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Accumulating evidence revealed the role of tryptophan (TRP) metabolism, especially its kynurenine pathway (KP), in the communication along the gut-brain axis. However, the underlying characterization of such interaction was not precise. In the present study, the rat depression model was induced by chronic restraint stress (CRS). After depression behavior tests, seven segments (cortex, hippocampus, striatum, hypothalamus, serum, cecum, and colon) along the gut-brain axis were collected to characterize their KP metabolism. mRNA expression of IL-1β, IFN-γ, IL-10 and indoleamine 2,3-dioxygenase 1 (IDO1) enzyme revealed a general inflammatory response and region-specific activated IDO1 along the gut-brain axis. Determination of KP metabolites and enzymes displayed a general KP activation with region-specificity, especially in the hippocampus and colon, where the changes were more pronounced. KYN and 3-HK were increased dramatically along the gut-brain axis; hippocampal KA revealed a significant decrease while colonic KA showed a notable increase, evidenced by the same alternation trends of the corresponding enzymes. The expression of quinolinic acid phosphoribosyltransferase (QPRT), the crucial enzyme to produce NAD+ from QA, was significantly upregulated in the gut but not changed in the brain. Pearson's correlation analysis suggested that kynurenine (KYN), 3-hydroxycaninuric acid (3-HK), serotonin (5-HT), TRP and kynurenic acid (KA) significantly correlated with depressive behaviors in rats. Furthermore, western blot analysis on nod-like receptor protein 3/2 (NLRP3/NLRP2) inflammasome signaling displayed that NLRP3 and cleaved IL-1β/caspase-1 were significantly activated in the hippocampus and colon of CRS rats. However, NLRP2 was only activated in the hippocampus. These results revealed CRS induced inflammatory responses along the brain-gut axis of rats might be controlled through the NLRP3/NLRP2 inflammasome signaling pathway, which may be the underlying regulator for CRS-induced TRP-KYN metabolic changes. This study provides a new experimental background for developing stress-related health products. [Display omitted] • CRS induced KP activation with region-specificity along the gut-brain axis of depressed rats. • TRP-KYN metabolic changes along the gut-brain axis were significantly associated with depressive behaviors in rats. • NLRP3/NLRP2 inflammasome signaling pathway may be the underlying regulator. [ABSTRACT FROM AUTHOR]

The hydrogenation reaction provided compound B 3 b (5 -H, major) and its isomer B 3' b (5 -H, minor) and the ratio (confirmed by SP 1 sp H NMR) was poor (84:16, Table 1, entry 1). The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate (3:1)) to give compound B 4 b and its 3 -OH isomer B 4' b ( B 4 b : B 4' b = 19:1). Compound B 2 b was prepared by a Wittig reaction in 98% yield and its double bond showed a single I trans i stereoisomer, based on SP 1 sp H NMR and SP 13 sp C NMR data. Cholesterol is metabolized to primary bile acids (BAs), such as cholic acid and chenodeoxycholic acid, by cytochrome P450 in the liver. [Extracted from the article]

Single-molecule fluorescence imaging is among the most advanced analytical technologies and has been widely adopted for biosensing due to its distinct advantages of simplicity, rapidity, high sensitivity, low sample consumption, and visualization capability. Recently, a variety of nucleic acid amplification approaches have been developed to provide a straightforward and highly efficient way for amplifying low abundance target signals. The integration of single-molecule fluorescence imaging with nucleic acid amplification has greatly facilitated the construction of various fluorescent biosensors for in vitro and in vivo detection of DNAs, RNAs, enzymes, and live cells with high sensitivity and good selectivity. Herein, we review the advances in the development of fluorescent biosensors by integrating single-molecule fluorescence imaging with nucleic acid amplification based on enzyme (e.g., DNA polymerase, RNA polymerase, exonuclease, and endonuclease)-assisted and enzyme-free (e.g., catalytic hairpin assembly, entropy-driven DNA amplification, ligation chain reaction, and hybridization chain reaction) strategies, and summarize the principles, features, and in vitro and in vivo applications of the emerging biosensors. Moreover, we discuss the remaining challenges and future directions in this area. This review may inspire the development of new signal-amplified single-molecule biosensors and promote their practical applications in fundamental and clinical research. [ABSTRACT FROM AUTHOR]

Construction of new carbon–carbon bonds is the cornerstone of organic chemistry. Organometallic reagents are amongst the most robust and versatile nucleophiles for this purpose. Polarization of the metal–carbon bonds in these reagents facilitates their reactions with a vast array of electrophiles to achieve chemical diversification. The dependence on stoichiometric quantities of metals and often organic halides as feedstock precursors, which in turn produces copious amounts of metal halide waste, is the key limitation of the classical organometallic reactions. Inspired by the classical Wolff–Kishner reduction converting carbonyl groups in aldehydes or ketones into methylene derivatives, our group has recently developed strategies to couple various alcohols, aldehydes, and ketones with a broad range of both hard and soft carbon electrophiles in the presence of catalytic amounts of transition metals, via the hydrazone derivatives: i.e., as organometallic reagent surrogates. This Tutorial Review describes the chronological development of this concept in our research group, detailing its creation in the context of a deoxygenation reaction and evolution to a more general carbon–carbon bond-forming strategy. The latter is demonstrated by the employment of carbonyl-derived alkyl carbanions in various transition-metal catalyzed chemical transformations, including 1,2-carbonyl/imine addition, conjugate addition, carboxylation, olefination, cross-coupling, allylation, alkylation and hydroalkylation. [ABSTRACT FROM AUTHOR]

A series of copolymers of thiazoloisoindigo (TzII) with different chalcogenophene trimers were synthesized to systematically investigate the chalcogen effect on their charge transport properties. When only the middle thiophene ring of terthiphene (T-T-T) is replaced by heavier chalcogenophenes, a preference (expressed by the ratio of μe/μh) towards electron transport was observed descending from T-T-T to T-Se-T then to T-Te-T (Se and Te stand for selenophene and tellurophene, respectively). On the other hand, with the increased number of heavier chalcogenophenes, a preference toward hole transport was observed descending from Se-T-Se to Se-Se-Se then to Se-Te-Se. This phenomenon is well-explained by the balance between the aromatic resonance energy of the chalcogenophenes and the electronegativity of the chalcogens. Specifically, P(TzII-T-Se-T) displayed relatively balanced ambipolar property (μhmax and μemax of 3.77 and 1.59 cm2·V−1·s−1 with a μe/μh of 0.42), while P(Tzll-Se-Te-Se) exhibited the best preference to hole transfer with a μe/μh of 0.09. P(Tzll-T-Te-T) exhibited the best preference to electron transfer with a μe/μh, of 16 and the μemax of 0.64 cm2·V−1·s−1 which is the highest electron mobility among the known conjugated polymers containing tellurophenes. [ABSTRACT FROM AUTHOR]

Protein fold recognition is one of the most critical tasks to explore the structures and functions of the proteins based on their primary sequence information. The existing protein fold recognition approaches rely on features reflecting the characteristics of protein folds. However, the feature extraction methods are still the bottleneck of the performance improvement of these methods. In this paper, we proposed two new feature extraction methods called MotifCNN and MotifDCNN to extract more discriminative fold-specific features based on structural motif kernels to construct the motif-based convolutional neural networks (CNNs). The pairwise sequence similarity scores calculated based on fold-specific features are then fed into support vector machines to construct the predictor for fold recognition, and a predictor called MotifCNN-fold has been proposed. Experimental results on the benchmark dataset showed that MotifCNN-fold obviously outperformed all the other competing methods. In particular, the fold-specific features extracted by MotifCNN and MotifDCNN are more discriminative than the fold-specific features extracted by other deep learning techniques, indicating that incorporating the structural motifs into the CNN is able to capture the characteristics of protein folds. [ABSTRACT FROM AUTHOR]

Protein fold recognition is critical for studying the structures and functions of proteins. The existing protein fold recognition approaches failed to efficiently calculate the pairwise sequence similarity scores of the proteins in the same fold sharing low sequence similarities. Furthermore, the existing feature vectorization strategies are not able to measure the global relationships among proteins from different protein folds. In this article, we proposed a new computational predictor called DeepSVM-fold for protein fold recognition by introducing a new feature vector based on the pairwise sequence similarity scores calculated from the fold-specific features extracted by deep learning networks. The feature vectors are then fed into a support vector machine to construct the predictor. Experimental results on the benchmark dataset (LE) show that DeepSVM-fold obviously outperforms all the other competing methods. [ABSTRACT FROM AUTHOR]

Herein, we report a ruthenium‐catalyzed redox‐neutral α‐alkylation of unsaturated alcohols based on a synergistic relay process involving olefin isomerization (chain walking) and umpolung hydrazone addition, which takes advantage of the interaction between the two rather inefficient individual reaction steps to enable an efficient overall process. This transformation shows the compatibility of hydrazone‐type "carbanions" and active protons in a one‐pot reaction, and at the same time achieves the first Grignard‐type nucleophilic addition using olefinic alcohols as latent carbonyl groups, providing a higher yield of the corresponding secondary alcohol than the classical hydrazone addition to aldehydes does. A broad scope of unsaturated alcohols and hydrazones, including some complex structures, can be successfully employed in this reaction, which shows the versatility of this approach and its suitability as an alternative, efficient means for the generation of secondary and tertiary alcohols. [ABSTRACT FROM AUTHOR]

Herein, we report a ruthenium‐catalyzed redox‐neutral α‐alkylation of unsaturated alcohols based on a synergistic relay process involving olefin isomerization (chain walking) and umpolung hydrazone addition, which takes advantage of the interaction between the two rather inefficient individual reaction steps to enable an efficient overall process. This transformation shows the compatibility of hydrazone‐type "carbanions" and active protons in a one‐pot reaction, and at the same time achieves the first Grignard‐type nucleophilic addition using olefinic alcohols as latent carbonyl groups, providing a higher yield of the corresponding secondary alcohol than the classical hydrazone addition to aldehydes does. A broad scope of unsaturated alcohols and hydrazones, including some complex structures, can be successfully employed in this reaction, which shows the versatility of this approach and its suitability as an alternative, efficient means for the generation of secondary and tertiary alcohols. [ABSTRACT FROM AUTHOR]

Abstract Human telomerase is responsible for the maintenance of chromosome end structures and is a valuable biomarker for malignant growth. However, the accurate measurement of telomerase activity at the single-cell level has remained a great challenge. Here we develop a simple quantum dot (QD)-based electrochemical biosensor for stripping voltammetric detection of telomerase activity at the single-cell level. We designed a thiol-modified capture DNA which may be immobilized on the gold electrode by the gold-sulfur bond. The presence of telomerase enables the addition of the telomere repeats of (TTAGGG) n to the 3′ end of the primer, accompanied by the incorporation of abundant biotins in the extension product with the assistance of the biotin-tagged dATP. The subsequent hybridization of extension product with the capture DNA and the addition of streptavidin-coated QDs induce the assembly of large amounts of QDs onto the electrode via specific biotin-streptavidin binding. After the acidic dissolution of QDs, the released Cd (II) can be simply quantified by anodic stripping voltammetry (ASV). Due to the introduction of large amounts of QDs by telomerase-induced primer extension reaction and the synergistic signal amplification induced by the release of Cd (II) from the QDs, this biosensor can detect telomerase activity at the single-cell level without the involvement of any thermal cycling and extra enzymes for signal amplification. Moreover, this assay exhibits a large dynamic range over four orders of magnitude and it is very simple without the involvement of specific hairpin probe design and complicated labelling, holding great potential in point-of-need testing. Highlights • A simple quantum dot-based electrochemical biosensor is developed for sensitive detection of telomerase activity. • This biosensor can detect telomerase activity at the single-cell level. • This biosensor can be used for the discrimination of cancer cells from normal cells. • This biosensor can be used for the screening of telomerase inhibitors. [ABSTRACT FROM AUTHOR]

We develop a triple-amplification strategy for sensitive detection of telomerase from cancer cells using telomere-based primer generation-triggered rolling circle amplification in combination with enzyme-assisted cyclic signal amplification. This method can detect telomerase at the single-cell level, and it can be further applied for the screening of telomerase inhibitors for anticancer drug discovery. [ABSTRACT FROM AUTHOR]

We combine single-molecule detection with magnetic separation for simultaneous measurement of human 8-oxoG DNA glycosylase 1 (hOGG1) and uracil DNA glycosylase (UDG) based on excision repair-initiated endonuclease IV (Endo IV)-assisted signal amplification. This method can sensitively detect multiple DNA glycosylases, and it can be further applied for the simultaneous measurement of enzyme kinetic parameters and screening of both hOGG1 and UDG inhibitors. [ABSTRACT FROM AUTHOR]

Quantum dots (QDs) are semiconductor nanocrystals with distinct characteristics of high brightness, large Stokes shift and broad absorption spectra, large molar extinction coefficients, high quantum yield, good photostability and long fluorescence lifetime. The QDs have replaced the conventional fluorophores with wide applications in immunoassays, microarrays, fluorescence imaging, targeted drug delivery and therapy. The integration of QDs with various nanomaterials such as noble metal nanoparticles, carbon allotropes, upconversion nanoparticles (UCNPs), metal oxides and metal–organic frameworks (MOFs) brings new opportunities and possibilities in nanoscience and nanotechnology. In this review, we summarize the recent advances in the integration of QDs with various nanomaterials for biomedical and environmental applications including sensing, bioimaging, theranostics and cancer therapy. We highlight the involved interactions such as fluorescence resonance energy transfer (FRET), plasmon enhanced fluorescence (PEF), and nanometal surface energy transfer (NSET) as well as the synergistic effect resulting from the integration of QDs with nanomaterials. In addition, we discuss the sensing and imaging mechanisms of different strategies and give new insight into the challenges and future direction as well. [ABSTRACT FROM AUTHOR]

Electromagnetic (EM) waves with orbital angular momentum (OAM) provide a new degree of freedom for channel multiplexing to improve the capacity of wireless communication. For OAM-based systems, it is important to design specific configurations to generate vortex radios. In this paper, a reconfigurable reflectarray antenna is proposed with independent control of dual polarizations. A reflective cell is proposed by properly assigning the variable capacitances of four varactors, which are placed between metal square rings of each unit. The varactors of each unit are divided into two groups and the capacitance value of each group controls the reflection phase for a single linear polarization. By using the equivalent circuit model, the reflective units and array can be designed efficiently. Smooth phase variation and good reflection efficiency are achieved. Then, the reflectarray is set into sectors and a simple phase-shifting surface model is used to generate vortex beam. Each sector is realized with reflective units satisfying desired reflection phases for different modes. This kind of OAM-generating method can reduce the required variation range of reflection phase and provide more choices for a specific OAM mode combination with dual polarization, which is helpful to reduce mutual coupling between the two linear polarizations. Finally, full-wave simulations show that the 0, ±1, ±2 modes of vortex beam are successfully generated at 3.5 GHz with arbitrary combination in dual-polarization, which is also supported by OAM modes purity and reflection efficiency analysis. Therefore, in our design, the reconfigurable OAM and spin angular momentum (SAM), related with polarization, can be utilized simultaneously and independently for high-capacity wireless communication. [ABSTRACT FROM AUTHOR]

A Rh/Ni-catalyzed cascade sequence of allylamine isomerization and hydrophosphonylation to synthesize α-aminophosphonates has been disclosed. The reaction, which not only allows the generation of widespread valuable α-aminophosphonates under simple systems and mild conditions, but also enriches the process of olefin isomerization–addition both in catalytic systems and various reaction types. [ABSTRACT FROM AUTHOR]

Even after decades of research, the preparation of mesoporous silica still depends on the sol–gel method. The major problem of sol–gel method is its infeasibility in industrial manufacturing. A large-scale preparation method is desired to meet the growing demand of mesoporous silica in multiple applications. A cost-effective and industrially feasible method was proposed to prepare mesoporous silica. The well-developed acid leaching technology was used as a novel pore forming method for treating coal fly ash. And mesoporous silica with specific surface area as high as 585.02 m 2 /g and pore volume of 0.54 cm 3 /g was successfully prepared under a control of reaction parameters. Reaction intensity was introduced as a new parameter to describe reaction conditions and help explain the variation of pore structure and shape prepared under different reaction conditions. This method is feasible in large-scale manufacturing of mesoporous silica and will satisfy the great demand for its wide applications. [ABSTRACT FROM AUTHOR]

Objective. This study aims to explore the relationships between serum indoxyl sulfate (IS) and Klotho protein levels with vascular calcification in patients with chronic kidney disease (CKD) stages 3–5. Methods. From December 2021 to January 2023, a total of 108 CKD patients in stages 3–5 were enrolled in this cross-sectional investigation. Demographic information and routine clinical biochemistry test results were gathered. Serum levels of IS and Klotho were quantified through enzyme-linked immunosorbent assays. Furthermore, multislice spiral computed tomography was employed to evaluate vascular calcification. The association between serum IS or Klotho levels and abdominal aorta calcification was assessed using univariate analysis and logistic regression analyses. Results. With the progression of CKD stages, serum creatinine, phosphorus, intact parathyroid hormone (iPTH), serum IS, and abdominal aortic calcification exhibited incremental trends, while serum calcium and Klotho protein levels showed a diminishing trend, with statistically significant differences (P < 0. 05). Significant differences were observed in age, blood phosphorus, calcium, total parathyroid hormone, serum IS, and Klotho protein levels between patients with and without aortic calcification (P < 0. 05). Logistic regression analysis demonstrated that advanced age, high IS level, and low Klotho protein level were independent risk factors for abdominal aortic calcification in CKD patients (P < 0. 05). Conclusion. This study indicates elevated serum IS levels and decreased Klotho protein levels in CKD patients. High IS level and low Klotho level were independent risk factors for abdominal aortic calcification. [ABSTRACT FROM AUTHOR]

Uracil-DNA glycosylase (UDG) is essential to the maintenance of genomic integrity due to its critical role in base excision repair pathway. However, existing UDG assays suffer from laborious procedures, poor specificity, and limited sensitivity. In this research, we construct a catalytic single-molecule Föster resonance energy transfer (FRET) biosensor for in vitro and in vivo biosensing of UDG activity. Target UDG can remove uracil base from the detection probe and cause the cleavage of detection probe by apurinic/apyrimidinic endonuclease (APE1), which exposes its toehold domain and initiates catalytic assembly of two fluorescently labeled hairpin probes via toehold-meditated strand displacement reaction (SDA) to generate abundant DNA duplexes with amplified FRET signal. In this assay, target UDG signal is amplified via enzyme-free catalytic reaction and the whole reaction may be completed in one step, which greatly simplifies the assay procedure, reduces the assay time, and facilitates the cellular imaging. This biosensor enables specific and sensitive measurement of UDG down to 0.00029 U/mL, and it is suitable for analyzing kinetic parameters, screening inhibitors, and even imaging endogenous UDG in live cells. Importantly, this biosensor can visually quantify various DNA repair enzymes by rationally altering DNA substrates. [ABSTRACT FROM AUTHOR]

Radix Polygalae, a commonly used traditional Chinese herb, has conventionally functioned in tranquilization and sedation, where anti-inflammation may be the underlying mechanism. Aim of the study : Chronic restraint stress (CRS), a risk factor for the etiology of intestinal disorders, was used in the present study to examine whether Radix Polygalae extract (RPE) could modulate colonic dysfunction in CRS rats. Wistar rats were exposed to 28-day CRS (6 h daily), and RPE (135 mg/kg and 270 mg/kg) was intragastrically administered 1 h before CRS. Subsequently, the gut microbiota was determined using metagenomic sequencing. Colonic proinflammatory interleukin-1β, −6, and −18 were assayed using qRT–PCR and ELISA. Tight junction proteins were quantified by qRT–PCR and western blotting (WB), and tryptophan metabolic enzymes and metabolites were determined using qRT–PCR and UFLC-QTRAP-5500/MS. Moreover, protein expression of colonic tight junction proteins, NF-κB-NLRP3 signaling involved in the underlying mechanism of RPE were detected by WB. RPE significantly decreased proinflammatory cytokines and reshaped the gut microbiota, especially the probiotics, including Lactobacillus and Bacteroides. Moreover, RPE could modulate the metabolite contents and enzyme expression associated with colonic tryptophan-kynurenine (TRP-KYN) metabolism and could increase tight junction protein expression in CRS rats. Furthermore, RPE inhibited the activation of NF-κB-NLRP3 signaling in the colon of CRS rats. RPE could modulate colonic inflammation, colonic microbiota, tight junction, TRP-KYN metabolism and NF-κB-NLRP3 signaling to reach a colonic balance of CRS rats. The present study helped us to better understand and appreciate the various beneficial effects of RPE. [Display omitted] • This study proved that Radix polygala could regulate intestinal dysfunction induced by CRS for the first time. • Based on brain-gut communication, the sedative and tranquilizing effects of Radix Polygalae may be mediated by intestinal flora. • NF-κB-NLRP3 signaling was involved in the modulating effect of RPE. [ABSTRACT FROM AUTHOR]

Acid leaching residue of coal gasification slag (ALR-CGS) is a by-product of the aluminum extraction process of CGS. Its amount increased with the industrialization of the CGS aluminum extraction process. Thanks to the high silica content of ALR-CGS, this research evaluated the synthesis of MCM-41 using this discarded material. Highly ordered MCM-41 with hexagonal shaped pore diameters of 2.91–3.65 nm was synthesized using ALR-CGS following a non-hydrothermal sol–gel method. The synthesized sample had a BET specific surface area of 1347 m 2 /g. ALR-CGS is a very competitive alternative silica source in the synthesis of MCM-41. [ABSTRACT FROM AUTHOR]

We develop a dual-functional dumbbell probe-based fluorescent biosensor for cascade amplification detection of miRNAs in lung cancer cells and tissues by integrating a primer exchange reaction (PER) with the CRISPR–Cas12a system. This biosensor can absolutely quantify the miR-486-5p expression in different lung cancer cells and distinguish non-small cell lung cancer (NSCLC) patients from healthy individuals, holding great potential in biomedical research and clinical diagnosis. [ABSTRACT FROM AUTHOR]

A straightforward and economical synthetic route for the preparation of cholesterol was developed from plant origin bisnoralcohol. [Display omitted] • Plant-derived cholesterol was synthesized from bisnoralcohol. • This promising route for production of cholesterol has a high overall yield. • The epicholesteorl and cholestanol were also synthesized. Currently, the market demand of the non-animal-derived cholesterol is increasing. A novel synthetic route of producing cholesterol was developed through multiple reactions from plant-sourced and commercially available bisnoralcohol (BA). The key reaction conditions, including solvents, reaction temperatures, bases and reducing agents of the route were investigated and optimized. In this straightforward synthetic pathway of cholesterol, most of the reaction steps possess high conversions with average yields of 94%, and the overall yield is up to 74% (5 steps) from the BA. The epicholesterol and were also synthesized. This promising route offers economical and efficient strategies for potential large-scale production of plant-derived cholesterol. [ABSTRACT FROM AUTHOR]

In this work we compute the determinant and inverse matrices for a certain symmetric matrix of Rayleigh sums. As a special case we also obtain the determinants and inverses for the matrices of the Bernoulli numbers and related numbers. [ABSTRACT FROM AUTHOR]

The operation and structure of the power system are becoming increasingly complex, and the probability of cascading fault increases. To this end, this paper proposes a cascading fault preventive control strategy that considers safety and the economy. First is to give a mathematical form to discriminate the cascading fault according to the action characteristics of the current-type backup protection. Second, the safety and economy of the system are evaluated in terms of power grid safety margin and generation operation cost, respectively, the initial faults are selected based on the power grid vulnerability and safety margin, and a cascading fault preventive control model is constructed for different initial faults' scenarios. The model is a two-layer optimization mathematical model, with the inner model being solved by particle swarm optimization to minimize the power grid safety margin. The outer model is solved by the multiobjective algorithm to minimize generation cost and maximizing power grid safety margin. Finally, the calculated Pareto set is evaluated using fuzzy set theory to determine the optimal generator output strategy. The feasibility of the proposed method is verified by conducting a simulation study with the IEEE39 node system as an example. [ABSTRACT FROM AUTHOR]

Several recent reports implicate an important role played by c-Jun N-terminal kinases (JNKs) in long-term potentiation (LTP). However, little is known about how the isoforms of JNKs participate in synaptic plasticity. Here we showed that short-term synaptic plasticity was impaired in the hippocampal area CA1 of JNK1-deficient (JNK1–/–) mice; these mice showed normal LTP in response to a strong tetanus and no alteration of N-methyl-d-aspartate receptor-dependent long-term depression (LTD) in the hippocampus. However, LTD induced either by group I metabotropic glutamate receptors (mGluRs) agonist dihydroxyphenylglycine or by paired-pulse low-frequency stimulation was absent in both the JNK1–/– slices and in JNK inhibitor anthrax [1, 9- cd] pyrazol-6(2 H)-1 (SP600125)-pretreated slices. Induction of mGluR-dependent LTD resulted in an increase in phosphorylation of JNK1 substrates, including p-c-Jun and p-ATF2 in wild-type (WT) mice, and these increases failed to occur in the JNK1–/– or SP600125-pretreated mice. These results demonstrated that JNK1 played a crucial role in the short-term synaptic plasticity and mGluR-dependent LTD, whereas hippocampus LTP was not affected by JNK1 deficiency. [ABSTRACT FROM AUTHOR]

The purpose of this study is to analyze and compare the differences in educational paradigm, curriculum design, developmental mode, and curriculum practice in culinary art between Taiwan and USA. Based on the findings of the study, recommendations are made with the purpose of improving culinary education in Taiwan. This study adopts comparative education methodology and content analysis. The points of comparison are educational objectives, definition, curriculum design, and development. The length of schooling, curriculum design, and degree offering are similar between Taiwan and USA. The article concludes with a series of recommendation. [ABSTRACT FROM AUTHOR]

Study objective: Previous studies have suggested that aggressive treatment of sinusitis can decrease bronchial hyperresponsiveness (BHR). However, there is still too little evidence to draw this conclusion, and the concept remains controversial. Design: A prospective, open-label study. Setting: University children's hospital allergy and immunology center and radiologic department. Patients: Sixty-one children with mild asthma and allergic rhinitis participated in the study. Forty-one of these 61 children had sinusitis, and the remainder had no sinusitis. Ten matched, nonatopic, healthy children were used as a control group. Intervention: Children with chronic sinusitis were placed into two groups. One group was treated with amoxicillin-clavulanate for 6 weeks and then with nasal saline solution irrigation for 6 weeks. For the other group, the treatment order was reversed. Children without chronic sinusitis received nasal saline solution irrigation for 12 weeks. Measurements: Clinical symptoms and signs of sinusitis, FEV[sub 1], and BHR were analyzed in the patients before and after treatment. Results: The clinical symptoms and signs of sinusitis, but not FEV[sub 1], showed a significant improvement after antibiotic treatment. After aggressive treatment for sinusitis, it was found that the provocative concentration of methacholine causing a 20% fall in FEV[sub 1] of children with mild asthma and sinusitis was significantly higher after treatment. Conclusion: The results suggest that every asthmatic patient needs to carefully evaluate to determine whether the patient has concomitant sinusitis. Respiratory infections that meet criteria for sinusitis, even if they do not exacerbate asthma, should be treated. It is suggested that sinusitis should always be kept in mind as a possible inducible factor for BHR, and that aggressive treatment of chronic sinusitis is indicated when dealing with an asthmatic patient who shows an unpredictable response to appropriate... [ABSTRACT FROM AUTHOR]

Chronic stressors represented risk factors for the etiology or exacerbation of several gastrointestinal diseases. The goal of the present study was to examine whether chronic restraint stress (CRS) could initiate and aggravate colonic inflammation, integrity damage and metabolic disturbance of rats. Firstly, increased inflammatory cytokines (interferon-γ (IFN-γ), tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10)) and decreased tight junction (TJ) proteins (occludin and zonula occludins-1 (ZO-1)) in rat colon were observed. Secondly, untargeted metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass (UPLC-Q-TOF/MS) revealed that TRP metabolism was the most prominently affected. Thirdly, quantification of TRP and its metabolites via prominence ultrafast liquid chromatography coupled with a QTRAP 5500 mass (UFLC-QTRAP-5500/MS) showed that TRP, kynurenine (KYN), kynurenic acid (KA) and 3-hydroxykynurenine (3−HK) were significantly increased. At the same time, 5-hydroxytryptamine (5-HT) was unchanged and 5-hydroxyindolacetic acid (5-HIAA) was significantly decreased in the colon of CRS rats. Besides, TRP metabolic enzyme changes were with the same trends as the corresponding metabolites. Thus, our data showed that CRS could initiate colonic inflammation, integrity damage and colonic metabolism disturbance, especially TRP-KYN metabolism pathway of rats, which may provide an experimental background for future research on stress-related gastrointestinal dysfunction. Chronic exposure to psychological stress could induce metabolic imbalance of the body, and stressful life events were intimately correlated with frequent relapses in patients with intestinal disorders. The present study showed that chronic restraint stress (CRS) could initiate and aggravate colonic inflammation, integrity damage and metabolic disturbance, especially tryptophan-kynurenine metabolism of rats. Tryptophan-kynurenine pathway may be involved in the initiation and development of diseases induced by chronic stress. This research may shed light on future research on stress-related gastrointestinal dysfunction. [Display omitted] • Chronic restraint stress (CRS) initiated colonic inflammation, integrity damage and metabolic disturbance of rats. • Metabolomic analysis revealed that CRS induced alteration in colonic TRP-kynurenine (KYN) metabolism of rats. • TRP-KYN metabolism pathway may play an important role in stress-related gastrointestinal dysfunction. [ABSTRACT FROM AUTHOR]

Recent studies have shown that adding active oxygen scavengers to edible coatings can maintain the storage quality and commercial value of postharvest fruit. In this research, the effect of a chitosan-based edible coating containing ascorbic acid (CH, 1% + AA, 1%) on Annona squamosa at storage conditions of 15 ± 1 °C was investigated for twelve days. The results showed that CH+AA could delay the decrease of firmness, appearance deterioration, weight loss, and accumulation of MDA content during the storage of Annona squamosa. The CH+AA composite coating also delayed the deterioration of quality by maintaining high titratable acidity, moisture content and antioxidant enzyme activities. In addition, CH+AA inhibited the softening of fruit by regulating the activities of cell wall degrading enzymes and their gene expression levels. In conclusion, the CH+AA composite coating can keep the quality of Annona squamosa stored after harvesting. [Display omitted] • CH+AA coating was better than that of single chitosan coating. • CH+AA coating can significantly improve the physicochemical properties of Annona squamosa. • CH+AA coating was significant influence in gene expression. [ABSTRACT FROM AUTHOR]

Tryptophan (TRP) metabolism could occur both peripherally and centrally, which plays an essential role in brain and gastrointestinal disorders. The participation of TRP metabolism in the bidirectional brain-gut interactions is of value to better understand the mechanism of the pathophysiology of depression. To compare the difference between peripheral and cerebral TRP metabolism in depression, the chronic unpredicted mild stress (CUMS) was used to induce depressive-like syndrome in rats. After the rats were subjected to CUMS for five weeks, TRP and its metabolites were determined by prominence ultrafast liquid chromatography (UFLC) coupled with a QTRAP 5500 mass spectrometer (UFLC-QTRAP-5500/MS), and the expression of TRP metabolic enzymes were examined by Real-time quantitative PCR (qRT-PCR). CUMS induced TRP metabolism abnormalities in the colon, cortex and hippocampus of rats. There were regional metabolism differences, but the common points were the upregulation of indoleamine-2,3-dioxygenase 1 (IDO1) and the increased contents of Kynurenine (KYN), which suggested that KYN pathway (KP) was more favored than the serotonin (5-HT) pathway in the TRP metabolism under CUMS in the three regions studied. More importantly, KYN was preferentially metabolized into neurotoxic 3-hydroxycaninuric acid (3-HK) branch in the cortex and hippocampus while Kynurenic acid (KA) branch in the colon under CUMS. Interestingly, according to the Pearson's correlation coefficients, there may be correlations between the colonic KYN and cerebral 3-HK and KA. It advances our understanding of the role of TRP metabolism in gut-brain communication and provides new research ideas and methods for depression. Image 1 • Tryptophan (TRP) metabolism plays an essential role in brain and gastrointestinal disorders. • Region-specific differences of TRP metabolism. • Correlations between colonic Kynurenine (KYN) and cerebral KYN,3-hydroxycaninuric acid (3-HK) and Kynurenic acid (KA). [ABSTRACT FROM AUTHOR]

Single-molecule fluorescence resonance energy transfer (smFRET) requires significant spectral overlap between the donor emission and the acceptor absorption, and its efficiency is strongly dependent on the donor-acceptor distance. Consequently, smFRET has the capability to study molecular interactions of biomolecules with sub-nanometer resolution in a homogeneous manner without the involvement of any separation steps. The smFRET has significant advantages of high signal-to-noise ratio, low sample consumption, and homogeneous assay, providing a new approach to detect low-abundant biomolecules with extremely high sensitivity. In this review, we summarize the strategies for improving smFRET efficiency and the applications of smFRET in sensitive detection of DNAs, microRNAs, enzymes, and in situ imaging of single-nucleotide mutation. Moreover, we provide new insight into the challenges and future perspectives of smFRET. • Single-molecule fluorescence resonance energy transfer (smFRET) provides a new approach to detect low-abundant biomolecules. • We summarize the strategies for improving smFRET efficiency. • We review the applications of smFRET in sensitive detection of DNAs, microRNAs and enzymes. • We provide new insight into the challenges and future perspectives of smFRET. [ABSTRACT FROM AUTHOR]

We develop a single-color multiplexing strategy by the integration of high-resolution melting pattern recognition with loop-mediated isothermal amplification (LAMP). This strategy can identify multiple amplicons with a small DNA melting temperature (Tm) difference (∼0.2 °C) without the involvement of either multicolor labels or parallelized multiplexing, and it can sensitively detect LAMP amplicons with the initial DNA concentrations ranging from 10 to 108 copies. [ABSTRACT FROM AUTHOR]

Abstract We develop for the first time a new electrochemical biosensor for signal-on detection of T4 polynucleotide kinase (PNK) based on the enhanced quasi-reversible redox signal of prussian blue generated by self-sacrificial label of iron metal-organic framework (FeMOF). The DNA hairpin probe modified with FeMOF@AuNPs at the 3'-thiol end acts as the substrate of PNK. The presence of PNK enables the 5'-phosphorylation of hairpin probe, which may subsequently function as the substrate of lambda exonuclease. Lambda exonuclease removes the 5' mononucleotides from the stem, unfolding the hairpin structure and releasing the single-stranded DNA (ssDNA). The resultant FeMOF@AuNP-modified ssDNA may specifically hybridize with the capture probe to form the double-strand DNA (dsDNA) duplex, enabling the immobilization of FeMOF on the electrode surface. The reaction of Fe3+ in the MOF with K 4 Fe(CN) 6 leads to the formation of prussian blue on the electrode surface and consequently the generation of a high electrochemical signal. This assay is very simple without the involvement of the pre-synthesized prussian blue which is unstable in neutral buffer, and the self-sacrificial label of FeMOF can achieve great signal amplification without the involvement of any extra functional materials. Due to the introduction of self-sacrificial label of FeMOF and the formation of prussian blue nanolayers with good quasi-reversible cyclic voltammetric electrochemical activity, this biosensor exhibits high sensitivity and a large dynamic range. Moreover, this biosensor can be used to screen the PNK inhibitors, holding great potential in disease diagnosis and drug discovery. Highlights • We develop a new electrochemical biosensor for signal-on detection of T4 polynucleotide kinase (PNK). • This electrochemical biosensor is based on the enhanced quasi-reversible redox signal of prussian blue generated by self-sacrificial label of iron metal-organic framework (FeMOF). • This assay is very simple without the involvement of the pre-synthesized prussian blue which is unstable in neutral buffer. • The self-sacrificial label of FeMOF can achieve great signal amplification without the involvement of any extra functional materials. [ABSTRACT FROM AUTHOR]

Palladium‐catalyzed allylic alkylation of nonstabilized carbon nucleophiles is difficult and remains a major challenge. Reported here is a highly chemo‐ and regioselective direct palladium‐catalyzed C‐allylation of hydrazones, generated from carbonyls, as a source of umpolung unstabilized alkyl carbanions and surrogates of alkyl organometallic reagents. Contrary to classical allylation techniques, this umpolung reaction utilizes hydrazones prepared not only from aryl aldehydes but also from alkyl aldehydes and ketones as renewable feedstocks. This strategy complements the palladium‐catalyzed coupling of unstabilized nucleophiles with allylic electrophiles by providing an efficient and selective catalytic alternative to the traditional use of highly reactive alkyl organometallic reagents. Surrogates: A highly chemo‐ and regioselective direct palladium‐catalyzed C‐allylation of hydrazones was developed using umpolung carbonyls as a source of unstabilized alkyl carbanions and surrogates of highly reactive alkyl organometallic reagents. The method requires only a catalytic amount of both metal and ligand, delivers products in high yields, is easily scaled‐up, and demonstrates wide substrate scope and good functional‐group compatibility. [ABSTRACT FROM AUTHOR]

Palladium‐catalyzed allylic alkylation of nonstabilized carbon nucleophiles is difficult and remains a major challenge. Reported here is a highly chemo‐ and regioselective direct palladium‐catalyzed C‐allylation of hydrazones, generated from carbonyls, as a source of umpolung unstabilized alkyl carbanions and surrogates of alkyl organometallic reagents. Contrary to classical allylation techniques, this umpolung reaction utilizes hydrazones prepared not only from aryl aldehydes but also from alkyl aldehydes and ketones as renewable feedstocks. This strategy complements the palladium‐catalyzed coupling of unstabilized nucleophiles with allylic electrophiles by providing an efficient and selective catalytic alternative to the traditional use of highly reactive alkyl organometallic reagents. [ABSTRACT FROM AUTHOR]

Detection of low-abundant DNA is essential for disease diagnosis and treatment. DNA polymerase-based amplification is frequently used due to its excellent sensitivity, but it suffers from time-consuming and labour-intensive procedures, complex template/primer design, and inherent nonspecific amplification. Alternatively, Exonuclease III (Exo III)-assisted target recycling provides a new approach for DNA assay because of its simplicity and general applicability, but it suffers from high background signal due to the nonspecific Exo III digestion and poor sensitivity due to single cycle signal amplification. Herein, we demonstrate the development of Exo III-assisted multiple cycle amplification (exonuclease chain reaction) for the sensitive detection of DNA with zero background signal. The binding of single-stranded DNA binding protein (SSB) to the hairpin probes can protect them from nonspecific digestion by Exo III, resulting in near zero background signal. The presence of the target DNA initiates the Exo III-triggered multiple cycle amplification, enabling the achievement of high sensitivity with a detection limit of 3 fM and excellent selectivity with single base mismatch discrimination capability, holding great potential in disease diagnosis and biomedical research. [ABSTRACT FROM AUTHOR]

• Innovates miRNA detection with cholesterol-enhanced 3D DNA Walker, enhancing precision. • Uses micelle structure for nuclease protection, cutting false positives in samples. • Allows cancer cell autonomous miRNA imaging, no need for external cofactors. • Enables precise cancer subtype identification via multiple miRNAs, boosting accuracy. • Advances molecular diagnostics, key for early detection and personalized medicine. Achieving reliable miRNA detection and imaging remains a critical and formidable challenge. To address this challenge, we developed a three-dimensional (3D) DNA walker nanoprobe (DWN), derived from a multifunctional molecular beacon with a lipidic moiety. This innovative structure employs a cholesterol-conjugated multifunctional molecular beacon (Chol-MMB) assembled through hydrophobic interactions, thereby bypassing the cumbersome and inefficient process of immobilizing DNA strands onto rigid surfaces. Once the walker nanoprobe enters cells, the binding between the target miRNA and the nanoprobe triggers an intermolecular polymerization process, leading to a conformational change in DWN. This change liberates a walking strand, initiating the walking reaction. As a result, the 3D DNA walker nanoprobe illuminates the fluorophore, enabling precise quantitative analysis. The efficacy of the DWN was demonstrated by the limit of detection of 0.326 fmol for miR-21 with a reaction duration of 1 h. In addition, this strategy effectively differentiates various cells based on the specific miRNA. Further refinement of this method will lead to an efficacious miRNA-based platform for cell typing and liquid biopsy. [ABSTRACT FROM AUTHOR]

We develop a label-free and high-throughput bioluminescence method for the sensitive detection of uracil DNA glycosylase (UDG) through enzyme-mediated tricyclic cascade signal amplification. This method exhibits high sensitivity with a detection limit as low as 0.00031 U mL−1, and it can be further applied for the measurement of enzyme kinetic parameters and the screening of UDG inhibitors as well as cancer cell analysis. [ABSTRACT FROM AUTHOR]

Traditional cross-couplings require stoichiometric organometallic reagents. A novel nickel-catalyzed cross-coupling reaction between aldehydes and aryl halides via hydrazone intermediates has been developed, merging the Wolff–Kishner reduction and the classical cross-coupling reactions. Aromatic aldehydes, aryl iodides and aryl bromides are especially effective in this new cross-coupling chemistry. [ABSTRACT FROM AUTHOR]

Single-molecule detection provides a simple and ultrasensitive platform to quantify target molecules by simply counting the individual fluorescence signals. Quantum dots (QDs) are novel semiconductor nanocrystals with distinct characteristics of high brightness, large Stokes shift and broad absorption spectra, high molar extinction coefficients, high quantum yield, good photostability and long fluorescence lifetime. The combination of single-molecule detection with QDs enables the development of single QD-based nanosensors with extremely high sensitivity. Single QD-based nanosensors may be divided into two categories based on single QD burst coincidence detection and single QD-fluorescence resonance energy transfer (FRET) detection, and have significant advantages of high signal-to-noise ratio, high sensitivity, rapidity, and low sample consumption. The single QD-based nanosensors have the capability of directly detecting low-abundance species without the need for nucleic acid amplification, and may elucidate a variety of biological and biochemical phenomena in real time using single QD tracking. In this review, we summarize the recent advances in single QD-based nanosensors and their applications for sensitive detection of DNAs, microRNAs, proteins, enzymes, small molecules and viruses. We highlight the challenges and future direction of single QD-based nanosensors as well. [ABSTRACT FROM AUTHOR]

DNA glycosylase assumes a pivotal role in the preservation of genome integrity by recognizing and excising damaged bases. Herein, we develop a single primer/self-template-powered cascade rolling circle amplification (RCA) and apurinic/apyrimidinic endonuclease (APE1)-mediated signal amplification for simultaneous detection of human alkyladenine DNA glycosylase (hAAG) and uracil DNA glycosylase (UDG). The uniqueness of this approach lies in the use of custom-designed hairpin probes to establish a prerequisite for RCA: the conformational change of hairpin probe to circular template, which effectively suppress undesired non-specific amplification. We design two hairpin probes featuring elongated stem structure and 3′-phosphate (3′-PO 4) modifications. The stems of hairpin probes are modified with glycosylase substrates and BER process can cleave hairpin probes, resulting in the generation of single-stranded DNAs (ssDNAs) with 3′-hydroxyl (3′-OH) ends. These ssDNAs can function as padlock probes to form circular template upon ligation by ligase. Ultimately, the self-template-initiated RCA and APE1-mediated signal amplification cascade occurs, generating a substantial number of free Cy3 and Cy5 fluorophores that can be simply visualized by single-molecule fluorescence detection. This method demonstrates excellent specificity and sensitivity, with a limit of detection (LOD) of 3.42 × 10-12 U/μL for hAAG and 2.41 × 10-12 U/μL for UDG. This method also can be used for screening of potential inhibitor and kinetic parameter measurement. Most importantly, this method enables accurate profiling of glycosylases expression levels in various cancer cell lines and detection of glycosylase activities at the single-cell level, offering a bright future in cancer detection, medical research, and precision medicine. • Simultaneous detection of multiple glycosylases at ultra-low concentrations. • Conformation-switchable hairpin probes and self-templated amplification reduce non-specific amplification. • One primer probe can simultaneously trigger two isothermal amplifications. • Accurate assessment of DNA glycosylase expression in different cancer cell lines. [ABSTRACT FROM AUTHOR]

Hybridization chain reaction (HCR) based enzyme-free amplification techniques have recently been developed for the visualization of intracellular messenger RNA (mRNA). However, the slow kinetics and potential interference with the intricate biological environments hinder its application in the clinic and in vivo. Herein, we designed a nanofirecracker probe-based strategy using i ntramolecular h ybridization c hain r eaction (IHCR) amplifier for rapid, efficient, sensitive, specific detection and imaging of survivin mRNA both in vitro and vivo. Two probes, HP1 and HP2, in IHCR were simultaneously incorporated into a DNA nanowire scaffolds to bring HP1 and HP2 to close proximity on the assembled nanowire scaffolds. Empowered by the DNA nanowire scaffolds and spatial confinement effect, the nanofirecracker probe-based IHCR sensing system exhibited improved biostability, accelerated reaction kinetics, and enhanced signal amplification. This new strategy has been successfully applied to imaging mRNA in both cultured cells and in mice. Importantly, this novel sensing method was capable of detecting survivin mRNA in clinical blood samples from subjects with colorectal cancer. Thus, this novel nanofirecracker probe-based IHCR strategy holds great potential in advancing both biomedical research and in molecular diagnostics. [ABSTRACT FROM AUTHOR]

Review: [30 refs. [ABSTRACT FROM AUTHOR]

Arylacrylamides (I), (IV), and (VI) are found to react with aryl bromides and benzyl chloride in the presence of a Rh-catalyst to yield oxindoles. [ABSTRACT FROM AUTHOR]

DNA repair enzymes are responsible for the repair of DNA lesions and are important disease biomarkers. Herein, we construct a target-triggered DNAzyme motor for electrochemical detection of multiple DNA glycosylases based on the DNAzyme motor-driven encoding of different electrochemical molecules. This assay involves two hairpin probes for sensing uracil DNA glycosylase (UDG) and human alkyladenine DNA glycosylase (hAAG), a AuNPs@locked DNAzyme motor which contains the locking strands and the Mg2+/Pb2+ DNAzyme strands, and a magnetic bead track which contains MB/Fc-labelled Mg2+/Pb2+ substrate strands. When UDG and hAAG are present, they can cleave the corresponding hairpin DNA probes to release two single-stranded DNAs (ssDNAs) which can hybridize with the locking strands to induce the liberation of Mg2+/Pb2+ DNAzyme strands from the AuNPs@DNAzyme motor. The subsequent hybridization of Mg2+/Pb2+ DNAzyme strands with their corresponding substrate strands results in the cleavage of Mg2+/Pb2+ substrate strands and the simultaneous release of MB/Fc-labelled ssDNAs from magnetic bead. The released MB/Fc labels can be electrochemically detected for accurate quantification of UDG/hAAG. This target-triggered DNAzyme motor exhibits high sensitivity and good specificity with the capability of simultaneously measuring multiple DNA glycosylases in HeLa cells and screening the potential inhibitors. • We develop a target-triggered DNAzyme motor for electrochemical detection of multiple DNA glycosylases. • The electrochemical signals result from the DNAzyme motor-driven encoding of different electrochemical molecules. • This DNAzyme motor exhibits high sensitivity and good specificity. • This DNAzyme motor can simultaneously measure multiple DNA glycosylases in HeLa cells. • This DNAzyme motor can be applied for the screening of potential inhibitors. [ABSTRACT FROM AUTHOR]

5-Aza-2ʹ-deoxycytidine (5-azaCdR) inhibits growth of breast cancer cells but increases their metastatic potential. Combining methylated DNA binding protein 2 depletion and 5-azaCdR has a synergistic antitumor effect enhancing tumor growth, while inhibiting invasiveness, pointing to a potential new epigenetic therapeutic for breast cancer.5-Aza-2ʹ-deoxycytidine (5-azaCdR) not only inhibits growth of non-invasive breast cancer cells but also increases their invasiveness through induction of pro-metastatic genes. Methylated DNA binding protein 2 (MBD2) is involved in silencing methylated tumor suppressor genes as well as activation of pro-metastatic genes. In this study, we show that a combination of MBD2 depletion and DNA methyltransferases (DNMT) inhibition in breast cancer cells results in a combined effect in vitro and in vivo, enhancing tumor growth arrest on one hand, while inhibiting invasiveness triggered by 5-azaCdR on the other hand. The combined treatment of MBD2 depletion and 5-azaCdR suppresses and augments distinct gene networks that are induced by DNMT inhibition alone. These data point to a potential new approach in targeting the DNA methylation machinery by combination of MBD2 and DNMT inhibitors. [ABSTRACT FROM AUTHOR]

Background evidence is largely available indicating benefits to adding a pharmacist on acute care wards. The benefits of maintaining pharmacotherapeutic consultant services on a geriatric ward remain unexplored. Objectives to determine the impact of the removal of a clinical pharmacist from an acute geriatric ward on patients' Medication Appropriateness Index (MAI) scores, admission-related outcomes and drug burdens. Methods researchers consulted the archives for records of patients admitted to the geriatric care unit before and after the pharmacist's withdrawal. The primary outcome of differential MAI scores and secondary outcomes of rehospitalisations, emergency department visits, durations of hospitalisation and differential drug count were compared pre- and post-intervention. An interrupted time series analysis regression model was used for the primary outcome. Results a total of 305 patients admitted before (n  = 208) and after (n  = 97) the pharmacist's withdrawal were included in the study. The intervention had a significant impact on the primary outcome, increasing the relative differential MAI score (adjusted mean) by 9.3 points (95% confidence interval 3.9–14.6). As for the secondary outcomes, differences in admission-related outcomes were non-significant but the mean differential drug count significantly increased post-intervention from 0.02 to 1.36 (P  < 0.001). Conclusion the removal of the pharmacist led to an increase in inappropriate drug prescription. Careful consideration should be given to decisions regarding the removal of the pharmacist from acute geriatric care teams. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) patients had an increased susceptibility to tuberculosis (TB). The aim of this study was to investigate the prevalence and clinical characteristics of TB in SLE patients, with focus on the differences between pulmonary and extra-pulmonary TB. This is a retrospective study that reviewed the medical records of 3,179 SLE patients from 1985 to 2004. The diagnosis of TB was confirmed by one of the following: positive acid-fast bacillus (AFB) smear, positive culture of Mycobacterium tuberculosis from appropriate specimens, or a histopathologic finding of caseating granuloma on specimen. During the 20-year review period, TB was documented in 19 SLE patients, with 21 episodes. Ten of 21 episodes (47.6%) were pulmonary TB while the other 11 episodes (52.4%) were extra-pulmonary TB. Among extra-pulmonary TB, there were joint and cutaneous involvements in five, miliary in two, Pott’s disease in two, peritoneum in one, and spleen in one. The most common manifestations of TB were fever and cough. Delayed diagnosis and adverse effects of anti-TB therapy were observed in the extra-pulmonary TB group. While SLE patients commonly present with prolonged fever or chronic cough, tuberculosis infection should be taken into consideration. [ABSTRACT FROM AUTHOR]

The article explores how Follicular helper T (TFH) cells are essential for generating protective humoral immunity. Topics discussed include thymocyte selection–associated HMG-box protein (TOX) was identified as a central transcription regulator in TFH cell development; TOX promotes the expression of multiple molecules that play critical roles in TFH cell differentiation and function; and understanding of the molecular mechanisms that govern the differentiation and function of TFH cells.

Carbon monoxide (CO) releasing molecule (CORM)-3, a water-soluble CORM, has protective effects against inflammatory and ischemia/reperfusion injury. We determined the effect of CORM-3 against neuronal pyroptosis in a model of hemorrhagic shock and resuscitation (HSR) in rats via mitochondrial regulation. Rats were treated with CORM-3 (4 mg/kg) in vitro after HSR. We measured cortical CO content 3–24 h after HSR; assessed neuronal pyroptosis, mitochondrial morphology, ROS production, and mitochondrial membrane potential at 12 h after HSR; and evaluated brain magnetic resonance imaging at 24 h after HSR and learning ability 30 days after HSR. We also measured soluble guanylate-cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway activity using a blocker of sGC, NS2028, and 125I-cGMP assay. Among rats that underwent HSR, CORM-3-treated rats had more CO in the cortical tissue than sham- and iCORM-3-treated rats. CORM-3-treated rats had significantly less neuronal pyroptosis in the cortical tissue; higher sGC activity and cGMP content; lower ROS production; better mitochondrial morphology, function, and membrane potential; and enhanced learning/memory ability than HSR-treated rats. However, these neuroprotective effects of CORM-3 were partially inhibited by NS2028. CORM-3 may alleviate neuronal pyroptosis and improve neurological recovery in HSR through mitochondrial regulation mediated by the sGC–cGMP pathway. Thus, CO administration could be a promising therapeutic strategy for hemorrhagic shock. A proposed diagram tying together the observations involved in CORM-3-induced neuroprotection against HSR. HSR increased neuronal pyroptosis, which might be associated with up-regulation of ROS. CORM-3 not only significantly reduced these neuronal pyroptosis, but also improved long-term learning ability and T2-weighted MRI, which might be associated with inhibition of mitochondrial dysfunction through regulating activity in sGC-cGMP signal pathway, whereas NS2028, a blocker of sGC, could partially inhibit these neuroprotective effects. Image 1 • Hemorrhage shock and resuscitation (HSR) induced cortical neuronal pyroptosis, mitochondrial injury, and decrased learning ability. • CORM-3 administration after resuscitation provided neuroprotection for HSR, and improved learning ability. • The neuroprotective mechanism of CROM-3 against HSR injury could be associated with sGC–cGMP pathway. [ABSTRACT FROM AUTHOR]