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For patients with non-small cell lung cancer, a negative margin status is required for radical pulmonary surgery. Residual disease of the margin has been thoroughly studied in the past few decades. However, the prognostic significance of tracheal tunica adventitia invasion after lobectomy remains unclear. In this study, we aimed to investigate the clinical influence of tracheal tunica adventitia invasion after lobectomy. We retrospectively collected the clinical data of 591 patients who consecutively underwent pulmonary lobectomy, including sleeve lobectomy, between 2012 and 2018 at Shanghai Chest Hospital. According to the tracheal tunica adventitia invasion status, we allocated the patients into 2 groups (tracheal tunica adventitia invasion and non-tracheal tunica adventitia). Disease-free and overall survival were evaluated, and we discussed the necessity of radiotherapy in patients with tracheal tunica adventitia. After propensity score matching to balance baseline characteristics, there were 167 individuals in the tracheal tunica adventitia invasion and non-tracheal tunica adventitia groups. In the hazard analysis, we found that tracheal tunica adventitia increased the risk of recurrence (hazard ratio: 0.652; P =.002) and impaired long-term survival (P <.001). Subgroup analysis revealed that tracheal tunica adventitia was an important risk factor, especially when the hilar lymph nodes were positive. In addition, tracheal tunica adventitia invasion promoted extra-thoracic lymph node metastasis. We discovered that radiotherapy did not improve the prognosis of patients in the tracheal tunica adventitia invasion group. After lobectomy, tracheal tunica adventitia invasion is a risk factor for non-small cell lung cancer and potentially increases extra-thoracic lymph node metastasis. Moreover, tracheal tunica adventitia invasion is not sensitive to postoperative radiotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

• The western and northeastern regions are high-risk areas for CRD mortality. • Stronger associations exist between construction industry and CRD mortality. • The internal spatial association for women shows stronger with age than men. • The male, under 65 groups had higher mortality affected manufacturing industry. • The female, elderly groups had higher mortality affected mining industry. Industry has long been a driving force in the national economy of Chongqing, a traditional industrial hub in China. Current research provides limited understanding of the spatial associations between industrial manufacturing enterprises and CRD mortality in urban areas of Western China. This study employs location data of CRD death patients and Points of Interest (POI) representing industrial manufacturing enterprises from 2012 to 2020. It explores their spatial patterns and associations through spatial clustering identification, co-location, and association effects. Key spatial association characteristics identified include: (1) High-risk CRD mortality areas are predominantly located in Tongnan District and Kaizhou District in the western and northeastern parts of Chongqing, with an increase in CRD mortality rates correlated with age and a higher prevalence among females. (2) The optimal bandwidths for spatial association characteristics are 0.18 m and 0.475 m, respectively. (3) The construction and mining industries exert a more substantial impact on the mortality rates of younger CRD patients, with a notably stronger spatial impact on male patients compared to female patients. These insights are critical for guiding public health policy and spatial planning of industrial manufacturing enterprises in Chongqing. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH), a subtype of stroke with high morbidity and mortality, occurs mainly in the basal ganglia and causes white matter injury (WMI), resulting in severe motor dysfunction and poor prognosis in patients. The preservation of the white matter around the hematoma is crucial for motor function recovery, but there is currently no effective treatment for WMI following ICH. Lithium has been widely used for the treatment of bipolar disorder for decades. Although the protective effects of lithium on neurodegenerative diseases and cerebral trauma have been studied in recent years, whether it can be used to alleviate WMI after ICH remains to be researched. The results of this study revealed that ICH caused significant functional and pathological abnormalities in mice. After LiCl was administered to mice with ICH, behavioural performance and electrophysiological functions were improved and ICH-induced white matter pathological injury, including myelin sheath and axonal degeneration, was ameliorated. Furthermore, LiCl treatment decreased the death of mature oligodendrocytes (OLGs) in ICH mice, which may have been attributed to the enhanced expression of brain-derived neurotrophic factor (BDNF) regulated by the LiCl-induced inhibition of glycogen synthase kinase-3β (GSK-3β). The decreased death of OLGs was closely associated with decreased destruction of the myelin sheath and alleviated degradation of the axons. In summary, this study suggests that the protective effect of lithium on WMI after ICH might be related to an increased level of BDNF and that LiCl treatment may be a potential therapeutic method to palliate WMI after ICH. [ABSTRACT FROM AUTHOR]

The minimally invasive surgery plus fibrinolysis has been identified as a promising treatment for spontaneous intracerebral hemorrhage (ICH). However, the fibrinolytic efficacy is not satisfactory. Neutrophil extracellular traps (NETs) have been demonstrated to impair fibrinolysis in sepsis and acute ischemic stroke. Therefore, we decided to explore the presence and potential effect of NETs in ICH fibrinolysis. Intracerebral hemorrhage was induced by autologous arterial blood injection into the basal ganglia in rats. First, at 0.5 hour, 1 hour, and 1.5 hours after blood injection, the brains were collected for NETs detection by immune-staining. Second, ICH rats were given intrahematoma fibrinolysis: rats were randomized to receive the equal amount of saline, DNAse 1, tissue-plasminogen activator (tPA), and tPA + DNAse 1 at 1 hour after hematoma placement. On day 3, animals were sacrificed for terminal deoxynucleotidyl transferase-mediated dUTP Nick-end labeling staining following MRI and behavioral tests. Third, on day 3 after ICH, the hematoma within brain were collected for ex vivo fibrinolysis assay to further evaluate the effect of NETs in ICH fibrinolysis. Co-staining of DAPI, H3, and MPO confirmed the presence of NETs in ICH. Disintegration of NETs using DNAse 1 enhanced tPA-induced hematoma fibrinolysis, relieved brain swelling, reduced cell death, and improved the functional outcome in ICH rats. Therefore, we concluded that NETs impaired the efficacy of tPA for ICH fibrinolysis in rats. Targeting NETs may be a new alternative to improve the fibrinolytic therapy following ICH. [ABSTRACT FROM AUTHOR]

• Tolvaptan attenuated brain edema after intracerebral hemorrhage. • Tolvaptan alleviated neurological deficits after intracerebral hemorrhage. • Tolvaptan prevented blood brain barrier destruction after intracerebral hemorrhage. Arginine-vasopressin (AVP) is believed to be positively correlated with the brain edema formation, but the underlying mechanism is still unclear. In this study, we explored the role of the V2 receptors antagonist tolvaptan on brain edema following intracerebral hemorrhage (ICH) with a rat model. Animals were randomly given tolvaptan or vehicle through oral gavage at 12 h, 36 h, and 60 h after ICH surgery. Brain swelling (%), brain water content(BWC), neurological scores, Evans blue fluorescence and blood-brain barrier (BBB) tight junction proteins were measured to evaluate the effect of tolvaptan in ICH. We found that tolvaptan alleviated the brain swelling (%), decreased the BWC growth, and attenuated the neurological deficits after ICH (p < 0.05, vs vehicle). What's more, tolvaptan increased the expression of ZO-1 and occludin (p < 0.05, vs vehicle), which might be attributed to the down-regulated effects of tolvaptan on MMP-9. These results provided evidence supporting the use of tolvaptan for ICH-induced brain edema. Large animal experiments are required to further explore the efficacy and mechanism of tolvaptan in ICH treatment. [ABSTRACT FROM AUTHOR]

Abstract Energy consumption continues to rise as society develops worldwide. Meanwhile, a lot of energy is wasted in the form of heat from various devices and systems. Here we report a new power generator, which works based on a difference in H+-ion concentration in a fuel cell structure and produces electricity by harvesting waste heat. The device works via the following three successive processes: H 2 is oxidized at anode to H+ ions, the H+ ions then penetrate through a phosphoric acid-treated polybenzimidazole (PBI-PA) membrane and finally the H+ ions get reduced to H 2 at cathode with electrons coming through external circuit from the anode. This system generates electricity at a current density of 21 mA cm−2 and a power density of 1.03 mW cm−2 at 170 °C. The cell's thermoelectric conversion efficiency at 170 °C is 13.72%, which is higher than typical values reported for many common thermoelectric materials in low temperature regimes. This innovative approach may allow for efficient generation of electricity from waste heat. Graphical abstract fx1 Highlights • A new power generator based on fuel cell structure, H+-ion concentration difference, and waste heat is reported. • The cell takes H 2 at anode and ultimately releases it at cathode, with no overall consumption, except heat while producing electricity. • A high current density of 21 mA cm−2 and a power density of 1.03 mW cm−2 at 170 °C can be obtained. • Thermoelectric conversion efficiency of 13.72% at 170 °C and 3.38% at 50 °C can be achieved by the cell. • The thermoelectric conversion efficiency of the cell is much higher than those of thermoelectric materials-based cells. [ABSTRACT FROM AUTHOR]

Fibrosis in ventricular system has a role in hydrocephalus following intraventricular hemorrhage (IVH). The cannabinoid receptor 2 (CB2) has been reported to participate in alleviating the fibrosis process of many diseases. However, its role in fibrosis after IVH was unclear so far, and we hypothesized that CB2 activation has potential to attenuate hydrocephalus after IVH via restricting fibrosis. So the present study was designed to investigate this hypothesis in a modified rat IVH model. Autologous non-anticoagulative blood injection model was induced to mimic ventricular extension of hemorrhage in adult Sprague-Dawley rats. Rats were randomized to receive JWH-133(CB2 agonist), SR144528 (CB2 antagonist) or saline. The lateral ventricular volumes, fibrosis in the subarachnoid space and ventricular wall, transforming growth factor-β 1(TGF-β1) in cerebrospinal fluid and brain tissue, and animal neurological scores were measured to evaluate the effects of CB2 in hydrocephalus following IVH. CB2 agonist JWH-133 significantly decreased the lateral ventricular volumes, improved the associated neurological deficits, down-regulated TGF-β1 expression, and alleviated fibrosis in the subarachnoid space and ventricular wall after IVH. All of these effects were reversed by SR144528. In conclusion, CB2 may have anti-fibrogenic effects after IVH. CB2 agonist suppressed fibrosis of ventricular system and alleviated hydrocephalus following IVH, which is partly mediated by inhibiting TGF-β1. [ABSTRACT FROM AUTHOR]

Background Primary tracheal cancer comprises a heterogeneous and rare group of neoplasms. Management of patients with primary tracheal carcinoma at our institution has improved in recent years. Methods This retrospective review included patients with localized primary tracheal adenoid cystic carcinoma treated surgically at our institution between January 1995 and December 2014. Patients were classified according to the timing of first operation: “early years” operation was performed between January 1995 and December 2002, and subsequent “recent years” operation was associated with improved management and a focus on early diagnosis. Results The proportion of patients with tracheal malignancy who underwent operation for adenoid cystic carcinoma increased with time. Patients in the recent group were significantly younger than those in the early group at diagnosis (49.3 ± 7.8 years versus 45.7 ± 9.4 years; p = 0.042), and the resected tumor size and tracheal lengths tended to be smaller (28.2 ± 7.6 mm versus 30.3 ± 7.0 mm; p = 0.161) and shorter (32.1 ± 7.7 mm versus 34.4 ± 6.7 mm; p = 0.123). The use of postoperative radiotherapy in patients with R1 resection was also managed more effectively in the recent group compared with the early group (90.6% versus 65.0%; p = 0.009). Five- and 10-year overall survival rates in the early and recent groups were 86.4% and 90.8%, and 31.8% and 61.2%, respectively ( p = 0.084), and the corresponding 5- and 10-year disease-free survival rates were 39.7% and 75.3%, and 9.9% and 21.2%, respectively ( p = 0.025). Conclusions There have been improved outcomes of adenoid cystic carcinomas. Early diagnosis, experienced surgical treatments, and postoperative adjuvant radiotherapy for patients with positive margins may contribute to the improved survival of patients with primary tracheal adenoid cystic carcinoma. [ABSTRACT FROM AUTHOR]

Abstract: The two enzymes in two disparate forms, d-amino acid oxidase (DAAO) in the permeabilized Pichia pastoris cells and immobilized glutaryl-7-aminocephalosporanic acid acylase (GA) on support, were employed to convert cephalosporin C (CPC) to 7-aminocephalosporanic acid (7-ACA) in a single reactor. As a catalyst used in the reaction, DAAO in the permeabilized cells was relatively stable and its half-life was up to 14.5 days at 30°C. In this study, CPC could be converted to 90.9% 7-ACA, 5% α-ketoadipyl-7-ACA (AKA-7-ACA) and 4.1% unidentified by-product within 2.5h. During the reaction process, the loss of DAAO activity in the reactor was at an average rate of 0.07Umin−1, but it could be compensated by continuous addition of the new permeabilized cell suspension. At the end of reaction, the stable immobilized GA was intercepted in a specially designed reactor, and reused for the next conversions. The permeabilized cells were separated outside the reactor by centrifugation and reused. Thus, the consecutive production of 7-ACA from CPC in a single reactor is achieved by a fed-batch strategy. In the reaction system, the used permeabilized cells and immobilized GA were renewed every four cycles and every seven cycles, respectively. The yield of 7-ACA reached around 90% at each reaction cycle. [Copyright &y& Elsevier]

Abstract: The discovery, synthesis, and SAR of chromanes as ERα subtype selective ligands are described. X-ray studies revealed that the origin of the ERα-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in vivo antagonism of estradiol in an immature rat uterine weight assay, effectively inhibited ovariectomy-induced bone resorption in a 42days treatment paradigm, and lowered serum cholesterol levels in ovx’d adult rat models. The best antagonists 8F and 12F also exhibited potent inhibition of MCF-7 cell growth and were shown to be estrogen receptor down-regulators (SERDs). [Copyright &y& Elsevier]

Dihydrobenzoxathiin analogs (1–11) with modifications on the basic side chain region were prepared and evaluated for estrogen/anti-estrogen activity in both in vitro and in vivo models. The compounds generally maintained a high degree of selectivity for ERα over ERβ, similar to the original lead compound I. Many of the compounds also maintained high potency in the inhibition of human carcinoma MCF-7 cell growth. However, all were less potent in the inhibition of estradiol-triggered uterine growth. This work demonstrates the sensitive nature of modification to the antagonist basic side chain region. [Copyright &y& Elsevier]

Abstract: The preparation and characterization of a series of thiophenyl oxime phosphonate beta-lactamase inhibitors is described. A number of these analogs were potent and selective inhibitors of class C beta-lactamases from Pseudomonas aeruginosa and Enterobacter cloacae. Compounds 3b and 7 reduced the MIC of imipenem against an AmpC expressing strain of imipenem-resistant P. aeruginosa. A number of the title compounds retained micromolar potency against the class D OXA-40 beta-lactamase from Acinetobacter baumannii and at high concentrations compound 3b was shown to reduce the MIC of imipenem against a highly imipenem-resistant strain of A. baumanii expressing the OXA-40 beta-lactamase. In mice compound 3b exhibited phamacokinetics similar to imipenem. [Copyright &y& Elsevier]

Abstract: 4,7-Dichloro-1-benzothien-2-yl sulfonylaminomethyl boronic acid (DSABA, Compound I) was discovered as the first boronic acid-based class D beta-lactamase inhibitor. It exhibited an IC50 of 5.6μM against OXA-40. The compound also inhibited class A and C beta-lactamases with sub to low μM IC50, and synergized with imipenem against Acinetobacter baumannii. [Copyright &y& Elsevier]

Hydroquinone (HQ), one of the main metabolites of benzene, is a well-known human leukemogen. However, the specific mechanism of how benzene or HQ contributes to the development of leukemia is unknown. In a previous study, we demonstrated the upregulation of DNA methyltransferase (DNMT) expression in HQ-induced malignant transformed TK6 (HQ-TK6) cells. Here, we investigated whether a regulatory loop between the long noncoding RNA FAS-AS1 and DNMT3b exists in HQ-TK6 cells and benzene-exposed workers. We found that the expression of FAS-AS1 was downregulated in HQ-TK6 cells and workers exposed to benzene longer than 1.5 years via histone acetylation, and FAS-AS1 expression was negatively correlated with the time of benzene exposure. Restoration of FAS-AS1 in HQ-TK6 cells promoted apoptosis and inhibited tumorigenicity in female nude mice. Interestingly, treatment with a DNMT inhibitor (5-aza-2-deoxycytidine), histone deacetylase inhibitor (trichostatin A), or DNMT3b knockout led to increased FAS-AS1 through increased H3K27ac protein expression in HQ-TK6 cells, and DNMT3b knockout decreased H3K27ac and DNMT3b enrichment to the FAS-AS1 promoter region, which suggested that DNMT3b and/or histone acetylation involve FAS-AS1 expression. Importantly, restoration of FAS-AS1 resulted in reduced expression of DNMT3b and SIRT1 and increased expression of FAS in both HQ-TK6 cells and xenograft tissues. Moreover, the average DNMT3b expression in 17 paired workers exposed to benzene within 1.5 years was decreased, but that of the remaining 103 paired workers with longer exposure times was increased. Conversely, DNMT3b was negatively correlated with FAS-AS1 expression. Both FAS-AS1 and DNMT3b influenced the enrichment of H3K27ac in the FAS promoter region by regulating the expression of SIRT1, consequently upregulating FAS expression. Taken together, these observations demonstrate crosstalk between FAS-AS1 and DNMT3b via a mutual inhibition loop and indicate a new mechanism by which FAS-AS1 regulates the expression of FAS in benzene-related carcinogenesis. Image 1 • LncRNA FAS-AS1 and DNMT3b were dynamically expressed in hydroquinone (HQ)-treated TK6 cells and peripheral blood samples of benzene-exposed workers. • LncRNA FAS-AS1 and DNMT3b formed a mutual inhibition loop. • The regulatory loop constituting lncRNA FAS-AS1 and DNMT3b downregulated the expression of FAS through histone acetylation in HQ-induced malignant transformed TK6 cells. [ABSTRACT FROM AUTHOR]

Dihydrobenzodithiin compounds (1–6) were prepared to explore the expansion of the dihydrobenzoxathiin lead compounds I–III as SERAMs (Selective Estrogen Receptor Alpha Modulators). The dihydrobenzodithiin compounds generally maintained a high degree of selectivity for ERα over ERβ, however, they lacked the in vivo antagonism/agonism activity exhibited by the lead class in an immature rat uterine growth model. [Copyright &y& Elsevier]

Similar to MXene, MAB is a group of 2D ceramic/metallic boride materials which exhibits unique properties for various applications. However, these 2D sheets tend to stack and therefore lose their active surface area and functions. Herein, an amorphous cobalt nickel boride (Co–Ni–B) nanocomposite is prepared with a combination of 2D sheets and nanoparticles in the center to avoid agglomeration. This unique structure holds the 2D nano-sheets with massive surface area which contains numerous catalytic active sites. This nanocomposite is prepared as an electrocatalyst for borohydride electrooxidation reaction (BOR). It shows outstanding catalytic activity through improving the kinetic parameters of BH 4 − oxidation, owing to abundant ultrathin 2D structure on the surface, which provide free interspace and electroactive sites for charge/mass transport. The anode catalyst led to a 209 mW/cm2 maximum power density with high open circuit potential of 1.06 V at room temperature in a miniature direct borohydride fuel cell (DBFC). It also showed a great longevity of up to 45 h at an output power density of 64 mW/cm2, which is higher than the Co–B, Ni–B and PtRu/C. The cost reduction and prospective scale-up production of the Co–Ni–B catalyst are also addressed. [Display omitted] • DBFC with Co–Ni–B nanocomposite as anode catalyst exhibited P max = 209 mW/cm2 which is over twice higher than PtRu/C. • MXene-like structure enhanced the exposure of active metallic species and the mass transfer. • The assembled DBFC has good stability of retaining 91.2% of the output voltage after 45 h. • The narrow band gap of Co–Ni–B nanocomposite urges the charge transfer kinetic. [ABSTRACT FROM AUTHOR]

H+-ion concentration cell, which can harvest thermal energy to generate electricity by hydrogen concentration difference principle with a fuel cell structure, is an innovative thermoelectric conversion device. In this system, phosphoric acid-doped polybenzimidazole (PA-doped PBI) membrane is a key component influencing the power generation performance of the cell. Herein, 30, 45, 60, 75, and 90 μm thick PBI membranes are successfully synthesized and doped with phosphoric acid. To achieve a good compromise between the proton conductivity and durability, the properties of PA-doped PBI membranes are experimentally evaluated to clarify the effect of the acid doping time and membrane thickness on cell performance. The results indicate that the higher the acid doping level, the worse the dimensional stability of the membrane. Also the thinner the PBI membrane, the smaller the membrane resistance to ions motion, while the poorer the stability. Upon reaction at 170 °C, this cell can boast a power density from 3.0 to 8.0 W m−2, which results in a thermoelectric conversion efficiency of 5.97–14.32%. This study potentially boosts the practical application of thermal-to-electrical conversion technology. Image 1 • The properties of different PBI membranes were studied. • Phosphoric acid-doped PBI membranes exhibited good proton conductivity and thermal stability. • The H+-ion concentration cell can boast a power density from 3.0 to 8.0 W m−2 at 170 °C. • The thermoelectric conversion efficiency across the H+-ion concentration cell is in the range of 5.97–14.32%. [ABSTRACT FROM AUTHOR]

Fibrosis of the subarachnoid space (SAS) after infection, inflammation, or hemorrhage can impair cerebrospinal fluid absorption and circulation, causing diffuse ventricular dilatation. In the present study, we tested the hypothesis that urokinase (also known as urokinase-type plasminogen activator [uPA]), a fibrinolytic agent, attenuates fibrosis and ventriculomegaly in a rat model of kaolin-induced communicating hydrocephalus and thus may have potential as a therapy for these conditions. Thirty microliters of sterile 25% kaolin suspension was injected into the basal cisterns of adult Sprague-Dawley rats to induce hydrocephalus, and 2 intraventricular injections of either uPA or vehicle (saline) were administered immediately and 3 days thereafter. Ventricular volumes were measured by magnetic resonance imaging (MRI) on days 3, 14, and 28 after kaolin injection. Fibrosis and reactive astrogliosis were evaluated on day 28 by immunofluorescence and Western blotting. Neurocognitive features were tested using the Morris water maze from days 23 to 28. MRI analysis demonstrated that kaolin administration successfully induced hydrocephalus in rats and that uPA treatment significantly attenuated ventricular enlargement. In addition, uPA inhibited the deposition of laminin and fibronectin, extracellular matrix molecules, in the SAS, attenuated gliosis, and improved learning and memory in kaolin-treated rats. Therefore, we concluded that uPA prevents the development of kaolin-induced communicating hydrocephalus by preventing the development of subarachnoid fibrosis and by eliciting improvements in neurocognition. The results of this study indicate that uPA may be a novel clinical therapy for communicating hydrocephalus. [ABSTRACT FROM AUTHOR]

Abstract Hydroquinone (HQ), one of the major metabolites of benzene, can induce aberrant gene expression. MiR-155, a tumor activator, participates in various biological processes, including DNA damage response. However, the molecular mechanism of aberrant miR-155 expression is still not completely elucidated. Here, we investigated the mechanism of abnormal expression of miR-155 induced by poly(ADP-ribose)polymerase-1 (PARP-1) expression in HQ-treated TK6 lymphoblastoid cells. We examined the expression of genes related to abnormal expression of miR-155 to explore the reason for this phenomenon. The results of the present study showed that miR-155 was significantly increased and reactive oxygen species (ROS) were decreased in cells treated with HQ for 72 h compared with PBS-treated cells. Meanwhile, E4F1, PARP-1 and PARP-1 related co-regulators (NF-κB, HDAC1, and HDAC2), acetylated histone H3 (H3Ac) were increased in a concentration-dependent manner. Experiments for treatment with 5-AzaC (DNMTs inhibitor), TSA (HDACs inhibitor), DOX (to activate PARP-1) or MG132 (proteasome inhibitor) revealed that the MBDs and PARP-1 was positively associated with miR-155 expression. Moreover, in cells treated with HQ in conjunction with PARP-1 knockdown, expression of miR-155, H3Ac and MBD2 protein were decreased, compared with negative control. In conclusion, PARP-1 activates expression of miR-155 via acetylation by regulating MBD2 in TK6 cells exposed to HQ. Highlights • HQ activates the expression of miR-155 and PARP-1 in a dose-dependent manner. • HQ induces the expression of PARP-1 related co-regualtors (HDAC1/2, NF-κB,). • Treatment of TSA and DOX promotes the expression of miR-155. • PARP-1 silencing inhibits the expression of miR-155 and MBD2. • PARP-1 promotes the expression of miR-155 via histone acetylation by targeting MBD2. [ABSTRACT FROM AUTHOR]