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The deteriorating global environment has attracted wide attention in various countries. How to curb environmental pollution and achieve sustainable economic growth has become an urgent problem that we must face. As an effective tool for pollution control, environmental tax has been implemented in many developed countries and has achieved good results. As the largest developing country in the world, China introduced the first environmental tax law in its history in December 2016, which is regarded as a major reform of the green tax system. To explore the implementation effect of environmental tax in China, this paper takes 3867 Chinese listed enterprises (2015-2020) in Shanghai and Shenzhen A shares as the research sample and explores the microeconomic effect of environmental tax reform using the difference in difference (DID) method. It is concluded that the environmental tax reform can produce a positive impact on the corporate profit margins while curbing the enterprise pollution behavior. This positive effect comes from the investment improvement effect and the cost-saving effect, and this effect is heterogeneous between different regions and property rights enterprises. Therefore, the design of the tax system must be implemented with different measures. Environmental taxes have achieved positive policy results in China, contributing to sustainable economic growth. This tax reform has an important reference value for the developing countries in the industrialization stage.

Background Pancreatic adenocarcinoma (PAAD) is a leading cause of malignancy-related deaths worldwide, and the efficacy of immunotherapy on PAAD is limited. Studies report that long non-coding RNAs (lncRNAs) play an important role in modulating genomic instability and immunotherapy. However, the identification of genome instability-related lncRNAs and their clinical significance has not been investigated in PAAD. Methods The current study developed a computational framework for mutation hypothesis based on lncRNA expression profile and somatic mutation spectrum in pancreatic adenocarcinoma genome. We explored the potential of GInLncRNAs(genome instability-related lncRNAs) through co-expression analysis and function enrichment analysis. We further analyzed GInLncRNAs by Cox regression and used the results to construct a prognostic lncRNA signature. Finally, we analyzed the relationship between GILncSig (genomic instability derived 3-lncRNA signature) and immunotherapy. Results A GILncSig was developed using bioinformatics analyses. It could divide patients into high-risk and low-risk groups, and there was a significant difference in OS between the two groups. In addition, GILncSig was associated with genome mutation rate in pancreatic adenocarcinoma, indicating its potential value as a marker for genomic instability. The GILncSig accurately grouped wild type patients of KRAS into two risk groups. The prognosis of the low-risk group was significantly improved. GILncSig was significantly correlated with the level of immune cell infiltration and immune checkpoint. Conclusions In summary, the current study provides a basis for further studies on the role of lncRNA in genomic instability and immunotherapy. The study provides a novel method for identification of cancer biomarkers related to genomic instability and immunotherapy.

Purpose The present study aimed to investigate the preliminary safety and efficacy of rheolytic thrombectomy (RT) using an AngioJet Zelante DVT catheter or a Solent Omni catheter for acute proximal deep vein thrombosis (DVT). Material and methods We conducted a retrospective review of 40 patients who were treated with an AngioJet RT between January 2019 and January 2021, and then the patients were divided into the ZelanteDVT group (n = 17) and the Solent group (n = 23). Data on demographics, clinical characteristics, technical success, clinical success, complications, and early follow-up were analysed. Results No significant differences regarding demographics were detected (all p > .05). The technical success rates were both 100%. The ZelanteDVT group had a shorter duration of RT and a higher primary RT success than the Solent group (all p p = .010). The clinical success rates for the ZelanteDVT group and Solent group were 100% (17/17) and 95.7% (22/23), respectively, and these values were high in the two groups (p > .05). Apart from transient macroscopic haemoglobinuria occurring in all the patients during the first 24 hours post-RT, none of the patients in either group suffered other procedure-related adverse events or major complications. Minor complications included bleeding events in 21.7% (5/23) of the patients in the Solent group and one (5.9%) patient in the ZelanteDVT group (p > .05). At 6 months, the frequency of PTS was 5.9% (1/17) in the ZelanteDVT group and 17.4% (4/23) in the Solent group (p > .05). Conclusion Both catheters are safe and effective in managing patients with proximal DVT, thus leading to improved clinical outcomes with few complications. The ZelanteDVT catheter was more effective than the Solent catheter in thrombectomy, thus allowing for faster extraction of the DVT with a shorter run time and lower proportions of patients with adjunctive CDT.

Integrins are considered the main cell-adhesion transmembrane receptors that play multifaceted roles as extracellular matrix (ECM)-cytoskeletal linkers and transducers in biochemical and mechanical signals between cells and their environment in a wide range of states in health and diseases. Integrin functions are dependable on a delicate balance between active and inactive status via multiple mechanisms, including protein-protein interactions, conformational changes, and trafficking. Due to their exposure on the cell surface and sensitivity to the molecular blockade, integrins have been investigated as pharmacological targets for nearly 40 years, but given the complexity of integrins and sometimes opposite characteristics, targeting integrin therapeutics has been a challenge. To date, only seven drugs targeting integrins have been successfully marketed, including abciximab, eptifibatide, tirofiban, natalizumab, vedolizumab, lifitegrast, and carotegrast. Currently, there are approximately 90 kinds of integrin-based therapeutic drugs or imaging agents in clinical studies, including small molecules, antibodies, synthetic mimic peptides, antibody–drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapy, imaging agents, etc. A serious lesson from past integrin drug discovery and research efforts is that successes rely on both a deep understanding of integrin-regulatory mechanisms and unmet clinical needs. Herein, we provide a systematic and complete review of all integrin family members and integrin-mediated downstream signal transduction to highlight ongoing efforts to develop new therapies/diagnoses from bench to clinic. In addition, we further discuss the trend of drug development, how to improve the success rate of clinical trials targeting integrin therapies, and the key points for clinical research, basic research, and translational research.

Stem cell senescence and exhaustion are closely related to organ failure and individual aging, which not only induces age-related diseases, but also hinders stem cell applications in regenerative medicine. Thus, it's imminent to find effective ways to delay and retrieve stem cell senescence. Metabolic abnormalities are one of the main characteristics of age-associated declines in stem cell function. Understanding the underlying mechanisms may reveal potential strategies for ameliorating age-associated phenotypes and treating age-related diseases. This review focuses on recent advances in the association between metabolism including glucose, lipid, glutamine and NAD

The "bivalent domain" is a unique histone modification region consisting of two histone tri-methylation modifications. Over the years, it has been revealed that the maintenance and dynamic changes of the bivalent domains play a vital regulatory role in the differentiation of various stem cell systems, as well as in other cells, such as immunomodulation. Tri-methylation modifications involved in the formation of the bivalent domains are interrelated and mutually regulated, thus regulating many life processes of cells. Tri-methylation of histone H3 at lysine 4 (H3K4me3), tri-methylation of histone H3 at lysine 9 (H3K9me3) and tri-methylation of histone H3 at lysine 27 (H3K27me3) are the main tri-methylation modifications involved in the formation of bivalent domains. The three form different bivalent domains in pairs. Furthermore, it is equally clear that H3K4me3 is a positive regulator of transcription and that H3K9me3/H3K27me3 are negative regulators. Enzymes related to the regulation of histone methylation play a significant role in the "homeostasis" and "breaking homeostasis" of the bivalent domains. Bivalent domains regulate target genes, upstream transcription, downstream targeting regulation and related cytokines during the establishment and breakdown of homeostasis, and exert the specific regulation of stem cells. Indeed, a unified mechanism to explain the bivalent modification in all stem cells has been difficult to define, and whether the bivalent modification is antagonistic in inducing the differentiation of homologous stem cells is controversial. In this review, we focus on the different bivalent modifications in several key stem cells and explore the main mechanisms and effects of these modifications involved. Finally, we discussed the close relationship between bivalent domains and immune cells, and put forward the prospect of the application of bivalent domains in the field of stem cells.

The viscoplastic behavior of solder material is investigated from different scales. Due to the thermal stress in Sn–3.0Ag–0.5Cu alloy at elevated temperatures, the continuous accumulation of unrecoverable deformation becomes the key of interconnections failure in microelectronic packaging. In the current study, the rate and temperature dependence of inelastic deformation and cyclic hardening properties of Sn–3.0Ag–0.5Cu alloy under different loading conditions are studied. A novel phenomenological constitutive model is developed to describe the deformation of lead-free solder interconnections in the microelectronic packaging. The developed model is verified by comparing with the experimental data of bulk solder materials. The results show that the proposed model can accurately describe the viscoplastic properties of bulk solder materials and shows excellent numerical stability. For understanding better the overall deformation behaviors of solder joins, especially the strain–stress relationship, uniaxial compression experiments of spherical joint-scale granules were conducted under different loading rates. The developed model is applied to simulate the compression testing of granules. It shows that the developed model can characterize the viscoplastic compression deformation of Sn–3.0Ag–0.5Cu solder on joint-scale with reasonable accuracy.

Background Stem cell senescence is considered as a significant driver of organismal aging. As individuals age, the number of stem cells is declined, and the ability to proliferate and survive is also weakened. It has been reported that metabolism plays an important role in stem cell self-renewal, multilineage differentiation, senescence and fate determination, which has aroused widespread concerns. However, whether metabolism-related genes or signalling pathways are involved in physiological aging remain largely undetermined. Results In the current study, we showed 868 up-regulated and 2006 down-regulated differentially expressed genes (DEGs) in bone marrow mesenchymal stem cells (MSCs) from old rats in comparison with that from young rats by performing RNA sequence. And DEGs functions and pathways were further selected by function enrichment analysis. The results indicated that the high expression of DEGs might participate in cell differentiation, growth factor binding and etc., while the down-regulated DEGs were majorly enriched in metabolism process, such as the cellular metabolic process and mitochondria. Then, we screened and verified DEGs related to glucose metabolism and investigated the glycolysis levels. We identified that glucose uptake, lactate secretion, ATP production and relative extracellular acidification rates (ECAR) were all diminished in MSCs from old rats. More importantly, we conducted microRNA prediction on the key DEGs of glycolysis to elucidate the potential molecular mechanisms of glucose metabolism affecting MSC senescence. Conclusions Our study unravelled the profiles of DEGs in age-associated MSC senescence and their functions and pathways. We also clarified DEGs related to glucose metabolism and down-regulated glycolysis level in age-associated MSC senescence. This study will uncover the metabolic effects on regulating stem cell senescence, and provide novel therapeutic targets for ameliorating age-associated phenotypes.

CdS/CdSe composite window layer is a better candidate than CdS or CdSe single layer for CdTe solar cells. In order to find the underlying reason, the properties of co-sputtered CdSe1−xSx thin films with different compositions ( $$0\le x\le 1$$ ) were examined. XRD patterns show that all CdSe1−xSx films ( $$0\le x\le 1$$ ) are polycrystalline with hexagonal structures and the prominent peak position shows an increasing trend with the increase of x. This suggests that CdSe1−xSx window layer with a gradient composition, formed during the high-temperature growth and heat treatment of CdTe films, has the gradient lattice constant, meaning the less defect density. This is beneficial to the device performance. Hall measurements show that CdS1−xSex films (x ≥ 0.772) are n-type semiconductors with carrier concentrations ranging from 1015 cm−3 to 1016 cm−3. It reveals that CdS/CdSe bi-layers can form a strong built-in electric field with CdTe layer as CdS does. The electronic band structure of CdSe1−xSx window layer with a gradient composition suggests that the spikes formed in the conduction band are lower than 0.3 eV, which would not impede the electron transport. The valence band alignment is beneficial for the hole transport. Therefore, an appropriate band alignment can be formed between CdSe1−xSx and CdTe layers. These results reveal that CdSe1−xSx film is a good candidate as the window layer for high-efficiency CdTe solar cells considering its structural, optical and electrical properties as well as its electronic structure.

Under asymmetrical stress-controlled cyclic loading accompanied by ratcheting, the evolution of microscopic substructures of stainless steel 304 (SS304), a face-centered cubic metal, was detected using transmission electron microscopy (TEM). This observation demonstrates that dislocation slip is the main mechanism of uniaxial ratcheting in the non-steady stage (stage I). Dislocation proliferate rapidly duo to the high stress level of the cyclic tests, and dislocation density increases continuously with the the number of cycles. The ratcheting rate decreases continuously due to the interaction of moveable dislocations, and the planar dislocation substructures (dislocation pileups and tangles) are the dominant patterns in this stage. In the later stage I, distinct lath $$\alpha $$ -martensite was observed in the material due to the nucleation of martensite and the phase transformation zones increase gradually with the growth of axial ratcheting strain in the stage II of uniaxial ratcheting. The multiply and cross-slip were activated gradually in increasing numbers of grains, and the prevailing dislocation configurations evolve into more complicated and stable ones (dislocation walls and cells). In addition the dislocation configurations after various prescribed tensile strain of the monotonic tension and creep deformation with three different holding times were also observed by TEM. Comparing the evolution of microscopic substructures in various loading modes, the physical mechanism of uniaxial ratcheting of SS304 can be revealed as combination of the evolution of dislocation configurations and martensite transformation in the stage II of uniaxial ratcheting.

A Monte Carlo Potts model was developed to simulate the recrystallization process of a cold-rolled ultra-thin grain-oriented silicon steel. The orientation and image quality data from electron backscatter diffraction measurements were used as input information for simulation. Three types of nucleation mechanisms, namely, random nucleation, high-stored-energy site nucleation (HSEN), and high-angle boundary nucleation (HABN), were considered for simulation. In particular, the nucleation and growth behaviors of Goss-oriented ({011} ) grains were investigated. Results showed that Goss grains had a nucleation advantage in HSEN and HABN. The amount of Goss grains was the highest according to HABN, and it matched the experimental measurement. However, Goss grains lacked a size advantage across all mechanisms during the recrystallization process.

The management of acute massive pulmonary embolism (PE) patients who did not respond to systemic thrombolysis (ST) has not been well established. The present study aimed to investigate the safety and effectiveness of catheter-based therapies (CDT) in this condition. We conducted a retrospective study of PE patients after unsuccessful ST (UST) between January 2012 and January 2018. Massive PE was identified in 408 patients and treated with full-dose ST therapy. Thrombolysis at 36 h was judged to be unsuccessful in 52 patients. Four ineligible patients were excluded, and the remaining 48 patients underwent rescue CDT: 30 patients underwent thrombus fragmentation with a rotating pigtail catheter; 8 patients underwent Straub rotational thrombectomy; and 10 patients underwent AngioJet rheolytic thrombectomy. In total, 42 patients subsequently underwent CDT relative to reduced-dose thrombolysis. Pooled clinical success was achieved in 45 patients, and the time-to-clinical instability relief for CDT was short (i.e., 48 h). Clinical findings significantly improved with oxygen saturation and the shock index (p