Exosomal miR-142-3p from M1-polarized macrophages suppresses cell growth and immune escape in glioblastoma through regulating HMGB1-mediated PD-1/PD-L1 checkpoint.

Glioblastoma (GBM) is one of the most prevalent cancerous brain tumors. Former studies have reported that exosomes derived from M1-polarized macrophages (M1 exosomes) inhibit tumor occurrence and development through delivery of tumor suppressor genes. Also, microRNA-142-3p (miR-142-3p) has been verified to function as a tumor suppressor. GBM cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8), colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay; cell apoptosis was determined by flow cytometry analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Mechanism investigations were conducted for analyzing the molecular mechanism by which miR-142-3p and M1 exosomes affect GBM progression. Upregulation of miR-142-3p expression was detected in M1-polarized macrophages and M1 exosomes. M1 exosomes inhibit GBM cell proliferation and trigger cell apoptosis. Functionally, miR-142-3p silencing promotes the proliferation and inhibits the apoptosis of GBM cells treated with M1 exosomes. As for molecular mechanism, miR-142-3p inhibits GBM cell growth via targeting high-mobility group box 1 (HMGB1). In addition, miR-142-3p/HMGB1 axis affects GBM cell immune escape through modulation of programmed death-1/programmed death ligand-1 (PD-1/PD-L1) checkpoint. Our study demonstrated that exosomal miR-142-3p from M1-polarized macrophages suppresses cell growth and immune escape in GBM through regulating HMGB1-mediated PD-1/PD-L1 checkpoint.

UBE2C enhances temozolomide resistance by regulating the expression of p53 to induce aerobic glycolysis in glioma.

UBE2C is overexpressed in gliomas, and its overexpression has been reported to be correlated with the drug resistance of gliomas to some extent. In this study, we explore the role of UBE2C in regulating temozolomide (TMZ) resistance in glioma and investigate the underlying mechanisms involved. Twenty normal brain tissues and 100 glioma tissues from 50 TMZ-resistant patients and 50 TMZ-sensitive patients are included in this study. TMZ-resistant cell lines are constructed to explore the role of UBE2C in regulating glioma cell viability and TMZ resistance. Our results show that both the mRNA and protein levels of UBE2C are significantly elevated in the brain tissues of glioma patients, especially in those of TMZ-resistant patients. Consistently, UBE2C expression is markedly upregulated in TMZ-resistant cell lines. Overexpression of UBE2C rescues glioma cells from TMZ-mediated apoptosis and enhances cell viability. In contrast, downregulation of UBE2C expression further enhances TMZ function, increases cell apoptosis and decreases cell viability. Mechanistically, UBE2C overexpression decreases p53 expression and enhances aerobic glycolysis level by increasing ATP level, lactate production, and glucose uptake. Downregulation of p53 level abolishes the role of UBE2C downregulation in inhibiting TMZ resistance and aerobic glycolysis in glioma cells. Moreover, an animal assay confirms that downregulation of UBE2C expression further suppresses tumor growth in the context of TMZ treatment. Collectively, this study reveals that downregulation of UBE2C expression enhances the sensitivity of glioma cells to TMZ by regulating the expression of p53 to inhibit aerobic glycolysis.

Mesenchymal stem cells-derived exosomal miR-24-3p ameliorates non-alcohol fatty liver disease by targeting Keap-1.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide with ill-defined etiology and pathogenesis, and no approved effective therapy is presently available. Exosome-dependent intercellular communication has been identified as a potential signaling involved in tissue repair. Unfortunately, the exact influence and underlying mechanism of mesenchymal stem cells (MSCs)-derived exosome (Exo) in modulating fatty liver have not been well determined. Here in our study, in vitro results initially showed that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)-derived Exo treatment significantly suppressed lipid accumulation, reactive oxygen species (ROS) generation and inflammatory response in palmitate (PA)-stimulated mouse hepatocytes. Consistently, MSCs-derived Exo administration strongly ameliorated metabolic disorders, hepatic dysfunction and steatosis in high fat diet (HFD)-induced mouse model with NAFLD. Furthermore, Exo derived from MSCs significantly alleviated hepatic lipid metabolism disturbance, inflammation and oxidative stress induced by HFD. Exo treatment resulted in a stronger increase in miR-24-3p expression in hepatocytes. Reducing miR-24-3p in MSCs markedly abrogated the protective effects of Exo in hepatocytes under PA stimulation. Mechanistically, miR-24-3p directly targeted Kelch-like ECH-associated protein 1 (Keap-1), and suppressed its expression. In addition, the effects of MSCs-derived exosomal miR-24-3p to restrain lipid accumulation, ROS generation and inflammation in vitro were largely Keap-1 dependent via Keap-1 depression. Collectively, our study demonstrated that MSCs-derived exosomal miR-24-3p had hepaprotective effects through targeting Keap-1 signaling, providing a potential therapeutic value for NAFLD treatment.

Anchor Link Prediction across Attributed Networks via Network Embedding.

Presently, many users are involved in multiple social networks. Identifying the same user in different networks, also known as anchor link prediction, becomes an important problem, which can serve numerous applications, e.g., cross-network recommendation, user profiling, etc. Previous studies mainly use hand-crafted structure features, which, if not carefully designed, may fail to reflect the intrinsic structure regularities. Moreover, most of the methods neglect the attribute information of social networks. In this paper, we propose a novel semi-supervised network-embedding model to address the problem. In the model, each node of the multiple networks is represented by a vector for anchor link prediction, which is learnt with awareness of observed anchor links as semi-supervised information, and topology structure and attributes as input. Experimental results on the real-world data sets demonstrate the superiority of the proposed model compared to state-of-the-art techniques.

Self-assembly of anisotropic red blood cell (RBC)-like colloidal particles.

Non-spherical colloidal particles, as basic building blocks, exhibit special capability in constructing novel materials. In this work, red blood cell (RBC)-like, anisotropic particles were synthesized and the self-assembly of the RBC-like particles was then carried out at the air-water interface. Subsequently, multilayer 3D structured colloidal crystals were also fabricated. The as-prepared colloidal crystal film displays beautiful Bragg diffraction, which can be used to construct a photonic crystal. After that, the self-assembly of binary colloidal particles was explored to design well-patterned binary colloidal crystals. This facile self-assembly approach to prepare colloidal crystals may extend to other anisotropic building blocks, providing guidance for the fabrication of more complex and flexible materials.

CDX2 inhibits pancreatic adenocarcinoma cell proliferation via promoting tumor suppressor miR-615-5p.

CDX2 has recently been identified as a prognostic marker for pancreatic adenocarcinoma. However, the role and mechanism of CDX2 in progression of pancreatic adenocarcinoma are still elusive. In this study, we observed that CDX2 expression was much lower in mouse pancreatic adenocarcinoma tissues and pancreatic cancer cells. A network integrated by ChIPBase platform hinted that miR-615-5p, a most newly discovered tumor suppressor, was probably bound by CDX2 in the promoter region. Chromatin immunoprecipitation (ChIP)-qPCR assay showed that CDX2 exhibited a high capacity of binding to miR-615-5p promoter region compared to the negative control. Real-time PCR and western blotting analyses revealed that CDX2 overexpression caused inflation of miR-615-5p and depression of insulin-like growth factor 2 (IGF2), a direct target of miR-615-5p. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and EdU approaches showed that CDX2 overexpression markedly suppressed pancreatic adenocarcinoma cell proliferation. CDX2 small interfering RNA (siRNA) transfection showed an opposite effect on gene expression and cell proliferation to that of CDX2 overexpression. Collectively, CDX2 inhibited pancreatic adenocarcinoma cell proliferation via promoting tumor suppressor miR-615-5p. Our findings suggested a potential molecular target for pancreatic adenocarcinoma therapy.

The value of oral contrast-enhanced gastric ultrasonography in the diagnosis and staging of benign peptic ulcer.

We evaluate the value of oral contrast-enhanced gastric ultrasonography (OCUS) by comparing it with conventional gastroscopy in diagnosing and staging benign peptic ulcer. From July 2018 to December 2020, 44 patients with gastroscopy-confirmed benign peptic ulcers (a total of 45 ulcers were detected), who also received OCUS, were retrospectively reviewed. Each patient's ultrasound images were compared with gastroscopy and pathology findings. The characteristics of ultrasonic images of different stages of ulcer were analysed. A total of 43 ulcers were detected by OCUS in 44 patients with benign peptic ulcers. There were no false positive results among the OCUS exams, but two ulcers were misdiagnosed. OCUS for benign peptic ulcer staging also shows acceptable clinical practice results. OCUS is useful for detecting and staging benign peptic ulcer, and may be considered an alternative method for conventional gastroscopy. OCUS is especially useful in the follow-up of BPU treatment, but futher study is needed to improve the diagnostic accuracy of benign and malignant ulcers.

Expression, Prognostic Value, and Biological Function of CTHRC1 in Different Types of Gliomas: A Bioinformatic Analysis and Experiment Validation.

Background: In recent years, abnormal expression of collagen triple helix repeat containing 1 (CTHRC1) has been found in some tumors, closely related to the poor prognosis of cancer patients. However, the clinical significance of CTHRC1 in gliomas is not completely understood. Methods: We investigated the expression, prognostic value, and potential biological function of CTHRC1 in different types of gliomas through bioinformatics analysis and experimental verification. Results: Bioinformatics analysis revealed several key findings regarding the expression and clinical significance of CTHRC1 in gliomas. First, the analysis demonstrated a positive correlation between CTHRC1 expression and the World Health Organization (WHO) grading of gliomas, a relationship that was validated through immunohistochemistry experiments. In addition, a trend was observed in which CTHRC1 expression increased with the extent of glioma invasion, as supported by Western blot experiments. Subsequent bioinformatics analysis identified the mesenchymal subtype of gliomas as having the highest levels of CTHRC1 expression, a finding reinforced by immunohistochemical staining. Moreover, high CTHRC1 expression was associated with poor prognosis in gliomas and emerged as an independent prognostic factor, with varying impacts on prognosis between low-grade gliomas (LGGs) and glioblastoma (GBM) subgroups. Notably, comparative analysis unveiled distinct patterns of immune infiltration of CTHRC1 in LGG and GBM. Furthermore, alterations in copy number variations and DNA methylation were identified as potential mechanisms underlying elevated CTHRC1 levels in gliomas. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that CTHRC1 and its associated genes mainly function in the extracellular matrix and participate in tumor-related signaling pathways. Conclusions: The CTHRC1 has shown significant clinical utility as a prognostic marker and mesenchymal subtype marker of glioma.

Thrombolytic therapy as a superior option: Insights from three cases of acute subdural hematoma following surgery for chronic subdural hematoma.

BACKGROUND: Chronic subdural hematoma (cSDH) ranks among the most prevalent neurosurgical conditions, with burr-hole drainage typically yielding favorable prognoses. Nevertheless, perioperative complications may arise, with remote intraparenchymal hemorrhage and subarachnoid hemorrhage occurring infrequently, while acute subdural hematoma (aSDH) remains a relatively common complication post-cSDH removal. The standard treatment for aSDH, typically large craniotomy, substantially elevates surgical risk. CASE DESCRIPTION: This study presents three cases of postoperative aSDH in elderly patients with cSDH, examining potential causative factors and proposing pertinent strategies. Three elderly patients, admitted urgently due to exacerbating symptoms, underwent preoperative assessment followed by emergency parietal burr-hole drainage. Regrettably, all three patients developed aSDH postoperatively. Various treatment approaches were employed: two cases received thrombolysis with 50,000 units of urokinase, while one case required a large craniotomy. Despite the patients achieving satisfactory outcomes without significant neurological deficits, this study advocates thrombolytic therapy as a potentially superior option for aSDH following cSDH surgery. CONCLUSION: Urokinase-mediated subdural thrombolysis enhances hematoma clearance rates, suggesting a shift towards minimally invasive treatments to mitigate greater trauma. However, the paucity of evidence necessitates extensive research to validate its safety and efficacy.

Colorimetric and fluorescent probes for cysteine detection: Applications in food safety and cellular imaging.

In this study, three BODIPY-based fluorescent probes were designed and synthesized. The ultraviolet-visible spectra, fluorescence spectra, smartphone color recognition application and bioimaging were utilized to evaluate the capacity of the probes. By comparing key parameters, BDP-SIN had optimal performances including fastest response (10 min), highest signal-to-noise ratio (815 times) and lowest limit of detection (LOD = 49 nM). The recovery rate ranged from 92.04 % to 103.25 %. Meanwhile, BDP-SIN was triumphantly employed for determination of Cys in different daily food samples. Moreover, the test strips and microporous filter membrane loaded with BDP-SIN were developed for the portable real-time visualization and quantitative detection of Cys in food samples, which the contents ranged from 0.27 µM to 0.49 µM. Besides, BDP-SIN could image Cys in the living cells and mice. The novelty of this work was that developed an effective tool for researching the roles of Cys in food industry and living organisms.

The antidepressant amitriptyline shows potent therapeutic activity against multiple myeloma.

Our previous study indicated that the antidepressant amitriptyline showed potent activity in inducing multiple myeloma (MM) cell apoptosis in vitro. In the present study, we further showed that amitriptyline was active against MM in vivo. Oral administration of amitriptyline significantly decreased tumor growth in two MM xenograft models derived from murine and human MM cells, respectively. Molecular pathological analysis showed that amitriptyline induced p53, activated caspase-3, and decreased antiapoptotic Bcl-2 and Mcl-1 in tumor tissues. Amitriptyline also significantly extended the survival period of MM-tumor-bearing mice. In the in-vitro study, we also found that amitriptyline synergistically induced MM cell apoptosis in combination with bortezomib, the most potent anti-MM agent. Because amitriptyline has been proposed to control cancer-associated pain, depression, and anxiety, proper application of amitriptyline will benefit MM patients.

Preparation of S14161 and its analogues and the discovery of 6-bromo-8-ethoxy-3-nitro-2H-chromene as a more potent antitumor agent in vitro.

The small chemical compound 8-ethoxy-2-(4-fluorophenyl)-3-nitro-2H-chromene (S14161) was recently identified as an inhibitor of the phosphoinositide 3-kinase (PI3K). In the present study, we designed a novel synthesis of S14161 and prepared a series of its analogues via the oxa-Michael-Henry reaction in the presence of catalytic amounts of l-proline and triethylamine. Further structural simplification led to the identification of 6-bromo-8-ethoxy-3-nitro-2H-chromene (BENC-511) that exhibited potent antiproliferative activities against a panel of 12 tumor cell lines. Compared with S14161, BENC-511 was more potent in blocking the AKT phosphorylation and inducing cancer cell apoptosis. BENC-511 also displayed more potent effects on human umbilical vein epithelial cells (HUVEC) migration, suggesting its anti-angiogenesis activity.

Craniopharyngioma involving the anterior, middle, and posterior cranial fossa in adults: A case report.

Craniopharyngioma (CP) is a rare benign tumor that develops from the residual epithelial cells of the craniopharynx, accounting for < 5% of intracranial tumors. It is common for CPs to grow in the sellar/parasellar region and extend suprasellar. The pathology classifies CPs into adamantinomatous craniopharyngiomas (ACP) and papillary craniopharyngiomas (PCP). The PCP is mainly solid and occurs only in adults. ACP is predominantly cystic and more common in childhood and adolescent. Multilocular cystic ACP involving the anterior, middle, and posterior cranial fossa is rare in adults. Here, we report a case of a 46-year-old adult male patient who presented with recurrent headaches for 1 year with choking and hoarseness. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple cystic masses in the anterior, middle, and posterior cranial fossa. Initial hypotheses included the following: CP, colloid cyst, enterogenous cyst, epidermoid cyst, and dermoid cyst. Subsequently, the patient underwent surgery and postoperative histopathology diagnosed ACP. Adults with ACP involving the anterior, middle, and posterior cranial fossae are uncommon. This is a rare condition that radiologists should be aware of.

BODIPY-based fluorescent probe for cysteine detection and its applications in food analysis, test strips and biological imaging.

Cysteine, as one of semi-essential amino acids, which is absorbed from protein-rich foods and acts considerable role in various physiological processes. Here, we designed and synthesized a BODIPY-based turn-on fluorescent probe BDP-S for detecting Cys. The probe displayed short reaction time (10 min), distinct color response (from blue to pink), large signal noise ratio (3150-fold), high selectivity and sensitivity (LOD = 11.2 nM) toward Cys. Moreover, BDP-S could not only be used for quantitative determination of Cys in food samples, but also be conveniently deposited on the test strips for qualitative detection of Cys. Notably, BDP-S was successfully used for imaging Cys in living cells and in vivo. Consequently, this work provided a hopefully powerful tool for detecting Cys in food samples and complex biological systems.

Comparison of subperiosteal or subgaleal drainage and subdural drainage in patients with chronic subdural hematoma: A systematic review and meta-analysis.

BACKGROUND: Chronic subdural hematoma (CSDH) is a relatively common disease, especially in the elderly, for which there is no clear standard of treatment available. The authors systematically evaluated the efficacy of various surgical procedures for the treatment of chronic subdural hematoma. METHODS: Electronic databases of PubMed, EmBase, Web of Science, Medicine, and the Cochrane Library were searched systematically. Based on the PRISMA template, we finally selected and analyzed 13 eligible papers to evaluate the effect of different drainage methods on CSDH. The primary outcomes were recurrence and clinical outcomes. Secondary outcomes were mortality and postoperative complications and other parameters. RESULTS: The meta-analysis included 3 randomized controlled trials and 10 retrospective studies (non-randomized controlled trials) involving 3619 patients. The pooled results showed no statistically significant difference between non-subdural drainage (NSD) and subdural drainage (SD) in mortality and complication rates (P > 0.05). Additionally, overall pooled results showed that the use of NSD (10.9%) has a lower recurrence rate than the use of SD (11.7%), but the results were not statistically significant (relative risk ratio [RR] = 0.98; 95% confidence interval [CI] = 0.70-1.45; I2 = 47%; P = .92). However, the difference between NSD and SD in postoperative bleeding rate reached statistical significance (RR = 2.39; 95% CI = 1.31-4.36; I2 = 0 %; P = .004). Subgroup analysis showed that SD was associated with similar recurrent CSDH (RR = 0.75; 95% CI = 0.52-1.09; I2 = 0%; P = .14), good recovery (RR = 0.98; 95% CI = 0.93-1.04; I2 = 0%; P = .50), and mortality (RR = 0.98; 95% CI = 0.37-2.57; I2 = 0%; P = .96), compared to NSD. CONCLUSIONS: These results suggest that NSD and SD are equally effective in the treatment of patients with CSDH, with no difference in final clinical characteristics and radiologic outcomes. However, in patients with limited subdural space after evacuation of a hematoma, NSD may be the preferred strategy to avoid iatrogenic brain injury.

Endoscopic surgery versus craniotomy in the treatment of spontaneous intracerebral hematoma: a systematic review and meta-analysis.

BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) has high morbidity and mortality, with no clear standard of treatment available. Compared with the craniotomy approach, neuroendoscopy is a relatively minimally invasive treatment method, and may be an efficient alternative. Therefore, this meta-analysis aimed to assess the clinical efficacy of neuroendoscopy and craniotomy in SICH patients. METHODS: The electronic databases Web of Science, PubMed, EmBase, MEDLINE, and the Cochrane Library were systematically searched. According to the PRISMA template, we finally selected and analyzed 14 eligible studies that evaluated neuroendoscopy versus craniotomy. Primary outcomes included operation time, intraoperative blood loss volume, evacuation rate, residual hematoma, complications, hospital stay duration, clinical outcomes, and other parameters. RESULTS: A total of 4 randomized controlled trials (RCTs) and 10 retrospective studies (non-RCTs) involving 1652 patients were included in the final analysis. In the neuroendoscopy (NE) group, operation time (p < 0.00001), intraoperative blood loss volume (p < 0.0001), hematoma evacuation rate (p = 0.0002), complications (p < 0.00001), hospitalization days (p = 0.004), and mortality (p < 0.0001) were significantly different from those of the craniotomy (C) group, with a higher rate of good recovery compared with the craniotomy group (P < 0.00001). CONCLUSIONS: These findings suggest that patients with SICH and physicians may benefit more from neuroendoscopic surgery than craniotomy.

Genetic Analysis of Adult Plant Resistance to Stripe Rust in Common Wheat Cultivar "Pascal".

Wheat stripe rust is an important foliar disease that affects the wheat yield globally. Breeding for resistant wheat varieties is one of the most economically and environmentally effective ways to control this disease. The common wheat (Triticum aestivum L.) cultivar "Pascal" exhibited susceptibility to stripe rust at the seedling stage but it showed high resistance to stripe rust at the adult plant stage over 20 years in Gansu, a hotspot of the disease in northwestern China. To understand the genetic mechanism of stripe rust resistance in this cultivar, a 55K SNP array was used to analyze the two parents and the 220 recombinant inbred lines (RILs) derived from the cross of "Huixianhong" × "Pascal." We detected three new stripe rust adult plant resistance (APR) quantitative trait locus (QTL) contributed by Pascal, viz. QYr.gaas-1AL, QYr.gaas-3DL, and QYr.gaas-5AS, using the inclusive composite interval mapping method. They were flanked by SNP markers AX-111218361-AX-110577861, AX-111460455-AX-108798599, and AX-111523523-AX-110028503, respectively, and explained the phenotypic variation ranging from 11.0 to 23.1%. Bulked segregant exome capture sequencing (BSE-Seq) was used for fine mapping of QYr.gaas-1AL and selection of candidate genes, TraesCS1A02G313700, TraesCS1A02G313800, and TraesCS1A02G314900 for QYr.gaas-1AL. KASP markers BSE-1A-12 and HXPA-3D for QYr.gaas-1AL and QYr.gaas-3DL were developed for breeders to develop durable stripe rust-resistant wheat varieties.

Near-Infrared Fluorescent Probe with a Large Stokes Shift for Detection of Hydrogen Sulfide in Food Spoilage, Living Cells, and Zebrafish.

Hydrogen sulfide (H2S) is a significant component of various physiological processes, and it can also cause a negative effect on foodstuffs. In this work, we designed and synthesized an NIR fluorescent turn-on responding probe (DDM-H2S) with a large Stokes shift (190 nm) for the detection of H2S. DDM-H2S exhibited high selectivity and sensitivity, obvious color changes, and a fast response time for tracing H2S. When DDM-H2S reacted with H2S, the PET process was eliminated, and the recovered ICT process and NIR fluorescence were observed. Moreover, DDM-H2S could image endogenous and exogenous H2S in living HeLa cells and zebrafish. What is more, the probe DDM-H2S could be deposited easily to test paper strips, which were able to detect the H2S gas produced during food spoilage (such as eggs, raw meat, and fishes) by the color of test paper strips changing from pink to purple. Therefore, this work provides a promising approach for monitoring H2S in complicated biological systems and practical food samples.

Polysaccharide conjugates from Chin brick tea (Camellia sinensis) improve the physicochemical stability and bioaccessibility of ß-carotene in oil-in-water nanoemulsions.

A natural antioxidant emulsifier, tea polysaccharide conjugate (TPC), was isolated from Chin brick tea. The impact of TPC on ß-carotene stability and bioaccessibility in oil-in-water nanoemulsions was assessed. TPC exhibited strong antioxidant activity and could be used to fabricate stable nanoemulsions (d < 140 nm). The extent of lipid digestion was considerably lower for lipid droplets coated by TPC (68%) than Tween 80 (94%) or whey protein isolate (WPI) (89%), probably because TPC formed interfacial layers that hindered the access of lipases to lipids. The chemical stability of ß-carotene in TPC-nanoemulsions was markedly higher than in those formulated with Tween 80 or WPI due to the high antioxidant activity of TPC. The bioaccessibility of ß-carotene (20-30%) was independent of emulsifier type. TPC from Chin brick tea can therefore be used as a dual-purpose functional ingredient in emulsified foods.

The effects of Intensive Supervision Mechanism on air quality improvement in China.

The Intensive Supervision Mechanism (hereafter referred to as ISM) is one of the most important institutional management innovations for air pollution control in China, but there is currently no consensus on the effects of the ISM on air quality improvement. In this study, a reliable quantitative model based on the Difference-in-Differences (DID) analysis was designed to evaluate the impacts of ISM on air quality (as indicated by good air quality days (hereafter referred to as GAD) and the concentrations of six major air pollutants (i.e. PM2.5, PM10, O3_8H, NO2, SO2, and CO)), in China with focuses on the implementation cities of Henan Province. To optimize the model design, six meteorological factors, five socio-economic indicators, and VIIRS (Visible Infrared Imaging Radiometer Suite) data were also considered as alternative control variables for more comprehensive and effective results. In addition, the redundancy analysis (RDA) and Monte Carlo simulation were conducted to determine the optimal combination of those control variables which can best reflect the changes in explanatory variables. The main findings are as follows: (1) the statistical model applied in this study can well evaluate the impacts of ISM; (2) the implementation of ISM can significantly reduce the concentrations of SO2, CO, and NO2, but the improvements for PM2.5, PM10, GAD and O3_8H were not significant. (3) the potential for air quality improvement due to ISM tends to be reduced over time, and thus the positive effects of ISM at its second stage were not increased significantly compared with those observed during its first stage. In general, those results not only demonstrate the effectiveness of ISM on air quality improvement, but also provide insights into how the ISM can be optimized to gain a sustained improvement of the ambient air quality in the future.Implications: As a policy measure implemented by the Chinese government, the Intensive Supervision Mechanism (ISM) has significantly contributed to the improvement of air quality since its execution. However, the potential for air quality improvement due to ISM tends to be reduced over time, and thus the positive effects of ISM at its second stage were not increased significantly compared with those observed during its first stage. In addition, the implementation of ISM requires a large amount of financial investment, and thus has limited sustainability. Considering the increased difficulty of this policy instrument, whether to insist on the ISM warrants further analyses on its cost and effectiveness. More importantly, more targeted measures of ISM should be applied to decrease the ozone concentration in the future.