Experimental and computational study on anti-gastric cancer activity and mechanism of evodiamine derivatives.

Introduction: Human topoisomerase 1 (TOP1) is an important target of various anticancer compounds. The design and discovery of inhibitors targeting TOP1 are of great significance for the development of anticancer drugs. Evodiamine and thieno [2,3-d] pyridine hybrids show potential antitumor activity. Herein, the anti-gastric cancer activities of these hybrids were investigated. Methods: The inhibitory effects of different concentrations of ten evodiamine derivatives on the gastric cancer cell line SGC-7901 were assessed using a methyl thiazolyl tetrazolium assay. Compounds EVO-1 and EVO-6 strongly inhibited gastric cancer cell proliferation, with inhibition rates of 81.17% ± 5.08% and 80.92% ± 2.75%, respectively. To discover the relationship between the structure and activity of these two derivatives, density functional theory was used to investigate their optimized geometries, natural population charges, frontier molecular orbitals, and molecular electrostatic potentials. To clarify their anti-gastric cancer mechanisms, molecular docking, molecular dynamics simulations, and binding free energy calculations were performed against TOP1. Results: The results demonstrated that these compounds could intercalate into the cleaved DNA-binding site to form a TOP1-DNA-ligand ternary complex, and the ligand remained secure at the cleaved DNA-binding site to form a stable ternary complex. As the binding free energy of compound EVO-1 with TOP1 (-38.33 kcal·mol-1) was lower than that of compound EVO-6 (-33.25 kcal·mol-1), compound EVO-1 could be a more potent anti-gastric cancer agent than compound EVO-6. Discussion: Thus, compound EVO-1 could be a promising anti-gastric cancer drug candidate. This study may facilitate the design and development of novel TOP1 inhibitors.

Bariatric Surgery Improves Cognition Function in the Patients with Obesity: A Meta-Analysis.

Obesity and related comorbidities have negative impacts on cognitive function. Weight loss seems to be associated with the improvement of cognitive function and the recovery of brain structure, but the underlying mechanism is not clear. This meta-analysis aimed to explore the status of cognitive function including memory, executive function, attention and language ability in patients with obesity, and to further investigate whether bariatric surgery can improve overall cognitive function in these patients. A total of 11 literatures with 728 subjects were included after retrieval and exclusion. The meta-analysis showed significant improvements in memory, attention and executive function scores after undergoing bariatric surgery in the patients with obesity. However, there was no significant improvement in language ability.

The effective combination therapies with irinotecan for colorectal cancer.

Colorectal cancer is the third most common type of cancer worldwide and has become one of the major human disease burdens. In clinical practice, the treatment of colorectal cancer has been closely related to the use of irinotecan. Irinotecan combines with many other anticancer drugs and has a broader range of drug combinations. Combination therapy is one of the most important means of improving anti-tumor efficacy and overcoming drug resistance. Reasonable combination therapy can lead to better patient treatment options, and inappropriate combination therapy will increase patient risk. For the colorectal therapeutic field, the significance of combination therapy is to improve the efficacy, reduce the adverse effects, and improve the ease of treatment. Therefore, we explored the clinical advantages of its combination therapy based on mechanism or metabolism and reviewed the rationale basis and its limitations in conducting exploratory clinical trials on irinotecan combination therapy, including the results of clinical trials on the combination potentiation of cytotoxic drugs, targeted agents, and herbal medicine. We hope that these can evoke more efforts to conduct irinotecan in the laboratory for further studies and evaluations, as well as the possibility of more in-depth development in future clinical trials.

Structure-based development of potent and selective type-II kinase inhibitors of RIPK1.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Construction of an enteral nutrition evaluation system for critically ill patients based on the Delphi method.

BACKGROUND: This study aimed to construct an enteral nutrition evaluation system for critically ill patients using the Delphi method to direct the formulation of enteral nutrition support strategies and reduce interruption to enteral feeding. METHODS: We used domestic and foreign databases to obtain and analyze the literature and form "The Whole-Proceeding Enteral Nutrition Evaluation System for Critically Ill Patients." The Delphi method was used to conduct two rounds of expert opinion consultation, combined with the suggestions from the research group to finalize the nutrition evaluation content of the system. RESULTS: After two rounds of expert consultation, a nutrition evaluation system was formed around three dimensions: before the start, during, and after the end of nutritional support. The effective recovery rates of the two rounds of expert consultation were 90.0% (18/20) and 100.0% (18/18), respectively. Authority coefficients were 0.865 and 0.908, while Kendall coordination coefficients were 0.108 ( P < 0.05) and 0.115 ( P < 0.001), respectively. Finally, the full enteral nutrition evaluation system for critically ill patients was constructed based on the Delphi method, including three primary items and seven secondary and 28 tertiary indicators. CONCLUSION: The established "Whole-Proceeding Enteral Nutrition Evaluation System for Critically Ill Patients" has high consistency from expert opinions and reliability, which can provide a practical evaluation tool for the process of enteral nutrition for severe patients.

Small molecule activators of TAK1 promotes its activity-dependent ubiquitination and TRAIL-mediated tumor cell death.

TAK1 is a key modulator of both NF-κB signaling and RIPK1. In TNF signaling pathway, activation of TAK1 directly mediates the phosphorylation of IKK complex and RIPK1. In a search for small molecule activators of RIPK1-mediated necroptosis, we found R406/R788, two small molecule analogs that could promote sustained activation of TAK1. Treatment with R406 sensitized cells to TNF-mediated necroptosis and RIPK1-dependent apoptosis by promoting sustained RIPK1 activation. Using click chemistry and multiple biochemical binding assays, we showed that treatment with R406 promotes the activation of TAK1 by directly binding to TAK1, independent of its original target Syk kinase. Treatment with R406 promoted the ubiquitination of TAK1 and the interaction of activated TAK1 with ubiquitinated RIPK1. Finally, we showed that R406/R788 could promote the cancer-killing activities of TRAIL in vitro and in mouse models. Our studies demonstrate the possibility of developing small molecule TAK1 activators to potentiate the effect of TRAIL as anticancer therapies.

New role of astrocytes in neuroprotective mechanisms after ischemic stroke.

Astrocytes are the most abundant cell subtypes in the central nervous system. Previous studies believed that astrocytes are supporting cells in the brain, which only provide nutrients for neurons. However, recent studies have found that astrocytes have more crucial and complex functions in the brain, such as neurogenesis, phagocytosis, and ischemic tolerance. After an ischemic stroke, the activated astrocytes can exert neuroprotective or neurotoxic effects through a variety of pathways. In this review, we will discuss the neuroprotective mechanisms of astrocytes in cerebral ischemia, and mainly focus on reactive astrocytosis or glial scar, neurogenesis, phagocytosis, and cerebral ischemic tolerance, for providing new strategies for the clinical treatment of stroke.

Os astrócitos são os subtipos de células mais abundantes no sistema nervoso central. Estudos anteriores acreditavam que os astrócitos são células de suporte no cérebro, que apenas fornecem nutrientes para os neurônios. No entanto, estudos recentes descobriram que os astrócitos têm funções mais cruciais e complexas no cérebro, como neurogênese, fagocitose e tolerância isquêmica. Após um acidente vascular cerebral isquêmico, os astrócitos ativados podem exercer efeitos neuroprotetores ou neurotóxicos através de uma variedade de vias. Nesta revisão, discutiremos os mecanismos neuroprotetores dos astrócitos na isquemia cerebral, e focaremos principalmente na astrocitose reativa ou cicatriz glial, neurogênese, fagocitose e tolerância isquêmica cerebral, para fornecer novas estratégias para o tratamento clínico do acidente vascular cerebral.

New role of astrocytes in neuroprotective mechanisms after ischemic stroke / Novo papel dos astrócitos nos mecanismos neuroprotetores após acidente vascular cerebral isquêmico

Abstract Astrocytes are the most abundant cell subtypes in the central nervous system. Previous studies believed that astrocytes are supporting cells in the brain, which only provide nutrients for neurons. However, recent studies have found that astrocytes have more crucial and complex functions in the brain, such as neurogenesis, phagocytosis, and ischemic tolerance. After an ischemic stroke, the activated astrocytes can exert neuroprotective or neurotoxic effects through a variety of pathways. In this review, we will discuss the neuroprotective mechanisms of astrocytes in cerebral ischemia, and mainly focus on reactive astrocytosis or glial scar, neurogenesis, phagocytosis, and cerebral ischemic tolerance, for providing new strategies for the clinical treatment of stroke.

Resumo Os astrócitos são os subtipos de células mais abundantes no sistema nervoso central. Estudos anteriores acreditavam que os astrócitos são células de suporte no cérebro, que apenas fornecem nutrientes para os neurônios. No entanto, estudos recentes descobriram que os astrócitos têm funções mais cruciais e complexas no cérebro, como neurogênese, fagocitose e tolerância isquêmica. Após um acidente vascular cerebral isquêmico, os astrócitos ativados podem exercer efeitos neuroprotetores ou neurotóxicos através de uma variedade de vias. Nesta revisão, discutiremos os mecanismos neuroprotetores dos astrócitos na isquemia cerebral, e focaremos principalmente na astrocitose reativa ou cicatriz glial, neurogênese, fagocitose e tolerância isquêmica cerebral, para fornecer novas estratégias para o tratamento clínico do acidente vascular cerebral.

Transcriptome analysis reveals the neuroprotective effect of Dlg4 against fastigial nucleus stimulation-induced ischemia/reperfusion injury in rats.

BACKGROUND: Previous studies have demonstrated that electrical stimulation of the cerebellar fastigial nucleus (FNS) can considerably decrease infarction volume and improve neurofunction restoration following cerebral ischemia. Nevertheless, the molecular mechanism of the neuroprotective effect of FNS is still vague. METHODS: In this study, we developed a rat model of ischemia/reperfusion that included 1 h FNS followed by reperfusion for 3, 6, 12, 24, and 72 h. The expression profile of molecular alterations in brain tissues was obtained by transcriptome sequencing at five different time points. The function and pathway of miRNA expression pattern and core genes were annotated by Allen Brain Atlas, STRING database and Cytoscape software, so as to explore the mechanism of FNS-mediated neuroprotection. RESULTS: The results indicated that FNS is associated with the neurotransmitter cycle pathway. FNS may regulate the release of monoamine neurotransmitters in synaptic vesicles by targeting the corresponding miRNAs through core Dlg4 gene, stimulate the Alternative polyadenylation (APA) incident's anti -apoptosis effect on the brain, and stimulate the interaction activation of neurons in cerebellum, cortex/thalamus and other brain regions, regulate neurovascular coupling, and reduce cerebral damage. CONCLUSION: FNS may activate neuronal and neurovascular coupling by regulating the release of neurotransmitters in synaptic vesicles through the methylation of core Dlg4 gene and the corresponding transcription factors and protein kinases, inducing the anti-apoptotic mechanism of APA events. The findings from our investigation offer a new perspective on the way brain tissue responds to FNS-driven neuroprotection.

Isotopic signatures unveil the lead sources and migration in surface mangrove sediments.

Mangrove sediments act as both sinks and secondary sources for lead (Pb), yet the sources, migration, and transformations of Pb in mangrove environments are poorly understood. In this study, Pb concentration in three mangrove sediments adjacent to different land-use types was evaluated. The Pb sources were quantitatively identified using Pb isotopes. Our data indicated minor Pb contamination in the mangrove sediments, possibly due to the relative lack of developed industry in this region. The Pb isotopic ratios suggested, on average, natural sources, coal combustion, agricultural activities, and traffic-related emissions respectively contributed approximately 61.4 %, 18.8 %, 14.0 %, and 5.8 % of the Pb accumulation in the mangrove sediments, suggesting that coal combustion and agriculture were important anthropogenic Pb sources. Significant relationships were observed between the 206Pb/207Pb ratios and total organic content (TOC) in mangrove sediments, which implied contrasting Pb cycling in two mangrove environments. We further suggested that organic matter and sulfur content significantly reduced Pb mobility and bioavailability in mangrove sediments. Our study provides isotopic method to investigate the Pb sources and migration in the mangrove environment.

Arsenic and Diabetes Mellitus: A Putative Role for the Immune System.

Diabetes mellitus (DM) is an enormous public health issue worldwide. Recent data suggest that chronic arsenic exposure is linked to the risk of developing type 1 and type 2 DM, albeit the underlying mechanisms are unclear. This review discusses the role of the immune system as a link to possibly explain some of the mechanisms of developing T1DM or T2DM associated with arsenic exposure in humans, animal models, and in vitro studies. The rationale for the hypothesis includes: (1) Arsenic is a well-recognized modulator of the immune system; (2) arsenic exposures are associated with increased risk of DM; and (3) dysregulation of the immune system is one of the hallmarks in the pathogenesis of both T1DM and T2DM. A better understanding of DM in association with immune dysregulation and arsenic exposures may help to understand how environmental exposures modulate the immune system and how these effects may impact the manifestation of disease.

Autoimmune Glial Fibrillary Acidic Protein (Gfap) Astrocytopa-Thy Accompanied with Reversible Splenial Lesion Syndrome (RESLES): A Case Report and Literature Review.

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy usually presents as meningoencephalomyelitis. Many patients developed flu-like symptoms preceding the neurologic symptoms. Reversible lesion in the splenium of the corpus callosum (SCC) is a clinical and radiological syndrome secondary to many kinds of etiologies, including infections, which is termed RESLES. CASE PRESENTATION: we reported a case developing irregularly high fever, both temporal pain, low limbs fatigue with frequent urination admitted to our neurology department. CSF test showed GFAP-IgG positive, elevated WBC counts and protein, with low glucose and chlorine, while MRI showed a reversible lesion on SCC, leading us to diagnose autoimmune GFAP autocytopathy accompanied with RESLES. The boy had significantly improved after anti-virus and steroids therapy. DISCUSSION: Autoimmune GFAP autocytopathy accompanied with RESLES is rarely seen, and pathogenesis for the co-existence has not been clarified. Autoimmune GFAP autocytopathy and RESLES are both related to viral infection. Our case covered infectious symptoms and improved after antiviral treatment, suggesting virus infection may perform a key role in pathogenesis.

Single-component full-color emitting Ca6Y2Na2(PO4)6F2:Eu2+,Tb3+,Mn2+ phosphors with superior performance: color-tunable and energy transfer study.

Highly efficient single-component full-color emitting Ca6Y2Na2(PO4)6F2 (CYNPF):Eu2+,Tb3+,Mn2+ phosphors have been synthesized by a high-temperature solid-state reaction. Coupled with the Eu2+, Tb3+, and Mn2+ emission bands centered at 455 nm, 547 nm, and 580 nm, color-tunable white light can be generated. The energy transfer (ET) process from Eu2+ to Tb3+ and Mn2+ is attributed to the resonant dipole-dipole/dipole-dipole interaction mechanism with ultra-high ET efficiency (>90%). The emission color of the phosphors can be tuned from blue to yellowish green and orange with the corresponding CIE chromaticity coordinates of (0.1719, 0.1215), (0.2852, 0.4289), and (0.4752, 0.3903), respectively. Through controlling the concentration ratio of Tb3+ and Mn2+ ions, optimal white light emission can be obtained with CIE coordinates of (0.3381, 0.3353) excited at 365 nm, which is very close to the National Television Standards Committee white (0.330, 0.330). The thermal stability of the Eu2+, Tb3+, and Mn2+ codoped CYNPF phosphors has been investigated systematically. A single-component white LED (wLED) device has been fabricated by combining the CYNPF:Eu2+,Tb3+,Mn2+ phosphor with a 365 nm near-ultraviolet (n-UV) LED chip, which exhibits a high color rendering index (Ra = 80.2) along with a low color temperature of 5207 K and CIE coordinates of (0.3212, 0.3221). The results suggest that the phosphors can be used as a candidate material for single-component white phosphors for n-UV excited full-visible-spectrum wLEDs.

Construction of pain prediction model for patients undergoing hepatic arterial chemoembolization.

OBJECTIVE: To construct a predictive model for pain in patients undergoing hepatic arterial chemoembolization (TACE) in interventional operating room. METHODS: Through literature review and expert interviews, a questionnaire was prepared for the assessment of pain factors in patients with hepatic arterial chemoembolization. A prospective cohort study was used to select 228 patients with hepatic arterial chemoembolization in a tertiary and first-class hospital. The data of the patients in the pain group and the non-pain group were compared, and a rapid screening prediction model was constructed by univariate analysis and logistic regression analysis, and its prediction effect was tested. RESULTS: Tumor size, liver cancer stage, and chemoembolization with drug-loaded microspheres and pirarubicin hydrochloride (THP) mixed with lipiodol were independent predictors of pain in patients after hepatic arterial chemoembolization. Finally, the pain prediction model after TACE was obtained. The results of Hosmer-Lemeshow test showed that the model fit was good (χ2 = 13.540, p = 0.095). The area under the receiver operating characteristic curve was 0.798, p < 0.001. CONCLUSION: The rapid screening and prediction model of pain in patients undergoing hepatic arterial chemoembolization has certain efficacy, which is helpful for clinical screening of patients with high risk of pain, and can provide reference for predictive pain management decision-making.

CDC42 Might Be a Molecular Signature of DWI-FLAIR Mismatch in a Nonhuman Primate Stroke Model.

No definitive blood markers of DWI-FLAIR mismatch, a pivotal indicator of salvageable ischemic penumbra brain tissue, are known. We previously reported that CDC42 and RHOA are associated with the ischemic penumbra. Here, we investigated whether plasma CDC42 and RHOA are surrogate markers of DWI-FLAIR mismatch. Sixteen cynomolgus macaques (3 as controls and 13 for the stroke model) were included. Guided by digital subtraction angiography (DSA), a middle cerebral artery occlusion (MCAO) model was established by occluding the middle cerebral artery (MCA) with a balloon. MRI and neurological deficit scoring were performed to evaluate postinfarction changes. Plasma CDC42 and RHOA levels were measured by enzyme-linked immunosorbent assay (ELISA). The stroke model was successfully established in eight monkeys. Based on postinfarction MRI images, experimental animals were divided into a FLAIR (-) group (N = 4) and a FLAIR (+) group (N = 4). Plasma CDC42 in the FLAIR (-) group showed a significant decrease compared with that in the FLAIR (+) group (p < 0.05). No statistically significant difference was observed for plasma RHOA. The FLAIR (-) group showed a milder neurological function deficit and a smaller infarct volume than the FLAIR (+) group (p < 0.05). Therefore, plasma CDC42 might be a new surrogate marker for DWI-FLAIR mismatch.

lncfos/miR-212-5p/CASP7 Axis-Regulated miR-212-5p Protects the Brain Against Ischemic Damage.

miR-212-5p has been reported to be involved in many biological processes. However, the role of miR-212-5p in ischemic stroke remains unclear. This study explored the biological role and potential mechanism of miR-212-5p in ischemic stroke by investigating the lncfos/miR-212-5p/CASP7 axis. A total of 32 patients with ischemic stroke and 32 age- and sex-matched healthy controls (HCs) were enrolled in this study. In addition, 336 rats were used in this study. The rats were subjected to middle cerebral artery occlusion (MCAO) and intracerebroventricular injection of a microRNA (miRNA) agomir, a miRNA antagomir, a short hairpin RNA (shRNA) lentiviral vector, or a negative control. The neurological deficit score was calculated; the infarct volume was measured; histopathological assays were performed; the neuronal apoptosis rate was determined; and the lncfos, miR-212-5p, and CASP7 expression levels in the peri-infarct area were assessed. In this study, we found that the expression level of miR-212-5p was significantly downregulated in the peri-infarct area and blood of the MCAO model rats and the blood of patients with ischemic stroke. A double-luciferase experiment showed that CASP7 was a direct target gene of miR-212-5p and that miR-212-5p was a target miRNA of lncfos. Lateral ventricular injection of the miR-212-5p agomir effectively inhibited the apoptosis induced by ischemic brain damage, reduced the infarct volume, attenuated the neurological deficit symptoms, and downregulated the expression of CASP7 in the peri-infarct area of the MCAO model rats. Suppressing lncfos with sh-fos led to the upregulated expression of miR-212-5p and played a neuroprotective role in the rat MCAO models. We concluded that miR-212-5p plays a neuroprotective role in ischemic stroke and that its function is regulated by the lncfos/miR-212-5p/CASP7 axis. Moreover, miR-212-5p may be a potential biomarker and therapeutic target for ischemic stroke.

Eukaryotic community succession on discarded face masks in the marine environment.

Wearing facemasks remains an essential strategy for combating the COVID-19 pandemic. However, used masks are becoming plastic wastes that are widespread in the oceans, which is raising concerns about the potential impacts of these novel plastic niches on marine organisms. To delve into this issue, we exposed surgical masks to coastal waters for 30 days. Valuable information was recorded weekly in regard to the succession of the eukaryotic community inhabiting the masks via high-throughput 18S rRNA gene sequencing. Generally, the community on masks was significantly distinct from that in the surrounding seawater. With 1150 different eukaryotic taxa identified, the diversity of the vigorous colonizers of masks peaked at the beginning and decreased over time. A hallmark of initial colonization was the aggregation of diatoms, which formed biofilms on masks, followed by dinoflagellates that acted as a turning point for subsequent development of calcified species and other predators. This study provides insight into the eukaryotic community dynamics on discarded masks in the marine environment and highlights that the potential mask-mediated harmful species clustering may threaten the marine ecosystem.

Summary of the evidence of best practices for the prevention and treatment of embolism syndrome after TACE in primary liver cancer.

Objective: This study aims to retrieve, evaluate, and summarize domestic and foreign evidence on the prevention and treatment of embolism syndrome following transcatheter arterial chemoembolization (TACE) for primary liver cancer and to provide an evidence-based foundation for clinical practice. Methods: Utilizing the "6S" model, we conducted a systematic search of UpToDate, BMJ Best Practice, domestic and foreign guidelines, and related databases on the prevention and treatment of embolism syndrome following TACE for primary liver cancer. This search included clinical decision-making, guidelines, systematic reviews, evidence summaries, randomized controlled trials, and expert consensus. The search time frame extended from January 1, 2013 to May 1, 2023. Evidence was synthesized after an independent review of the included studies by two investigators. Results: A total of 11 articles were included in the analysis, comprising one clinical decision-making article, three clinical guidelines, six expert consensus articles, and one randomized controlled trial. We summarized 31 pieces of evidence across three categories: preoperative preparation, intraoperative interventions, and postoperative symptom management. Conclusion: This study presents a comprehensive summary of the best available evidence on the prevention and treatment of embolism syndrome following TACE for primary liver cancer. These findings can serve as a valuable reference for clinical practitioners, enabling nurses to deliver individualized care based on the symptoms and specific needs of liver cancer patients. Systematic review registration: http://ebn.nursing.fudan.edu.cn, identifier ES20232398.

Evaluation of synergy between low-carbon development and socio-economic development based on a composite system: a case study of Anhui Province (China).

Low-carbon development has been the favorite subject with the aim of making a synergy environment. Extensive research on low-carbon development and socio-economic synergy has been conducted by scholars from different perspectives. This paper explores the synergy between low-carbon development and socio-economic development as a composite system from four levels: resource, energy, economy and society, and improves the theory of low-carbon economic development in a "dual-carbon" perspective. Meanwhile, based on the theoretical research, this paper constructs a synergy model and evaluation index system of low-carbon development and socio-economic development, and conducts an empirical analysis by combining the relevant data of low-carbon governance and socio-economic development in Anhui Province from 2011 to 2020. After obtaining the level of synergistic development and constraints of the composite system, the trend of changes in the level of synergy of the composite system is verified by R/S model. It is found that: (1) the composite system composed of low-carbon development and socio-economic development in Anhui Province has certain synergistic effects, and the level of synergistic development is increasing; (2) the studied time series has significant correlation over a long period of time, while it will continue the past development trend. The contribution of this paper is to take the synergy model as the basis and build the R/S model to extend the time cycle of synergy level, which extends the previous theoretical research system of low-carbon development, helps to deepen the theoretical understanding of the synergy between low-carbon development and socio-economic development, and improves the discussion on building ecological civilization and helping to achieve the goal of "dual-carbon".