 35 patients with bTMB available. The developed DL model achieved an area under the curve of 0.703 in all patients. Importantly, the predictive performance of the integrated model improved to an area under the curve of 0.820 when combining the DL score with bTMB and clinical factors. Baseline circulating tumor DNA (ctDNA) status was not associated with pathologic response and survival. Compared with ctDNA residual, ctDNA clearance before surgery was associated with significantly greater MPR rates (88.2% vs 11.1%, P < .001) and improved disease-free survival (P = .010)., Conclusions: The integrated model shows promise as a predictor of tumor response to neoadjuvant chemoimmunotherapy. Serial ctDNA dynamics provide a reliable tool for monitoring tumor response., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Chronic inflammatory pain is a pervasive condition, and electroacupuncture (EA) is an effective treatment, but its mechanisms are not fully understood. AMP-activated protein kinase (AMPK), a key energy sensor, is involved in pain relief and EA's effects. EA may work by increasing endocannabinoids, upregulating CB2 receptors (CB2R), and stimulating β-endorphin (β-END). This study tests if EA activates AMPK via CB2R to modulate β-END and reduce pain., Methods: The inflammatory pain model was established with Complete Freund's adjuvant (CFA), and EA was administered daily for six consecutive days, targeting the acupoints "Zusanli" (ST36) and "Shangjuxu" (ST37). Pain sensitivity was evaluated using Von Frey filaments for mechanical thresholds and a hot plate for thermal thresholds. Ultra-high Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) was used to quantitatively determine the levels of endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA). The expression levels of the CB2R and β-END were measured by Western blotting, along with the activation of AMPK. Immunofluorescence double-labeling was applied to visualize AMPK activation and β-END expression within CD68-positive macrophages. The study encompassed both wild-type and CB2R gene knockout mice, elucidating the role of CB2R in EA-induced AMPK activation., Results: CFA-induced inflammatory pain model mice exhibited mechanical allodynia and thermal hyperalgesia. EA activated AMPK in the inflamed skin tissue when it exerted analgesic effect on the inflammatory pain. Pre-administration of the AMPK inhibitor Compound C significantly inhibited the effect of EA on pain relief. EA elevated β-END expression in inflamed skin tissue, which was reversed by Compound C, indicating that AMPK has a regulatory role in EA inducing β-END expression. In addition, EA significantly upregulated the levels of 2-AG, AEA and the expression of CB2Rs in the inflamed skin tissue compared with the CFA group. In wild-type mice, EA activates AMPK in macrophages, while CB2 knockout reduced EA's ability to activate AMPK in these cells., Conclusion: EA activates AMPK through CB2R, enhancing β-END expression in inflamed skin to alleviate inflammatory pain. This study reveals a new link between endocannabinoids, endorphins, and AMPK in analgesic effects of EA, highlighting the CB2R-AMPK-β-END pathway., Competing Interests: Declarations. Ethics approval and consent to participate: All experimental procedures were reviewed and approved by the Ethics Committee for Experimental Animals at Tongji Medical College, Huazhong University of Science and Technology. Consent for publication: We declare that the Publisher has the Author’s permission to publish the relevant contribution. Competing interests: The authors declare no competing conflict of interests., (© 2024. The Author(s).)

Background: This study was carried out to evaluate the impact of neoadjuvant therapy on long-term survival of patients with non-small cell lung cancer undergoing sleeve lobectomy., Methods: A total of 613 patients were retrospectively analyzed, including 124 who received neoadjuvant therapy. A 1:2 propensity score matching method was adopted to create a balanced cohort including 110 with neoadjuvant therapy and 169 without neoadjuvant therapy. Survival was estimated by the Kaplan-Meier method and compared with the log-rank test and Cox proportional hazards models., Results: Neoadjuvant therapy was associated with improved 3-year disease-free survival (DFS; 73.6% vs 54.4%; P < .001) and overall survival (OS; 80.9% vs 63.9%; P = .002) compared with patients without neoadjuvant therapy. Moreover, neoadjuvant chemoimmunotherapy significantly improved 3-year DFS (85.3% vs 54.4%; P = .001) and OS (88.2% vs 63.9%; P = .006), whereas chemotherapy alone did not show a significant effect. Multivariable Cox regression analysis revealed neoadjuvant therapy to be an independent predictor of improved DFS and OS, whereas pathologic N2 stage was independently associated with poorer DFS and OS. Furthermore, subgroup analysis in the neoadjuvant arm revealed that pathologic N2 stage is an independent risk factor for DFS (hazard ratio, 3.830; 95% CI, 1.687-8.694; P = .001), and achieving major pathologic response is an independent predictor for better OS (hazard ratio, 0.120; 95% CI, 0.015-0.933; P = .043)., Conclusions: Neoadjuvant therapy before sleeve lobectomy significantly increased DFS and OS in locally advanced non-small cell lung cancer. Sleeve lobectomy is advisable after neoadjuvant therapy, especially following chemoimmunotherapy., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: The advent of robot-assisted thoracoscopic surgery (RATS) has completely revolutionized the modality of thymectomy, which could reportedly achieve equivalent efficacy compared with a minimally invasive approach. This study was conducted to further compare the perioperative outcomes between these two modalities., Methods: A retrospective single-center study that included patients receiving either a robotic or video-assisted thoracoscopic (VAT) thymectomy between February 2021 and January 2023 was conducted. All the patients were pathologically confirmed with thymic epithelial tumors. Clinical and pathological characteristics and perioperative outcomes were collected and compared between these two cohorts., Results: A total of 190 patients were included in this study, with 61 (32.1%) and 129 (67.9%) receiving robotic and video-assisted thymectomy, respectively. The clinicopathological characteristics were not significantly different between these 2 groups. The size of the resected specimens in the RATS cohort was larger than the VATS cohort [median (IQR), 13.0 (8.0-16.0) vs. 9.0 (6.7-12.0) cm, p < 0.001], while the procedural duration was longer for the RATS group than its counterpart [median (IQR), 105 (85-143) vs. 85 (69-115) min, p = 0.001]. Moreover, no other significant difference was observed between these two groups. Since more than half of the robotic thymectomy was performed using a subxiphoid approach, a subgroup analysis was further conducted. Similarly, the robotic group through a subxiphoid approach harbored a longer procedural duration, and the size of the specimens obtained was larger than the VATS group [median (IQR), 14.0 (11.0-16.5) vs. 12.5 (8.5-15.0) cm, p = 0.061]., Conclusions: The early clinical efficacy of robotic thymectomy was proven comparable to the established VATS approach, and such a modality might have strength when obtaining larger specimens, which could contribute to improving long-term efficacy. Despite the longer procedural duration recorded in the early stage of conducting robotic thymectomy, further accumulation would help decrease the time., (© 2023. Italian Society of Surgery (SIC).)

Protein tyrosine phosphatase SHP2 activates RAS signaling, which is a novel target for colorectal cancer (CRC) therapy. However, SHP2 inhibitor monotherapy is ineffective for metastatic CRC and a combination therapy is required. In this study, we aimed to improve the antitumor efficacy of SHP2 inhibition and try to explore the resistance mechanism of SHP2 inhibitor. Results showed that WWP1 promoted the proliferation of CRC cells. Genetic or pharmacological inhibition of WWP1 enhanced the effect of SHP2 inhibitor in suppressing tumor growth in vitro and in vivo. WWP1 may mediate feedback reactivation of AKT signaling following SHP2 inhibition. Furthermore, nomogram models constructed with IHC expression of WWP1 and SHP2 greatly improved the accuracy of prognosis prediction for patients with CRC. Our findings indicate that WWP1 inhibitor I3C can synergize with SHP2 inhibitor and is expected to be a new strategy for clinical trials in treating advanced CRC patients., (© 2024. The Author(s).)

Objectives: Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm., Methods: Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer-specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model., Results: In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157-5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830)., Conclusions: Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm., (© 2024. The Author(s).)

CD19-specific CAR-T immunotherapy has been extensively studied for the treatment of B-cell lymphoma. Recently, cholesterol metabolism has emerged as a modulator of T lymphocyte function and can be exploited in immunotherapy to increase the efficacy of CAR-based systems. Acetyl-CoA acetyltransferase 1 (ACAT1) is the major cholesterol esterification enzyme. ACAT1 inhibitors previously shown to modulate cardiovascular diseases are now being implicated in immunotherapy. In the present study, we achieved knockdown of ACAT1 in T cells via RNA interference technology by inserting ACAT1-shRNA into anti-CD19-CAR-T cells. Knockdown of ACAT1 led to an increased cytotoxic capacity of the anti-CD19-CAR-T cells. In addition, more CD69, IFN-γ, and GzmB were expressed in the anti-CD19-CAR-T cells. Cell proliferation was also enhanced in both antigen-independent and antigen-dependent manners. Degranulation was also improved as evidenced by an increased level of CD107a. Moreover, the knockdown of ACAT1 led to better anti-tumor efficacy of anti-CD19 CAR-T cells in the B-cell lymphoma mice model. Our study demonstrates novel CAR-T cells containing ACAT1 shRNA with improved efficacy compared to conventional anti-CD19-CAR-T cells in vitro and in vivo.

Background: Pulmonary adenocarcinoma with neuroendocrine differentiation (ADE&#95;ned) is a relatively uncommon pathological classification, and there exists considerable debate regarding its prognosis and treatment. The purpose of this study was to analyze the survival difference between patients with neuroendocrine carcinoma (NEC), adenocarcinoma (ADE), or ADE&#95;ned and to investigate the prognostic factors influencing the outcomes of individuals diagnosed with pulmonary ADE&#95;ned., Methods: We retrieved information on 316 cases of ADE&#95;ned, 188,823 cases of ADE, and 71,154 cases of NEC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. To account for potential confounding variables, propensity score matching (PSM) was employed. Comparative analyses were conducted to estimate the overall survival (OS) and cancer-specific survival (CSS). Finally, the Cox regression models were used to identify prognostic factors associated with pulmonary ADE&#95;ned., Results: Prior to PSM, patients with lung ADE&#95;ned had a worse OS rate than did those with lung ADE or NEC (5-year OS rate: 13.3% vs . 26.6% vs . 15.6%; P<0.001 and P=0.009, respectively). In terms of CSS, the 5-year CSS rate of patients with ADE&#95;ned was superior to that of NEC but inferior to that of ADE (28.7% vs . 26.8% vs . 43.8%; P=0.006 and P<0.001, respectively). Following PSM, the 5-year survival rate of patients with ADE&#95;ned remained lower than that of individuals with ADE or NEC in terms of OS (13.3% vs . 24.4% vs . 23.0%; P<0.001 and P<0001, respectively) and CSS (28.8% vs . 58.6% vs . 43.1%; P<0.001 and P=0.006, respectively). Finally, the results of the competitive risk regression analysis demonstrated that several variables, including sex, T stage, N stage, M stage, and surgery, were found to be independent prognostic factors for patients diagnosed with pulmonary ADE&#95;ned (all P values <0.05)., Conclusions: Patients with lung ADE&#95;ned had a significantly poorer survival outcome compared to those with lung ADE or NEC. Furthermore, sex, tumor-node-metastasis (TNM) stage, and surgery were found to be independent prognostic indicators for cases with lung ADE&#95;ned., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1811/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Trace metals have relatively high density and high toxicity at low concentrations. Willow (Salix genus) is an excellent phytoremediation species for soil contaminated by trace metal ions. This study identified a cell number regulator (CNR) gene family member in Salix linearistipularis exhibiting strong metal ion resistance: SlCNR8. SlCNR8 expression was affected by various metal ions, including cadmium (Cd), zinc (Zn), copper (Cu), iron (Fe), and manganese (Mn). SlCNR8 overexpression enhanced Cd, Zn, Cu, and Fe resistance in transgenic poplar seedlings (84K) compared with the wild-type (WT). Moreover, transgenic poplar seedlings showed lower root Cd uptake and less Cd accumulation than WT under Cd stress. SlCNR8 was primarily localized to the nucleus and the plasma membrane-like cell periphery. Furthermore, SlCNR8 had transcriptional activation activity in yeast. The transcript levels of multiple metal ion transporters were altered in the roots of transgenic poplar seedlings compared to WT roots under Cd stress. These results suggest that SlCNR8 may enhance Cd resistance in transgenic poplar by reducing Cd uptake and accumulation. This may be related to altered transcription levels of other transporters or to itself. Our study suggests that SlCNR8 can be used as a candidate gene for genetic improvement of phytostabilisation of trace metals by genetic engineering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: The eighth edition of nodal classification is defined only by the anatomical location of metastatic lymph nodes and has limited prognostic discrimination power. The authors aimed to evaluate the prognostic significance and discriminatory capability of the number of metastatic lymph nodes (nN) in resected nonsmall cell lung cancer., Materials and Methods: Patients with stage IA to IIIB resected nonsmall cell lung cancer between 1 January 2009 and 31 December 2013 were analyzed as a Chinese cohort. The optimal thresholds for the nN classification were determined by the X-tile. The receiver operating characteristic curve, net reclassification improvement and standardized net benefit calculated by decision curve analysis was estimated to quantify the nN classification's performance in prognostic stratification. External validation in the surveillance, epidemiology, and end results database was performed to test the robustness of the nN classification., Results: Both cohorts showed a stepwise prognosis deterioration with increasing nN. One to three, four to six, and more than six were selected as optimal thresholds of nN classification in the Chinese cohort, which included 4432 patients, then validated in the SEER cohort ( n =28 022 patients). Multivariate Cox analysis showed the nN classification was an independent predictive factor for overall survival in both cohorts (Chinese cohort and SEER cohort: N 0 vs. N 1-3 , P <0.001; N 0 vs. N 3-6 , P <0.001; N 0 vs. N >6 , P <0.001). And prognostic discriminatory capability was improved in the nN classification compared with location-based N classification [5-year NRI score, 0.106 (95% CI: 0.049-0.132) and 5-year time-independent AUC, 0.593 (95% CI: 0.560-0.625) vs. 0.554 (95% CI: 0.520-0.588), P <0.001]., Conclusions: The nN classification tended to be a superior prognostic indicator than the location-based N classification. The number of metastatic lymph nodes should be considered in the future revision of the TNM system., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The benefits of adjuvant chemoradiation therapy (CRT) for heterogeneous pathological N2 (pN2) diseases remain unclear in non-small cell lung cancer (NSCLC). This study aimed to investigate suitable pN2 patients for adjuvant CRT., Material and Methods: This study retrospectively reviewed the data of patients with pN2 NSCLC in Shanghai Pulmonary Hospital from January 2012 to December 2016. Included cases were subdivided as highest mediastinal lymph node (HM) (n = 732) metastasis and non-HM metastasis (n = 677) groups according to the International Association for the Study of Lung Cancer (IASLC). Furthermore, the Kaplan-Meier and Cox models were used to evaluate the prognostic benefits of adjuvant CRT in heterogeneous pN2 subgroups., Results: A total of 1409 patients were enrolled in this study, with a median follow-up time of 63.8 months. Patients with HM involvement had worse prognoses (p < 0.001 for recurrence-free survival (RFS) and overall survival (OS)). Furthermore, the survival improvement of adjuvant CRT was significant for these patients (p < 0.001 for RFS and p = 0.032 for OS), regardless of whether it was single (p < 0.001 for RFS and p = 0.029 for OS) or multiple pN2 (p < 0.001 for RFS and p = 0.026 for OS) diseases. According to multivariable cox analysis, the long-term RFS and OS in the cancerous HM group were independently predicted by pathological N stage (p = 0.002 for RFS and p < 0.001 for OS) and adjuvant CRT (p < 0.001 for RFS and p = 0.011 for OS)., Conclusion: Metastatic HM was associated with a worse prognosis in pN2 disease. Our analysis supported that adjuvant CRT significantly improved both RFS and OS for these patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to develop a robust predictive model for tetracycline (TC) adsorption onto biochar (BC) by employing machine learning techniques to investigate the underlying driving factors. Four machine learning algorithms, namely Random Forest (RF), Gradient Boosting Decision Tree (GBDT), eXtreme Gradient Boosting (XGBoost) and Artificial Neural Networks (ANN), were used to model the adsorption of TC on BC using the data from 295 adsorption experiments. The analysis revealed that the RF model had the highest predictive accuracy (R 2  = 0.9625) compared to ANN (R 2  = 0.9410), GBDT (R 2  = 0.9152), and XGBoost (R 2  = 0.9592) models. This study revealed that BC with a specific surface area (S (BET)) exceeding 380 cm 3 ·g -1 and particle sizes ranging between 2.5 and 14.0 nm displayed the greatest efficiency in TC adsorption. The TC-to-BC ratio was identified as the most influential factor affecting adsorption efficiency, with a weight of 0.595. The concentration gradient between the adsorbate and adsorbent was demonstrated to be the principal driving force behind TC adsorption by BC. A predictive model was successfully developed to estimate the sorption performance of various types of BC for TC based on their properties, thereby facilitating the selection of appropriate BC for TC wastewater treatment., (© 2023. The Author(s).)

FKBP10, a member of the FK506-binding protein (FKBP) family, has been implicated in cancer development, although its prognostic function remains controversial. In this study, we analyzed the expression of FKBP10 in tumor tissues using online databases (TCGA) as well as our CRC cohort, and investigated the relationship between its subcellular expression pattern and patient outcomes. Cox regression analysis was used to determine the associations between different subcellular expression patterns of FKBP10 and clinical features of patients. We also discussed the expression level of FKBP10 based on different subcellular expression patterns. Our results showed that FKBP10 was significantly elevated in CRC tissues and exhibited three different subcellular expression patterns which were defined as 'FKBP10-C' (concentrated), 'FKBP10-T' (transitional) and 'FKBP10-D' (dispersive). The FKBP10-D expression pattern was only found in tumor tissues and was associated with unfavorable disease-free survival in CRC patients. High expression levels of FKBP10-C predicted an unfavorable prognosis of recurrence of CRC, while FKBP10-D did not. Our findings suggest that the subcellular expression patterns and expression level of FKBP10 play crucial prognostic roles in CRC, which revealed that FKBP10 may be a viable prognostic and therapeutic target for the diagnosis and treatment of CRC.

Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, has shown beneficial physiological effects in various disease models and is used as a prebiotic to regulate intestinal function. However, its role in healthy states remains unclear. The purpose of this study was to investigate the effects of PHGG on gut flora composition and predict metabolic function in healthy mice. Our study showed that PHGG supplementation had significant duration-dependent effects on the composition and function of the intestinal flora of healthy mice. In specific, although the long-term supplementation of PHGG may increase the abundance of some beneficial bacterial species and promote beneficial phenotypes, it may also cause increased body weight and decreased abundance and diversity of gut microorganisms. Therefore, the long-term use of PHGG as a nutritional product still requires further investigation. PRACTICAL APPLICATIONS: As the importance of the gut microbiota has become more widely recognized, interventions that modulate the microbiome and its interaction with the host have gained much attention. While the capability of some prebiotics has largely been shown to have many beneficial effects, the evidence leaves much desirable, and microbiota regulation is explored differently in healthy or diseased states. Currently, the scientific community and regulatory authorities are beginning to pay attention to these unregulated and over-the-counter products claiming to possess probiotic and prebiotic properties. Studies exploring the rationality of these prebiotics as nutraceuticals for use in health states are essential. This study focuses on the effects of PHGG, a prebiotic, on intestinal flora, metabolism, and function when used in a healthy state over a long period. It is helpful to have a clearer understanding of the effect of PHGG on intestinal flora and the possible mechanisms of action to exert effects, which are indicative for the future application of PHGG as a nutraceutical or therapeutic agent.., (© 2022 Wiley Periodicals LLC.)

BRD4, a member of the bromodomain and extraterminal (BET) family, is elevated in multiple cancer tissues, including gastric cancer (GC). Targeted therapy with BRD4 may help improve the overall survival of patients with GC. Meanwhile, the approved multi-target kinase inhibitor, dasatinib, was recently reported to show varied tumor-suppressive effects in GC cells. This study investigated BRD4 expression in vivo and in vitro using immunohistochemistry and western blotting, respectively. We discussed the relationship between BRD4 expression and patient prognosis. Next, the antitumor efficacy of dasatinib was measured in BRD4-knockdown GC cells to determine the role of BRD4 blockage in dasatinib treatment. Finally, molibresib, a BET inhibitor, was used to measure the cooperative function of BRD4 inhibition and dasatinib treatment in three GC cell lines. Epithelial BRD4 expression was higher in tumoral and metastatic tissues and was strongly associated with unfavorable tumor, node, and metastasis stages and survival. BRD4 expression was heterogeneous in the three GC cell lines tested in vitro. In SGC7901, a BRD4-high GC cell line, knockdown of BRD4 using specific siRNAs suppressed cell growth individually and cooperatively with dasatinib. Moreover, molibresib and dasatinib showed a cooperative effect in suppressing the proliferation of BRD4-high GC cells. In conclusion, we confirmed that increased epithelial BRD4 expression is associated with poor disease stage and prognosis in GC and BRD4 blockage might be a valuable strategy to improve the sensitivity of dasatinib and other drugs in the chemotherapy of advanced GC., (© 2022. The Author(s).)

Phytoextraction in phytoremediation is one of the environmentally friendly methods used for restoring soils contaminated by heavy metals (HMs). The screening and identification of HM-resistant plants and their regulatory genes associated with HM ion transport are the key research aims in this field. In this study, a plant cadmium (Cd) resistance (PCR) gene family member, SlPCR6, was identified in roots of Salix linearistipularis, which exhibits strong HM resistance. The results revealed that SlPCR6 expression was induced in S. linearistipularis roots in response to Cd stress. Furthermore, SlPCR6 was mainly localized on the plasma membrane. Compared with the wild type, SlPCR6 overexpression reduced the Cd and copper (Cu) contents in the transgenic poplar (84 K) and increased its Cd and Cu resistance. The roots of transgenic poplar seedlings had lower net Cd and Cu uptake rates than wild type roots. Further investigation revealed that the transcript levels of multiple HM ion transporters were not significantly different between the roots of the wild type and those of the transgenic poplar. These results suggest that SlPCR6 is directly involved in Cd and Cu transport in S. linearistipularis roots. Therefore, SlPCR6 can serve as a candidate gene to improve the phytoextraction of the HMs Cd and Cu through genetic engineering., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to explore novel targets for celastrol sensitization in colorectal cancer (CRC) based on differentially regulated signals in response to high- or low-dose celastrol. Targeting signals were investigated using Western blotting or phosphorylated receptor tyrosine kinase (RTK) arrays. Corresponding inhibitors for the signals were individually combined with low-dose celastrol for the assessment of combined anti-CRC effects, based on proliferation, apoptosis, colony assays, and xenograft models. The potential mechanism for the combination of celastrol and SHP2 inhibition was further examined. Low-dose celastrol (<1 µM) did not effectively suppress AKT and ERK signals in CRC cells compared to high-dose celastrol (>1 µM). However, when combined with an AKT or ERK inhibitor, low-dose celastrol could cooperatively suppress CRC proliferation. Furthermore, failed AKT or ERK inhibition by low-dose celastrol may be due to reactivated RTK-SHP2 signaling with negative feedback. The combination of celastrol and the SHP2 inhibitor resulted in greatly reduced AKT and ERK signals, as well as greater inhibition of CRC growth than celastrol alone. Moreover, the mechanism underlying combination suppression was also involved in the activation of immune cell infiltration (mainly for CD8 + cells) in CRC tissues. Failure to inhibit RTK-SHP2-AKT/ERK signaling contributed to the lack of CRC growth suppression by low-dose celastrol. However, the combination of celastrol and the SHP2 inhibitor resulted in synergistic inhibition of CRC growth and provided a promising therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Hu, Meng, Li, Shen, Fu, Zhang, Chen, Zhang, Chang and Pan.)

In this study, 897 surgical instruments used for comprehensive management of hand supply from January to December 2019 were selected as the control group. Similarly, 1086 surgical instruments administered with 6Sigma from January to December 2020 were selected as the observation group. By observing and comparing the differences between the two groups of patients in the operating room equipment cleaning pass rate and general indicators, other related pass rate, operating room equipment defects, and doctors' satisfaction with equipment, to explore the application value and influence of comprehensive nursing in operating room and disinfection supply center combined with 6Sigma management in operating room equipment management. The results show that the application of hand-supply integration combined with 6Sigma management has a good effect on operating room equipment management, which significantly improves the qualified rate of operating room equipment cleaning and the satisfaction of doctors to the equipment, and reduces the defects of operating room equipment, which has a certain reference value for operating room equipment management., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Xiaomin Zhu et al.)

Objectives: This study intends to appraise the feasibility of double sleeve lobectomy after neoadjuvant chemotherapy in central non-small-cell lung cancer with bronchovascular aggression., Methods: This retrospective study included non-small-cell lung cancer patients who received double sleeve lobectomy from January 2014 to June 2020. Patients were divided into 2 groups: the neoadjuvant chemotherapy group and the non-neoadjuvant chemotherapy group. Demographic data and perioperative outcomes were compared between these 2 groups., Results: Of the 110 patients who received double sleeve lobectomy during this period, 35 patients (31.8%) received neoadjuvant chemotherapy. Compared with the non-neoadjuvant chemotherapy group, patients who received neoadjuvant chemotherapy were associated with younger age (P = 0.026), smaller pathologic tumour size (P = 0.005), higher forced expiratory volume in 1 s (P = 0.007), higher forced expiratory volume in 1 s of predicted value (P = 0.005) and higher clinical stage (P < 0.001). In the neoadjuvant chemotherapy group, 18 patients (51.4%) attained a partial response and 17 patients (48.6%) achieved stable disease. The postoperative hospital stays (P = 0.042) and chest tube drainage duration (P = 0.030) were longer in the neoadjuvant chemotherapy group and other perioperative performances were similar between these 2 groups. No statistically significant difference was reported in postoperative complications and mortality between these 2 groups., Conclusions: The intraoperative performance and postoperative outcomes of double sleeve lobectomy following neoadjuvant chemotherapy were similar to direct surgery, indicating that double sleeve lobectomy after neoadjuvant chemotherapy is feasible and safe in central lung cancer involving both the pulmonary artery and bronchus., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators. Intriguingly, the cyclin-dependent protein kinase (CDK) inhibitor Palbociclib was found to directly bind STING and inhibit its activation in both mouse and human cells. Mechanistically, Palbociclib targets Y167 of STING to block its dimerization, its binding with cyclic dinucleotides, and its trafficking. Importantly, Palbociclib alleviates autoimmune disease features induced by dextran sulphate sodium or genetic ablation of three prime repair exonuclease 1 (Trex1) in mice in a STING-dependent manner. Our work identifies Palbociclib as a novel pharmacological inhibitor of STING that abrogates its homodimerization and provides a basis for the fast repurposing of this Food and Drug Administration-approved drug for the therapy of autoinflammatory diseases., (© 2022 The Authors.)

Background: Occupational exposure seriously threatens the physical and mental health of professionals and has become an important public health problem. In clinical medical and nursing work, medical staff, especially nursing staff, are faced with the status quo of occupational exposure with high risk, serious harm, and severe situation. Therefore, a sound management system must be established to control the occupational exposure of nurses., Aims: According to the PRECEDE management model, evaluate the operating room nurses' knowledge, belief, and behavior scores on the protection of surgical smoke, understand their awareness of surgical smoke and the current status of protection, improve the mastery rate and protection compliance of surgical smoke-related knowledge in the operating room, reduce the harm of surgical smoke to the human body, and provide a basis for smoke protection. Materials and methods . 125 doctors working in the operating room of our hospital were selected as the control group of this study, and 112 nonsmoke-exposed nurses working in the operating room of our hospital were selected as the observation group. The nurses' knowledge-belief behavior scores and self-evaluation scores of smoke influence were counted before and after the intervention in the operating room. SPSS25.0 was used to process the data. Tests and repeated measures analysis of variance were used to compare the effects before and after intervention., Results: After one month of intervention, the knowledge scores of nurses in the operating room on the protection of surgical smoke increased significantly, and the difference was significant ( P < 0.05); the scores of related concepts, physical properties, chemical properties, and authoritative protection standards increased significantly ( P < 0.05). There was no significant increase in the scores of smoke hazards ( P > 0.05); the attitude of smoke protection increased significantly, which was statistically significant ( P < 0.05); and the behavior compliance of smoke protection was significantly increased, which was statistically significant ( P < 0.05). After one month of intervention, the self-evaluation score of smoke effect of operating room nurses decreased significantly, and the difference was statistically significant ( P < 0.05). The data was analyzed by repeated measure analysis of variance. The knowledge of surgical smoke ( F = 65.570, P < 0.001), attitude ( F = 78.307, P < 0.001), and behavior ( F = 403.015, P < 0.001) scores gradually increased. The observation group's total cholesterol, low-density lipoprotein cholesterol, and the proportion of low-density lipoprotein cholesterol were higher than that of the control group, and the proportion of high-density lipoprotein cholesterol was lower than that of the control group. The difference was statistically significant P < 0.05., Conclusion: After the intervention of operating room nurses under the guidance of PRECEDE management mode, the theoretical knowledge of operating room nurses is effectively improved, the operations are standardized, the self-evaluation scores of smoke influence are reduced, and the safety level of operating room is improved. More importantly, the health of nursing staff is fully guaranteed., Competing Interests: There are no conflicts of interest., (Copyright © 2022 Hong Ye et al.)

Stem cell spheroids are advanced building blocks to produce chondroid. However, the multi-step operations including spheroids preparation, collection and transfer, the following 3D printing and shaping limit their application in 3D printing. The present study fabricates an 'ALL-IN-ONE' bioink based on granular hydrogel to not only produce adipose derived stem cell (ASC) spheroids, but also realize the further combination of chondrocytes and the subsequent 3D printing. Microgels (6-10 μ m) grafted with β-cyclodextrin (β-CD) (MG β-CD ) were assembled and crosslinked by in-situ polymerized poly (N-isopropylacrylamide) (PNIPAm) to form bulk granular hydrogel. The host-guest action between β-CD of microgels and PNIPAm endows the hydrogel with stable, shear-thinning and self-healing properties. After creating caves, ASCs aggregate spontaneously to form numerous spheroids with diameter of 100-200 μ m inside the hydrogel. The thermosensitive porous granular hydrogel exhibits volume change under different temperature, realizing further adsorbing chondrocytes. Then, the granular hydrogel carrying ASC spheroids and chondrocytes is extruded by 3D printer at room temperature to form a tube, which can shrink at cell culture temperature to enhance the resolution. The subsequent ASC spheroids/chondrocytes co-culture forms cartilage-like tissue at 21 d in vitro , which further matures subcutaneously in vivo , indicating the application potential of the fully synthetic granular hydrogel ink toward organoid culture., (© 2022 IOP Publishing Ltd.)

Background: This study evaluated the efficacy of bronchial sleeve lobectomy with pulmonary arterioplasty compared with pneumonectomy in centrally located non-small cell lung cancer with bronchovascular invasion., Methods: The cohort consisted of 212 patients receiving pneumonectomy and 156 patients undergoing bronchial sleeve lobectomy with pulmonary arterioplasty. Propensity score matching was used to create a fully balanced cohort, after which, baseline characteristics, perioperative performance, and oncologic results were compared between the 2 groups., Results: A total of 139 pneumonectomy patients were matched with 139 sleeve lobectomy patients. In the matched cohort, bronchial sleeve lobectomy with pulmonary arterioplasty was associated with longer operative time (P < .001), decreased perioperative transfusion rate (P = .002), shorter postoperative hospital stays (P < .001), shorter intensive care unit stays (P = .040), and lower Clavien-Dindo Classification (P = .016). In respect to survival outcomes, a log-rank test revealed no significant difference in overall survival (P = .381) and recurrence-free survival (P = .619) between the 2 surgical procedures., Conclusions: Bronchial sleeve lobectomy with pulmonary arterioplasty could achieve superior perioperative outcomes and equivalent oncologic efficacy compared with pneumonectomy, indicating that this complex procedure is safe and reliable for centrally located non-small cell lung cancer concurrently involving the pulmonary artery and bronchus., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Group 2 innate lymphoid cells (ILC2s) are highly heterogeneous tissue-resident lymphocytes that regulate inflammation and tissue homeostasis in health and disease. However, how these cells integrate into the tissue microenvironment to perform tissue-specific functions is unclear. Here, we show neuropilin-1 (Nrp1), which is induced postnatally and sustained by lung-derived transforming growth factor beta-1 (TGFβ1), is a tissue-specific marker of lung ILC2s. Genetic ablation or pharmacological inhibition of Nrp1 suppresses IL-5 and IL-13 production by ILC2s and protects mice from the development of pulmonary fibrosis. Mechanistically, TGFβ1-Nrp1 signaling enhances ILC2 function and type 2 immunity by upregulating IL-33 receptor ST2 expression. These findings identify Nrp1 as a tissue-specific regulator of lung-resident ILC2s and highlight Nrp1 as a potential therapeutic target for pulmonary fibrosis., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Zebrafish is broadly used as a model organism in gene loss-of-function studies in vivo, but its employment in vitro is greatly limited by the lack of efficient gene knockdown approaches in zebrafish cell lines such as ZF4. In this article, we attempted to induce silencing of telomere associated genes in ZF4 by applying the frequently-used siRNA transfection technology and a novel moiety-linked morpholino (vivo-MO). By proceeding with integrated optimization of siRNAs transfection and vivo-MOs treatment, we compared five transfection reagents and vivo-MOs simultaneously to evaluate the efficiency of terfa silencing in ZF4. 48 h after siRNAs transfection, Lipofectamine™ 3000 and X-tremeGENE™ HP leaded to knockdown in 35% and 43% of terfa transcription, respectively, while vivo-MO-terfa modulated 58% down-expression of zfTRF2 in contrast to vivo-MO-ctrl 72 h after treatment. Further siRNAs transfection targeting telomere associated genes by X-tremeGENE™ HP showed silencing in 40-68% of these genes without significant cytotoxicity and off-target effect. Our results confirmed the feasibility of gene loss-of-function studies in a zebrafish cell line, offered a systematic optimizing strategy to employ gene silencing experiments, and presented Lipofectamine™ 3000, X-tremeGENE™ HP and vivo-morpholinos as candidate gene silencing approaches for zebrafish in vitro gene loss-of-function studies. Successfully knockdown of shelterin genes further opened a new field for telomeric study in zebrafish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Electroacupuncture (EA) has been accepted to effectively relieve neuropathic pain. Current knowledge of its neural modulation mainly covers the spinal cord and subcortical nuclei, with little evidence from the cortical regions. Using in vivo two-photon imaging in mice with chronic constriction injury, we found that EA treatment systemically modulated the Ca 2+ activity of neural circuits in the primary somatosensory cortex, including the suppression of excitatory pyramidal neurons, potentiation of GABAergic somatostatin-positive interneurons, and suppression of vasoactive intestinal peptide-positive interneurons. Furthermore, EA-mediated alleviation of pain hypersensitivity and cortical modulation were dependent on the activation of endocannabinoid receptor 1. These findings collectively reveal a cortical circuit involved in relieving mechanical or thermal hypersensitivity under neuropathic pain and identify one molecular pathway directing analgesic effects of EA., Competing Interests: The authors declare no conflict of interests., (© 2021 The Authors.)

We apply convolutional neural network (CNN) model for estimating daily 24-h averaged ground-level PM 2.5 of the conterminous United States in 2011 by incorporating aerosol optical depth (AOD) data, meteorological fields, and land-use data. Unlike some of the recent supervised learning-based approaches, which only utilized the predictors from the location of which PM 2.5 value is estimated, we naturally aggregate predictors from nearby locations such that the spatial correlation among the predictors can be exploited. We carefully evaluate the performance of our method via overall, temporally-separated, and spatially-separated cross-validations (CV) and show that our CNN achieves competitive estimation accuracy compared to the recently developed baselines. Furthermore, we develop a novel predictor importance metric for our CNN based on the recent neural network interpretation method, Layerwise Relevance Propagation (LRP), and identify several informative predictors for PM 2.5 estimation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Nutritional factors such as extensively hydrolyzed casein (eHC) have been proposed to exert anti-inflammatory activity and affect clinical outcomes such as tolerance development in cow's milk allergy. Granzyme B (GrB) induces apoptosis in target cells and also controls the inflammatory response. Whether eHC could affect the activity of granzyme B and play a role in GrB-mediated inflammatory responses in vitro was unknown., Methods: The activity of GrB was measured using the substrate Ac-IEPD-pNA. Inflammatory responses were induced with GrB in HCT-8 and THP-1 cells, and pro-inflammatory cytokines were determined at the transcriptional and protein level., Results: GrB could induce the expression of IL-1β in HCT-8 cells, and IL-8 and MCP-1 in THP-1 cells, respectively. Interestingly, GrB acted synergistically on LPS-induced inflammation in HCT-8 cells and eHC reduced pro-inflammatory responses in both GrB and LPS-mediated inflammation. Further analyses revealed that eHC could inhibit the biological activities and cytotoxic activities of GrB and then could reduce GrB-mediated inflammatory response., Conclusion: The results from the current study suggest that anti-inflammatory activity of extensively hydrolyzed casein is, to a certain extent, mediated through modulation of granzyme B activity and responses.

To investigate the involvement of peripheral adenosine receptors in the effect of electroacupuncture (EA) on visceral pain in mice with inflammatory bowel disease (IBD). 2,4,6-Trinitrobenzene sulfonic acid (TNBS) was used to induce the visceral pain model. EA (1 mA, 2 Hz, 30 min) treatment was applied to bilateral acupoints "Dachangshu" (BL25) 1 day after TNBS injection once daily for 7 consecutive days. Von Frey filaments were used to measure the mechanical pain threshold. Western blot was used to detect the protein expression levels of adenosine 1 receptor (A1R), adenosine 2a receptor (A2aR), adenosine 2b receptor (A2bR), adenosine 3 receptor (A3R), substance P (SP), and interleukin 1 beta (IL-1β) in colon tissue. EA significantly ameliorated the disease-related indices and reduced the expression of SP and IL-1β in the colon tissues of mice with IBD. EA increased the expression of A1R, A2aR, and A3R and decreased the expression of A2bR in the colon tissue. Furthermore, the administration of adenosine receptor antagonists influenced the effect of EA. EA can inhibit the expression of the inflammatory factors SP and IL-1β by regulating peripheral A1, A2a, A2b, and A3 receptors, thus inhibiting visceral pain in IBD mice.

Long noncoding RNAs (lncRNAs) played in authentic biological cell roles such as cell apoptosis, cycle, differentiation, development, migration and invasion. However, the expression pattern and function of a new lncRNA LINC01296 in non-small cell lung cancer (NSCLC) are unknown and need to be studied. In our study, we indicate that the expression of LINC01296 was overexpressed in NSCLC samples compared to adjacent non-tumor tissues. Ectopic expression of LINC01296 promoted NSCLC cell proliferation and migration. Moreover, we demonstrated that LINC01296 has a potential binding site for miR-5095 by using online program tool StarBase. Overexpression of LINC01296 inhibited the expression of miR-5095 in the A549 cell. Furthermore, the miR-5095 expression was downregulated in the NSCLC tissues than in the adjacent non-tumor tissues. In addition, we found that there is a negative correlation between miR-5095 expression and LINC01296 level in the NSCLC tissues. Overexpression of miR-5095 suppressed NSCLC cell proliferation and migration. Finally, we demonstrate that ectopic expression of LINC01296 promoted cell proliferation and migration via inhibiting miR-5095 expression. These results suggested that LINC01296 might act a role as an oncogene in the tumorigenesis and development of NSCLC., Competing Interests: None.

There has been growing interest in extending the coverage of ground particulate matter with aerodynamic diameter ≤ 2.5 μm (PM 2.5 ) monitoring networks based on satellite remote sensing data. With broad spatial and temporal coverage, a satellite-based monitoring network has a strong potential to complement the ground monitor system in terms of the spatiotemporal availability of the air quality data. However, most existing calibration models focus on a relatively small spatial domain and cannot be generalized to a national study. In this paper, we proposed a statistically reliable and interpretable national modeling framework based on Bayesian downscaling methods to be applied to the calibration of the daily ground PM 2.5 concentrations across the conterminous United States using satellite-retrieved aerosol optical depth (AOD) and other ancillary predictors in 2011. Our approach flexibly models the PM 2.5 versus AOD and the potential related geographical factors varying across the climate regions and yields spatial- and temporal-specific parameters to enhance model interpretability. Moreover, our model accurately predicted the national PM 2.5 with an R ² at 70% and generated reliable annual and seasonal PM 2.5 concentration maps with its SD. Overall, this modeling framework can be applied to national-scale PM 2.5 exposure assessments and can also quantify the prediction errors.

Our aim is to estimate associations between acute increases in particulate matter with diameter of 2.5 µm or less (PM 2.5 ) concentrations and risk of infant bronchiolitis and otitis media among Massachusetts births born 2001 through 2008.Our case-crossover study included 20,017 infant bronchiolitis and 42,336 otitis media clinical encounter visits. PM 2.5 was modeled using satellite, remote sensing, meteorological and land use data. We applied conditional logistic regression to estimate odds ratios (ORs) and confidence intervals (CIs) per 10-µg/m 3 increase in PM 2.5. We assessed effect modification to determine the most susceptible subgroups. Infant bronchiolitis risk was elevated for PM 2.5 exposure 1 day (OR = 1.07, 95% CI = 1.03-1.11) and 4 days (OR = 1.04, 95% CI = 0.99-1.08) prior to clinical encounter, but not 7 days. Non-significant associations with otitis media varied depending on lag. Preterm infants were at substantially increased risk of bronchiolitis 1 day prior to clinical encounter (OR = 1.17, 95% CI = 1.08-1.28) and otitis media 4 and 7 days prior to clinical encounter (OR = 1.09, 95% CI = 1.02-1.16 and OR = 1.08, 95% CI = 1.02-1.15, respectively). In conclusion, preterm infants are most susceptible to infant bronchiolitis and otitis media associated with acute PM 2.5 exposures.

Satellite-retrieved aerosol optical properties have been extensively used to estimate ground-level fine particulate matter (PM 2.5 ) concentrations in support of air pollution health effects research and air quality assessment at the urban to global scales. However, a large proportion, ~70%, of satellite observations of aerosols are missing as a result of cloud-cover, surface brightness, and snow-cover. The resulting PM 2.5 estimates could therefore be biased due to this non-random data missingness. Cloud-cover in particular has the potential to impact ground-level PM 2.5 concentrations through complex chemical and physical processes. We developed a series of statistical models using the Multi-Angle Implementation of Atmospheric Correction (MAIAC) aerosol product at 1 km resolution with information from the MODIS cloud product and meteorological information to investigate the extent to which cloud parameters and associated meteorological conditions impact ground-level aerosols at two urban sites in the US: Atlanta and San Francisco. We find that changes in temperature, wind speed, relative humidity, planetary boundary layer height, convective available potential energy, precipitation, cloud effective radius, cloud optical depth, and cloud emissivity are associated with changes in PM 2.5 concentration and composition, and the changes differ by overpass time and cloud phase as well as between the San Francisco and Atlanta sites. A case-study at the San Francisco site confirmed that accounting for cloud-cover and associated meteorological conditions could substantially alter the spatial distribution of monthly ground-level PM 2.5 concentrations., Competing Interests: The authors declare no conflict of interest.

Objectives  Whether pneumonectomy is needed for the treatment of destroyed lungs is still controversial and unresolved in the clinic. Pneumonectomy is destructive and is associated with a significant incidence of postoperative complications. The purpose of this study is to analyze the operative techniques, postoperative morbidity, mortality, and long-term outcomes of patients with destroyed lungs who underwent pneumonectomy. Patients and Methods  We retrospectively analyzed 137 patients with destroyed lungs who underwent pneumonectomy. The data were queried for the details of operative technique, development of perioperative complications, mortality, and long-term survival. Univariate and multivariate analyses were performed to investigate the risk factors of pneumonectomy among the patients. Results  A total of 77 male and 60 female patients were reviewed. The youngest patient was 18 years, and the oldest was 75 years, with a mean age of 40.1 years. Postoperative complications were observed in 25 patients (18.2%). The rate of bronchopleural fistula (BPF) was 5.1% (7/137). Two perioperative deaths (1.5%) were noted. Univariate and multivariate analyses indicated the blood loss (hazard ratio [HR], 5.32; 95% confidence interval [CI], 1.27-18.50; p  = 0.021) was the independent risk factor of postoperative complications, and the type of the disease (HR, 4.50; 95% CI, 1.19-9.69; p  = 0.034) was the independent risk factor of the BPF, for the patients with destroyed lung after pneumonectomy. Conclusion  Pneumonectomy for destroyed lung is a high risk for postoperative complications. Our findings suggested that pneumonectomy in destroyed lung was satisfactory with strict surgical indications, adequate preoperative preparation, and careful operative technique, and the long-term outcomes can be especially satisfactory. Pneumonectomy for destroyed lung is still a treatment option., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated demyelination and degeneration of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is the preferential experimental rodent model for MS. Previous study demonstrated histamine H3 receptor (H3R) was an important factor in pathophysiology of EAE and immethridine was the most selective agonist of H3R. However, whether immethridine has therapeutic effect on EAE and its mechanism remained to be defined. Here we constructed EAE mouse model by immunization of MOG 35-55 peptides with complete Freund's adjuvant, immethridine was used to treat EAE and its therapeutic effect was evaluated. The results showed that the treatment of immethridine could alleviate EAE. The percentage of Th1 and Th17 in the spleen from the treated EAE mice decreased and the surface molecules such as CD40, CD86 or MHCII on dendritic cells (DCs) were also down-regulated. To understand the effect of immethridine on DCs, bone marrow-derived DCs were prepared and the immunological functions were analyzed. The data demonstrated that immethridine could change the expression profiles of cytokines in DCs and inhibit the expression of the co-stimulatory molecules such as CD40 and CD86. Furthermore, immethridine also inhibited the antigen-presenting function of DCs and T cell differentiation induced by DCs. Signaling pathway analysis demonstrated that the phosphorylation of NF-κB p65 but not ERK1/2 in DCs was inhibited after the treatment of immethridine. These data strongly suggested that immethridine could inhibit the function of DCs and indicated the therapeutic potential on EAE., Competing Interests: CONFLICTS OF INTEREST The authors have no financial conflicts of interest.

Tissue-engineered trachea provides a promising approach for reconstruction of long segmental tracheal defects. However, a lack of ideal biodegradable scaffolds greatly restricts its clinical translation. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration owing to natural tubular structure, cartilage matrix components, and biodegradability. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. To address these problems, a laser micropore technique (LMT) was applied in the current study to modify trachea sample porosity to facilitate decellular treatment and cell ingrowth. Decellularization processing demonstrated that cells in LMT treated samples were more easily removed compared with untreated native trachea. Furthermore, after optimizing the protocols of LMT and decellular treatments, the LMT-treated DTM (LDTM) could retain their original tubular shape with only mild extracellular matrix damage. After seeding with chondrocytes and culture in vitro for 8 weeks, the cell-LDTM constructs formed tubular cartilage with relatively homogenous cell distribution in both micropores and bilateral surfaces. In vivo results further confirmed that the constructs could form mature tubular cartilage with increased DNA and cartilage matrix contents, as well as enhanced mechanical strength, compared with native trachea. Collectively, these results indicate that LDTM is an ideal scaffold for tubular cartilage regeneration and, thus, provides a promising strategy for functional reconstruction of trachea cartilage., Statement of Significance: Lacking ideal biodegradable scaffolds greatly restricts development of tissue-engineered trachea. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. By laser micropore technique (LMT), the current study efficiently enhanced the porosity and decellularized efficacy of DTM. The LMT-treated DTM basically retained the original tubular shape with mild matrix damage. After chondrocyte seeding followed by in vitro culture and in vivo implantation, the constructs formed mature tubular cartilage with matrix content and mechanical strength similar to native trachea. The current study provides an ideal scaffold and a promising strategy for cartilage regeneration and functional reconstruction of trachea., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

To estimate PM 2.5 concentrations, many parametric regression models have been developed, while nonparametric machine learning algorithms are used less often and national-scale models are rare. In this paper, we develop a random forest model incorporating aerosol optical depth (AOD) data, meteorological fields, and land use variables to estimate daily 24 h averaged ground-level PM 2.5 concentrations over the conterminous United States in 2011. Random forests are an ensemble learning method that provides predictions with high accuracy and interpretability. Our results achieve an overall cross-validation (CV) R 2 value of 0.80. Mean prediction error (MPE) and root mean squared prediction error (RMSPE) for daily predictions are 1.78 and 2.83 μg/m 3 , respectively, indicating a good agreement between CV predictions and observations. The prediction accuracy of our model is similar to those reported in previous studies using neural networks or regression models on both national and regional scales. In addition, the incorporation of convolutional layers for land use terms and nearby PM 2.5 measurements increase CV R 2 by ∼0.02 and ∼0.06, respectively, indicating their significant contributions to prediction accuracy. A pair of different variable importance measures both indicate that the convolutional layer for nearby PM 2.5 measurements and AOD values are among the most-important predictor variables for the training process.

Dys-regulation of serine-arginine protein kinase 1 (SRPK1) has been reported in non-small cell lung cancer (NSCLC). However, its functions in the progression of NSCLC remain poorly understood. In this study, the expression of SRPK1 in NSCLC tissues was determined using real-time PCR, and the roles of SRPK1 in the progression of NSCLC were investigated. It was found that both the mRNA level and the protein level of SRPK1 were up-regulated in NSCLC tissues. Forced expression of SRPK1 promoted the growth and migration of NSCLC cells, while knocking down the expression of SRPK1 inhibited the growth, migration, and tumorigenicity of NSCLC cells. Mechanism studies showed that SRPK1 activated the transcriptional activity of beta-catenin/T-cell factor (TCF) complex, and knocking down the expression of SRPK1 attenuated the expression of target genes of beta-catenin/T-cell factor (TCF) complex. In addition, silencing the expression of SRPK1 down-regulated the phosphorylation of GSK3beta. Taken together, SRPK1 might play an oncogenic role in NSCLC, and SRPK1 might be a therapeutic target for NSCLC.

Exposures to particulate matter with diameter of 2.5µm or less (PM2.5) may influence risk of birth defects. We estimated associations between maternal exposure to prenatal traffic-related air pollution and risk of cardiac, orofacial, and neural tube defects among Massachusetts births conceived 2001 through 2008. Our analyses included 2729 cardiac, 255 neural tube, and 729 orofacial defects. We used satellite remote sensing, meteorological and land use data to assess PM2.5 and traffic-related exposures (distance to roads and traffic density) at geocoded birth addresses. We calculated adjusted odds ratios (OR) and confidence intervals (CI) using logistic regression models. Generalized additive models were used to assess spatial patterns of birth defect risk. There were positive but non-significant associations for a 10µg/m(3) increase in PM2.5 and perimembranous ventricular septal defects (OR=1.34, 95% CI: 0.98, 1.83), patent foramen ovale (OR=1.19, 95% CI: 0.92, 1.54) and patent ductus arteriosus (OR=1.20, 95% CI: 0.95, 1.62). There was a non-significant inverse association between PM2.5 and cleft lip with or without palate (OR=0.76, 95% CI: 0.50, 1.10), cleft palate only (OR=0.89, 95% CI: 0.54, 1.46) and neural tube defects (OR=0.77, 95% CI: 0.46, 1.05). Results for traffic related exposure were similar. Only ostium secundum atrial septal defects displayed significant spatial variation after accounting for known risk factors., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The level, distribution, compositional pattern and possible sources of polycyclic aromatic hydrocarbons (PAHs) in Lanzhou urban soil of Northwest China were investigated in this study. The total level of 22 PAHs ranged from 115 to 12,100 µg kg(-1) and that of 16 priority PAHs from 82.4 to 10,900 µg kg(-1). Seven carcinogenic PAHs generally accounted for 6.18-57.4% of total 22 PAHs. Compared with data from those reported about urban areas, PAH contamination in Lanzhou urban soils was moderate. Among different functional areas, higher level of PAHs was found along roadsides and in the industrial district (p<0.01), while lower levels were detected in the commercial, park and residential districts. The composition of PAHs was characterized by high molecular weight PAHs (≥4 rings), among which fluoranthene, benz[a]anthracene and phenanthrene were the most dominant components. Correlation analysis suggested that low molecular weight PAHs and high molecular weight PAHs originated from different sources and further corroborated that TOC was an important factor in the accumulation of PAHs in soil. Isomer ratios and principal component analysis indicated that PAHs in urban soil derived primarily from emissions resulting from the combustion of biomass, coal and petroleum products. Toxic equivalent concentrations (BaP(eq)) of soil PAHs ranged from 6.12 to 1302 µg BaP(eq) kg(-1), with a mean of 138 µg BaP(eq) kg(-1). The results suggested that human exposure to those soils which polluted by high concentrations of PAHs through direct ingestion or inhalation of suspended soil particles probably poses a significant risk to human health from the carcinogenic effects of PAHs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Multiple studies have developed surface PM 2.5 (particle size less than 2.5 µm in aerodynamic diameter) prediction models using satellite-derived aerosol optical depth as the primary predictor and meteorological and land use variables as secondary variables. To our knowledge, satellite-retrieved fire information has not been used for PM 2.5 concentration prediction in statistical models. Fire data could be a useful predictor since fires are significant contributors of PM 2.5 . In this paper, we examined whether remotely sensed fire count data could improve PM 2.5 prediction accuracy in the southeastern U.S. in a spatial statistical model setting. A sensitivity analysis showed that when the radius of the buffer zone centered at each PM 2.5 monitoring site reached 75 km, fire count data generally have the greatest predictive power of PM 2.5 across the models considered. Cross validation (CV) generated an R 2 of 0.69, a mean prediction error of 2.75 µg/m 3 , and root-mean-square prediction errors (RMSPEs) of 4.29 µg/m 3 , indicating a good fit between the dependent and predictor variables. A comparison showed that the prediction accuracy was improved more substantially from the nonfire model to the fire model at sites with higher fire counts. With increasing fire counts, CV RMSPE decreased by values up to 1.5 µg/m 3 , exhibiting a maximum improvement of 13.4% in prediction accuracy. Fire count data were shown to have better performance in southern Georgia and in the spring season due to higher fire occurrence. Our findings indicate that fire count data provide a measurable improvement in PM 2.5 concentration estimation, especially in areas and seasons prone to fire events.

We present the first report of a rare case of typical carcinoid tumor of the lung in a patient with complete situs inversus. The patient was a 65-year-old woman with the chief complaint of productive and mild chest pain. Chest X-ray and computed tomography (CT) scans of the thorax showed a mirror image of the organs and vessels and revealed a tumor 2.5 cm in diameter in the left middle lobe. The patient underwent resection of the left middle lobe through posterolateral incision. Postoperative pathological examination returned a diagnosis of typical carcinoid tumor. The patient made an uneventful recovery. This case highlights the importance of considering malignant tumors in pulmonary nodules in patients with complete situs inversus.

The status, source and health risk of street-dust-borne polycyclic aromatic hydrocarbons (PAHs) in Lanzhou of Northwest China were investigated. The total level of the 21 PAHs ranged from 1470 to 13,700 µg kg(-1) and that of the 16 priority PAHs from 1240 to 10,700 µg kg(-1). Higher levels of PAHs were mainly distributed in the Chengguan and Qilihe districts at Lanzhou central areas, and the lower levels were in Anning and Xigu districts. The level of seven potential carcinogenic PAHs generally accounted for 35-40 percent of total PAHs, and the PAHs contained two to four rings, mainly phenanthrene, benzo[b]fluoranthene and fluoranthene. The total level of PAHs increased with the decreasing particle size in the street dust. The correlation analysis suggested that the total organic carbon (TOC) was only slightly affected the PAH accumulation in street dust. The isomer ratios and principal component analysis indicated that the dust-borne PAHs in the dust were derived primarily from the combustion of biomass, coal and petroleum emission. The toxic equivalent concentrations (BaP(eq)) of dust-borne PAHs ranged from 115 to 827 µg BaP(eq) kg(-1), with a mean of 300 µg BaP(eq) kg(-1). The 95 percent upper confidence limit of Incremental Lifetime Cancer Risk due to human exposure to urban surface dust-borne PAHs in Lanzhou urban area was 2.031 × 10(-6) for children and 1.935 × 10(-6) for adults., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Most of currently reported models for predicting PM(2.5) concentrations from satellite retrievals of aerosol optical depth are global methods without considering local variations, which might introduce significant biases into prediction results. In this paper, a geographically weighted regression model was developed to examine the relationship among PM(2.5), aerosol optical depth, meteorological parameters, and land use information. Additionally, two meteorological datasets, North American Regional Reanalysis and North American Land Data Assimilation System, were fitted into the model separately to compare their performances. The study area is centered at the Atlanta Metro area, and data were collected from various sources for the year 2003. The results showed that the mean local R(2) of the models using North American Regional Reanalysis was 0.60 and those using North American Land Data Assimilation System reached 0.61. The root mean squared prediction error showed that the prediction accuracy was 82.7% and 83.0% for North American Regional Reanalysis and North American Land Data Assimilation System in model fitting, respectively, and 69.7% and 72.1% in cross validation. The results indicated that geographically weighted regression combined with aerosol optical depth, meteorological parameters, and land use information as the predictor variables could generate a better fit and achieve high accuracy in PM(2.5) exposure estimation, and North American Land Data Assimilation System could be used as an alternative of North American Regional Reanalysis to provide some of the meteorological fields., (Copyright © 2012 Elsevier Inc. All rights reserved.)