Post-translational protein lactylation modification in health and diseases: a double-edged sword.

As more is learned about lactate, it acts as both a product and a substrate and functions as a shuttle system between different cell populations to provide the energy for sustaining tumor growth and proliferation. Recent discoveries of protein lactylation modification mediated by lactate play an increasingly significant role in human health (e.g., neural and osteogenic differentiation and maturation) and diseases (e.g., tumors, fibrosis and inflammation, etc.). These views are critically significant and first described in detail in this review. Hence, here, we focused on a new target, protein lactylation, which may be a "double-edged sword" of human health and diseases. The main purpose of this review was to describe how protein lactylation acts in multiple physiological and pathological processes and their potential mechanisms through an in-depth summary of preclinical in vitro and in vivo studies. Our work aims to provide new ideas for treating different diseases and accelerate translation from bench to bedside.

MicroRNAs in Helicobacter pylori-infected gastric cancer: Function and clinical application.

Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and it is associated with a combination of genetic, environmental, and microbial risk factors. Helicobacter pylori (H. pylori) is classified as a type I carcinogen, however, the exact regulatory mechanisms underlying H. pylori-induced GC are incompletely defined. MicroRNAs (miRNAs), one of small non-coding RNAs, negatively regulate gene expression through binding to their target genes. Dysregulation of miRNAs is crucial in human cancer. A noteworthy quantity of aberrant miRNAs induced by H. pylori through complex regulatory networks have been identified. These miRNAs substantially affect genetic instability, cell proliferation, apoptosis, invasion, metastasis, autophagy, chemoresistance, and the tumor microenvironment, leading to GC development and progression. Importantly, some H. pylori-associated miRNAs hold promise as therapeutic tools and biomarkers for GC prevention, diagnosis, and prognosis. Nonetheless, clinical application of miRNAs remains in its infancy with multiple issues, including sensitivity and specificity, stability, reliable delivery systems, and off-target effects. Additional research on the specific molecular mechanisms and more clinical data are still required. This review investigated the biogenesis, regulatory mechanisms, and functions of miRNAs in H. pylori-induced GC, offering novel insights into the potential clinical applications of miRNA-based therapeutics and biomarkers.

Design, Synthesis and Insecticidal Activity of Novel meta-Diamide Compounds Containing Pyridine Rings.

In order to discover new meta-diamide compounds with good activity and novel structure, 15 related compounds were designed and synthesized by the bioisosterism principle with cyproflanilide as the lead compound. The insecticidal activities of these compounds against Plutella xylostella and Tetranychus cinnabarinus were tested, and the results of biological activity test showed that some compounds had more than 90 % insecticidal activity against Plutella xylostella at 1 mg/L and Tetranychus cinnabarinus at 100 mg/L. Especially, N-(2-bromo-6-(difluoromethoxy)-4-(perfluoro propan-2-yl)phenyl)-6-(isonicotinamido)picolinamide against Tetranychus cinnabarinus at 10 mg/L was 100 %, which was better than that of cyproflanilide. Molecular docking studies suggested that N-(2-bromo-6-(difluoromethoxy)-4-(perfluoropropan-2-yl)phenyl)-6-(4-cyano-2-methylbenzamido)picolinamide had a closely combined with the Plutella xylostella 3RHW (a glutamate-gated chloride channel). This study provides an avenue for designing and synthesizing a new generation of more effective pesticides.

DNA nanosensor based on bipedal 3D DNA walker-driven proximal catalytic hairpin assembly for sensitive and fast TK1 mRNA detection.

Hyperproliferative  diseases are the first step for tumor formation; thymidine kinase 1 (TK1) mRNA is closely related to cell proliferation. Therefore, the risk of malignant proliferation can be identified by sensitively detecting the variance in TK1 mRNA concentration, which can be used for tumor auxiliary diagnosis and monitoring tumor treatment. Owing to the low abundance and instability of TK1 mRNA in real samples, the development of a sensitive and fast mRNA detection method is necessary. A DNA nanosensor that can be used for detecting TK1 mRNA based on bipedal 3D DNA walker-driven proximal catalytic hairpin assembly (P-CHA) was developed. P-CHA hairpins were hybridized to a linker DNA strand coupled with magnetic nanoparticles to increase their local concentrations. The bipedal DNA walking on the surface of NPs accelerates reaction kinetics using the proximity effect. Taking advantage of the signal amplification of P-CHA as well as the rapid reaction rate of the DNA walker in 80 min, the proposed sensor detects TK1 mRNA with a low detection limit of 14 pM and may then be applied to clinical diagnosis.

Construction of a thermoresponsive molecularly imprinted biomimetic hydrogel-based virus sensor and non-invasive cyclable detection of EV71.

A thermoresponsive molecularly imprinted hydrogel sensor was constructed for the specific selective recognition of enterovirus 71 (EV71). Due to the introduction of the thermosensitive monomer N-isopropylacrylamide (NIPAM), when the imprinted hydrogel is incubated with the virus at 37℃, the surface specific imprinting cavity will specifically recognize and capture the target virus EV71. When the temperature rises to 45℃, the combined EV71 is rapidly released due to changes in the shape and function of the imprinted sites. The MIP hydrogel-based viral sensor developed recognized, captured, and released the target virus in a non-invasive way. The imprinting factor of the target virus was 5.2, suggesting high selectivity, and the detection limit was 7.1 fM, suggesting high sensitivity. Detection was rapid, as adsorption equilibrium was achieved within 30 min. This method provides a new sustainable avenue for the simple and rapid detection of viruses.

Ultra-Sensitive Portable Visual Paper-Based Viral Molecularly Imprinted Sensor without Autofluorescence Interference.

Detection of the virus is the primary factor to discover and block the occurrence and development of the virus epidemic. Here, an ultrasensitive paper-based virus molecular imprinting sensor is developed to detect two viruses simultaneously in which the detection limit of the influenza virus (H5N1) is 16.0 aM (9.63 × 103 particles/mL) while that of the Hepatitis B Virus (HBV) is 129 fM (7.77 × 107 particles/mL). This paper-based sensor is low cost and is easy to cut, store, and carry. In addition, the visual semiquantitative detection of two viruses is achieved by using two aptamer-functionalized persistent luminescent nanoparticles as signal probes. These probes and the imprinted cavities on the paper-based material formed sandwich-type double recognition of the target viruses. This sensor has extremely high sensitivity to the H5N1 virus, which is of great value to solve the influenza epidemic with the most outbreaks in history, and also opens up a new way for the prevention and control of other virus epidemics. This cheap and portable visual sensor provides the possibility for self-service detection and can greatly reduce the pressure on medical staff and reduce the risk of virus infection caused by the concentration of people to be tested.

Construction of benzoheterocycles by the reaction of α-arylglyoxylic acids and ortho-functionalized aniline under mild and minimal conditions.

This work describes an environmentally friendly method for the synthesis of benzoxazinones, quinoxalinones and benzothiazoles by the reaction of α-arylglyoxylic acids and ortho-functionalized aniline. In this reaction, no other reagents are needed except for reactants and solvents. The reaction was carried out at a mild temperature of 50 °C with only water and/or carbon dioxide as the by-product. Therefore, the reaction has high practical atom economy. In addition, this strategy could be scaled up to the gram level, and the natural product Cephamandole A could be synthesized on a mass scale.

Engineering of catalytic hairpin-rigidified Y-shaped DNA-functionalized nanomachine to rapidly detect mRNA.

The catalytic hairpin-rigidified Y-shaped DNA through layer-by-layer assembly has been fixed on the surface of copper sulfide nanoparticles for the detection of survivin mRNA. The distance between the CHA probes fixed on the Y-shaped DNA is significantly shortened. The results show that the fluorescence of this nanomachine reached the maximum value in 50 min (excitation wavelength at 488 nm and emission wavelength 526 nm), and its reaction rate is more than 5-fold faster than that of the free-CHA control system. In addition, the nanomachine showed high sensitivity (LOD of 3.5 pM) and high specificity for the survivin mRNA detection. Given its fast response time and excellent detection performance, we envision that the catalytic hairpin-rigidified Y-shaped DNA-functionalized nanomachine will offer potential applications in disease diagnostics and clinical applications.

Construction of an Ultrasensitive Molecularly Imprinted Virus Sensor Based on an "Explosive" Secondary Amplification Strategy for the Visual Detection of Viruses.

Viral outbreaks have caused great disruptions to the economy and public health in recent years. The accurate detection of viruses is a key factor in controlling and overcoming epidemics. In this study, an ultrasensitive molecularly imprinted virus sensor was developed based on an "explosive" secondary amplification strategy. Magnetic particles coated with carbon quantum dots (Fe3O4@CDs) were used as carriers and fluorescent probes, while aptamers were introduced into the imprinting layer to enhance the specific recognition of the target virus enterovirus 71 (EV71). When EV71 was captured by the imprinted particles, the fluorescence of the CDs was quenched, especially after binding to the aptamer-modified ZIF-8 loaded with a large amount of phenolphthalein, thereby resulting in signal amplification. Then, when adjusting the pH of the solution to 12, the decomposition of ZIF-8 released phenolphthalein, which turned the solution red, leading to the second "explosive" amplification of the signal. Therefore, the detection of EV71 with ultrasensitivity was achieved, which allows for visual detection by the naked eye in the absence of any instruments. The detection limits for fluorescence and visualization detection were 8.33 fM and 2.08 pM, respectively. In addition, a satisfactory imprinting factor of 5.4 was achieved, and the detection time only needed 20 min. It is expected that this fluorescence-colorimetric dual-mode virus molecularly imprinted sensor will show excellent prospects in epidemic prevention and rapid clinical diagnosis.

Radical Cross-Coupling Reaction Based on Hydrogen Atom Abstraction of DMF and Decarboxylation of α-Ketoacid under Electricity.

The cleavage of DMF into a dimethyl carbamoyl radical under mild electrochemical conditions was revealed for the first time. Meanwhile, an electrochemical decarboxylation of α-ketoacid occurred to produce an acyl radical. The radical cross-coupling reaction of these two electron-deficient acyl radicals was carried out with high selectivity. This discovery provides a new electrochemical way for the cracking of DMF, and a milder and safer method for its application in organic synthesis.

pH-activated DNA nanomachine for miRNA-21 imaging to accurately identify cancer cell.

MicroRNA (miRNA) imaging has been employed to distinguish cancer cells from normal cells by exploiting the overexpression of miRNA in cancer. Inspired by the acidic extracellular tumor microenvironment, we designed a pH-activated DNA nanomachine to enable the specific detection of cancer cells using miRNA imaging. The DNA nanomachine was engineered by assembling two hairpins (Y1 and Y2) onto the surface of a ZIF-8 metal-organic framework (MOF), which decomposed under acidic conditions to release the adsorbed DNA hairpin molecules in situ. The released hairpins were captured by the target miRNA-21 and underwent catalytic hairpin assembly amplification between Y1 and Y2. The detection limit for miRNA assays using the DNA nanomachine was determined to be 27 pM, which is low enough for sensitive detection in living cells. Living cell imaging of miRNA-21 further corroborated the application of the DNA nanomachine in the identification of cancer cell.

A sandwich sensor based on imprinted polymers and aptamers for highly specific double recognition of viruses.

Highly selective and highly efficient identification of large viruses has been a major obstacle in the field of virus detection. In this work, a novel sandwich resonance light scattering sensor was designed based on molecularly imprinted polymers (MIPs) and aptamers for the first time. One of the recognition probes was obtained by molecular imprinting using environmentally friendly carbon spheres as carriers and the other by modification of the aptamer that can specifically recognize hepatitis B virus (HBV) on the surface of silicon spheres. In the presence of both probes, an MIP-HBV-aptamer sandwich structure was formed continuously in the system with the increase in HBV concentration, resulting in a strong resonance light scattering response. Finally, satisfactory selectivity and sensitivity were obtained, and the imprinting factor was as high as 7.56, which was higher than that reported in previous works of viral molecular imprinting sensor. In addition, it is of great significance to solve the problem of insufficient selectivity of traditional detection methods for macromolecular targets.

Specific determination of HBV using a viral aptamer molecular imprinting polymer sensor based on ratiometric metal organic framework.

An approach is reported based on the combination of aptamer and metal organic frameworks (MOF) to prepare a molecularly imprinted sensor that recognizes viruses with high specificity and sensitivity. Using MIL-101-NH2 as a polymer carrier, viral aptamers were introduced into the carrier surface through an amide reaction to specifically identify the target, and surface imprinting is carried out through tetraethyl silicate (TEOS) self-polymerization. The MIL-101-NH2 is also used as the reference fluorescence signal (λex/λem = 290/460 nm) and rhodamine B as the change signal (λex/λem = 550/570 nm). The ratiometric fluorescence detection and dual recognition strategy not only reduce environmental interference but also greatly improve the sensor's anti-interference ability, the obtained imprinting factor was 5.72, and the detection limit as low as 1.8 pmol L-1. Therefore, the molecular imprinting sensor designed realizes the specific and highly sensitive identification of viruses, which provides theoretical support for the application of molecular imprinting technology in clinical diagnosis of viruses. Graphical abstract Aptamer-molecular imprinting polymer based on metal-organic framework ratiometric fluorescent detect virus.

The study of the association between immune monitoring and pneumonia in kidney transplant recipients through machine learning models.

BACKGROUND: Kidney transplantation is the optimal treatment to cure the patients with end-stage renal disease (ESRD). However, the infectious complication, especially pneumonia, is the main cause of mortality in the early stage. Immune monitoring by relevant biomarkers provides direct evidence of immune status. We aimed to study the association between immune monitoring and pneumonia in kidney transplant patients through machine learning models. METHODS: A total of 146 patients receiving the immune monitoring panel in our center, including 46 pneumonia recipients and 100 stable recipients, were retrospectively reviewed to develop the models. All the models were validated by external data containing 10 pneumonia recipients and 32 stable recipients. The immune monitoring panel consisted of the percentages and absolute cell counts of CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+ B cells and natural killer (NK) cells, and median fluorescence intensity (MFI) of human leukocyte antigen (HLA)-DR on monocytes and CD64 on neutrophils. The machine learning models including support vector machine (SVM), logistic regression (LR), multi-layer perceptron (MLP) and random forest (RF) were applied for analysis. RESULTS: The pneumonia and stable groups showed significant difference in cell counts of each subpopulation and MFI of monocyte HLA-DR and neutrophil CD64. The SVM model by monocyte HLA-DR (MFI), neutrophil CD64 (MFI), CD8+ T cells (cells/µl), NK cells (cell/µl) and TBNK (T cells, B cells and NK cells, cells/µl) had the best performance with the average area under the curve (AUC) of 0.940. The RF model best predicted the patients who would progress into severe pneumonia, with the average AUC of 0.760. All the models had good performance validated by external data. CONCLUSIONS: The immune monitoring panel was tightly associated with pneumonia in kidney transplant recipients. The models developed by machine learning techniques identified patients at risk and predicted the prognosis. Based on the results of immune monitoring, better individualized therapy might be achieved.

Iron-Catalyzed Cleavage Reaction of Keto Acids with Aliphatic Aldehydes for the Synthesis of Ketones and Ketone Esters.

The radical-radical coupling reaction is an important synthetic strategy. In this study, the iron-catalyzed radical-radical cross-coupling reaction based on the decarboxylation of keto acids and decarbonylation of aliphatic aldehydes to obtain valuable aryl ketones is reported for the first time. Remarkably, when tertiary aldehydes were used as carbonyl sources, ketone esters were selectively obtained instead of ketones. The gram-scale preparation of aryl ketone through this strategy was easily achieved by using only 3 mol % of the iron catalyst. As a proof-of-concept, the bioactive molecule flurprimidol was synthesized in two steps by using this strategy.

Amination of Aromatic Halides and Exploration of the Reactivity Sequence of Aromatic Halides.

A base-promoted amination of aromatic halides has been developed using a limited amount of dimethylformamide (DMF) or amine as an amino source. Various aryl halides, including F, Cl, Br, and I, have been successfully aminated in good to excellent yields. Although the amination of aromatic halides with amines or DMF is usually considered as an aromatic nucleophilic substitution (SNAr) process, and the reactivity of an aromatic halide is F > Cl > Br > I, the reactivity of aromatic halides in this system was found to be I > Br ≈ F > Cl. This protocol also showed a good regioselectivity for multihalogenated aromatics. This protocol is valuable for industrial application due to the simplicity of operation, the unrestricted availability of amino sources and aromatic halides, transition metal-free conditions, no requirement for solvent, and scalability.

Double G-quadruplexes in a copper nanoparticle based fluorescent probe for determination of HIV genes.

A DNA-templated copper nanoparticle (CuNP) probe has been developed for the determination of the human immunodeficiency virus oligonucleotide (HIV-DNA). The function of the probe relies on affinity binding-induced DNA hybridization associated with the use of double G-quadruplexes. Double-stranded DNA (dsDNA) with poly(AT-TA) bases was used as a template for synthesis of dsDNA-CuNPs. These have weak fluorescence. In the next step, two G-rich sequences that are linked to both sides of the ds-DNA are locked by HIV complementary DNA (cDNA). If HIV-DNA is introduced, it will hybridize with cDNA, thereby transforming the two G-rich sequences into G-quadruplexes. This enhances the fluorescence of the adjacent dsDNA-CuNPs. Fluorescence increases linearly in the 1 to 200 and 250-1000 nM HIV-DNA concentration range, and the detection limit is 13 pM. This enzyme-free fluorometric assay is time-saving, easily operated, and therefore has large potential in biosensing because it may be extended to various other DNA targets. Graphic abstract Double-strand DNA-templated copper nanoparticles (DNA-CuNPs) have weak fluorescence. When Human Immunodeficiency Virus oligonucleotide (HIV-DNA) is added, it completely hybridized with HIV complementary DNA (cDNA). As a result, the two exposed G-rich sequences are transformed into G-quadruplexes, and an apparent increase in the fluorescence intensity can be observed. (AA: ascorbic acid).

Rhodium(I)-catalyzed regiospecific dimerization of aromatic acids: two direct C-H bond activations in water.

2,2'-Diaryl acids are key building blocks for some of the most important and high-performance polymers such as polyesters and polyamides (imides), as well as structural motifs of MOFs (metal-organic frameworks) and biological compounds. In this study, a direct, regiospecific and practical dimerization of simple aromatic acids to generate 2,2'-diaryl acids has been discovered, which proceeds through two rhodium-catalyzed C-H activations in water. This reaction can be easily scaled up to gram level by using only 0.4-0.6 mol % of the rhodium catalyst. As a proof-of-concept, the natural product ellagic acid was synthesized in two steps by this method.

High-sensitivity detection of glycoproteins by high-density boric acid modified metal-organic framework surface molecularly imprinted polymers resonant light scattering sensor.

Glycoproteins are difficult to be detected by imprinting strategy due to their low natural abundance, high flexible conformation and large size. Herein, a high-density boric acid modified metal-organic framework (MOF) surface molecularly imprinted polymer (SMIP) resonant light scattering sensor was constructed for the high-sensitivity detection of target glycoproteins. A MOF with large specific surface area was selected as the substrate material to support the boric acid group with high loading density (4.66 %). The introduction of the boric acid group in the SMIP provided a high-affinity binding site for the recognition and binding of glycoproteins. Shallow surface cavities with rapid mass transfer (equilibrium time 20 min) were thus formed by surface imprinting. Furthermore, high sensitivity (limit of detection 15 pM) was achieved at physiological pH (7.4), which was conducive to the detection of glycoproteins with low natural abundance in complex biological samples and maintaining physiological activity.