Comprehensive metabolic profiling of dioxin-like compounds exposure in laying hens: Implications for toxicity assessment.

The evaluation of toxicity related to polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) is crucial for a comprehensive risk assessment in real-world exposure scenarios. This study employed a controlled feeding experiment to investigate the metabolic effects of dioxin-like compounds (DLCs) on laying hens via feed exposure. Diets enriched with two concentrations (1.17 and 5.13 pg toxic equivalents (TEQ)/g dry weight (dw)) were administered over 14 days, followed by 28 days of clean feed. Metabolomics analyses of blood samples revealed significant metabolic variations between PCDD/Fs and DL-PCBs exposed groups and controls, reflecting the induced metabolic disruption. Distinct changes were observed in sphingosine, palmitoleic acid, linoleate, linolenic acid, taurocholic acid, indole acrylic acid, and dibutyl phthalate levels, implying possible connections between PCDD/Fs and DL-PCBs toxic effects and energy-neuronal imbalances, along with lipid accumulation and anomalous amino acid metabolism, impacting taurine metabolism. Moreover, we identified three differential endogenous metabolites-L-tryptophan, indole-3-acetaldehyde, and indole acrylic acid-as potential ligands for the aryl hydrocarbon receptor (AhR), suggesting their role in mediating PCDD/Fs and DL-PCBs toxicity. This comprehensive investigation provides novel insights into the metabolic alterations induced by PCDD/Fs and DL-PCBs in laying hens, thereby enhancing our ability to assess risks associated with their exposure in human populations.

Molecular-phylogenetic analyses of Babesia and Theileria species from small mammals and their ticks in northern China suggest new reservoirs of bovine and equine piroplasms.

Babesia and Theileria species (Apicomplexa: Piroplasmida) are tick-borne protozoan parasites that can cause mild to severe infection in humans, wildlife, livestock and companion animals. To date, reports on the molecular study of piroplasms from wild living small mammals and their ticks are still limited, especially in Asia. This study encompassed an extensive survey involving 907 liver samples and 145 ixodid ticks from 16 different species of small mammals (Rodentia, Lagomorpha, Eulipotyphla). These were collected in 13 cities and counties in northern China. DNA extracts from these samples were screened for the presence of piroplasm 18S rRNA gene. Samples that tested positive were further evaluated for other genetic markers of piroplasms, including the cox1 gene and the ITS1-5.8S rDNA-ITS2 region. Several piroplasm species were identified, including Babesia sp. tavsan2, Babesia occultans, Theileria sp. Xinjiang, Theileria equi, and Theileria sp. Kalecik. Among these, Theileria sp. Xinjiang was shown to be the most prevalent. Importantly, Babesia sp. tavsan2 was identified in the tick Rhipicephalus sanguineus from the Yarkand hare and Theileria sp. Kalecik in Hyalomma asiaticum from the long-eared hedgehog, in line with the detection of these pathogens in tissue samples of the relevant hosts. This study further disclosed the presence of DNA from B. occultans and T. equi, typically found in cattle and horses respectively, with an additional discovery in small mammals. Moreover, Theileria sp. Kalecik, which was first detected in small-sized mammals, and Babesia sp. tavsan2, were both reported for the first time in China.

Plasma proteomic signature of neonates in the context of placental histological chorioamnionitis.

BACKGROUND: Placental histological chorioamnionitis (HCA) is recognised as a significant risk factor for various adverse neonatal outcomes. This study aims to explore if the inflammatory protein levels in neonates were associated with HCA. METHODS: All women with singleton births from February 2020 to November 2022 were selected and divided into three groups based on maternal placental pathology results: the HCA-stage 1 group (n=24), the HCA-stage 2 group (n=16) and the control group (n=17). Olink Target 96 Inflammation Panel was used to detect the levels of 92 inflammation-related proteins in the plasma of newborns from all three groups within 24 hours after birth. We compared the protein profiles through differential protein expression analysis. RESULTS: A total of six inflammation-related proteins exhibited significant differences between the HCA-stage 1 and the control group. Specifically, TRANCE and CST5 were significantly upregulated (p=0.006, p=0.025, respectively), whereas the expression of IFN-gamma, CXCL9, CXCL10 and CCL19 was significantly downregulated (p=0.040, p=0.046, p=0.007, p=0.006, respectively). HCA-stage 2 newborns had significantly elevated levels of CD5 and CD6 and decreased IFN-gamma, CXCL10 and CCL19 in comparison to controls. These differential proteins were significantly enriched in positive regulation of cytokine activity, leucocyte chemotaxis and positive regulation of T-cell activation pathway-related Gene Ontology terms. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that viral protein interaction with cytokine and cytokine receptor, interleukin-17/NF-kappa B/toll-like receptor/chemokine signalling pathway, and cytokine-cytokine receptor interaction exhibited significant differences. Spearman analysis demonstrated a significant positive connection between the levels of CD6 and CD5 proteins, not only in neonatal leucocytes but also in maternal leucocytes. Additionally, CD6 was found to be associated with neonatal birth weight. CONCLUSIONS: In conclusion, placental histological changes associated with chorioamnionitis appear to influence the expression of inflammatory proteins in offspring. Notably, CD6 and CD5 proteins may potentially contribute to the pathogenesis of HCA-related neonatal diseases.

Effective alleviation of depressive and anxious symptoms and sleep disorders in benzodiazepine-dependent patients through repetitive transcranial magnetic stimulation.

Benzodiazepine (BZD) dependence poses a significant challenge in mental health, prompting the exploration of treatments like repetitive transcranial magnetic stimulation (rTMS). This research aims to assess the impact of rTMS on alleviating symptoms of BZD dependence. A randomized control trial was employed to study 40 BZD-dependent inpatients. Their symptoms were quantified using the Hamilton Anxiety Rating Scale (HAMA), Montgomery-Åsberg Depression Rating Scale (MADRS) and Pittsburgh Sleep Quality Index (PSQI). Participants were divided into a conventional treatment group (daily diazepam with gradual tapering) with supportive psychotherapy and another group receiving the same treatment supplemented with rTMS (five weekly sessions for 2 weeks). Significant improvements were observed in both groups over baseline in MADRS, HAMA and PSQI scores at the 2nd, 4th, 8th and 12th week assessments (p < 0.05). The group receiving rTMS in addition to conventional treatment exhibited superior improvements in all measures at the 8th and 12th weeks. The addition of rTMS to conventional treatment methods for BZD dependence significantly betters the recovery in terms of depression, anxiety and sleep quality, highlighting the role of rTMS as an effective adjunct therapy.

Bartonella, Blechomonas and Trypanosoma in fleas from the long-tailed ground squirrel (Spermophilus undulatus) in northwestern China.

Fleas are known to be vectors for a variety of pathogens in veterinary medicine. However, no information is available on the presence of Bartonella and Trypanosomatidae in fleas of the long-tailed ground squirrel (LTGR, Spermophilus undulatus). The present study shows detection of these pathogens in LTGR fleas. During 2022-2023, a total of 396 fleas were collected from 91 LTGRs in 4 alpine regions of Xinjiang Uygur Autonomous Region (northwestern China) and grouped into 54 flea pools. Flea species were identified according to morphological characteristics and molecular data. In addition, all flea samples were analyzed for Bartonella with amplification and sequencing of a 380-bp part of the gltA gene and Trypanosomatidae with targeting the 18S rRNA (850-bp) and gGAPDH (820-bp) genes. The flea species included Frontopsylla elatoides elatoides (203), Neopsylla mana (49), and Citellophilus tesquorum dzetysuensis (144). Of 54 flea pools, seven (12.96%) tested positive for Bartonella, and three (5.56%) were positive for Trypanosomatidae. Based on BLASTn and phylogenetic analyses, i) Bartonella washoensis in F. elatoides elatoides and C. tesquorum dzetysuensis, and Bartonella rochalimae in F. elatoides elatoides were identified. Interestingly, a new haplotype within the species Ba. washoensis was discovered in C. tesquorum dzetysuensis; and ii) Blechomonas luni was confirmed in C. tesquorum dzetysuensis and Trypanosoma otospermophili in F. elatoides elatoides. Two Bartonella species and two Trypanosomatidae members were discovered for the first time in fleas from LTGRs. This study broadens our understanding of the geographic distribution and potential vectors for Bartonella and Trypanosomatidae.

t-SMILES: a fragment-based molecular representation framework for de novo ligand design.

Effective representation of molecules is a crucial factor affecting the performance of artificial intelligence models. This study introduces a flexible, fragment-based, multiscale molecular representation framework called t-SMILES (tree-based SMILES) with three code algorithms: TSSA (t-SMILES with shared atom), TSDY (t-SMILES with dummy atom but without ID) and TSID (t-SMILES with ID and dummy atom). It describes molecules using SMILES-type strings obtained by performing a breadth-first search on a full binary tree formed from a fragmented molecular graph. Systematic evaluations using JTVAE, BRICS, MMPA, and Scaffold show the feasibility of constructing a multi-code molecular description system, where various descriptions complement each other, enhancing the overall performance. In addition, it can avoid overfitting and achieve higher novelty scores while maintaining reasonable similarity on labeled low-resource datasets, regardless of whether the model is original, data-augmented, or pre-trained then fine-tuned. Furthermore, it significantly outperforms classical SMILES, DeepSMILES, SELFIES and baseline models in goal-directed tasks. And it surpasses state-of-the-art fragment, graph and SMILES based approaches on ChEMBL, Zinc, and QM9.

First identification of Cytauxzoon manul in Eurasian lynx (Lynx lynx) in northwestern China.

BACKGROUND: Multiple species of the genera Cytauxzoon and Hepatozoon can infect wild felines, but the diversity of these and other apicomplexan parasites in Eurasian lynx is scarcely known. The aim of this study was to detect Cytauxzoon and Hepatozoon species with molecular methods in Eurasian lynxes and their ticks in northwestern China. METHODS: DNA was extracted from the heart, liver, spleen, lung, and kidney samples of three Eurasian lynxes as well as from their five ixodid ticks. These DNA samples were screened with polymerase chain reactions (PCRs) for Cytauxzoon with the partial cytochrome b gene (CytB), cytochrome c oxidase subunit I gene (COI), and small subunit ribosomal RNA gene (18S rRNA), and Hepatozoon with three different fragments of small subunit ribosomal RNA gene (18S rRNA). PCR products were sequenced, aligned, and phylogenetically analyzed. RESULTS: One adult female of Eurasian lynx (#1, adult female) was co-infected with Cytauxzoon manul and Hepatozoon felis genotype I, while an adult male lynx (#2) was infected with C. manul. Interestingly, H. felis genotype I was both detected in a male cub (#3) and two out of five infesting Hyalomma asiaticum ticks. CONCLUSIONS: For the first time, Cytauxzoon manul is reported here from Eurasian lynx. In addition, H. felis has not been known to occur in this host species in China and Central Asia. Thus, the findings of this study extend our knowledge on the geographical distribution and host range of these haemoprotozoan parasites. Moreover, this is also the first evidence of C. manul and H. felis co-infection in Eurasian lynx.

Localized light chain amyloidosis involving the lacrimal sac: A case report.

Amyloidosis involving the lacrimal sac is extremely rare. In this study, we demonstrated a rare case of localized light chain amyloidosis in the lacrimal sac region. The lacrimal sac lesion presented as infiltrative with bony erosion. Given the slow growth of the lesion and the absence of a blood flow signal inside, we concluded that the lesion was less likely to be malignant. Complete removal of the lacrimal sac lesion combined with simultaneous lacrimal passage reconstruction was performed. The diagnosis of light chain amyloidosis was confirmed by histology. The surgical results were favorable, and no recurrence was observed over one-year follow-up. Our case report enriches the understanding of amyloid deposition in the ocular adnexa.

Efficacy and safety of hyperbaric oxygen therapy for long COVID: a protocol for systematic review and meta-analysis.

INTRODUCTION: There is still a lack of therapeutic options for long COVID. Several studies have shown the benefit of hyperbaric oxygen therapy (HBOT) on long COVID. However, the efficacy and safety of HBOT for long COVID remain unclear. Therefore, we will conduct this systematic review to assess the feasibility of HBOT as a primary or complemental therapy for long COVID. METHODS AND ANALYSIS: Databases such as Web of Science, PubMed, Embase, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, International Clinical Trials Registry Platform, Wanfang Database, China National Knowledge Infrastructure, SINOMED, VIP Database and the Chinese Clinical Trial Registry will be searched systematically from the establishment to 9 December 2023. All articles will be reviewed by two independent reviewers. Cochrane risk of bias tool will be used to assess the risk of bias in the study. We will evaluate heterogeneity using a visual inspection of the funnel plot. If an available number of studies are identified, we will perform a meta-analysis. ETHICS AND DISSEMINATION: No ethical approval is required since this study is based on published articles. The findings will be published in a peer-reviewed journal or disseminated through conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023482523.

Outdoor artificial light at night exposure and gestational diabetes mellitus: a case-control study.

Objective: This study aims to explore the association between outdoor artificial light at night (ALAN) exposure and gestational diabetes mellitus (GDM). Methods: This study is a retrospective case-control study. According with quantiles, ALAN has been classified into three categories (Q1-Q3). GDM was diagnosed through oral glucose tolerance tests. Conditional logistic regression models were used to evaluate the association between ALAN exposure and GDM risk. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Restricted cubic spline analysis (RCS) was utilized to investigate the no liner association between ALAN and GDM. Results: A total of 5,720 participants were included, comprising 1,430 individuals with GDM and 4,290 matched controls. Pregnant women exposed to higher levels of ALAN during the first trimester exhibited an elevated risk of GDM compared to those with lower exposure levels (Q2 OR = 1.39, 95% CI 1.20-1.63, p < 0.001); (Q3 OR = 1.70, 95% CI 1.44-2.00, p < 0.001). Similarly, elevated ALAN exposure during the second trimester also conferred an increased risk of GDM (second trimester: Q2 OR = 1.70, 95% CI 1.45-1.98, p < 0.001; Q3 OR = 2.08, 95% CI 1.77-2.44, p < 0.001). RCS showed a nonlinear association between ALAN exposure and GDM risk in second trimester pregnancy, with a threshold value of 4.235. Conclusion: Outdoor ALAN exposure during pregnancy is associated with an increased risk of GDM.

Anaplasma bovis and Bartonella spp. in Libyan Jirds (Meriones libycus) from China.

Anaplasma bovis (1), Bartonella krasnovii (3), and Bartonella sp. (17) were detected in 80 Libyan jirds (Meriones libycus) from China. These findings extend the known host and geographic ranges of these pathogens, with neither A. bovis nor B. krasnovii previously confirmed in Libyan jirds.

Exposure to di-2-ethylhexyl phthalate and breast neoplasm incidence: A cohort study.

BACKGROUND: Phthalates are ubiquitous environmental endocrine disruptors. As the predominant phthalate, di-2-ethylhexyl phthalate (DEHP) has been considered possibly carcinogenic to humans but large-scale longitudinal evidence is needed to further clarify its carcinogenicity. OBJECTIVES: To examine the association between DEHP exposure and incidence of breast malignant neoplasm, carcinoma in situ and benign neoplasm. METHODS: A total of 273,295 women from UK Biobank cohort were followed up for a median of 13.5 years. Disease information was collected from National Health Service Cancer Registry and National Death Index. Baseline and yearly-average level of DEHP exposure were estimated for each individual by linking chemical monitoring record of European Environment Agency with home address of the participants by Kriging interpolation model. Cox proportional hazard model was employed to estimate the association between DEHP exposure and breast neoplasms. RESULTS: The median (IQR) of baseline and yearly-average DEHP concentration were 8000.25 (interquartile range: 6657.85-11,948.83) and 8000.25 (interquartile range: 1819.93-11,359.55) µg/L. The highest quartile of baseline DEHP was associated with 1.11 fold risk of carcinoma in situ (95 % CI, 1.00, 1.23, p < 0.001) and 1.27 fold risk of benign neoplasm (95 % CI, 1.05, 1.54, p < 0.001). As for yearly-average exposure, each quartile of DEHP was positively associated with higher risk of malignant neoplasm (HR, 1.05; 95 % CI, 1.03, 1.07, p < 0.001), carcinoma in situ (HR, 1.08; 95 % CI, 1.04, 1.11, p < 0.001) and benign neoplasm (HR, 1.13; 95 % CI, 1.07, 1.20, p < 0.001). Stratification analysis showed no significant modification effects on the DEHP-neoplasm relationship by menopausal status or ethnicity but a suggestive higher risk in younger women and those who underwent oral contraceptive pill therapy. In sensitivity analysis, the associations remained when excluding the cases diagnosed within 2 years post baseline. CONCLUSIONS: Real-world level of DEHP exposure was associated with higher risk of breast neoplasms. Because of the health risks associated with DEHP, its release to the environment should be managed.

Single-cell and Bulk RNA-Seq reveal angiogenic heterogeneity and microenvironmental features to evaluate prognosis and therapeutic response in lung adenocarcinoma.

Background: Angiogenesis stands as a pivotal hallmark in lung adenocarcinoma (LUAD), intricately shaping the tumor microenvironment (TME) and influencing LUAD progression. It emerges as a promising therapeutic target for LUAD, affecting patients' prognosis. However, its role in TME, LUAD prognosis, and its clinical applicability remain shrouded in mystery. Methods: We employed integrated single-cell and bulk transcriptome sequencing to unravel the heterogeneity of angiogenesis within LUAD cells. Through "consensus clustering", we delineated distinct angiogenic clusters and deciphered their TME features. "Monocle2" was used to unravel divergent trajectories within malignant cell subpopulations of LUAD. Additionally, regulon submodules and specific cellular communication patterns of cells in different angiogenic states were analyzed by "pyscenic" and "Cellchat" algorithms. The "univariate Cox" and "LASSO" algorithms were applied to build angiogenic prognostic models. Immunohistochemistry (IHC) on clinical samples validated the role of model factors in LUAD angiogenesis. We utilized CTRP 2.0 and PRISM databases for pinpointing sensitive drugs against lung adenocarcinoma. Results: Two clusters for the activation of angiogenesis were identified, with Cluster 1 showing a poor prognosis and a pro-cancerous TME. Three differentiated states of malignant epithelial LUAD cells were identified, which had different degrees of angiogenic activation, were regulated by three different regulon submodules, and had completely different crosstalk from other cells in TME. The experiments validate that SLC2A1 promotes angiogenesis in LUAD. ARS (Angiogenesis related score) had a high prognostic value; low ARSs showed immunotherapy benefits, whereas high ARSs were sensitive to 15 chemotherapeutic agents. Conclusion: The assessment of angiogenic clusters helps to determine the prognostic and TME characteristics of LUAD. Angiogenic prognostic models can be used to assess the prognosis, immunotherapeutic response, and chemotherapeutic drug sensitivity of LUAD.

Spatial-temporal characteristics and driving factors' contribution and evolution of agricultural non-CO2 greenhouse gas emissions in China: 1995-2021.

Comprehending the spatial-temporal characteristics, contributions, and evolution of driving factors in agricultural non-CO2 greenhouse gas (GHG) emissions at a macro level is pivotal in pursuing temperature control objectives and achieving China's strategic goals related to carbon peak and carbon neutrality. This study employs the Intergovernmental Panel on Climate Change (IPCC) carbon emissions coefficient method to comprehensively evaluate agricultural non-CO2 GHG emissions at the provincial level. Subsequently, the contributions and spatial-temporal evolution of six driving factors derived from the Kaya identity were quantitatively explored using the Logarithmic Mean Divisia Index (LMDI) and Geographical and Temporal Weighted Regression (GTWR) methods. The results revealed that the distribution of agricultural non-CO2 GHG emissions is shifting from the central provinces to the northwest regions. Moreover, the dominant driving factors of agricultural non-CO2 GHG emissions were primarily economic factor (EDL) with positive impact (cumulative promotion is 2939.61 million metric tons (Mt)), alongside agricultural production efficiency factor (EI) with negative impact (cumulative reduction is 2208.98 Mt). Influence of EDL diminished in the eastern coastal regions but significantly impacted underdeveloped regions such as the northwest and southwest. In the eastern coastal regions, EI gradually became the absolute dominant driver, demonstrating a rapid reduction effect. Additionally, a declining birth rate and rural-to-urban population migration have significantly amplified the driving effects of the population factor (RP) at a national scale. These findings, in conjunction with the disparities in geographic and socioeconomic development among provinces, can serve as a guiding framework for the development of a region-specific roadmap aimed at reducing agricultural non-CO2 GHG emissions.

Near-infrared fluorogenic imaging of carbon monoxide in live cells using palladium-mediated carbonylation.

Here we develop a near infrared (NIR) fluorogenic probe for carbon monoxide (CO) detection and imaging based on palladium-mediated carbonylation using a NIR boron-dipyrromethene difluoride as a fluorophore and tetraethylene glycols as aqueous moieties. The probe is utilized to image exogenous and endogenous CO under different stimulated conditions in live cells.

Myeloid-specific knockout of Notch-1 inhibits MyD88- and TRIF-mediated TLR signaling pathways by regulating oxidative stress-SHP2 axis, thus restraining aneurysm progression.

OBJECTIVE: Notch-1 is a signal regulatory protein with extensive effects in myeloid cells, but its role in aneurysms remains to be fully clarified. In this study, therefore, the aneurysm mouse model with myeloid-specific knockout of Notch-1 was established to observe the role of Notch-1 in aneurysm progression. METHODS AND RESULTS: The effect of Notch-1 was assessed by pathological staining and Western blotting. It was found that after myeloid-specific knockout of Notch-1 in the aneurysm mouse model, the area of aneurysms and the macrophage infiltration were significantly reduced, the damage to arterial elastic plates was significantly relieved, and the oxidative stress level significantly declined. The results of Western blotting showed that after myeloid-specific knockout of Notch-1, the levels of oxidative stress-related proteins p22 and p47 in aneurysm tissues significantly declined, accompanied by a significant increase in the protein level of Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2). In addition, the levels of phosphorylated myeloid differential protein-88 (MyD88), TIR domain-containing adaptor-inducing interferon-ß (TRIF) and nuclear factor-κB (NF-κB), and inflammatory cytokines interferon-γ (IFN-γ), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) also significantly decreased after myeloid-specific knockout of Notch-1. Following myeloid-specific knockout of Notch-1, the phagocytic capacity of macrophages was enhanced by promoting the SHP2 signaling pathway. CONCLUSION: Notch-1 in monocytes/macrophages can activate the Toll-like receptor (TLR)-mediated inflammatory and stress responses by activating oxidative stress and inhibiting the SHP2 protein expression, thus facilitating aneurysm progression.

Global, regional, and national burdens of depressive disorders in adolescents and young adults aged 10-24 years from 1990 to 2019: A trend analysis based on the Global Burden of Disease Study 2019.

BACKGROUND: Depressive disorders (DD) including dysthymia and major depressive disorder (MDD) are common among adolescents and young adults. However, global trends in DD burden remain unclear. METHODS: We analysed data from the Global Burden of Disease 2019 study on incidence, prevalence, disability-adjusted life years (DALYs), and mortality due to DD from 1990 to 2019 at global, regional and national levels. RESULTS: Globally, dysthymia incidence increased notably in females, older age groups, and lower-middle income countries from 1990 to 2019. In contrast, MDD incidence decreased slightly over this period except in high-income North America. Females and middle-income countries had the highest dysthymia burden while North America had the highest MDD incidence and DALYs. Oman and Malaysia experienced largest increases in dysthymia and MDD burden respectively. CONCLUSION: Despite certain global indicators suggesting a leveling off or decrease, it's clear that depressive disorders continue to be a significant and increasing issue, particularly among women, teenagers, and young adults. Differences between regions and countries indicate that specific interventions aimed at addressing economic inequalities, improving healthcare systems, and taking cultural factors into account could make a real difference in lessening the burden of depressive disorders. More research is needed to understand what's driving these trends so that we can develop better strategies for preventing and managing these conditions.

Evaluation of industrial green development based on set pair analysis.

Industrial green development is an important part of the global sustainable development goals, and it is the only way for China to achieve the "dual carbon goals". This paper aims to explore the methods and indicators for the assessment of the level of industrial green development, and emphasizes its applicability in the "city area" scale. According to the characteristics of industrial green development, an evaluation system including 4 first-level indicators of economic benefits and structure, technological innovation and investment, environmental impact and governance, resource consumption and reuse, and a total of 16 s-level indicators were established, each indicator was determined using the entropy value theory The weight value is based on the conditions of 15 sub-provincial cities across the country to determine the standard value of each indicator. Through the set pair analysis of the five-element connection number and partial connection number, the comprehensive connection degree and the full partial connection number are obtained, so as to evaluate the level of industrial green development in Chengdu static evaluation and dynamic analysis. The results show that the constructed index system and evaluation method are applicable to the evaluation of industrial green development at the "city" scale. The current status of Chengdu's industrial green development is at a qualified level, and the industrial process will have a more active and green development trend in the future. The government management department should formulate appropriate management policies and strengthen comprehensive evaluation and research, so as to take the green industrial development process of Chengdu to a new level.

Sequential inspiratory muscle exercise-noninvasive positive pressure ventilation alleviates oxidative stress in COPD by mediating SOCS5/JAK2/STAT3 pathway.

BACKGROUND: Pulmonary rehabilitation training is of great significance for the prognosis of chronic obstructive pulmonary disease (COPD) patients. The purpose of this study was to investigate the therapeutic effect and pathway of a new sequential noninvasive positive pressure ventilation (NIPPV) + inspiratory muscle training (IMT) therapy. METHODS: A total of 100 COPD patients were enrolled and randomly divided into oxygen therapy (OT), NIPPV, IMT and sequential (NIPPV + IMT) group. Lung function, exercise endurance, quality of life, and dyspnea symptoms were examined and recorded. Then, reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) levels were detected by enzyme-linked immunoassay, and suppressor of cytokine signaling 5 (SOCS5)/janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway expression changes were detected by quantitative real time-polymerase chain reaction (qRT-PCR) and western blot. A mouse model of COPD was then established to further verify the effects of SOCS5/JAK2/STAT3 pathways on lung function and oxidative stress. RESULTS: After 8 weeks of treatment, NIPPV, IMT or sequential (NIPPV + IMT) significantly improved exercise endurance, quality of life and dyspnea, reduced oxidative stress, promoted SOCS5 expression and inhibited the activation of JAK2/STAT3 pathway, and no significant effect was observed on lung function of COPD patients. Notably, sequential (NIPPV + IMT) showed better therapeutic outcomes than either IMT or NIPPV alone. Moreover, results at the animal level showed that overexpression of SOCS5 significantly reduced pulmonary inflammatory infiltration, pathological changes and oxidative stress levels in COPD mice, enhanced lung function, and inhibited the activation of JAK2/STAT3 pathway. CONCLUSION: Our results elucidated that sequential (NIPPV + IMT) significantly relieved COPD development by regulating SOCS5/JAK2/STAT3 signaling-mediated oxidative stress.

Genetically Encoded RNA Sensors for Ratiometric and Multiplexed Imaging of Small Molecules in Living Cells.

Genetically encoded sensors afford powerful tools for studying small molecules and metabolites in live cells. However, genetically encoded sensors with a general design remain to be developed. Here we develop genetically encoded RNA sensors with a modular design for ratiometric and multiplexed imaging of small molecules in live cells. The sensor utilizes aptazyme as a recognition module and the light-up RNA aptamer as a signal reporter. The conformation of light-up aptamers is abrogated by a blocking sequence, and aptazyme-mediated cleavage restores the correct conformation, delivering activated fluorescence for small molecule imaging. We first developed a genetically encoded ratiometric sensor using Mango aptamer as a reference and SRB2 as a reporter. It is shown that the sensor allows quantitative imaging and detection of theophylline in live cells. The generality of the design is further demonstrated for imaging other small molecules by replacing the aptazymes. Its ability for multiplexed imaging of small molecules is further explored via the integration of different small-molecule responsive aptazymes and light-up RNA aptamers. This modular design could offer a versatile platform for imaging diverse molecules in living cells.