On-site preparation of sandwich plasmonic coupled SERS tape toward pesticide residue determination on food surface.

A sandwich plasmonic coupled surface enhanced Raman spectroscopy (SERS) tape is proposed prepared by peeling the chemical printed silver nanocorals (AgNCs) from Cu sheet with adhesive tape, which can sample targets from food surface and sandwich them between substrates and Cu sheet for SERS detection. The solid-to-solid transformation method for fabricating SERS tapes can effectively avoid the weakening of tape stickiness during the preparation process. The sandwich plasmonic coupled structure of AgNC substrate, targets, and Cu sheet display excellent SERS activity (EF = 1.62 × 107) for sensitive determination of analytes. In addition, due to the high heat conductivity of Cu sheet, the thermal effect of laser irradiation during SERS detection cannot damage the AgNC tapes, which ensures the reproducibility of subsequent quantification. The sandwich plasmonic coupled SERS tape is demonstrated to quantify malachite green (MG) and methyl parathion (MP) with good linear coefficients (> 0.98) by two typical calibration plots under different concentration ranges. The limit of detection (LOD) of the method is 0.17 ng/cm2 and 0.48 µg/cm2 (S/N = 3) for MG and MP. This method can realize the quantitative determination of MP and MG on the surface of fruits and fish scale with recoveries of 93-113%. The satisfactory detection results demonstrate the proposed sandwich plasmonic coupled AgNC tape can be successfully applied to SERS-based point-of-care testing (POCT) for pesticide residue determination, which will provide a new path for designing and constructing SERS tapes.

SERS-Temperature Dual-Mode T-type Lateral Flow Strip for Accurate Detection of Free and Total Prostate-Specific Antigens in Blood.

Accurate point-of-care (POC) analysis of cancer markers is the essence in the comprehensive early screening and treatment of cancer. Dual-mode synchronous detection is one of the effective approaches to reduce the probability of false negatives or false positives. As a result, this can greatly improve the accuracy of diagnosis. In this work, a surface-enhanced Raman scattering (SERS)-temperature dual-mode T-type lateral flow strip was fabricated to direct and simultaneous POC detection of total and free prostate-specific antigens (t-PSA and f-PSA) in blood. With the advantage of high stability of T-type lateral flow strip and simultaneous acquirement of assay results for t-PSA and f:t PSA ratio, the proposed method has high accuracy in the diagnosis of prostate cancer, especially in the diagnostic gray zone between 4.0 and 10.0 ng/mL. The SERS-temperature dual-signal has a good linear correlation with either f-PSA or t-PSA. To evaluate the clinical diagnostic performance of the proposed method, spiked human serum samples and the whole blood sample were analyzed. The assay results showed good recovery, and compared with traditional electrochemiluminescence immunoassay (ECLIA) method (t-PSA: 43.151; f/t ratio: 0.08), the results obtained by the proposed method were similar (t-PSA: 40.15 (SERS), 36.21 (temperature); f/t ratio: 0.08 (SERS), 0.08 (temperature), but the detection time (15 min) and cost ($0.05) had been greatly reduced. Therefore, the proposed SERS-temperature synchronous dual-mode T-type lateral flow strip has a strong application potential in the field of accurate large-scale diagnostics of prostate cancer on-site by simultaneous POC detection of t-PSA and f-PSA in blood.

Gold nanoparticle dimer-based immunochromatography for in situ ultrasensitive detection of porcine epidemic diarrhea virus.

The low detection sensitivity of lateral-flow immunochromatography assay (LFIA) based on spherical gold nanoparticle (AuNP) limits its wide applications. In the present study, AuNP dimers with strong plasma scattering and robust signal output were synthesized via the Ag ion soldering (AIS) strategy and used as labeled probes in LFIA to boost the sensitivity without any extra operation process and equipment. The established LFIA exhibited high sensitivity with a limit of detection (LOD) of 2.0 × 102 TCID50/mL for PEDV, which provides 50 times higher sensitivity than commercial LFIA based on spherical colloidal gold. In addition, the AuNP dimer-based LFIA showed strong specificity, good reproducibility, high stability, and good accordance to reverse transcription polymer chain reaction (RT-PCR) when detecting 109 clinical samples. Thus, the AuNP dimers is a promising probe for LFIA and the developed AuNP dimer-based LFIA is suitable for the rapid detection of PEDV in the field.

DNA-Condensed Plasmonic Supraballs Transparent to Molecules.

DNA nanotechnology offers an unrivaled programmability of plasmonic nanoassemblies based on encodable Watson-Crick basepairing. However, it is very challenging to build rigidified three-dimensional supracolloidal assemblies with strong electromagnetic coupling and a self-confined exterior shape. We herein report an alternative strategy based on a DNA condensation reaction to make such structures. Using DNA-grafted gold nanoparticles as building blocks and metal ions with suitable phosphate affinities as abiological DNA-bonding agents, a seedless growth of spheroidal supraparticles is realized via metal-ion-induced DNA condensation. Some governing rules are disclosed in this process, including kinetic and thermodynamic effects stemming from electrostatic and coordinative forces with different interaction ranges. The supraballs are tailorable by adjusting the volumetric ratio between DNA grafts and gold cores and by overgrowing extra gold layers toward tunable plasmon coupling. Various appealing and highly desirable properties are achieved for the resulting metaballs, including (i) chemical reversibility and fixation ability, (ii) stability against denaturant, salt, and molecular adsorbates, (iii) enriched and continuously tunable plasmonic hotspots, (iv) permeability to small guest molecules and antifoulingness against protein contaminates, and (v) Raman-enhancing and photocatalytic activities. Innovative applications are thus foreseeable for this emerging class of meta-assemblies in contrast to what is achieved by DNA-basepaired ones.

Cav3.2 T-Type calcium channels downregulation attenuates bone cancer pain induced by inhibiting IGF-1/HIF-1α signaling pathway in the rat spinal cord.

Background: Bone cancer pain (BCP) is one of the most ubiquitous and refractory symptoms of cancer patients that needs to be urgently addressed. Substantial studies have revealed the pivotal role of Cav3.2 T-type calcium channels in chronic pain, however, its involvement in BCP and the specific molecular mechanism have not been fully elucidated. Methods: The expression levels of Cav3.2, insulin-like growth factor 1(IGF-1), IGF-1 receptor (IGF-1R) and hypoxia-inducible factor-1α (HIF-1α) were detected by Western blot in tissues and cells. X-ray and Micro CT used to detect bone destruction in rats. Immunofluorescence was used to detect protein expression and spatial location in the spinal dorsal horn. Electrophoretic mobility shift assay used to verify the interaction between HIF-1α and Cav3.2. Results: The results showed that the expression of Cav3.2 channel was upregulated and blockade of this channel alleviated mechanical allodynia and thermal hyperalgesia in BCP rats. Additionally, inhibition of IGF-1/IGF-1R signaling not only reversed the BCP-induced upregulation of Cav3.2 and HIF-1α, but also decreased nociceptive hypersensitivity in BCP rats. Inhibition of IGF-1 increased Cav3.2 expression levels, which were abolished by pretreatment with HIF-1α siRNA in PC12 cells. Furthermore, nuclear HIF-1α bound to the promoter of Cav3.2 to regulate the Cav3.2 transcription level, and knockdown of HIF-1α suppresses the IGF-1-induced upregulation of Cav3.2 and pain behaviors in rats with BCP. Conclusion: These findings suggest that spinal Cav3.2 T-type calcium channels play a central role during the development of bone cancer pain in rats via regulation of the IGF-1/IGF-1R/HIF-1α pathway.

SYK-mediated epithelial cell state is associated with response to c-Met inhibitors in c-Met-overexpressing lung cancer.

Genomic MET amplification and exon 14 skipping are currently clinically recognized biomarkers for stratifying subsets of non-small cell lung cancer (NSCLC) patients according to the predicted response to c-Met inhibitors (c-Metis), yet the overall clinical benefit of this strategy is quite limited. Notably, c-Met protein overexpression, which occurs in approximately 20-25% of NSCLC patients, has not yet been clearly defined as a clinically useful biomarker. An optimized strategy for accurately classifying patients with c-Met overexpression for decision-making regarding c-Meti treatment is lacking. Herein, we found that SYK regulates the plasticity of cells in an epithelial state and is associated with their sensitivity to c-Metis both in vitro and in vivo in PDX models with c-Met overexpression regardless of MET gene status. Furthermore, TGF-ß1 treatment resulted in SYK transcriptional downregulation, increased Sp1-mediated transcription of FRA1, and restored the mesenchymal state, which conferred resistance to c-Metis. Clinically, a subpopulation of NSCLC patients with c-Met overexpression coupled with SYK overexpression exhibited a high response rate of 73.3% and longer progression-free survival with c-Meti treatment than other patients. SYK negativity coupled with TGF-ß1 positivity conferred de novo and acquired resistance. In summary, SYK regulates cell plasticity toward a therapy-sensitive epithelial cell state. Furthermore, our findings showed that SYK overexpression can aid in precisely stratifying NSCLC patients with c-Met overexpression regardless of MET alterations and expand the population predicted to benefit from c-Met-targeted therapy.

Facial Preparation of Cyclometalated Iridium (III) Nanowires as Highly Efficient Electrochemiluminescence Luminophores for Biosensing.

In this study, highly efficient ECL luminophores composed of iridium complex-based nanowires (Ir-NCDs) were synthesized via covalently linking bis(2-phenylpyridine)-(4-carboxypropyl-2,2'-bipyridyl) iridium(III) hexafluorophosphate with nitrogen-doped carbon quantum dots (NCDs). The ECL intensity of the nanowires showed a five-fold increase in ECL intensity compared with the iridium complex monomer under the same experimental conditions. A label-free ECL biosensing platform based on Ir-NCDs was established for Salmonella enteritidis (SE) detection. The ECL signal was quenched linearly in the range of 102-108 CFU/mL for SE with a detection limit of 102 CFU/mL. Moreover, the relative standard deviations (RSD) of the stability within and between batches were 0.98% and 3.9%, respectively. In addition, the proposed sensor showed high sensitivity, selectivity and stability towards SE in sheep feces samples with satisfactory results. In summary, the excellent ECL efficiency of Ir-NCDs demonstrates the prospects for Ir(III) complexes in bioanalytical applications.

One-Step, On-Site Chemical Printing of a 3D Plasmon-Coupled Silver Nanocoral Substrate toward SERS-Based POCT.

Surface-enhanced Raman scattering (SERS) with the advantages of high sensitivity, nondestructive analysis, and a unique fingerprint effect shows great potential in point-of-care testing (POCT). However, SERS faces challenges in rapidly constructing a substrate with high repeatability, homogeneity, and sensitivity, which are the key factors that restrict its practical applications. In this study, we propose a one-step chemical printing strategy for synthesizing a three-dimensional (3D) plasmon-coupled silver nanocoral (AgNC) substrate (only need about 5 min) without any pretreatments and complex instruments. The galvanic replacement between AgNO3 and Cu sheets will provide both Ag0 for the formation of silver nanostructures and Cu2+ for the polymerization of fish sperm DNA (FSDNA). The protection of AgNCs is facilitated by the crosslinked FSDNA, which can improve the stability of the substrate and promote the control of its coral-like morphology. The obtained substrate displays excellent capacity of signal enhancement due to the 3D plasmon coupling both between nanocoral tentacles and between nanocorals and Cu sheets as well. Therefore, the AgNC substrates display high activity (enhancement factor = 1.96 × 108) and uniformity (RSD < 6%). Food colorants have been widely used in various foods to improve their color, but the inevitable toxicity of colorants seriously threatens food safety. Therefore, the proposed AgNC substrates were used to directly quantify three kinds of weak-affinity food colorant molecules including Brilliant Blue, Allura Red, and Sunset Yellow assisted by the capture by cysteamine hydrochloride (CA), showing the detection limits (S/N = 3) of 0.053, 0.087, and 0.089 ppm, respectively. The SERS method has been further applied in the detection of the three kinds of food colorants in both complex food samples and urine with recoveries of 91-119%. The satisfactory detection results suggest that the facile preparation strategy of AgNC substrates will be widely used in SERS-based POCT to promote the development of food safety and on-site healthcare.

A two-dimensional disposable full-history time-temperature indicator for cold chain logistics.

Monitoring temperature change in the distribution process is one of the crucial points to guarantee the safety and efficacy of temperature-sensitive products such as drugs, vaccines, and foods. The traditional time-temperature indicators (TTIs) for this work are digital thermometers. However, due to their high cost, only a few digital sensors can be mounted in each refrigerator car. It is not possible to record the situation of each individual products. In addition, the time-temperature history curves measured by digital thermometer are easy to be tampered, limiting their application on indicating the validity of products. Although some low-cost and disposable chemical or physical TTIs have been reported, they always work based on only one parameter to indicate the experienced highest temperature, which cannot indicate how long does the products experience in different temperature. Here, multicolor plasmonic hydrogels allowing the in-situ formation of gold nanoparticles have been fabricated as the full-history time-temperature indicator (FHTTI). Different from traditional indicators, the two-dimensional FHTTI can separately indicate temperature and time with two non-interfering parameters: color and length, which guarantees the accuracy and completeness of reported time-temperature information. The FHTTI has achieved to monitor the time-temperature changes up to more than 30 days under complex variable-temperature conditions, showing great application potentials for the accurate full-history time-temperature indication of each single packaged product in cold chain logistics.

Steering DNA Condensation on Engineered Nanointerfaces.

DNA has received increasing attention in nanotechnology due to its ability to fold into prescribed structures. Different from the commonly adopted base-pairing strategy, an emerging class of amorphous DNA materials are formed by DNA's abiological interactions. Despite the great successes, a lack of nanoscale nucleation/growth control disables more advanced considerations. This work aims at harnessing the heterogeneous nucleation of metal-ion-glued DNA condensates on nanointerfaces. Upon unveiling key orthogonal factors including solution pH, ionic cross-linkers, and surface functionalities, chemically programmable DNA condensation on nanoparticle seeds is achieved, resembling a famous Stöber process for silica coating. The nucleation rules discovered on individual nanoseeds can be passed on to their dimeric assemblies, where broken spherical symmetry and the existence of interparticle gaps help a regiospecific DNA gelation. The steerable DNA condensation, and the multifunctions from DNA, metal ions, and nanocores, hold a great promise in noncanonical DNA nanotechnology toward novel applications.

Strategies for Enhancing the Sensitivity of Electrochemiluminescence Biosensors.

Electrochemiluminescence (ECL) has received considerable attention as a powerful analytical technique for the sensitive and accurate detection of biological analytes owing to its high sensitivity and selectivity and wide dynamic range. To satisfy the growing demand for ultrasensitive analysis techniques with high efficiency and accuracy in complex real sample matrices, considerable efforts have been dedicated to developing ECL strategies to improve the sensitivity of bioanalysis. As one of the most effective approaches, diverse signal amplification strategies have been integrated with ECL biosensors to achieve desirable analytical performance. This review summarizes the recent advances in ECL biosensing based on various signal amplification strategies, including DNA-assisted amplification strategies, efficient ECL luminophores, surface-enhanced electrochemiluminescence, and ratiometric strategies. Sensitivity-enhancing strategies and bio-related applications are discussed in detail. Moreover, the future trends and challenges of ECL biosensors are discussed.

Sub-1.5 nm-gapped heterodimeric plasmonic nanomolecules.

Plasmonic molecules are discrete assemblies of similar/dissimilar nanomaterials (atomic equivalents) with efficient inter-unit coupling toward electromagnetic hybridization. Albeit fundamentally and technologically very important, these structures are rare due to the lack of a general way to manipulate the structure, composition, and coupling of the nanoassemblies. While DNA nanotechnology offers a precious chance to build such structures, the weak coupling of DNA-bonded materials and the very limited material building blocks are two obstacles. This work aims to remove the bottlenecking barriers on the road to dimeric (and possibly more complicated) plasmonic molecules. After solving key synthetic issues, DNA-guided, solvo-driven Ag ion soldering is utilized to build a whole set (10 combinations of 4 metals) of homo/heterodimeric plasmonic nanomolecules with prescribed compositions. Importantly, strong in-solution electric-dipole coupling mediated by a sub-1.5 nm interparticle dielectric gap is achieved for materials with strong (Au, Ag) or damped (Pt, Pd) plasmonic responses. The involvement of Pt/Pd materials is of great value for plasmon-mediated catalysis. The broken dimeric symmetry is desirable for Fano-like resonance and photonic nanodiode devices, as well as lightening-up of plasmon dark states. The generality and reliability of the method would allow excitonic, nonlinear-optical, and magnetic units to be involved toward correspondingly enhanced functions.

Research on Dynamic Measurement Method of Flow Rate in Tea Processing.

Tea flow rate is a key indicator in tea production and processing. Due to the small real-time flow of tea leaves on the production line, the noise caused by the transmission system is greater than or close to the real signal of tea leaves. This issue may affect the dynamic measurement accuracy of tea flow. Therefore, a variational mode decomposition combined with a wavelet threshold (VMD-WT) denoising method is proposed to improve the accuracy of tea flow measurement. The denoising method of the tea flow signal based on VMD-WT is established, and the results are compared with WT, VMD, empirical mode decomposition (EMD), and empirical mode decomposition combined with wavelet threshold (EMD-WT). In addition, the dynamic measurement of different tea flow in tea processing is carried out. The result shows that the main noise of tea flow measurement comes from mechanical vibration. The VMD-WT method can effectively remove the noise in the tea dynamic weighing signal, and the denoising performance is better than WT, VMD, EMD, and EMD-WT methods. The average cumulative measurement accuracy of the tea flow signal based on the VMD-WT algorithm is 0.88%, which is 55% higher than that before denoising. This study provides an effective method for dynamic and accurate measurement of tea flow and offers technical support for digital control of the tea processing.

Surface-Enhanced Electrochemiluminescence Imaging for Multiplexed Immunoassays of Cancer Markers in Exhaled Breath Condensates.

Recently we have demonstrated that the surface plasmon of noble metal nanoparticles can effectively enhance the ECL intensity of Ru(bpy)32+, and we named this detection principle as surface-enhanced electrochemiluminescence (SEECL-I). However, SEECL based on photomultiplier tube (PMT) detection can only detect one target at a time, which is not suitable for multiple targets detection. In this work, we combined our previous developed SEECL with a bioimaging device to develop a novel multiplexed immunassay for simultaneous and fast analysis of cancer markers. A core-shell nanocomposite consisted of gold-silicon dioxide nanoparticles doped with Ru(bpy)32+(Au@SiO2-Ru) with strong ECL emission was employed as ECL label due to the localized surface plasmon resonance (LSPR) of AuNPs, which can significantly enhance the ECL emission of Ru(bpy)32+. The ECL signals from the 4 × 4 electrode arrays were collected using the constant potential method (current-time curve method) imaging with a sCOMS camera. As a proof-of-concept application, we demonstrated the use of the proposed SEECL-I for simultaneous detection of carcinoembryonic antigen (CEA), neuron specific enolase (NSE), and squamous cell carcinoma antigen (SCC) in exhaled breath condensates (EBCs) with low detection limit (LOD) of 0.17, 0.33, and 0.33 pg/mL (S/N = 3), respectively. The results demonstrated that the proposed SEECL-I strategy can provide a high sensitivity, fast analysis, and high-throughput platform for clinical diagnosis of cancer markers in EBCs.

Toehold-mediated strand displacement coupled with single nanoparticle dark-field microscopy imaging for ultrasensitive biosensing.

Highly sensitive detection of biomarkers is essential for disease prevention and early diagnosis. Herein, a highly sensitive strategy was proposed for microRNA-21 (miRNA-21) detection by the incorporation of programmable toehold-mediated strand displacement (TMSD) and dark-field microscopy imaging. Firstly, efficient and specific TSMD was carried out via hybridization between the substrate strand (Sub) and two short probe strands (P1, P2). Then, miRNA-21 could specifically hybridize with Sub due to the toehold that existed on its tail, which triggered the amplification with the help of the assist strands, and forming a large number of Sub-assist double-stranded DNA (dsDNA). This process realized the targeted highly specific recognition of miRNA-21 and the amplification of the trace target to high-output dsDNA. Additionally, as glucose oxidase (Gox) was modified on the end of the assist strands in advance, hydrogen peroxide was generated after adding glucose to the system, which further etched gold-silver core-shell nanocubes (Au@Ag NCs). As a result, the size of Au@Ag NCs decreased and the scattering intensity reduced simultaneously. The scattering intensity reduction value of Au@Ag NCs has a linear relationship with miRNA-21 concentration in the range of 1.0 to 100.0 fM with a limit of detection of 1.0 fM. Finally, the proposed method has been successfully demonstrated for the determination of miRNA-21 in lung cancer cell A549 lysate.

Oil-Free Gold Nanobipyramid@Ag Microgels as a Functional SERS Substrate for Direct Detection of Small Molecules in a Complex Sample Matrix.

Surface-enhanced Raman scattering (SERS) is a super-sensitive analysis technology based on the target molecular fingerprint information. The enhancement of local electromagnetic field of the SERS substrate would increase the target molecules' Raman intensity which adsorb on the surface of nanoparticles. However, the existing adhesive macromolecules in the complex mixed sample would interfere with the adsorption of small target molecules, and it weakens the Raman intensity of target molecules. Microgels are one of the potential materials to suppress the interference of adhesive macromolecules and to avoid the complex pretreatments. However, most of the current microgel synthesis methods involve complex operations with precise instrumentation or the interference of oil and organic reagents. In this work, a simple and oil-free method was proposed to synthesize the gold nanobipyramid (Au NBP)@Ag@hyaluronic acid microgel via the condensation reaction of carboxyl and amino groups. As a proof-of-concept demonstration for small-molecule detection, the rhodamine 6G (R6G) molecules were allowed to enter inside the microgel through the meshes and adsorb on the surface of Au NBP@Ag nanoparticles within 30 min, while the macromolecule (bovine serum albumin in this case) was retained outside the microgel in the meantime. In addition, under the combined action of lightning rod effect of Au NBP and surface plasmon resonance effect of silver render the microgels with high SERS activity. The synthetic Au NBP@Ag@hyaluronic acid microgels were applied to detect 6-thioguanine in the human serum without any pretreatment process, and it showed a high signal enhancement and stable SERS signal, which can satisfy the requirement of clinical diagnosis. These results show that the proposed microgels have potential applications in the field of point-of-care testing.

A universal strategy for the incorporation of internal standards into SERS substrates to improve the reproducibility of Raman signals.

The uneven distribution of metal nanoparticles is a vital influencing factor in the poor uniformity of surface-enhanced Raman scattering (SERS) substrates, which is a challenge in SERS quantitative analysis. Recent reports showed that the reproducibility of a nonuniform SERS substrate can be effectively improved by the use of an internal standard (IS). However, most of these approaches require the investment of time for precise regulation, and those approaches based on the addition of an IS are specific to a certain substrate. In this work, we proposed a simple, rapid and universal method to incorporate an IS into a SERS substrate for improving the reproducibility of Raman signals based on the systematic evaluation of the influencing factors of the competitive adsorption between the IS and the target analytes. Following the proposed pressure drop-coating (PDC) method, an IS-modified gold nanobipyramids (Au NBPs)/anodic aluminum oxide (AAO) SERS substrate was fabricated within 1 min, showing high reproducibility of Raman signals. In addition, the IS-modified Au NBPs/AAO SERS substrate was successfully applied to analyze thiram in freshly squeezed apple juice and the result showed a stable Raman signal with a relative standard deviation of less than 6.00%. What is more, three different commercial SERS chips were modified with an IS molecule using the PDC method. Compared to the traditional SERS chips, the Raman signal reproducibility of the functionalized SERS chips was improved significantly. Since the addition of an IS is not based on a certain substrate, the proposed approach could be useful for all the researchers working in the field of SERS.

Facile Fabrication of a Functional Filter Tip for Highly Efficient Reduction of Nicotine Content in Mainstream Smoke.

The nicotine addiction problem is of great concern, particularly in adolescents. Notably, nicotine addiction drives humans to continue smoking. Notably, several diseases and disorders are caused by smoking. To date, various adsorbents have been proposed to develop a functionalization filter tip for reducing nicotine content in mainstream smoke. However, the nicotine adsorption efficiencies of most of the reported functionalization filter tips were not satisfactory, and their preparation process was complex and time-consuming. Herein, we demonstrate a highly active and adsorbing filter tip for cigarettes, fabricated by decorating polydopamine (PDA) on the surface of a commercial filter tip in situ. The PDA coating on the filter tip was obtained by the self-polymerization of dopamine (DA) within 16 h, which was quicker and easier than the preparation processes of other reported functionalized filter tips. Significantly, the PDA-decorated filter tip had a nicotine adsorption efficiency as high as ∼95%, which was much higher than most of the commercial filter tips.

The effectiveness of diaphragmatic breathing relaxation training for improving sleep quality among nursing staff during the COVID-19 outbreak: a before and after study.

OBJECTIVES: Recent studies have demonstrated that first-line nurses involved in the coronavirus disease-2019 (COVID-19) crisis may experience sleep disturbances. As breathing relaxation techniques can improve sleep quality, anxiety, and depression, the current study aimed to evaluate the effectiveness of diaphragmatic breathing relaxation training (DBRT) for improving sleep quality among nurses in Wuhan, China during the COVID-19 outbreak. METHODS: This study used a quasi-experimental (before and after) intervention strategy, with 151 first-line nurses from four wards in Leishenshan hospital. The Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) to evaluate the effectiveness of DBRT before and after the intervention. Data were examined using the Shapiro-Wilk test, Levene's test, and paired t-test. RESULTS: A total of 140 nurses completed the DBRT sessions. First-line nurses achieved significant reductions in global sleep quality (p < 0.01), subjective sleep quality (p < 0.001), sleep latency (p < 0.01), sleep duration (p < 0.001), sleep disturbances (p < 0.001), habitual sleep efficiency (p = 0.015), daytime dysfunction (p = 0.001), and anxiety (p = 0.001). There were no significant reductions in the use of sleeping medication (p = 0.134) and depression (p = 0.359). CONCLUSION: DBRT is a useful non-pharmacological treatment for improving sleep quality and reducing anxiety among first-line nurses involved in the COVID-19 outbreak. The study protocol was clinically registered by the Chinese Clinical Trial Registry. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2000032743.

DW14383 is an irreversible pan-FGFR inhibitor that suppresses FGFR-dependent tumor growth in vitro and in vivo.

Fibroblast growth factor receptor (FGFR) is a promising anticancer target. Currently, most FGFR inhibitors lack sufficient selectivity and have nonnegligible activity against kinase insert domain receptor (KDR), limiting their feasibility due to the serious side effects. Notably, compensatory activation occurs among FGFR1-4, suggesting the urgent need to develop selective pan-FGFR1-4 inhibitors. Here, we explored the antitumor activity of DW14383, a novel irreversible FGFR1-4 inhibitor. DW14383 exhibited equivalently high potent inhibition against FGFR1, 2, 3 and 4, with IC50 values of less than 0.3, 1.1, less than 0.3, and 0.5 nmol/L, respectively. It is a selective FGFR inhibitor, exhibiting more than 1100-fold selectivity for FGFR1 over recombinant KDR, making it one of the most selective FGFR inhibitors over KDR described to date. Furthermore, DW14383 significantly inhibited cellular FGFR1-4 signaling, inducing G1/S cell cycle arrest, which in turn antagonized FGFR-dependent tumor cell proliferation. In contrast, DW14383 had no obvious antiproliferative effect against cancer cell lines without FGFR aberration, further confirming its selectivity against FGFR. In representative FGFR-dependent xenograft models, DW14383 oral administration substantially suppressed tumor growth by simultaneously inhibiting tumor proliferation and angiogenesis via inhibiting FGFR signaling. In summary, DW14383 is a promising selective irreversible pan-FGFR inhibitor with pan-tumor spectrum potential in FGFR1-4 aberrant cancers, which has the potential to overcome compensatory activation among FGFR1-4.