Electroactive polymer tag modified nanosensors for enhanced intracellular ATP detection.

ATP plays a crucial role in cell energy supply, so the quantification of intracellular ATP levels is particularly important for understanding many physio-pathological processes. The intracellular quantification of this non-electroactive molecule can be realized using aptamer-modified nanoelectrodes, but is hindered by the limited quantity of modification and electroactive tags on the nanosized electrodes. Herein, we developed a simple but effective electrochemical signal amplification strategy for intracellular ATP detection, which replaces the regular ATP aptamer-linked ferrocene monomer with a polymer, thus greatly magnifying the amounts of electrochemical reporters linked to one chain of the aptamer and enhancing the signals. This ferrocene polymer-ATP aptamer was further immobilized onto Au nanowire electrodes (SiC@C@Au NWEs) to achieve accurate quantification of intracellular ATP in single cells, presenting high electrochemical signal output and high specificity. This work not only provides a powerful tool for quantifying intracellular ATP but also offers a simple and versatile strategy for electrochemical signal amplification in the detection of broader non-electroactive molecules involved in different kinds of intracellular physiological processes.

Ester-Linked Crystalline Covalent Organic Frameworks.

Ester-linked, crystalline, porous covalent organic frameworks (COFs) have been synthesized and structurally characterized. Transesterification reactions between ditopic 2-pyridinyl aromatic carboxylates and tri- or tetratopic phenols gave the corresponding ester-linked COFs. They crystallize as 2D structures in kgm (COF-119) and hcb (COF-120, 121, 122) topologies with surface areas of up to 2092 m2/g. Notably, crystalline COF-122 comprises edges spanning over 10 phenylene units, an aspect that had only been achieved in metal-organic frameworks. This work expands the scope of reticular chemistry to include, for the first time, crystalline ester-linked COFs related to common polyesters.

Highly Acidic Conjugate-Base-Stabilized Carboxylic Acids Catalyze Enantioselective oxa-Pictet-Spengler Reactions with Ketals.

Acyclic ketone-derived oxocarbenium ions are involved as intermediates in numerous reactions that provide valuable products, however, they have thus far eluded efforts aimed at asymmetric catalysis. We report that a readily accessible chiral carboxylic acid catalyst exerts control over asymmetric cyclizations of acyclic ketone-derived trisubstituted oxocarbenium ions, thereby providing access to highly enantioenriched dihydropyran products containing a tetrasubstituted stereogenic center. The high acidity of the carboxylic acid catalyst, which exceeds that of the well-known chiral phosphoric acid catalyst TRIP, is largely derived from stabilization of the carboxylate conjugate base through intramolecular anion-binding to a thiourea site.

Urea-Linked Covalent Organic Frameworks.

2D covalent organic frameworks (COFs) with flexible urea linkages have been synthesized by condensation of 1,3,5-triformylphloroglucinol (TFP) with 1,4-phenylenediurea (BDU) or 1,1'-(3,3'-dimethyl-[1,1'-biphenyl]-4,4'-diyl)diurea (DMBDU). The resulting COF-117 and COF-118 undergo reversible structural dynamics within their layers, in response to inclusion and removal of guest molecules, emanating from urea C-N bond rotation and interlayer hydrogen-bonding interactions. These compounds are the first urea-linked COFs, serving to expand the scope of reticular chemistry.

Reductive Etherification via Anion-Binding Catalysis.

Reductive condensations of alcohols with aldehydes/ketones to generate ethers are catalyzed by a readily accessible thiourea organocatalyst that operates in combination with HCl. 1,1,3,3-tetramethyldisiloxane serves as a convenient reducing reagent. This strategy is applicable to challenging substrate combinations and exhibits functional group tolerance. Competing reductive homocoupling of the carbonyl component is suppressed.

Direct Formation of Oxocarbenium Ions under Weakly Acidic Conditions: Catalytic Enantioselective Oxa-Pictet-Spengler Reactions.

Two catalysts, an amine HCl salt and a bisthiourea, work in concert to enable the generation of oxocarbenium ions under mild conditions. The amine catalyst generates an iminium ion of sufficient electrophilicity to enable 1,2-attack by an alcohol. Catalyst turnover is achieved by amine elimination with concomitant formation of an oxocarbenium intermediate. The bisthiourea catalyst accelerates all of the steps of the reaction and controls the stereoselectivity via anion binding/ion pair formation. This new concept was applied to direct catalytic enantioselective oxa-Pictet-Spengler reactions of tryptophol with aldehydes.

Enantioselective A(3) reactions of secondary amines with a Cu(I)/acid-thiourea catalyst combination.

Pyrrolidine and related amines undergo asymmetric A(3) reactions in the presence of copper iodide and an easily accessible cocatalyst possessing both a carboxylic acid and a thiourea moiety. Propargylamines are obtained with up to 96% ee, and catalyst loadings can be as low as 1 mol %. Pyrrolidine-derived propargylamines, in the absence of directing groups, can be transformed to the corresponding allenes without loss of enantiopurity.

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids.

Copper(II) acetate/acetic acid/O2 and potassium iodide/tert-butylhydroperoxide systems are shown to affect the selective oxidation of ring-fused aminals to dihydroquinazolines and quinazolinones, respectively. These methods enable the facile preparation of a number of quinazoline alkaloid natural products and their analogues.

Application of Ag@Cu Water-Based Nanomaterial Conductive Ink in 3D Printing.

Copper (Cu) nanoparticles are considered a promising alternative to silver (Ag) and gold (Au) for printed electronics applications. Because Cu has higher electrical conductivity, it is significantly cheaper than Ag and Au. To study the applicability of electronic printing, we prepared Ag@Cu conductive ink by using a stepwise feeding method to disperse nano Ag and nano Cu in ethanol and water. The ink has the advantages of nontoxic, low content, and low cost. A three-dimensional (3D) model was designed, and a conductive pattern was printed on the photo paper substrate using extrusion 3D printing technology. The influence of waterborne resin on the adhesion of conductive patterns is discussed. The printed conductive pattern can maintain the stability of conductivity after 100 bending cycles. The conductive pattern has good thermal stability. It can be tested 10 times under 2 conditions of 85°C and room temperature to maintain good conductivity. This shows that Ag@Cu conductive ink printed flexible electronic products are competitive.

Co Nanoparticles Embedded in Mesoporous Walls of Carbon Nanoboxes for Rechargeable Zinc-air Batteries.

Design of non-noble metal electrocatalysts with high catalytic activity and stability to replace commercial Pt/C is crucial in the commercialization development of Zn-air batteries (ZABs). In this work, Co catalyst nanoparticles coupled with nitrogen-doped hollow carbon nanoboxes were well designed through zeolite-imidazole framework (ZIF-67) carbonization. As a result, the 3D hollow nanoboxes reduced the charge transport resistance, and the Co nanoparticles loaded on nitrogen-doped carbon supports exhibited excellent electrocatalytic performance for oxygen reduction reaction (ORR, E1/2 =0.823 V vs. RHE), similar to that of commercial Pt/C. Moreover, the designed catalysts showed an excellent peak density of 142 mW cm-2 when applied on ZABs. This work provides a promising strategy for the rational design of non-noble electrocatalysts with high performance for ZABs and fuel cells.

Mechanism of a Dually Catalyzed Enantioselective Oxa-Pictet-Spengler Reaction and the Development of a Stereodivergent Variant.

Enantioselective oxa-Pictet-Spengler reactions of tryptophol with aldehydes proceed under weakly acidic conditions utilizing a combination of two catalysts, an indoline HCl salt and a bisthiourea compound. Mechanistic investigations revealed the roles of both catalysts and confirmed the involvement of oxocarbenium ion intermediates, ruling out alternative scenarios. A stereochemical model was derived from density functional theory calculations, which provided the basis for the development of a highly enantioselective stereodivergent variant with racemic tryptophol derivatives.

Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function.

Calf thymus polypeptide (CTP), with a molecular mass of <10 kDa, is prepared from the thymus of less than 30-day-old newborn cattle. In the present study, the inhibitory function of CTP in colorectal cancer (CRC) was investigated in B6/JGpt-Apc em1Cin(MinC) /Gpt (Apc Min/+) mice. CTP hampered tumor development and enhanced the ratio of CD3e-NK1.1+ cells by 113.0% and CD3e+CD28+ cells by 84.7% in the peripheral blood of Apc Min/+ mice. CTP improved the richness, diversity, and evenness of the intestinal microbiota of Apc Min/+ mice, particularly by regulating the abundance of immune-related microorganisms. CTP effectively regulated the expression of immune-related cytokines, such as interleukin (IL)-2 (15.19% increment), IL-12 (17.47% increment), and transforming growth factor (TGF)-ß (11.19% reduction). Additionally, it enhanced the levels of CD4 and CD8, as well as the ratio of helper T lymphocytes (Th)1/Th2 in the spleen and tumors of Apc Min/+ mice. In CTP-treated mice, reduced levels of programmed death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), activated nuclear factor of activated T cells 1 (NFAT1), and nuclear factor κB (NF-κB) p65 signaling were noted. Collectively, the anti-CRC effect of CTP is related to the modulation of intestinal microbiota-mediated immune function, which provides a reference for CTP as a therapeutic drug or a combination drug used in CRC treatment in a clinical setting.

Alterations in the gut microbiota of AIDS patients with pneumocystis pneumonia and correlations with the lung microbiota.

Background: Due to the inability to be cultured in vitro, the biological characteristics and pathogenicity of Pneumocystis jirovecii remain unclear. Intestinal microflora disorder is related to the occurrence and development of various pulmonary diseases. This work explores the pathogenesis of pneumocystis pneumonia (PCP) in acquired immune deficiency syndrome (AIDS) patients from a microbiome perspective, to provide better strategies for the diagnosis, treatment, and prevention of PCP. Methods: Subjects were divided into three groups: human immunodeficiency virus (HIV)-infected patients combined with PCP, HIV-infected patients without PCP, and HIV-negative. Stool and bronchoalveolar lavage fluid (BALF) samples were collected, total DNA was extracted, and 16S rRNA high-throughput sequencing was performed using an Illumina MiSeq platform. PICRUSt and BugBase were used to predict microflora functions, and correlation analysis of intestinal and lung bacterial flora was conducted. Results: Compared with the HIV- group, prevotella and another 21 genera in the intestinal microbiome were statistically different in the HIV+ group; 25 genera including Escherichia-Shigella from HIV+PCP+ group were statistically different from HIV+PCP- group. The abundance of Genera such as Porphyromonas was positively or negatively correlated with CD16/CD56+ (µL). Compared with the HIV- group, identification efficiency based on area under the curve (AUC) >0.7 for the HIV+ group identified seven genera in the gut microbiota, including Enterococcus (total AUC = 0.9519). Compared with the HIV+PCP- group, there were no bacteria with AUC >0.7 in the lung or intestine of the HIV+PCP+ group. The number of shared bacteria between BALF and fecal samples was eight species in the HIV- group, 109 species in PCP- patients, and 228 species in PCP+ patients, according to Venn diagram analysis. Changes in various clinical indicators and blood parameters were also closely related to the increase or decrease in the abundance of intestinal and pulmonary bacteria, respectively. Conclusions: HIV infection and PCP significantly altered the species composition of lung and intestinal microbiomes, HIV infection also significantly affected intestinal microbiome gene functions, and PCP exacerbated the changes. The classification model can be used to distinguish HIV+ from HIV- patients, but the efficiency of bacterial classification was poor between PCP+ and PCP- groups. The microbiomes in the lung and gut were correlated to some extent, providing evidence for the existence of a lung-gut axis, revealing a potential therapeutic target in patients with HIV and PCP.

Reasonable design of an MXene-based enzyme-free amperometric sensing interface for highly sensitive hydrogen peroxide detection.

Sensitive detection of H2O2 in the nano- to micromolar range is critical for health monitoring and disease diagnosis. Two-dimensional transition metal carbides or/and nitrides (called MXenes, MXs) have excellent potential applications in the electrochemical field due to their outstanding electrical conductivity and catalytic properties. In this work, Ti3C2Tx (MX) was employed for the construction of a sensitive and enzyme-free electrochemical sensing interface for the detection of hydrogen peroxide (H2O2) through a simple and effective method. Prussian blue (PB) was electrochemically deposited on the surface of a glassy carbon electrode (GCE). Chitosan (CS) and MX were sequentially dripped onto the PB modified GCE surface. The reasonable fabrication of the MX/CS/PB/GCE sensing interface presented good electrochemical sensing performance towards H2O2 with a low limit of detection (4 nM), a wide linear range from 50 nM to 667 µM and good selectivity. The proposed MX/CS/PB/GCE has been proven to monitor H2O2 in food samples and biological samples with recoveries between 94.7% and 100.3%. This work has made a beneficial attempt and research for exploring and expanding the application of MXs in the field of electrochemical sensing.

Pathogenic microorganism detection in AIDS patients using bronchoalveolar lavage fluid.

This study aimed to investigate the use of fiberoptic bronchoscopy and bronchoalveolar lavage in the diagnosis of pulmonary pathogenic microorganism infection in AIDS patients. We retrospectively analyzed the clinical data, fiberoptic bronchoscopy and bronchoalveolar lavage fluid laboratory examinations of 209 AIDS patients with pulmonary infection. Among 209 patients, we found 42 cases of mycobacterial infection, 3 cases of bacterial infection, 58 cases of pneumocystis carinii pneumonia (PCP), 27 cases that were fungal positive, 99 cases of CMV, and 103 cases positive for GM test of which 83 cases were considered Aspergillus positive. BALF pathogen distribution was related to CD4+ T lymphocyte count. The primary pathogens of pulmonary infection in AIDS patients were cytomegalovirus, Mycobacterium tuberculosis, fungi, and Pneumocystis carinii. Fiberoptic bronchoscopy and bronchoalveolar lavage are important in the diagnosis of pathogenic microorganisms in lung infections of AIDS patients.