Magnetically controlled nanorobots induced oriented and rapid clearance of the cytokine storm for acute lung injury therapy.

Cytokine storms characterized by excessive secretion of circulating cytokines and immune-cell hyperactivation are life-threatening systemic inflammatory syndromes. The new strategy is in great demand to inhibit the cytokine storm. Here, we designed a type of magnetically controlled nanorobots (MAGICIAN) by fusing neutrophil membranes onto Fe3O4 nanoparticles (Fe3O4NPs). In our study, the receptors of neutrophil membranes were successfully coated to the surface of Fe3O4NPs. The associated membrane functions of neutrophils were highly preserved. MAGICIAN could in vitro neutralize the inflammatory cytokines including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Interestingly, MAGICIAN could be navigated to the liver sites under magnetic control and accelerated the cytokine clearance by the liver. Administration of MAGICIAN could efficiently relieve the inflammation in the acute lung injury mouse model. In addition, MAGICIAN displayed good biosafety in systemic administration. The present study provides a safe and convenient approach for the clearance of cytokine storms, indicating the potential for clinical application in acute lung injury therapy.

Roll to roll in situ preparation of recyclable, washable, antibacterial Ag loaded nonwoven fabric.

Functional fabrics with antibacterial performance are more welcome nowadays. However, the fabrication of functional fabrics with durable, steady performance via a cost-effective way remains a challenge. Polypropylene (denoted as PP) nonwoven fabric was modified by polyvinyl alcohol (denoted as PVA), followed by the in-situ deposition of silver nanoparticles (denoted as Ag NPs) to afford PVA-modified and Ag NPs-loaded PP (denoted as Ag/PVA/PP) fabric. The encapsulation of PP fiber by PVA coating contributes to greatly enhancing the adhesion of the loaded Ag NPs to the PP fiber, and the Ag/PVA/PP nonwoven fabrics exhibit significantly improved mechanical properties as well as excellent antibacterial activity against Escherichia coli (coded as E. coli). Typically, the Ag/PVA/PP nonwoven fabric obtained at a silver ammonia concentration of 30 mM has the best mechanical properties and the antibacterial rate reaches 99.99% against E. coli. The fabric retains excellent antibacterial activity even after washing for 40 cycles, showing prospects in reuse. Moreover, the Ag/PVA/PP nonwoven fabric could find promising application in industry, thanks to its desired air-permeability and moisture-permeability. In addition, we developed a roll-to-roll production process and conducted preliminary exploration to verify the feasibility of this method.

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model.

Background: Ischemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat. Methods: Rat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed. Results: Pre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators. Conclusion: Our result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.

N-2-(Phenylamino) Benzamide Derivatives as Dual Inhibitors of COX-2 and Topo I Deter Gastrointestinal Cancers via Targeting Inflammation and Tumor Progression.

Given the close association between inflammation and cancer, combining anti-inflammation therapy is prominent to improve the anticancer effect. Based on I-1, a series of agents targeting COX-2 and Topo I were designed by combining fenamates and phenols. The optimal compound 1H-30 displayed an enhanced inhibitory effect on COX-2 compared to tolfenamic acid and I-1 and showed better inhibition of Topo I than I-1. Importantly, 1H-30 showed potential anticancer effects and suppressed the activation of the NF-κB pathway in cancer cells. 1H-30 inhibited the nuclear translocation of NF-κB and suppressed the production of NO, COX-2, and IL-1ß in RAW264.7. In vivo, 1H-30 showed acceptable pharmacokinetic parameters, decreased the tumor growth without affecting the body weight, down-regulated COX-2 and MMP-9, and induced apoptosis in the CT26.WT tumor-bearing mice. Accordingly, 1H-30 as a potential Topo I/COX-2 inhibitor which possessed anti-inflammatory and anticancer effects, with inhibition of the NF-κB pathway, is promising for gastrointestinal cancer therapy.

Discovery of dual inhibitors of topoisomerase I and Cyclooxygenase-2 for colon cancer therapy.

Novel tolfenamic acid derivatives based on the structure of I-1 were designed and synthesized to improve its poor target inhibition and solubility. Among them, W10 was identified as a potent dual-target inhibitor of Topo I (IC50 = 0.90 ± 0.17 µM) and COX-2 (IC50 = 2.31 ± 0.07 µM) with improved water solubility (32.33 µg/mL). Moreover, W10 also exhibited fairly potent anti-proliferative and pro-apoptosis activity via the mitochondrial pathway, as well as suppressed aberrant NF-κB/IκB activation in colon cancer cells in vitro. Additionally, W10 possessed favorable pharmacokinetic properties and excellent antitumor effects in vivo. In general, our study has demonstrated the potency of a novel Topo I/COX-2 dual inhibitor, which can potentially be developed into a chemotherapeutic candidate for colon cancer.

Design, synthesis and bioactivity evaluation of favorable evodiamine derivative scaffold for developing cancer therapy.

Natural product evodiamine is one of the most privileged scaffolds in drug discovery and is suitable for derivatization, which can be conducted quickly for structure optimization and structure-activity relationship research. In this work, a comprehensive SAR study on evodiamine scaffold with N14-3'-fluorophenyl substituted was completed, and compounds with high anti-tumor activity and good inhibitory effect on Top1 and Top2 were screened out. Tested evodiamine derivatives exhibited excellent broad-spectrum anti-tumor activity. Among them, compound 8b revealed 55.15% and 55.50% inhibition for Top1 and Top2 at 25 µM, as well as 0.16 and 0.13 µM IC50 value for MGC-803 and SGC-7901 cells, respectively; compound 9a revealed 70.50% and 71.81% inhibition for Top1 and Top2 at 25 µM, as well as 0.22 and 0.27 µM IC50 value for MGC-803 and SGC-7901 cells, respectively. The further biological evaluation showed that they could functionally induce apoptosis, significantly arrest the cell cycle at the G2/M phase, and markedly inhibit cell proliferation, migration and invasion. In addition, compound 9a performed a tumor inhibitory rate of 36.35% and showed no apparent toxicity in vivo. Overall, these optimized protocols will advance the progression of cancer chemotherapy and can be used to expand the options for screening therapeutic cancer drugs.

Design, Synthesis, and Biological Evaluation of Novel Evodiamine Derivatives as Potential Antihepatocellular Carcinoma Agents.

Evodiamine has many biological activities. Herein, we synthesize 23 disubstituted derivatives of N14-phenyl or the E-ring of evodiamine and conduct systematic structure-activity relationship studies. In vitro antiproliferative activity indicated that compounds F-3 and F-4 dramatically inhibited the proliferation of Huh7 (IC50 = 0.05 or 0.04 µM, respectively) and SK-Hep-1 (IC50 = 0.07 or 0.06 µM, respectively) cells. Furthermore, compounds F-3 and F-4 could double inhibit topoisomerases I and II, inhibit invasion and migration, block the cell cycle to the G2/M stage, and induce apoptosis as well. Additionally, compounds F-3 and F-4 could also inhibit the activation of HSC-T6 and reduce the secretion of collagen type I to slow down the progression of liver fibrosis. Most importantly, compound F-4 (TGI = 60.36%) inhibited tumor growth more significantly than the positive drug sorafenib. To sum up, compound F-4 has excellent potential as a strong candidate for the therapy of hepatocellular carcinoma.

Design, synthesis and biological evaluation of novel o-aminobenzamide derivatives as potential anti-gastric cancer agents in vitro and in vivo.

Although gastric cancer has become a major public health problem, oral agents applied in clinics for gastric cancer therapy are scarce. Therefore, to explore new oral chemical entities with high efficiency and low toxicity, 41 o-aminobenzamide derivatives based on the scaffolds of MS-275 and SAHA were designed, synthesized, and evaluated for their anti-gastric cancer abilities in vitro and in vivo. Structure-activity relationships were discussed, leading to the identification of compounds F8 (IC50 = 0.28 µM against HGC-27 cell) and T9 (IC50 = 1.84 µM against HGC-27 cell) with improved cytotoxicity, anti-gastric cancer proliferation potency, induction of cell apoptosis and cell cycle arrest ability, inhibition of cell migration and invasion. What is worth mentioning is that compound F8 was more efficient and less toxic than the positive drug capecitabine in vivo on the HGC-27-xenograft model. Meanwhile, compound F8 exhibited suitable pharmacokinetic properties and less acute toxicity (LD50 > 1000 mg/kg). Besides, western blotting analysis, IHC analysis, differentially expressed proteins analysis and ABPP experiment indicated that compound F8 could modulate molecular pathways involved in apoptosis and cell cycle progression. Consequently, compound F8 is a strong candidate for the development of human gastric cancer therapy.

Novel piperazine based benzamide derivatives as potential anti-glioblastoma agents inhibiting cell proliferation and cell cycle progression.

Highly efficacious and tolerable agents for the treatment of glioblastoma (GBM), the most common and aggressive primary brain tumor, are urgently needed. Herein, we reveal the design, synthesis and biological evaluation of several piperazine based benzamide derivatives, which are based on the non-classical isostere principle and combination principle for GBM therapy. After structure-activity relationship (SAR) study, compound L19 was demonstrated as the most promising compound with IC50 values of 0.15 µM, 0.29 µM, 1.25 µM against GBM C6, U87-MG, U251 cells, respectively. Moreover, compound L19 could inhibit the proliferation, migration and invasion, as well as induce apoptosis and cell cycle arrest of GBM cell lines in vitro. From mechanism perspective, compound L19 could regulate the cell cycle-related proteins and influence the p16INK4a-CDK4/6-pRb pathway by western blotting experiment. What is worth mentioning is that compound L19 could penetrate the blood-brain barrier (BBB) with an exceptional brain-to-plasma ratio of 1.07 in vivo. Besides, the superior anti-glioblastoma potency in vivo of compound L19 was identified on U87-MG-xenograft model without any apparent host toxicity. Overall, the potential of compound L19 warrants further pre-clinical investigation for GBM therapy.

Design, synthesis and bioactivity evaluation of novel evodiamine derivatives with excellent potency against gastric cancer.

Gastric cancer represents a significant health burden worldwide. Previously, inspired by the traditional Chinese medicine Wu-Chu-Yu to treat the spleen and stomach system for thousands of years, we identified N14-phenyl substituted evodiamine derivatives as potential antitumor agents with favorable inhibition on Top1. Herein, structural optimization and structure-activity relationship studies (SARs) led us to discovering a highly active evodiamine derivative compound 6t against gastric cancer. Further anti-tumor mechanism studies revealed that compound 6t played as the inhibition of topoisomerase 1 (Top1), effectively induced apoptosis, obviously arrested the cell cycle at the G2/M phase, and significantly inhibited the migration and invasion of SGC-7901 and MGC-803 cell lines in a dose-dependent manner. Moreover, the compound 6t was low toxicity in vivo and exhibited excellent anti-tumor activity (TGI = 70.12%) in the MGC-803 xenograft models. In summary, compound 6t represents a promising candidate as a potential chemotherapeutic agent against gastric cancer.

Direct copolymerization of ethylene with protic comonomers enabled by multinuclear Ni catalysts.

Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.

N-2-(phenylamino) benzamide derivatives as novel anti-glioblastoma agents: Synthesis and biological evaluation.

Glioblastoma is one of the most lethal brain tumors. The crucial chemotherapy is mainly alkylating agents with modest clinical success. Given this desperate need and inspired by the encouraging results of a phase II trial via concomitant Topo I inhibitor plus COX-2 inhibitor, we designed a series of N-2-(phenylamino) benzamide derivatives as novel anti-glioblastoma agents based on structure modification on 1,5-naphthyridine derivatives (Topo I inhibitors). Notably, the target compounds I-1 (33.61 ± 1.15 µM) and I-8 (45.01 ± 2.37 µM) were confirmed to inhibit COX-2, while a previous reported compound (1,5-naphthyridine derivative) resulted nearly inactive towards COX-2 (IC50 > 150 µM). Besides, I-1 and I-8 exhibited higher anti-proliferation, anti-migration, anti-invasion effects than the parent compound 1,5-naphthyridine derivative, suggesting the success of modification based on the parent. Moreover, I-1 obviously repressed tumor growth in the C6 glioma orthotopic model (TGI = 66.7%) and U87MG xenograft model (TGI = 69.4%). Besides, I-1 downregulated PGE2, VEGF, MMP-9, and STAT3 activation, upregulated E-cadherin in the orthotopic model. More importantly, I-1 showed higher safety than temozolomide and different mechanism from temozolomide in the C6 glioma orthotopic model. All the evidence demonstrated that N-2-(phenylamino) benzamide derivatives as novel anti-glioblastoma agents could be promising for the glioma management.

Design, synthesis and bioactivity study of evodiamine derivatives as multifunctional agents for the treatment of hepatocellular carcinoma.

Topoisomerase has been found extremely high level of expression in hepatocellular carcinoma (HCC) and proven to promote the proliferation and survival of HCC. Cancer-associated fibroblasts (CAFs) as a kind of key reactive stromal cell that abundantly present in the microenvironment of HCC, could enhance the metastatic ability and drug resistance of HCC. Therefore, developing new drugs that address the above conundrums would be of the upmost significant in the fight against HCC. Evodiamine, as a multi-target natural product, has been found to exert various biological activities such as anti-cancer and anti-hepatic fibrosis via blocking topoisomerase, NF-κB, TGF-ß/HGF, and Smad2/3. Inspired by these facts, 15 evodiamine derivatives were designed and synthesized for HCC treatment by simultaneously targeting Topo I and CAFs. Most of them displayed preferable anti-HCC activities on three HCC cell lines and low cytotoxicity on one normal hepatic cell. In particular, compound 8 showed the best inhibitory effect on HCC cell lines and a good inhibition on Topo I in vitro. Meanwhile, it also induced obvious G2/M arrest and apoptosis, and significantly decreased the migration and invasion capacity of HCC cells. In addition, compound 8 down-regulated the expression of type I collagen in the activated HSC-T6 cells, and induced the apoptosis of activated HSC-T6 cells. In vivo studies demonstrated that compound 8 markedly decreased the volume and weight of tumor (TGI = 40.53%). In vitro and in vivo studies showed that its effects were superior to those of evodiamine. This preliminary attempt may provide a promising strategy for developing anti-HCC lead compounds taking effect through simultaneous inhibition on Topo I and CAFs.

Design, synthesis and biological evaluation of N-anthraniloyl tryptamine derivatives as pleiotropic molecules for the therapy of malignant glioma.

COX-2 and STAT3 are two key culprits in the glioma microenvironment. Herein, to inhibit COX-2 and block STAT3 signaling, we disclosed 27 N-anthraniloyl tryptamine compounds based on the combination of melatonin derivatives and N-substituted anthranilic acid derivatives. Among them, NP16 showed the best antiproliferative activity and moderate COX-2 inhibition. Of note, NP16 decreased the level of p-JAK2 and p-STAT3, and blocked the nuclear translocation of STAT3 in GBM cell lines. Moreover, NP16 downregulated the MMP-9 expression of BV2 cells in a co-culture system of BV2 and C6 glioma cells, abrogated the proliferative/invasive/migratory abilities of GBM cells, induced apoptosis by ROS and the Bcl-2-regulated apoptotic pathway, and induced obvious G2/M arrest in glioma cells in vitro. Furthermore, NP16 displayed favorable pharmacokinetic profiles covering long half-life (11.43 ± 0.43 h) and high blood-brain barrier permeability. Finally, NP16 effectively inhibited tumor growth, promoted the survival rate, increased the expression of E-cadherin and reduced overproduction of PGE2, MMP-9, VEGF-A and the level of p-STAT3 in tumor tissue, and improved the anxiety-like behavior in C6 glioma model. All these evidences demonstrated N-anthraniloyl tryptamine derivatives as multifunctional anti-glioma agents with high potency could drain the swamp to beat glioma.

Design, synthesis and antitumor activity evaluation of Chrysamide B derivatives.

Marine natural products derived from special or extreme environment provide an important source for the development of anti-tumor drugs due to their special skeletons and functional groups. In this study, based on our previous work on the total synthesis and structure revision of the novel marine natural product Chrysamide B, a group of its derivatives were designed, synthesized, and subsequently of which the anti-cancer activity, structure-activity relationships and cellular mechanism were explored for the first time. Compared with Chrysamide B, better anti-cancer performance of some derivatives against five human cancer cell lines (SGC-7901, MGC-803, HepG2, HCT-116, MCF-7) was observed, especially for compound b-9 on MGC-803 and SGC-7901 cells with the IC 50 values of 7.88 ± 0.81 and 10.08 ± 1.08 µM, respectively. Subsequently, cellular mechanism study suggested that compound b-9 treatment could inhibit the cellular proliferation, reduce the migration and invasion ability of cells, and induce mitochondrial-dependent apoptosis in gastric cancer MGC-803 and SGC-7901 cells. Furthermore, the mitochondrial-dependent apoptosis induced by compound b-9 is related with the JAK2/STAT3/Bcl-2 signaling pathway. To conclude, our results offer a new structure for the discovery of anti-tumor lead compounds from marine natural products.

Cost-Effectiveness Analysis of PEG-rhG-CSF as Primary Prophylaxis to Chemotherapy-Induced Neutropenia in Women With Breast Cancer in China: Results Based on Real-World Data.

Background: Pegylated recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are more commonly and widely used than recombinant human granulocyte colony-stimulating factors (rhG-CSFs) in preventing chemotherapy-induced neutropenia in patients with stage II-IV breast cancer. To reduce the financial burden on these patients, the corresponding medical insurance directory needs to be revised. Objectives: To evaluate the cost-effectiveness of PEG-rhG-CSF versus rhG-CSF in patients with stage II-IV breast cancer in central China. Methods: Two Markov models, a chemotherapy model and a post-chemotherapy model, were developed to study the effects and costs, with a time horizon of 12 weeks and 35 years, respectively. Cost and probability input data were primarily obtained from a retrospective real-world study conducted in five tertiary hospitals. Propensity score matching was adopted to overcome retrospective bias. Other parameters were extracted from literature as well as advice from clinical experts. Univariate and probabilistic sensitivity analyses were conducted. Results: In the first chemotherapy model, PEG-rhG-CSF was associated with fewer episodes of febrile neutropenia (FN) (N = 19 per 1000 patients treated), infections (N = 24 per 1000 patients treated) and deaths (N = 2 per 1000 patients treated), but higher costs (¥36 more per patient treated). The post-chemotherapy model indicated that PEG-rhG-CSF led to higher gains in quality-adjusted life years (QALYs) (11.695 versus 11.516) in comparison to rhG-CSF. Sensitivity analysis showed that the cost of PEG-rhG-CSF had the greatest impact on the incremental costs, and incremental QALYs were very sensitive to the risk of RDI <85%. The probability of PEG-rhG-CSF being cost-effective compared to rhG-CSF was 66% at the willingness to pay (WTP) thresholds of ¥72,371 per QALY gained. Conclusion: According to this economic evaluation based on real-world data, PEG-rhG-CSF may be considered as a more cost-effective strategy relative to rhG-CSF for stage II-IV breast cancer patients in central China. However, to reflect a national perspective, further evidence is needed using data from larger-scale studies.

An injectable, self-healing hydrogel system from oxidized pectin/chitosan/γ-Fe2O3.

Injectable hydrogels with self-healing ability present great potential for drug delivery. They could be facilely implanted in vivo and maintained structural and functional integrity till the hydrogel arriving at target sites. Herein, a series of injectable and self-healing composite hydrogel were developed as delivery vehicles for anti-cancer drug. The hydrogels were obtained with varying ratios of oxidized pectin/chitosan to nano γ-Fe2O3, which present excellent injectable, self-healing, magnetic, high biocompatible, and anti-cancer properties. The nano γ-Fe2O3 with particle size of about 0.25 µm loaded on the surface of hydrogel. Magnetic hysteresis loops of the hydrogel presented S-shape over the applied magnetics and the MS value was 4.86 emu/g. When pH dropped from 7.4 to 6.5 or temperature increased form 36 °C to 37 °C, the percentage increase in the swelling rate of OP4-400 reached to 35.89% and 25.13%, respectively. The composite hydrogels could continuously release water-soluble 5-FU for more than 12 h. In addition, the drug delivery systems indicated acceptable anti-cancer property though trace amounts of 5-FU were added in the hydrogel systems. The addition of γ-Fe2O3 could not only be beneficial to the targeting but also collectively enhance the anti-cancer property.

Diagnostic value of mitral regurgitant jet volume in the assessment of mitral regurgitation severity by general imaging three-dimensional quantification.

Accurate quantification of mitral regurgitation (MR) severity is critical for appropriate clinical decision making regarding surgical intervention. General imaging three-dimensional quantification (GI3DQ) method allows for direct measurement of mitral regurgitant jet volume (MRJvol) with the help of three-dimensional (3D) color flow Doppler imaging. The aim of this study was to evaluate diagnostic value of MRJvol by GI3DQ for MR grading severity, using the guideline recommended integrated approach as a reference. The study included ninety-seven patients with varying degree of MR, and all MR cases were divided into central MR group (n = 44) and eccentric MR group (n = 53). The MRJvol was measured by GI3DQ. The severity of MR was graded on the basis of recommended integrated approach as mild, moderate, or severe. As assessed by receiver operating characteristic analysis, MRJvol by GI3DQ at a cutoff value of 43.4 ml yielded 76.9% of sensitivity and 86.9% of specificity to differentiate moderate from severe MR in all cases, a cutoff value of 47.5 ml yielded 98.9% of sensitivity and 94.4% of specificity to differentiate moderate from severe MR in central MR, and a cutoff value of 40.7 ml yielded 80.0% of sensitivity and 78.6% of specificity to differentiate moderate from severe MR in eccentric MR. MRJvol measured by GI3DQ could assess MR severity, especially in central MR group, which has higher sensitivity and specificity to differentiate moderate from severe MR.

Gas-Sensing Activity of Amorphous Copper Oxide Porous Nanosheets.

In this paper, the gas-sensing properties of copper oxide porous nanosheets in amorphous and highly crystalline states were comparatively investigated on the premise of almost the same specific surface area, morphology and size. Unexpectedly, the results show that amorphous copper oxide porous nanosheets have much better gas sensing properties than highly crystalline copper oxide to a serious of volatile organic compounds, and the lowest detection limit (LOD) of the amorphous copper oxide porous nanosheets to methanal is even up to 10 ppb. By contrast, the LOD of the highly crystalline copper oxide porous nanosheets to methanal is 95 ppb. Experiments prove that the oxygen vacancies contained in the amorphous copper oxide porous nanosheets play a key role in improving gas sensitivity, which greatly improve the chemical activity of the materials, especially for the adsorption of molecules containing oxygen-groups such as methanal and oxygen.