Machine learning-driven SERS analysis platform for rapid and accurate detection of precancerous lesions of gastric cancer.

A novel approach is proposed leveraging surface-enhanced Raman spectroscopy (SERS) combined with machine learning (ML) techniques, principal component analysis (PCA)-centroid displacement-based nearest neighbor (CDNN). This label-free approach can identify slight abnormalities between SERS spectra of gastric lesions at different stages, offering a promising avenue for detection and prevention of precancerous lesion of gastric cancer (PLGC). The agaric-shaped nanoarray substrate was prepared using gas-liquid interface self-assembly and reactive ion etching (RIE) technology to measure SERS spectra of serum from mice model with gastric lesions at different stages, and then a SERS spectral recognition model was trained and constructed using the PCA-CDNN algorithm. The results showed that the agaric-shaped nanoarray substrate has good uniformity, stability, cleanliness, and SERS enhancement effect. The trained PCA-CDNN model not only found the most important features of PLGC, but also achieved satisfactory classification results with accuracy, area under curve (AUC), sensitivity, and specificity up to 100%. This demonstrated the enormous potential of this analysis platform in the diagnosis of PLGC.

Advances in Exosome Research in the Management of Lung Cancer.

Lung cancer is one of the most common malignant tumors, and its death rate is much higher than that of colon, kidney, breast, and prostate cancers, and its 5-year survival rate is only 18%. Lung cancer has no specific clinical symptoms in its early stages and lacks effective detection, making early detection difficult. The survival rate for advanced lung cancer is meager, with a median survival of only 12 months for stage IIIB/IV non-small cell lung cancer treated with platinumbased chemotherapy. Exosomes could provide vital information for the early diagnosis of lung cancer and have the potential to become a tumor marker for lung cancer. In addition, scientists have proposed encouraging ways to treat lung cancer by loading drugs, proteins, microRNAs, and siRNAs into exosomes. Therefore, studying lung cancer exosomes and exosomal nano drugs will provide new ideas and approaches for the diagnosis and treatment of lung cancer. This paper reviews the progress of research on the biological functions of exosomes and exosomal nanomedicines and their applications in clinical practice.

Au/SiNCA-based SERS analysis coupled with machine learning for the early-stage diagnosis of cisplatin-induced liver injury.

Cisplatin has been widely applied in the clinical treatment of various cancers, whereas liver injury induced by its hepatotoxicity is still a severe issue. Reliable identification of early-stage cisplatin-induced liver injury (CILI) can improve clinical care and help to streamline drug development. Traditional methods, however, cannot achieve enough information at the subcellular level due to the requirement of the labeling process and low sensitivity. To overcome these, we designed an Au-coated Si nanocone array (Au/SiNCA) to fabricate the microporous chip as the surface-enhanced Raman scattering (SERS) analysis platform for the early diagnosis of CILI. A CILI rat model was established, and the exosome spectra were obtained. The principal component analysis (PCA)-representation coefficient-based k-nearest centroid neighbor (RCKNCN) classification algorithm was proposed as the multivariate analysis method to build the diagnosis and staging model. The PCA-RCKNCN model has been validated to achieve a satisfactory result, with accuracy and AUC of over 97.5%, and sensitivity and specificity of over 95%, indicating that SERS combined with the PCA-RCKNCN analysis platform can be a promising tool for clinical applications.

Serum-based surface-enhanced Raman spectroscopy combined with PCA-RCKNCN for rapid and accurate identification of lung cancer.

Early and precise diagnosis of lung cancer is critical for a better prognosis. However, it is still a challenge to develop an effective strategy for early precisely diagnose and effective treatments. Here, we designed a label-free and highly accurate classification serum analytical platform for identifying mice with lung cancer. Specifically, the microarray chip integrated with Au nanostars (AuNSs) array was employed to measure the surface-enhanced Raman scattering (SERS) spectra of serum of tumor-bearing mice at different stages, and then a recognition model of SERS spectra was constructed using the principal component analysis (PCA)-representation coefficient-based k-nearest centroid neighbor (RCKNCN) algorithm. The microarray chip can realize rapid, sensitive, and high-throughput detection of SERS spectra of serum. RCKNCN based on the PCA-generated features successfully differentiated the SERS spectra of serum of tumor-bearing mice at different stages with a classification accuracy of 100%. The most prominent spectral features for distinguishing different stages were captured in PCs loading plots. This work not only provides a practical SERS chip for the application of SERS technology in cancer screening, but also provides a new idea for analyzing the feature of serum at the spectral level.

Nickel-Catalyzed Stereoselective Alkenylation of Ketones Mediated by Hydrazine.

The direct conversion of naturally abundant carbonyl compounds provides a powerful platform for the efficient synthesis of valuable chemicals. In particular, the conversion of ketones to alkenes is a commonly encountered chemical transformation, often achieved via the multistep Shapiro reaction with tosylhydrazone and over stoichiometric organolithium or Grignard reagent. Herein, we report an earth abundant nickel-catalyzed alkenylation of naturally abundant methylene ketones to afford a wide range of alkene derivatives, mediated by hydrazine. The protocol features a broad substrate scope (including alkyl ketones, aryl ketones, and aldehydes), good functional group compatibility, mild reaction conditions, water tolerance, and only environmentally friendly N2, H2, and H2O as theoretical byproducts. Moreover, gram-scale synthesis with good yield and generation of pharmaceutical intermediates highlighted its practical applicability.

A Comparison between Silver Nanosquare Arrays and Silver Thin-Films as a Blood Cancer Prognosis Monitoring Electrode Design Using Optical and Electrochemical Characterization.

The development of silver (Ag) thin films and the fabrication of Ag nanosquare arrays with the use of an anodic aluminum oxide (AAO) template and leaf extracts were successfully carried out using the DC sputtering and spin coating deposition methods. Ag thin films and Ag nanosquare arrays are developed to monitor cancer prognosis due to the correlation between serum albumin levels and prognostic factors, as well as the binding of serum albumin to the surface of these electrodes. Nanosquare structures were fabricated using AAO templates with varying diameters and a gap distance between adjacent unit cells of 100 nm. The nanosquare array with a diameter of 250 nm and irradiated with electromagnetic waves with a wavelength of around 800 nm possessed the greatest electric field distribution compared to the other variations of diameters and wavelengths. The results of the absorption measurement and simulation showed a greater shift in absorption peak wavelength when carried out using the Ag nanosquare array. The absorption peak wavelengths of the Ag nanosquare array in normal blood and blood with cancer lymphocytes were 700-774 nm and 800-850 nm, respectively. The electrochemical test showed that the sensitivity values of the Ag thin-film electrode deposited using DC sputtering, the Ag thin-film electrode deposited using spin coating, and the Ag nanosquare array in detecting PBS+BSA concentration in the cyclic voltammetry (CV) experiment were 1.308 µA mM-1cm-2, 0.022 µA mM-1cm-2, and 39.917 µA mM-1cm-2, respectively. Meanwhile, the sensitivity values of the Ag thin film and the Ag nanosquare array in detecting the PBS+BSA concentration in the electrochemical impedance spectroscopy (EIS) measurement were 6593.76 Ohm·cm2/mM and 69,000 Ohm·cm2/mM, respectively. Thus, our analysis of the optical and electrochemical characteristics of Ag thin films and Ag nanosquare arrays showed that both can be used as an alternative biomedical technology to monitor the prognosis of blood cancer based on the concentration of serum albumin in blood.

C(sp3)-C(sp3) bond formation via nickel-catalyzed deoxygenative homo-coupling of aldehydes/ketones mediated by hydrazine.

Aldehydes and ketones are widely found in biomass resources and play important roles in organic synthesis. However, the direct deoxygenative coupling of aldehydes or ketones to construct C(sp3)-C(sp3) bond remains a scientific challenge. Here we report a nickel-catalyzed reductive homo-coupling of moisture- and air-stable hydrazones generated in-situ from naturally abundant aldehydes and ketones to construct challenging C(sp3)-C(sp3) bond. This transformation has great functional group compatibility and can suit a broad substrate scope with innocuous H2O, N2 and H2 as the by-products. Furthermore, the application in several biological molecules and the transformation of PEEK model demonstrate the generality, practicability, and applicability of this novel methodology.

Changes of clinical characteristics of asymptomatic patients with positive SARS-Cov-2 nucleic acid test during treatment cycle and related risk factors.

OBJECTIVE: This study was designed to explore the clinical characteristics, outcomes, and related influencing factors for asymptomatic patients with positive Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-Cov-2) nucleic acid test. METHODS: Clinical data of 1568 patients with positive SARS-Cov-2 nucleic acid test (SNAT) were collected retrospectively. The patients were assigned to an asymptomatic group and a symptomatic group according to the existence of clinical symptoms when they got positive result in nucleic acid test, and the clinical data of the two groups were analyzed and compared. In addition, the data of asymptomatic patients who showed clinical symptoms later and the results of two-week follow-up after cure were analyzed. RESULTS: Among all enrolled patients, there were 1489 patients with positive symptoms and 79 asymptomatic patients, including 34 patients who developed symptoms during treatment. Logistic analysis revealed that age ≤45 years (OR=2.722, P<0.001), history of diabetes mellitus (OR=0.446, P=0.007), and history of cancer (OR=0.259, P=0.008) were independent factors for asymptomatic presentation in patients with positive SNAT, and age ≥46 years (OR=1.562, P=0.012) and history of hypertension (OR=2.077, P<0.001) were risk factors for the occurrence of clinical symptoms in asymptomatic patients with positive SNAT during hospitalization. During the follow-up after cure, 8 patients got reoccurring positive SNAT result. CONCLUSION: Asymptomatic patients with positive SNAT are mostly young and middle-aged people, and old age and hypertension are risk factors for the occurrence of positive clinical characteristics in asymptomatic patients.

SERS Based Lateral Flow Assay for Rapid and Ultrasensitive Quantification of Dual Laryngeal Squamous Cell Carcinoma-Related miRNA Biomarkers in Human Serum Using Pd-Au Core-Shell Nanorods and Catalytic Hairpin Assembly.

Non-invasive early diagnosis is of great significant in disease pathologic development and subsequent medical treatments, and microRNA (miRNA) detection has attracted critical attention in early cancer screening and diagnosis. However, it was still a challenge to report an accurate and sensitive method for the detection of miRNA during cancer development, especially in the presence of its analogs that produce intense background noise. Herein, we developed a surface-enhanced Raman scattering (SERS)-based lateral flow assay (LFA) biosensor, assisted with catalytic hairpin assembly (CHA) amplification strategy, for the dynamic monitoring of miR-106b and miR-196b, associated with laryngeal squamous cell carcinoma (LSCC). In the presence of target miRNAs, two hairpin DNAs could self-assemble into double-stranded DNA, exposing the biotin molecules modified on the surface of palladium (Pd)-gold (Au) core-shell nanorods (Pd-AuNRs). Then, the biotin molecules could be captured by the streptavidin (SA), which was fixed on the test lines (T1 line and T2 line) beforehand. The core-shell spatial structures and aggregation Pd-AuNRs generated abundant active "hot spots" on the T line, significantly amplifying the SERS signals. Using this strategy, the limits of detections were low to aM level, and the selectivity, reproducibility, and uniformity of the proposed SERS-LFA biosensor were satisfactory. Finally, this rapid analysis strategy was successfully applied to quantitatively detect the target miRNAs in clinical serum obtained from healthy subjects and patients with LSCC at different stages. The results were consistent with the quantitative real-time PCR (qRT-PCR). Thus, the CHA-assisted SERS-LFA biosensor would become a promising alternative tool for miRNAs detection, which showed a tremendous clinical application prospect in diagnosing LSCC.

Hydrogen bonding promoted simple and clean photo-induced reduction of C-X bond with isopropanol.

We herein report a simple and clean photo-induced metal-free reduction of C-X bond under an atmosphere of air at room temperature. Isopropanol is used as both the reducing reagent and solvent. Various functional groups (acids, esters, alcohols, anilines, phenols, indoles, pyridines, cyano and trifluoromethyl groups) and other heterocyclic compounds are tolerated. Different organic halides (including C-I, C-Br and C-Cl bonds) can be dehalogenated with moderate to excellent yields. Polyhalides are also reduced chemoselectively and efficiently. DFT calculation suggests a six-membered ring transition state via C-XH-O hydrogen bonding to decrease the activation energy.

[Hydrogen isotopes analysis by gas chromatography using metal-organic framework CPL-1 packed column].

CPL-1 is a metal organic framework (MOF) with potential application as stationary phase material in gas chromatographic (GC) analysis, due to its large specific surface area, uniform pore size and good quantum sieving effect on hydrogen isotopes at low temperatures. Herein, a microporous column packed with CPL-1 was used at cryogenic temperature (77 K), and the column was 1.0 mm in inner diameter, 0.5 m in length. Single crystals of Al2O3 was used to build flow path for chromatographic carrier gas. The results showed that the adsorption of H2 and D2 with CPL-1 was 4 mmol/g at 77 K, which was better than MnCl2/γ -Al2O3 and γ -Al2O3. With the injection volume increasing from 0.25 mL to 2 mL, the results showed good linear relationship, and the relative error was less than 4%. The results indicated that the column packed with CPL-1 has wide linear range, good repeatability and high accuracy, and it has potential use in hydrogen isotope analysis with gas chromatography.

Recombinant rat CC16 protein inhibits LPS-induced MMP-9 expression via NF-κB pathway in rat tracheal epithelial cells.

Clara cell protein (CC16) is a well-known anti-inflammatory protein secreted by the epithelial Clara cells of the airways. It is involved in the development of airway inflammatory diseases such as chronic obstructive pulmonary disease and asthma. Previous studies suggest that CC16 gene transfer suppresses expression of interleukin (IL)-8 in bronchial epithelial cells. However, its role in the function of these cells during inflammation is not well understood. In this study, we evaluated the effect of CC16 on the expression of matrix metalloproteinase (MMP)-9 in lipopolysaccharide (LPS)-stimulated rat tracheal epithelial cells and its underlying molecular mechanisms. We generated recombinant rat CC16 protein (rCC16) which was bioactive in inhibiting the activity of phospholipase A2. rCC16 inhibited LPS-induced MMP-9 expression at both mRNA and protein levels in a concentration-dependent (0-2 µg/mL) manner, as demonstrated by real time RT-PCR, ELISA, and zymography assays. Gene transcription and DNA binding studies demonstrated that rCC16 suppressed LPS-induced NF-κB activation and its binding of gene promoters as identified by luciferase reporter and gel mobility shift assays, respectively. Western blotting and immunofluorescence staining analyses further revealed that rCC16 concentration dependently inhibited the effects of LPS on nuclear increase and cytosol reduction of NF-κB, on the phosphorylation and reduction of NF-κB inhibitory IκBα, and on p38 MAPK-dependent NF-κB activation by phosphorylation at Ser276 of its p65 subunit. These data indicate that inhibition of LPS-mediated NF-κB activation by rCC16 involves both translocation- and phosphorylation-dependent signaling pathways. When the tracheal epithelial cells were pretreated with chlorpromazine, an inhibitor of clathrin-mediated endocytosis, cellular uptake of rCC16 and its inhibition of LPS-induced NF-κB nuclear translocation and also MMP-9 production were significantly abolished. Taken together, our data suggest that clathrin-mediated uptake of rCC16 suppresses LPS-mediated inflammatory MMP-9 production through inactivation of NF-κB and p38 MAPK pathways in tracheal epithelial cells.

MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2.

MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer.