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Antimicrobial resistance in Gram-negative bacteria has become one of the leading causes of morbidity and mortality and a serious worldwide public health concern due to the fact that Gram-negative bacteria have an additional outer membrane protecting them from an unwanted compound invading. It is still very difficult for antimicrobials to reach intracellular targets and very challenging to treat Gram-negative bacteria with the current strategies. Here, we found that (o-(bromomethyl)phenyl)boronic acid was incorporated into poly((2-N,N-diethyl)aminoethyl acrylate) (PDEA), forming a copolymer (poly(o-Bn-DEA)) having both phenylboronic acid (B) and ((2-N,N-diethyl)amino) (DEA) units. Poly(o-Bn-DEA) exhibits very strong intramolecular B-N coordination, which could highly promote the covalent binding of phenylboronic acid with lipopolysaccharide (LPS) on the outer membrane of E. coli and lodge poly(o-Bn-DEA) on the LPS layer on the surface of E. coli. Meanwhile, the strong electrostatic interaction between poly(o-Bn-DEA) and the negatively charged lipid preferred tugging the poly(o-Bn-DEA) into the lipid bilayer of E. coli. The combating interactions between covalent binding and electrostatic interaction form a tug-of-war action, which could trigger the lysis of the outer membrane, thereby killing Gram-negative E. coli effectively without detectable resistance.

Lei Xia,1,* Li Wen,1,2,* Xiangxi Meng,1 Nina Zhou,1 Xiaoyi Guo,1 Teli Liu,1 Xiaoxia Xu,1 Feng Wang,1 Hua Zhu,1 Zhi Yang1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China; 2Guizhou University School of Medicine, Guiyang, Guizhou, 550025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua Zhu; Zhi YangKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of ChinaTel +86 010-88196196; +86 010-88196495Email zhuhuananjing@163.com; pekyz@163.comBackground: In recent years, nuclear medicine imaging and therapy for prostate cancer have radically changed through the introduction of radiolabeled prostate-specific membrane antigen (PSMA)-binding peptides. However, these small molecular probes have some inherent limitations, including high nephrotoxicity and short circulation time, which limits their utility in biological systems.Methods and Results: In this study, organic melanin nanoparticles were used to directly label the long half-life radionuclide 124I (t1/2=100.8 h), and PSMA small molecular groups were efficiently bonded on the surface of nanoparticles to construct the PSMA-targeted long-retention nanoprobe 124I-PPMN, which has the potential to increase tumor uptake and prolong residence time. The results showed that the nanoprobe could substantially aggregate in the tumors of prostate cancer xenograft mice and was visible for more than 72 h. Positron Emission Computed Tomography (PET) imaging showed that the nanoprobe could be used for precise imaging of prostate cancer with high expression of PSMA. In addition, organic melanin nanoparticles labeled with an elemental radionuclide achieved a stable, metal-free structure. Cell experiments and mouse toxicity experiments indicated that the nanoprobe has high safety.Conclusion: The new nanoprobe constructed in this study has high specificity and biocompatibility. In the future, combined with the multifunctional potential of melanin nanoparticles, this nanoprobe is expected to be used in the integrated theranostics of prostate cancer.Keywords: prostate cancer, 124I, PET, PSMA, melanin nanoparticles

This study presented the lignin amine/cellulose acetate (LA/CA) nanofibers prepared by centrifugal spinning for heavy metal ion adsorption. First, lignin alkali is modified by Mannich reaction to prepare lignin amine with amino content of 16 mmol/g, and then the lignin amine was mixed with cellulose acetate to spin LA/CA nanofibers by centrifugal spinning. The effects of spinning parameters and lignin amine content on LA/CA nanofibers morphology were discussed. The optimum performing LA/CA nanofibers with the highest lignin amine content (1.6 wt.%) and the smallest average diameter (756 nm) were obtained when the spinneret rotating speed was about 6000 rpm, collection distance of 15 cm and spinneret hole diameter of 0.16 mm at room temperature. The obtained optimum LA/CA nanofibers were used to adsorb Cu(II) and Co(II) ions, and the influence of temperature, absorb time and initial pH of adsorption system on the adsorption capacity of the nanofibers were analyzed. Furthermore, the adsorption behavior of heavy metal ions Cu(II) and Co(II) was investigated. The results showed that the LA/CA nanofibers presented a quite high adsorption selectivity for Cu(II), the adsorption rates of LA/CA nanofibers to Cu(II) and Co(II) were mainly controlled by chemical adsorption and the adsorption mode was single molecular layer adsorption.

Purpose: To study the effectiveness and safety of apatinib as second-line treatment for advanced pancreatic cancer (APC) in a Chinese tertiary cancer hospital. Methods: Two groups of APC patients who received treatment with single-agent or two-drug combination of gemcitabine-based first-line therapy (50 per group) in The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing were assessed. The study group received apatinib at or above the second line treatment, while the control group was treated with second-line chemotherapy, which was different from first-line single-drug chemotherapy. Patients received treatments until there was improvement in their conditions, or until adverse reactions became intolerable. Complete remission (CR), partial remission (PR), disease stabilization (SD), disease progression (PD), incidence of adverse reactions, and progression-free survival (PFS) of the patients were recorded. Results: The number of PR cases in APC patients who received apatinib as second-line therapy, and the number of PD patients were higher than the corresponding populations in the control group (p < 0.05). Treatment effectiveness was significantly higher in study group patients than in control subjects (p < 0.05). However, the incidence of adverse reactions was lower in the study group than in control group. Median PFS in the study group (5 months) was significantly higher than that of the control group (4.1 months, p < 0.05). Conclusion: The clinical efficacy of apatinib as second-line treatment for advanced pancreatic cancer is higher than that of the single drug. Apatinib is associated with low incidence of adverse reactions which prolongs PFS. Thus, apatinib has potentials for the clinical management of pancreatic cancer.

Methamphetamine (MA) is a highly addictive and illegal psychostimulant drug and is currently one of the most commonly abused illicit drugs in the world. The on-site rapid detection of trace amounts of MA and screening illicit drugs in clandestine laboratories is important for drug enforcement agencies and the forensic community in general. However, detecting methamphetamine in the presence of nicotine and cigarette smoke by ion mobility spectrometry faces difficulty due to the overlapped spectral peaks of methamphetamine and nicotine. In this work, a new method was developed to detect MA using pyridine as a dopant in the presence of nicotine by a homemade ion mobility spectrometry. The reduced mobilities of MA and nicotine were measured under the temperatures of the drift tube from 40 to 120 °C and doping with pyridine. The result shows that the temperature of 100 °C is beneficial to resolve the two substances. The concentration of doped pyridine is optimized to be 18 ppm. In this doped experiment, the reaction rate of nicotine is higher than that of MA by measuring the instrumental responses of MA and nicotine. No matter how high the nicotine content is, the interference of nicotine can be eliminated in the detection of MA doped with pyridine. This method is also successfully applied for the determination of MA and nicotine simultaneously in real saliva samples. The limit of detection of MA was measured to be about 0.5 ng/μL. The promising results in this work provide an effective method for on-site detection of MA.

This paper proposes and designs a (Graphene/TiO2/Metal/TiO2/Graphene)N structure based on the symmetrical periodic arrangement of graphene photonic crystals, metals and titanium dioxide. In a single layer of this structure, nano-scale metal materials are used as the center. Graphene and titanium dioxide materials are arranged symmetrically to form a period. The transfer matrix method is used for the numerical simulation study of the GPC (Graphene Photonic Crystals) structure in the ultraviolet, visible light and near-infrared ranges. The optical response of the GPC structure under different parameters (periods, TiO2 thickness and metal layer thickness) is analyzed. The results are displayed in the ultraviolet, visible light and near-infrared band, this structure can accurately shield and reflect ultraviolet and near-infrared, while maintaining a high transmittance in the visible band, which is conducive to improving the growth quality and yield of plants. Greenhouse covering materials have high potential application prospects in the field of agriculture.

Blending graphene oxide (GO) directly with polymers and then inducing the in situ reduction of GO is a promising method to alleviate the dilemma of dispersion. In this work, solution-mixed polycarb...

Air pollution and public health incidents have become a serious global concern. Hierarchical nanofibrous membranes are considered as high-performance filters with an advanced structure, but their reliable fabrication is still challenging. Herein, a novel methodology involving the combination of a multi-orifices solution blowing technique process and low molecule organogel self-assembly strategy is reported to construct a hierarchical dual-nanonet of polymer nanofibers and supramolecular nanofibrils. Through an adsorption–nucleation–growth model, ultrathin supramolecular nanofibrils (10–30 nm) were assembled in situ within a fluffy solution-blown nanofiber mat with strong inter-fiber connections. Benefiting from the synergistic effects of the ultrathin diameter, small pore size, high porosity and stable inter-fiber connections, the hierarchical dual-nanonet demonstrates robust mechanical strength, a high filtration efficiency (99.999% for 0.3 μm), low pressure drop (32 Pa), a high quality factor (0.189 Pa−1), and a boosted moisture permeation. The comprehensive performances indicate promising applications in various filtration applications, especially in the field of personal protective equipment.

In this article, we reported the hybrid copolymerization of ethylene and cyclic ketene acetals (CKAs) mediated by dithiocarbamate, in which the propagating radicals could open the rings of CKAs to incorporate cleavable ester units into the polyethylene backbone. The molecular weights and ester incorporation in the produced copolymers could be easily regulated. Furthermore, lipase could degrade the ester-containing polyethylene (PE)-based copolymers into short fragments effectively.

Bacterial infection and biofilms cause non-healing chronic wounds and threaten human health. Although antibiotics still play an irreplaceable role to treat infectious diseases in clinics, increasing attention has been paid to the problem of multidrug resistance (MDR). As a novel strategy to deal with bacterial infection, photodynamic antimicrobial therapy (PDAT) has shown promising potential to reduce bacterial infection, and stimuli-responsive nanomaterials have been shown to enhance the antibacterial efficiency and postpone the emergence of drug-resistant bacteria. In this work, we developed a bacterial microenvironment-responsive nanoplatform to eliminate bacteria and bacterial biofilms under 650 nm laser irradiation. Reversible addition-fragmentation chain transfer (RAFT) polymerization was applied to synthesize an H2O2 responsive block copolymer of POEGMA-b-PBMA, and the antibacterial drug of porphyrin TAPP was loaded to form nanoparticles (PT) by a co-assembled approach. At the infection area with overexpressed peroxide, nanoparticles were disintegrated due to the cleaved boronic ester leading to the release of TAPP. Furthermore, the released TAPP became protonated in the acidic infection area (pH = 5.5) and then enhanced its photodynamic antibacterial efficacy by producing higher singlet oxygen (1O2) levels under light irradiation. Both in vitro and in vivo antimicrobial and biofilm elimination experiments demonstrated that the responsive nanoplatform combined with PDAT has tremendous potential for the treatment of infections.

Background: Naringenin has been reported to play an anticancer role by inhibiting the metastasis of tumor cells, but the roles of naringenin and the molecular mechanisms mediated by it in lung canc...

The next-generation positron zirconium-89 (89 Zr, T1/2 = 3.27 days) is a novel nuclide for immunological positron emission tomography because of its favorite longer half-life. The aim of this work is to develop optimized methods for routine production and purification of 89 Zr through Monte Carlo (MC) simulation and laboratory experiments. 89 Y(p,n)89 Zr reaction was used for 89 Zr production. Optimized thicknesses of Al degrader (0.11 cm) and 89 Y foil (0.064 cm) were simulated through MC method. 89 Zr (15.0-40.7 mCi) with an average production rate of 0.92 ± 0.12 mCi/μA·h was produced after 1- to 2-h bombardment at the proton beam energy of 20 MeV and current of 20 μA. High radio-purity 89 Zr (6.14-26.8 mCi) obtained eluted from hydroxamate resin using 1-mol/L oxalic acid solution, with the concentration of 2.7 × 104 mCi/L. The gamma spectrum showed that the characteristic peak of 89 Zr was 511 and 909 keV, and no impurities were found. [89 Zr]Zr-DFO-trastuzumab was successfully labeled and performed good radiochemical purity (>95%) and stability that showed potential application in tumor molecular imaging.

Ring-opening polymerization of lactones has served as one of the most resourceful and versatile methods for the production of polyesters. However, the photocontrolled ring-opening polymerization of lactones with the advantages of being inexpensive, green, and noninvasive, is still rarely reported. In this work, we developed a series of composite photoacid generators containing a common photocatalyst and an onium salt to induce the living/controlled cationic ring-opening polymerization of lactones using benzyl alcohol or butyl alcohol as an initiator under visible light. The wavelength of the light could be easily adjustable by applying different photocatalysts. Moreover, radical species are generated concurrently during the electron transfer processes; as a result, simultaneous living/controlled cationic ring-opening polymerization of lactones and reversible addition–fragmentation chain transfer radical (RAFT) polymerization can be performed using hydroxy group capped trithiocarbonate to produce hybrid block copolymers. Photocontrolled ring-opening polymerization of lactones with the advantages of being inexpensive, green, and noninvasive, is still rarely reported. In this work, we developed a series of composite photoacid generators containing a common photocatalyst and an onium salt to induce the living/controlled cationic ring-opening polymerization of lactones using alcohol compound as an initiator under visible light. The wavelength of the light could be easily adjustable by applying different photocatalysts. Moreover, simultaneous living/controlled cationic ring-opening polymerization of lactones and reversible addition–fragmentation chain transfer radical (RAFT) polymerization of methyl acrylate can be performed using hydroxy group capped trithiocarbonate to produce hybrid block copolymers in one step.

Aim To survey the use of alcohol, and its correlates by mental health professions in China, a nation where there is rapid increase in alcohol consumption and problems. Methods As a part of a large-scale, nation-wide online survey of healthcare professionals, we collected demographic variables and other health-related variables anonymously. The Alcohol Use Disorder Identification Test-Concise (AUDIT-C) was used to collect data on alcohol use. Results 13,980 mental health professionals completed the survey (4382 doctors, 9339 nurses and 259 clinical psychologists), representing 64% of the total targeted. Respondents were predominantly female (75.1%). Alcohol consumption was reported by 41.8% of participants (by 53.9% of doctors, 36.2% of nurses and 40.5% of clinical psychologists). Based on the cut-off scores of the AUDIT-C (≥3 for women and ≥4 for men), 7.5% were classified as probable alcohol misusers in the past year, and the rates were 10.2% in doctors, 6.3% in nurses and 5.8% in clinical psychologists. Multiple logistic regression showed that male sex (OR = 3.772; CI = 3.206–4.439), being a doctor (OR = 1.259; CI = 1.052–1.506), being divorced or widowed (OR = 1.979; CI = 1.467–2.666), having an associate degree or less (OR = 1.809; CI = 1.040–3.147), working in Northeast China (OR = 1.538; CI = 1.281–1.848) and the habit of smoking (OR = 3.345; CI = 2.280–3.967) were significantly associated with alcohol misuse. Conclusions Alcohol use and misuse were relatively common among mental health professionals in China, and male sex, being a doctor, with lower education, working in Northeast China and cigarette smoking were significant associations. Awareness and interventions are recommended to promote healthier use of alcohol in this professional group, especially among risk subgroups.

Multicomponent nanohybrids of nickel/ferric oxides and nickel cobaltate spinel (denoted as NiO/Fe2O3/NiCo2O4) have been prepared through pyrolyzing the hierarchical nanostructure of MOF-on-MOF and explored as efficient scaffolds for sensitively determining insulin. As for the MOF-on-MOF preparation, the ultra-thin bimetallic CoNi-zeolitic imidazolate framework (CoNi-ZIF) nanosheets were grown tightly around the bimetallic CoFe Prussian blue analogue (CoFe PBA) nanocube (denoted as CoNi-ZIF@CoFePBA). Basic characterizations revealed the original core-shell structure shape was still maintained in the NiO/Fe2O3/NiCo2O4 pyrolyzed at 300 °C, which was composed of multi-metal oxides and NiCo2O4 spinel, along with low crystallinity. Conversely, the NiO/Fe2O3/NiCo2O4 nanohybrid calcined at 600 °C consisted of large amounts of nanoparticles, while the nanohyrbid obtained at 900 °C demonstrated aggregated NiO and Fe2O3 nanoparticles coexisted with the NiCo2O4 phase. Owing to the porous nanostructure, the synergistic effect among different components, excellently electrochemical conductivity, and good biocompatibility of the NiO/Fe2O3/NiCo2O4 nanohybrid obtained at 600 °C, the relevant aptasensor displayed superior sensing performance for the determination of insulin. It gave an ultra-low detection limit of 9.1 fg mL−1 (0.16 fM) within a wide linear insulin concentration ranging from 0.01 pg mL−1 (0.172 fM) to 100 ng mL−1 (1.72 nM) determined by the electrochemical technique. The constructed aptasensor also had high selectivity, good stability, excellent reproducibility, and acceptable applicability in human serum. By integrating the advantages of aptasensors and electrochemical approach with features of multi-metallic metal-organic frameworks, this work widely broadens the applications of MOF-driven nanohybrids in biosensing fields.

There is no information regarding the influence of heat stress (HS) on host metabolic profile. In this study, we investigated the effects of different environmental temperatures on oxidative status, hormone levels, HS indicators, and plasma metabolites in broilers. A total of 1,680 yellow-feather broilers (28 D old) were randomly allotted to 4 groups with 6 replicates. The broilers (29–57 D old) were maintained in thermostatic rooms (20°C, 25°C, 28°C, and 30°C) for 28 consecutive days. The results showed that the plasma cortisol and adrenocorticotropic hormone levels and creatine kinase and lactate dehydrogenase activities gradually increased when the temperature increased from 20°C to 30°C. However, the insulin-like growth factor-І level decreased gradually. Furthermore, heat shock protein 70 expression significantly increased in the liver and breast muscle (P

Production of efficient and cost-effective metal-based catalysts for electrocatalytic nitrogen reduction reaction (NRR) under ambient conditions is quite challenging. In this work, metal bismuth (B...

Mitochondrial malfunction is considered to be a decisive signal of apoptosis. It would be a promising strategy to target mitochondria in cancer cells to generate reactive oxygen species (ROS), thus directly inducing mitochondrial damage. We herein reported a mitochondria-targeted, photo-responsive polymer (Mito-PNBE), which can self-assemble into nanoparticles (Fe–CO@Mito-PNBE) encapsulated with diphenylcyclopropenone (light-responsive CO prodrugs) and aminoferrocene-based prodrugs via hydrophobic interactions. Upon UV-irradiation, the rapid release of CO and aminoferrocene-based prodrugs caused by disassembly was observed. On one hand, the released carbon monoxide in mitochondria could enhance ROS generation and accelerate oxidative metabolism. On the other hand, the aminoferrocene-based prodrugs will release Fe3+/Fe2+ ions in the tumor microenvironment, thus triggering the Fenton reaction, which generates more ROS and damages the mitochondria. Thus, the synergistic effect of the two drugs produces enough amounts of ROS in the mitochondria, leading to mitochondrial collapse with an enhanced cancer therapeutic effect. This multifunctional platform has potential in precision cancer therapy.

Black phosphorus (BP) has exhibited excellent biocompatibility and high photothermal conversion efficiency under near-infrared light, which makes it very promising for photothermal therapy. However, practical applications are highly hampered because it lacks a targeting property and rapidly degrades in cancer cells, especially in response to strong intracellular oxidative stress. Here, we reported that the mitochondrial targeting peptide functionalized black phosphorus nanosheets covered with an acid-labile polymer shell (doubly functionalized black phosphorus (DFBP) nanosheets) exhibited good stability. DFBP nanosheets not only have excellent ability of accumulating in tumor tissue via surface charge switching but also can target mitochondria. The doubly functionalized black phosphorus nanosheets resulted in robust cancer cell uptake but very poor normal cell accumulation.

In nature, the chemical energy and electrons stored in ATP and NADPH generated during irradiation can facilitate biochemical reactions under dark conditions. However, in artificial photoreaction systems, it is still very difficult to perform photoreactions under dark conditions due to the fact that the photogenerated charge pairs can recombine immediately upon ceasing the irradiation. Preventing the recombination of photogenerated charge pairs still constitutes a major challenge at present. Here, it is reported that functionalized carbon nitride nanomaterials having many heptazine rings with a positive charge distribution, which can tightly trap photogenerated electrons, efficiently prevent the recombination of photogenerated charges. These stored charges are exceedingly long-lived (up to months) and can drive photopolymerization without light irradiation, even after one month. The system introduced here demonstrates a new approach for storing light energy as long-lived radicals, enabling photoreactions under dark conditions.

Runjing Decoction (RJD) is a prescription of traditional Chinese medicine for the treatment of oligoasthenospermia. However, the molecular mechanism of RJD on oligoasthenospermia still remains unknown. A model of oligoasthenospermia was induced in 30 Sprague Dawley rats by intraperitoneal injection of cyclophosphamide at 35 mg/kg per day for 5 days and treated by intragastric RJD (13.5 g/kg) or L-carnitine (100 mg/kg) for 14 days. The body weight, testis and epididymis weight, grade A spermatozoa, grade B spermatozoa, the percentage of sperm forward motility (PR%), the sperm activity rate and the sperm density of rats were evaluated before and after RJD treatment. The testis apoptosis was determined by TUNEL staining. The expressions of RXFP1, FoxO1, PI3K, Akt, Bax and Bcl-2 were determined by qRT-PCR and Western blot, respectively. After RJD treatment, the grade A spermatozoa, sperm PR%, sperm activity and sperm density were significantly increased relative to those in model rats. Cell apoptosis of testis tissue was reversed by RJD. RJD suppressed cell apoptosis, inhibited the expression of RXFP1, FOXO1, PI3K, AKT and Bax, and promoted the expression levels of Bcl-2 in testicular tissue of oligoasthenospermia rats. RJD could alleviate sperm quality and testis damage in oligoasthenospermia rats by inhibiting RXFP1/AKT/FOXO1 pathway.

Based on the finite-difference time domain (FDTD) method, this paper has studied the absorption characteristics of the all-dielectric absorbers composed of silicon thin film with a multilayer dielectric stack. Broadband absorption was achieved in this paper. For instance, one-dimensional planar structure composed of 60nmSiO2–30nmMgF2–60nmGaN–3000nmSi maintains a broadband absorption ≥ 95% over a wavelength range from 440 to 770 nm. And the whole absorptance maintains 90% in the above spectral band, at an oblique incidence angle of 0.25π, while compared to the absorption property of pure silicon film in the same thickness but less than 70%, the new structure shows the greatly improving.

Programmed cell death 1 (PD-1) blockade is considered contraindicated in liver transplant (LT) recipients due to potentially lethal consequences of graft rejection and loss. Though post-transplant PD-1 blockade had already been reported, pre-transplant use of PD-1 blockade has not been thoroughly investigated. This study explores the safety and efficacy of neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC) after registration on the waiting list. Seven transplant recipients who underwent neoadjuvant PD-1 blockade combined with lenvatinib and subsequent LT were evaluated. The objective response rate (ORR) and disease control rate (DCR) was 71% and 85% according to the mRECIST criteria. Additionally, a literature review contained 29 patients were conducted to summarize the PD-1 blockade in LT for HCC. Twenty-two LT recipients used PD-1 inhibitors for recurrent HCC. 9.1% (2/22) and 4.5% (1/22) recipients achieved complete remission (CR) and partial remission (PR), respectively; 40.9% (9/22) recipients had progressive disease (PD). Allograft rejection occurred in 45% of patients. In total, seven patients from our center and three from the literature used pretransplant anti-PD-1 antibodies, eight patients (80%) had a PR, and the disease control rate was 100%. Biopsy-proven acute rejection (BPAR) incidence was 30% (3 in 10 patients), two patients died because of BPAR. This indicated that neoadjuvant PD-1-targeted immunotherapy plus tyrosine kinase inhibitors (TKI) exhibited promising efficacy with tolerable mortality in transplant recipients under close clinical monitoring.

We report herein a novel multiple electrochemical aptasensor based on covalent–organic framework (COF) for sensitive and simultaneous detection of miRNA 155 and miRNA 122, by using shell-encoded gold nanoparticles (Au NPs) as signal labels (AgNCs@AuNPs and Cu2O@AuNPs, respectively, NCs = nanoclusters). A new COF nanowire was synthesized via condensation polymerization of 1,3,6,8-tetra(4-carboxylphenyl)pyrene and melamine (represented by TBAPy-MA–COF–COOH) for multiple aptasensor fabrication. The nanowire was then used as a platform for anchoring single-strand DNA (ssDNA), which was hybridized with the complementary aptamer (cApt) probes of miRNA 155 and miRNA 122. AgNCs@AuNPs and Cu2O@AuNPs modified with cApts show separated differential pulse voltammetry (DPV) peaks at 0.08 and −0.1 V, respectively. The signal labels immobilized with cApts were released from the hybridized DNA complex and bound to their corresponding targets when contacting miRNAs. This phenomenon results in the substantial decline of the DPV peak current density of the signal labels. The developed TBAPy-MA–COF–COOH-based aptasensor has superior performance for sensing miRNA 155 and miRNA 122 simultaneously, with ultrasensitive low detection limits of 6.7 and 1.5 fM (S/N = 3), respectively, a wide linear range of 0.01–1000 pM, and high selectivity and applicability for serum samples. The proposed TBAPy-MA-based aptasensor demonstrates potential for simultaneous detection of multiple cancer biomarkers by replacing other ssDNA and aptamer strands.

Synthesizing artificial polymers with precise sequence structures, such as their biological analogues, is a serious challenge and of great importance in polymer science. Recently, step-growth polymerization and chain growth polymerization have been the main synthesis methods for preparing artificial sequence-regulated polymers. However, it is difficult to obtain sequence-controlled polymers with sufficient molecular diversity via step-growth polymerization; on the other hand, chain-growth polymerization generally requires laborious repetitive monomer feeding. In this focus review, the sequential multicomponent reactions for preparing periodic sequence-controlled polymers with sufficient molecular diversity and complexity and the interconvertible hybrid copolymerizations producing hybrid multiblock copolymers rapidly in one pot are highlighted. We have developed sequential multicomponent reaction and interconvertible hybrid copolymerization methods to prepare sequence-controlled polymers. The sequential multicomponent reaction combines more than two different multicomponent reactions in one pot to prepare periodic sequence˗controlled polymers with sufficient molecular diversity. The interconvertible hybrid copolymerization method uses trithiocarbonate compounds to combine radical polymerization of vinyl monomers and anionic ring-opening polymerization of thiirane monomers, resulting in hybrid multiblock sequence-regulated polymers.

We synthesized three kinds of nitrogen-doped nanoporous carbon nanomaterials (represented by N-mC) through a cost-effective method, that is, pyrolysis of plant biomasses (grass, flower, and peanut shells). We further explored their potential as sensitive bioplatforms for electrochemical label-free aptasensors to facilitate the early detection of alpha-fetoprotein (AFP). Chemical structure characterizations revealed that rich functional groups coexisted in as-synthesized N-mC nanomaterials, such as C-C, C-O, C=O, C-N, and COOH. Among the three kinds of N-mC nanomaterials, the one derived from grass (N-mCg) exhibited the lowest carbon defect degree, the highest ID/IG ratio in the Raman spectra, and the largest specific surface area (186.2 m2 g−1). Consequently, N-mCg displayed excellent electrochemical activity and strong affinity toward aptamer strands, further endowing the corresponding aptasensor with sensitive detection ability for AFP. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) were used to investigate the whole detection procedure for AFP. The EIS and DPV results showed that the fabricated N-mCg-based aptasensor possessed an extremely low limit of detection of 60.8 and 61.8 fg·mL−1 (s/n = 3), respectively, for detecting AFP within a wide linear range from 0.1 pg mL−1 to 100 ng mL−1. Moreover, the aptasensor displayed acceptable selectivity and applicability, high reproducibility, and excellent stability in serum samples of cancer patients. Therefore, the proposed cost-effective and label-free strategy based on the nitrogen-doped nanoporous carbon derived from plant biomass is a promising approach for the early detection of various tumor markers.

Objective To identify the potent metabolic biomarkers of cauda equina injury (CEI). Methods A total of 50 Sprague–Dawley rats were used to establish the CEI model in this study. The serum was collected at 12 hours, 1 day, 2 days, and 7 days after surgery. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was performed to analyze metabolic changes in the serum of the CEI rats from different groups. The differences between the metabolic profiles of the rats in 5 groups were analyzed using partial least squares discriminant analysis (PLS-DA). Results Metabolic profiling revealed significant differences between the sham operated and other groups. A total of 57 potential CEI metabolite biomarkers were identified between the sham operated group and the model groups at the different time points. Principal component analysis and PLS-DA analyses revealed clear segregation between CEI versus sham operation group. These potential biomarkers appear in 15 metabolic pathways. Conclusions Using metabolomic analysis, we were able to identify the novel serum biomarkers of CEI that may be relevant to the diagnosis and prognosis of CEI. In addition, our pathway analysis provides important insights into the etiology of CEI and a basis for clinical diagnosis, locating biomarkers in the early stages of the pathological process.

Renal ischemia-reperfusion injury (IRI) is one of the most common causes of acute kidney injury (AKI), which is closely related to high morbidity and mortality. However, the pathogenesis underlying renal IRI is complex and not fully defined. N6-methyladenosine (m6A) was recently found to be an abundant modification in mammalian messenger RNAs. It is implicated in various biological processes, while the role of m6A in IRI is not illustrated. Here we show that the m6A-methylated RNA level and its methyltransferase METTL14 are elevated in human AKI renal tissues and IRI HK-2 cells. Moreover, METTL14 knockdown protects the kidney against IRI in vitro and in vivo. Mechanistically, we identified that YAP1 is a direct target of METTL14 in AKI progression. Inhibition of YAP1-TEAD signaling by peptide 17 abrogates the protective effect of METTL14 against IRI in vitro and in vivo. Taken together, these results reveal that the N6-methyladenosine mRNA methylase METTL14 promotes the renal IRI via suppressing YAP1. The discovery of the METTL14-YAP1 pathway provides an important new perspective for understanding AKI and is conducive to revealing new therapeutic strategies and targets.

Asymmetric dearomatization reactions have recently emerged as a powerful tool for the rapid build-up of the molecular complexity. Chiral three-dimensional polycyclic molecules bearing contiguous stereogenic centers can be synthesized from readily available planar aromatic feedstocks. Here we report that an intermolecular asymmetric dearomatization reaction of α-naphthols bearing a tethered nucleophile at the C4 position of the naphthol ring is achieved by a chiral phosphoric acid. The reaction proceeds via a highly chemo- and regioselective aminative dearomatization/Michael addition sequence, affording a wide array of functionalized cyclic ketones in good yields (up to 93%) with excellent enantioselectivity (up to >99% ee). The catalyst loading can be reduced to 0.1 mol%. Preliminary mechanistic investigations identify that the enantioselectivity is established in the dearomatization step, while the Michael addition is the rate-limiting step. A working model accounting for the origin of the stereochemistry is proposed based on DFT calculations., Catalytic asymmetric dearomatization (CADA) reactions readily convert common aromatic compounds to diverse 3D chiral, polycyclic molecules. Here, the authors report an intermolecular asymmetric dearomatization of nucleophile-tethered α-naphthols affording functionalized cyclic ketones with high enantioselectivity.

Nitrogen-containing compounds are important components in human breath. However, their origins have not yet been clearly understood. In this study, a modified electrospray ionization (ESI) source coupling with quadrupole time-of-flight mass spectrometry has been used for breath analysis. Fourteen nitrogen-containing compounds were identified in mouth-exhaled breath, and 10 of them were from the oral cavity and oropharynx. Moreover, 8 of these nitrogen-containing compounds were recognized as endogenous metabolites. This result provides important clues for exploring the biological origins of these nitrogen-containing compounds. Observation of the ion suppression phenomenon also indicates that breath analysis should be carried out after clearing of the oral cavity and oropharynx, or directly through nose-breathing to eliminate the influence of those nitrogen-containing compounds from the oral cavity.

Excessive oxidative stress induces significant injury and cytotoxicity to neuronal cells. The current study tested expression and the potential function of the circular RNA PRKCI (circPRKCI) in oxidative stress-injured neuronal cells. In cultured SH-SY5Y neuronal cells, hydrogen peroxide (H2O2) downregulated circPRKCI expression, causing accumulation of miR-545 and miR-589, but reduction of their target, the transcription factor E2F7. Importantly, ectopic overexpression of circPRKCI in SH-SY5Y cells significantly attenuated H2O2-induced cytotoxicity. Conversely, siRNA-mediated knockdown of circPRKCI induced SH-SY5Y cell death and apoptosis. Further studies demonstrated that H2O2-induced cytotoxicity in SH-SY5Y cells was inhibited by miR-545/589 inhibitors, but mimicked by miR-545/589 mimics. Importantly, CRISPR/Cas9-mediated knockout (KO) of E2F7 induced potent SH-SY5Y cell death and apoptosis. Furthermore, transfection of circPRKCI siRNA or miR-545/589 mimics were ineffective in E2F7 KO cells. In the primary human neurons, H2O2 stimulation similarly induced circPRKCI downregulation, miR-545/589 accumulation and E2F7 reduction. Moreover, H2O2-induced death and apoptosis in the primary neurons were significantly inhibited by circPRKCI overexpression or miR-545/589 inhibitors. Taken together, our results show that dysregulation of circPRKCI-miR-545/589-E2F7 axis mediated H2O2-induced neuronal cell injury. Targeting this novel cascade could be a fine strategy to protect neurons from oxidative stress.

Efficacy of minimally invasive craniopuncture with the YL-1 puncture needle (hard-channel) and soft drainage tube (soft-channel) in treating hypertensive intracerebral hemorrhage (HICH).A total of 150 patients with HICH were randomly assigned into 3 groups: conservative group (n = 50), hard-channel group (n = 50), and soft-channel group (n = 50). Computed tomography, National Institutes of Health Stroke Scale (NIHSS) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) in serum and in drainage fluid were examined on days 2, 4, and 6 after operation.Compared with the conservative group, the serum levels of IL-6, TNF-α, and MDA were decreased and SOD was increased (P0.05); volumes of hematoma and perihematomal edema as well as NIHSS were reduced (P0.05) in minimally invasive groups on days 7, 14, and 28 after operation. Compared with the hard-channel group, the serum levels of IL-6, TNF-α, MDA, and SOD showed the same trend as above in the soft-channel group. In the soft-channel group, MDA was reduced and SOD was increased in brain drainage fluid on days 2, 4, and 6 (P0.05); volumes of hematoma and perihematomal edema on days 14 and 28 were found to be reduced compared with the hard-channel group (P0.05). There was no significant difference of volumes of hematoma and perihematomal edema on day 7 between minimally invasive groups. NIHSS of the soft-channel group appeared to be significantly reduced on days 7, 14, and 28 after operation (P0.05).Soft-channel minimally invasive craniopuncture is an ideal technique for treating HICH, with advantages of alleviating cerebral edema, reducing oxidative stress, and inhibiting inflammatory response.

Ammonia is one of the major environmental pollutants in freshwater aquatic systems that affects the survival and growth of organisms. In the present study, a nine-week experiment was conducted to investigate the chronic toxicity of ammonia on survival and selected hematological parameters, antioxidant ability, and histological structure in juvenile Chinese blunt snout bream, Megalobrama amblycephala. Fish were exposed to one of five different ammonia concentrations (0, 5, 10, 15, and 20 mg L −1 total ammonia-N, pH = 7.86 ± 0.41, temperature = 28.23 ± 0.79 °C). Growth performance of fish in the high-ammonia treatment was lower than that of fish in the control group. The survival rate in the group exposed to the highest ammonia-N concentration (20 mg L−1) was significantly lower than that of the control group. The lowest level of white blood cell count (WBC), red blood cell count (RBC), hemoglobin, hematocrit, and plasma glucose and the highest level of plasma ammonia, cortisol and aspartate transaminase were observed in fish exposed to ammonia-N at 20 mg L −1 compared with the control group. The liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities in fish exposure to 20 mg L −1 ammonia-N group were significantly lower than those in the control group, while oxidative stress indices (levels of malondialdehyde, MDA) was significantly higher than those in the control group. Regression analysis found that growth performance, plasma parameters, hematological parameters, and antioxidant status of fish were significant linear correlated to ammonia-N concentration. Fish exposed to various concentrations of ammonia displayed histopathologic alterations in both gill and liver tissue. Furthermore, morphological examination by transmission electron microscopy revealed that gill tissues displayed vacuolation of the cytoplasm, damaged mitochondria, increased heterochromatin, and intense desquamation of pavement epithelial cells on the gill lamellae. Our findings suggest that the stress responses induced in juvenile blunt snout bream by chronic exposure to ammonia are not limited to simple growth inhibition, but are accompanied by changes in oxidative stress, plasma parameter effects, and alterations in the histology of the liver and gill. Blunt snout bream had a dose-dependent effect on ammonia-N. We preliminarily suggest that the level of plasma ammonia, MDA, CAT, AST, FER, and SGR can be used as an indicator for chronic ammonia-N toxicity, but further research and verification are needed in the future.

Although a great deal of work has been dedicated to revealing the annealing-induced structure and mechanical changes in isotactic polypropylene (iPP), its effect on the photo-degradation behavior is seldom investigated so far. In this work, the correlation between microstructure induced by annealing in vacuum and photo-oxidative degradation behavior of iPP is studied. Lamellae thickening and perfection with increasing crystallinity are observed upon increasing annealing temperature. Besides, the formation of looser amorphous phase due to descendant chain segment concentration and decreased mechanical coupling between crystalline and amorphous regions are also corroborated. Annealing under elevated temperatures leads to decreased solubility coefficient of oxygen, improved radical scavenging ability of crystals and inhibited chain scission, which all synergistically contribute to an enhanced resistance to the photo-oxidation of iPP. However, the UV light absorption is not significantly changed by annealing before photo-oxidation. Electron Paramagnetic Resonance (EPR) results suggest that an effective removal of reactive sites by annealing can also be probably ruled out. In addition, EPR confirms that the total free radical concentration of annealed iPP is lower than that of unannealed samples after chain initiation step during photo-oxidation.

Prostate specific membrane antigen (PSMA) is a promising target for the diagnosis and therapy of prostate cancer. In this report, a NOTA-conjugated precursor, NOTA-PSMA (also named PSMA-BCH), was synthesized by peptide synthesizer with the chemical purity over 95%. 68Ga-PSMA-BCH was obtained by radiolabeling NOTA-PSMA with 68GaCl3 with >99% radiochemical purity and 59–74 GBq/μmol specific activity. In vitro and in vivo study of 68Ga-PSMA-BCH showed high stability, high uptake in PSMA-expressing cells and tumor, fast clearance and low non-target uptake. 22Rv1 tumors were clearly observed in micro-PET images of and showed good retention. Compared with 68Ga-PSMA-617, 68Ga-PSMA-BCH showed comparable tumor uptake and tumor-background ratios. Indicating 68Ga-PSMA-BCH is a promising candidate for prostate cancer imaging and worthy of further clinical investigations.

To broaden the operating temperature range of phosphoric acid (PA) doped polybenzimidazole membrane-based proton exchange membrane fuel cells (PEMFCs) toward low temperatures, a novel series of poly(2,5-benzimidazole) (ABPBI)/sulfonated sepiolite (S-Sep) composite membranes (ABPBI/S-Sep) with low PA doping levels (DLs) were prepared via in-situ synthesis. The desirably enhanced mechanical, thermal, and oxidative stabilities of ABPBI/S-Sep composite membranes were achieved by constructing ABPBI chains arranged along the sepiolite (Sep) fibers and acid-base crosslinks formed between S-Sep fibrous particles and ABPBI chains. Benefiting from the richness of high temperature stable bound water and the excellent water absorbability of Sep particles that enable the formation of additive proton conducting paths, the composite membranes retained bounded PA and achieved much higher proton conductivities under both anhydrous and hydrous conditions compared to PA-doped ABPBI membranes. Proton conductivity values above 0.01 S/cm at 40–90 °C/20–98% RH conditions and 90–180 °C/anhydrous conditions as well as peak power density of 0.13 and 0.23 W/cm2 at 80 and 180 °C with 0% RH, respectively from the ABPBI/2S-Sep composite membrane are more holistic compared to Nafion at low temperatures and polybenzimidazole-based membranes at high temperatures, respectively. The excellent properties of ABPBI/S-Sep composite membranes suggest them as prospective candidates for PEMFCs applications in a wide temperature range.

Carbonic anhydrase IX (CAIX) plays an important role in glioma cell proliferation, invasion, metastasis, and resistance to radiotherapy and chemotherapy. An effective and noninvasive PET molecular imaging agent targeting CAIX would help its diagnosis and treatment but is not currently available. Recently, a low-molecular-weight (LMW) CAIX targeting agent, [64Cu]XYIMSR-06, was reported to have significantly improved properties for targeting clear cell renal cell carcinoma (ccRCC). We are encouraged to investigate the feasibility of adapting this agent for the diagnosis and treatment of CAIX-overexpressing malignant glioma. In vitro cell uptake and binding affinity assays were used to verify the binding capacity of [64Cu]XYIMSR-06 to U87 MG tumor cells in which CAIX overexpression was confirmed. The U87 MG tumor-bearing mouse (in situ and subcutaneous) model was built, and mice were injected with the radiotracer and/or coinjected with acetazolamide (0.2 g/kg) as a blocking agent for noninvasive micro-PET imaging. Micro-PET imaging was performed at 2, 4, and 8 h postinjection. ROI (region of interest)-based semiquantification was performed in an orthotopic glioma tumor model. Biodistribution throughout each organ was performed at 2, 4, 4 h block, 8, and 24 h postinjection. Hematoxylin and eosin (HE) staining and immunofluorescence or immunohistochemistry (IF/IHC) staining were implemented postimaging to assess the expression of CAIX in tumor organs. In vitro, [64Cu]XYIMSR-06 exhibits greater uptake in glioma cells (high CAIX expression) than in HCT116 cells (low CAIX expression). The binding affinity of [64Cu]XYIMSR-06 to U87 MG cell lines reaches up to 4.22 nM. Both orthotopic and subcutaneous tumors were clearly visualized at 2-8 h postinjection. Biodistribution studies demonstrated a maximum tumor uptake of 3.13% ID/g at 4 h postinjection, and the tumor to brain ratio (T/brain) was 6.51 at 8 h postinjection. The ROI-based T/brain values were 7.03 and 5.46 at 2 and 8 h postinjection, respectively. Histopathological analysis confirmed the overexpression of CAIX in gliomas, and the area of CAIX-positive IF staining is extremely consistent with the morphology on micro-PET imaging. In this study, [64Cu]XYIMSR-06 demonstrated specific accumulation in CAIX-expressing U87 MG glioma tumors, indicating that the radiotracer has the potential for noninvasively monitoring and guiding personalized treatment of malignant glioma and other tumors overexpressing CAIX.

This study was conducted to examine the effects of fish meal (FM) replacement by rice protein concentrate (RPC) supplemented with xylooligosaccharides (XOS) on the growth, intestinal digestive and absorptive capabilities and amino acid metabolism of blunt snout bream. Fish were randomly divided into six groups, and were fed with the control diet (containing 10% FM), the RPC diet (FM entirely replaced by RPC) and the RPC diet supplemented with 0.5, 1.5, 2.3 and 3% XOS, respectively, for 8 weeks. Fish fed the RPC diet obtained significantly lower values in daily growth index, feed efficiency ratio, nitrogen and energy retention and plasma concentrations of methionine, leucine, phenylalanine, lysine and histidine compared to the control. However, the supplement of 1.5% XOS restored these parameters to the levels similar to the control group. Fish fed the RPC diet showed no statistical difference in intestinal lipase, alkaline phosphatase and Na+K+-ATPase activities compared to the control group, but exhibited lower protease, carboxypeptidase A, aminopeptidase N and γ-glutamyl transpeptidase activities. However, these effects were reserved with the administration of 1.5% XOS. Also, the transmission electron microscopy analysis showed a significantly lower microvilli length in the mid-intestine of fish fed the RPC diet compared to the control, but it improved significantly with the supplementation of XOS. Hepatic activities of alanine transaminase, aspartate aminotransferase and glutamate dehydrogenase were significantly lower in fish fed the RPC diet compared to the control, but they improved with the supplementation of 1.5% XOS. Similarly, fish fed the RPC diet obtained relatively low expression levels of the target of rapamycin (TOR) and ribosomal protein S6 kinase 1 but higher expressions of eukaryotic translation initiation factor 4E-binding protein 2 in the intestine, liver and muscle. Opposite trend was observed in fish fed the RPC diet supplemented with 1.5% XOS. Overall, these results showed that RPC supplemented with 1.5% XOS could completely replace FM in the feed of blunt snout bream without any adverse effect on the growth performance, intestinal enzymes activities, gut morphology, amino acid metabolism and TOR signaling.

Background & Aims Chemokine-mediated immune cell recruitment plays pivotal roles in liver inflammation. C-C motif chemokine ligand 5 (CCL5) has been shown to be responsible for the recruitment of monocytes/macrophages and has been implicated in various liver diseases, including nonalcoholic fatty liver disease, fibrosis, and hepatocellular carcinoma. Previous studies have also shown that inhibition of CCL5 appears to be a promising therapeutic approach for several chronic liver diseases. However, whether blocking CCL5 could benefit immune cell–mediated hepatitis remains largely elusive. Methods By adopting a specific agonist, alpha-galactosylceramide (α-Galcer), of invariant natural killer T cells (iNKTs), we investigated the function and mechanism of CCL5 in the iNKT induced murine hepatitis model. Results We found significantly increased CCL5 expression in α-Galcer–induced hepatitis murine model. Such an increase in CCL5 is mainly enriched in non-parenchymal cells such as macrophages and iNKTs but not in hepatocytes. Surprisingly, CCL5 blockage by genetic deletion of Ccl5 does not affect the α-Galcer–induced iNKT activation but greatly worsens α-Galcer–induced liver injury accompanied by an increased hepatic neutrophil infiltration. Mechanistically, we demonstrated that greater neutrophil accumulation in the liver is responsible for the enhanced liver injury in Ccl5-/- mice. Such an increased hepatic neutrophil infiltration is mainly caused by an enhanced CXCL1-CXCR2 signal in Ccl5-/- mice. Therapeutically, either antibody-mediated neutrophil depletion or a CXCR2 antagonist, SB225002, mediated CXCR2 signaling blockage significantly ameliorated α-Galcer–induced liver injury in Ccl5-/- mice. Conclusions Our present study demonstrates that (1) α-Galcer–induced murine hepatitis could greatly induce CCL5 production in macrophages and iNKT cells; (2) loss of CCL5 could enhance CXCL1 expression in hepatocytes and activate CXCL1-CXCR2 axis in neutrophils to augment their hepatic infiltration; and (3) neutrophil depletion or blockage of CXCL1-CXCR2 axis greatly improves α-Galcer–induced liver injury in Ccl5-/- mice. This study suggests that clinical utilization of CCL5 blockage may compensatorily induce the activation of other chemokine pathways to enhance neutrophil recruitment and liver injury in hepatitis., Graphical abstract

Herein, we present the successful preparation of a new family of porphyrin-functionalized coordination star polymers through the combination of coordination-driven self-assembly and post-assembly polymerization. Their ordered self-assembly behaviour in water and potential applications in photodynamic therapy have been demonstrated.

Hybrid copolymerization of two or more structurally distinct monomers (e.g., cyclic monomers and vinyl-type monomers) is very interesting because it can produce new types of copolymers and open up new research directions in the field of polymer chemistry. However, it has long been a challenge because the reactivity and polymerization mechanism of different monomers are extremely different. Here, we report a new hybrid copolymerization via an interconvertible living free radical and anion ring-opening polymerization mechanism, in which the copolymerization of cyclic monomers and vinyl-type monomers can be achieved. Via this novel hybrid copolymerization, the cyclic monomers and vinyl monomers, which generally cannot be copolymerized, now can be copolymerized into one polymer chain. Furthermore, the monomer arrangement in the chains could be easily regulated by the interconverting behavior. This new hybrid copolymerization will provide a powerful means for producing materials that have not been accessible by any other means.

Objective Epidermal growth factor receptor (EGFR) is overexpressed in a wide variety of solid tumors, serving as a well-characterized target for cancer imaging or therapy. In this study, we aimed to design and synthesize a radiotracer, 64Cu-NOTA-C225, targeting EGFR for tumor positron emission tomography (PET) imaging. Methods Cetuximab (C225) was conjugated to a bifunctional chelator, p-isothiocyanatobenzyl-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), and further radiolabeled with copper-64 for PET imaging. 64Cu-NOTA-IgG and Cy5.5-C225 were also synthesized as control probes. A431 and A549 mouse models were established for micro-PET and/or near-infrared fluorescence (NIRF) imaging. Results 64Cu-NOTA-C225 exhibited stability in vivo and in vitro up to 24 h and 50 h post-injection, respectively. A431 tumors with average standard uptake values (SUVs) of 5.61±0.69, 6.68±1.14, 7.80±1.51 at 6, 18 and 36 h post-injection, respectively, which were significantly higher than that of moderate EGFR expressing tumors (A549), with SUVs of 0.89±0.16, 4.70±0.81, 2.01±0.50 at 6, 18 and 36 h post-injection, respectively. The expression levels of A431 and A549 were confirmed by western blotting. Additionally, the tracer uptake in A431 tumors can be blocked by unlabeled cetuximab, suggesting that tracer uptake by tumors was receptor-mediated. Furthermore, NIRF imaging using Cy5.5-C225 showed that the fluorescence intensity in tumors increased with time, with a maximal intensity of 8.17E+10 (p/s/cm2/sr)/(μW/cm2) at 48 h post-injection, which is consistent with the paradigm from micro-PET imaging in A431 tumor-bearing mice. Conclusions The 64Cu-NOTA-C225 PET imaging may be able to specifically and sensitively differentiate tumor models with different EGFR expression levels. It offers potentials as a PET radiotracer for imaging of tracer EGFR-positive tumors.