Implementation of micelle-enabled C(sp2)-C(sp3) cross-electrophile coupling in pharmaceutical synthesis.

A sustainable C(sp2)-C(sp3) cross-electrophile coupling was developed between readily available 5-bromophthalide and 1-benzyl-4-iodopiperidine under micellar conditions, leading to a key intermediate of one of our development compounds. Copper was found to play a crucial role as a co-catalyst in this dual catalysis system. The chemistry and process were successfully demonstrated in a kilo scale to deliver sufficient drug substance to the clinical campaigns. This is the first reported scale-up of such a challenging cross-electrophilic coupling that uses an aqueous medium, and not undesirable reprotoxic polar aprotic solvents (e.g. DMF, DMAc, and NMP).

Clinical Microfluidic Chip Platform for the Isolation of Versatile Circulating Tumor Cells.

Circulating tumor cells (CTCs) are significant in cancer prognosis, diagnosis, and anti-cancer therapy. CTC enumeration is vital in determining patient disease since CTCs are rare and heterogeneous. CTCs are detached from the primary tumor, enter the blood circulation system, and potentially grow at distant sites, thus metastasizing the tumor. Since CTCs carry similar information to the primary tumor, CTC isolation and subsequent characterization can be critical in monitoring and diagnosing cancer. The enumeration, affinity modification, and clinical immunofluorescence staining of rare CTCs are powerful methods for CTC isolation because they provide the necessary elements with high sensitivity. Microfluidic chips offer a liquid biopsy method that is free of any pain for the patients. In this work, we present a list of protocols for clinical microfluidic chips, a versatile CTC isolating platform, that incorporate a set of functionalities and services required for CTC separation, analysis, and early diagnosis, thus facilitating biomolecular analysis and cancer treatment. The program includes rare tumor cell counting, clinical patient blood preprocessing, which includes red blood cell lysis, and the isolation and recognition of CTCs in situ on microfluidic chips. The program allows the precise enumeration of tumor cells or CTCs. Additionally, the program includes a tool that incorporates CTC isolation with versatile microfluidic chips and immunofluorescence identification in situ on the chips, followed by biomolecular analysis.

Relationship between sodium-glucose cotransporter-2 inhibitors and muscle atrophy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Aim: This study aims to assess the association between sodium-glucose cotransporter type-2 inhibitor (SGLT-2i) treatment and muscle atrophy in patients with type 2 diabetes mellitus (T2DM). Methods: We searched six databases from 1 January 2012 to 1 May 2023, without language restrictions. The primary outcome was muscle. Secondary outcomes were weight loss, weakness, malaise, or fatigue. Subgroup analyses were performed according to different definitions of muscle, treatment duration, and measurement methods. The quality of the studies was assessed using the Cochrane tool. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. Results: Nineteen randomized controlled trials (RCTs) involving 1,482 participants were included. Compared with the control group, a meta-analysis showed that T2DM participants in the group treated with SGLT-2i demonstrated statistically significant reductions in lean body mass of 0.66 (95% confidence interval (CI), -1.05 to -0.27; p = 0.0009) and skeletal muscle mass of 0.35 (95% CI, -0.66 to -0.04; p = 0.03). No deaths or serious adverse events were reported. The quality of evidence in the included trials was low. Conclusions: SGLT-2i may lead to a reduction in muscle strength in the treatment of T2DM compared to the control group. However, there is still a lack of high-quality evidence to evaluate muscle atrophy caused by SGLT-2i. Systematic review registration: https://inplasy.com/inplasy-2022-12-0061/, identifier 2022120061.

A Review on Wine Flavour Profiles Altered by Bottle Aging.

The wine flavour profile directly determines the overall quality of wine and changes significantly during bottle aging. Understanding the mechanism of flavour evolution during wine bottle aging is important for controlling wine quality through cellar management. This literature review summarises the changes in volatile compounds and non-volatile compounds that occur during wine bottle aging, discusses chemical reaction mechanisms, and outlines the factors that may affect this evolution. This review aims to provide a deeper understanding of bottle aging management and to identify the current literature gaps for future research.

Vibrational non-Boltzmann effects on the dissociation rate of oxygen.

Both the internal energy nonequilibrium and the NB effects of the vibrational state distribution influence the calculation of the dissociation rate coefficient. The state-to-state (STS) method gives the exact dissociation rate coefficients under the influence of two nonequilibrium effects, while the single group linear maximum-entropy (SGLM) model only considers the internal energy nonequilibrium effects. Therefore, the ratio ζ of the dissociation rate coefficient calculated by the STS method and the SGLM model is used in this paper to describe the NB effects on the dissociation rate coefficient. The zero-dimensional (0D) heating adiabatic thermochemical nonequilibrium process of oxygen was simulated by the STS method with a post-surge temperature of 7000-11 000 K. The variation regularity of the NB effects in the relaxation process were investigated using ζ, and it was found that the NB effects were mainly affected by temperature. And then the relaxation process after the normal shock with the same post-surge temperature of 7000-11 000 K was simulated. The NB effects in the two non-equilibrium processes were compared, and it was found that although there is a conversion between internal energy and fluid kinetic energy in the latter, the NB effects in both processes have similar change rules with similar temperature change rules. If the specific internal energy is the same, the NB effects in both processes are also quantitatively consistent. This finding provides a basis for the improvement of the nonequilibrium model considering the NB effects.

miR-100 rs1834306 a > G polymorphism decreases neuroblastoma risk in Chinese children.

BACKGROUND: Neuroblastoma is a common malignant tumor stemming from the sympathetic nervous system in children, which is often life-threatening. The genetics of neuroblastoma remains unclear. Studies have shown that miRNAs participate in the regulation of a broad spectrum of biological pathways. The abnormity in the miRNA is associated with the risk of various cancers, including neuroblastoma. However, research on the relationship of miRNA polymorphisms with neuroblastoma susceptibility is still in the initial stage. METHODS: In this research, a retrospective case-control study was conducted to explore whether miR-100 rs1834306 A > G polymorphism is associated with neuroblastoma susceptibility. We enrolled 402 cases and 473 controls for the study. The logistic regression analysis was adopted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between miR-100 rs1834306 A > G and neuroblastoma risk. RESULTS: Our results elucidated that the miR-100 rs1834306 A > G polymorphism was associated with the decreased risk of neuroblastoma (AG versus AA: adjusted OR = 0.72, 95% CI = 0.53-0.98, and P = 0.038). The subsequent stratified analysis further found that rs1834306 AG/GG genotype reduced the risk of neuroblastoma in the subgroup with tumors of the mediastinum origin (adjusted OR = 0.63, 95% CI = 0.41-0.95, and P = 0.029). CONCLUSIONS: In summary, miR-100 rs1834306 A > G polymorphism was shown to associate with decreased neuroblastoma risk in Chinese children, especially for neuroblastoma of mediastinum origin. This conclusion needs to be verified in additional large-size case-control studies.

Transcriptomic Study on the Lungs of Broilers with Ascites Syndrome.

Although broiler ascites syndrome (AS) has been extensively studied, its pathogenesis remains unclear. The lack of cardiopulmonary function in broilers causes relative hypoxia in the body; hence, the lung is the main target organ of AS. However, the transcriptome of AS lung tissue in broilers has not been studied. In this study, an AS model was successfully constructed, and lung tissues of three AS broilers and three healthy broilers were obtained for RNA sequencing (RNA-seq) and pathological observation. The results showed that 614 genes were up-regulated and 828 genes were down-regulated in the AS group compared with the normal group. Gene Ontology (GO) functional annotation revealed the following up-regulated genes: FABP4, APLN, EIF2AK4, HMOX1, MMP9, THBS1, TLR4, BCL2; and down-regulated genes: APELA, FGF7, WNT5A, CDK6, IL7, IL7R, APLNR. These genes have attracted much attention in cardiovascular diseases such as pulmonary hypertension. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that multiple metabolic processes were enriched, indicating abnormal lung metabolism of AS in broilers. These findings elucidate the potential genes and signal pathways in the lungs of broilers with AS and provide a potential target for studying the pathogenesis and preventing AS.

Underlying mechanism of Qiling Jiaogulan Powder in the treatment of broiler ascites syndrome.

Broiler ascites syndrome (AS), is a nutritional and metabolic disease that occurs in fast-growing commercial broiler chickens. AS can cause poor growth and a significant increase in the rate of broiler deaths, which has resulted in serious economic losses to the poultry industry. The classic traditional Chinese medicine Qiling Jiaogulan Powder (QLJP) has been demonstrated to have a certain therapeutic effect on broiler AS. However, its pharmacological mechanism remains to be elucidated. This study was performed to investigate the multitarget action mechanism of QLJP in the treatment of broiler AS based on network pharmacology analysis using a broiler AS model. First, all chemical components and targets of QLJP were obtained from the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP). Targets related to broiler AS were further obtained through the GeneCards database and the NCBI Gene sub-database. A protein-protein interaction (PPI) network was constructed. Then, enrichment analyses were performed to predict the potential mechanisms of QLJP in the treatment of broiler AS. Finally, the treatment effect of QLJP on AS was verified in a broiler AS model. Network pharmacology analysis generated 49 active ingredients and 167 core targets of QLJP, and a QLJP-single drug-target-disease network was successfully constructed. Gene enrichment analysis indicated that the core targets have played major roles in the Cell cycle, FOXO signaling pathways, etc. We demonstrated that QLJP improved clinical and organ damage symptoms and significantly reduced the ascites heart index in broilers with AS induced by administration of high-energy, high-protein diets and high-sodium drinking water in a low-temperature environment. QLJP may regulate lung oxidative stress, the cell cycle and apoptosis by activating the FOXO3a signaling pathway to interfere with the occurrence and development of AS in broilers. QLJP administration may be a good clinical strategy for the prevention and treatment of broiler AS.

Accelerating Effects of Flow Behavior Index n on Breakup Dynamics for Droplet Evolution in Non-Newtonian Fluids.

This paper studied the evolution of NaAlg solution micro-droplet in a coaxial microchannel. The Bird-Carreau model was used to characterize the flow properties of NaAlg solution. As the mass fraction decreased, the flow behavior index n also decreased, indicating that the NaAlg solution was increasingly shear-thinning. There were three stages during the micro-droplet evolution, which were the growth stage, the squeezing stage, and the pinch-off stage. This paper led the flow behavior index n to estimate the effects of rheological property on the breakup dynamics of micro-droplet. We proposed two new prediction models of the minimum neck width wm which were affected by |n| in the squeezing and pinch-off stages for the non-Newtonian fluids. In addition, this paper indicated the rate ratio Qd/Qc was another factor on the wm model in the squeezing stage and the H(λ) of Stokes mechanism was a function governed by |n|2 in the pinch-off stage.

Analysis of P wave induced second-order harmonic field at solid-fluid interface with potential matrix algorithm.

Based on the second-order harmonic potential theory, the characteristics of the second-order harmonic field generated at the solid-liquid interface induced by P wave incidence are analyzed. A planar model of the solid-liquid interface is established to study the variation of the second-order displacement field versus the incident angles. The homogeneous solution coefficient matrix, refraction and reflection coefficient matrix are introduced. According to the boundary conditions and Lagrange's various parameters method, the second-order displacement field is obtained, and its dependence on the solid-liquid interface is investigated. The different effects of boundary on the tangential displacement and normal displacement are demonstrated. Numerical simulation shows that the complete solution varies slightly at the incident angle, and the tangential displacement and the normal displacement change sharply at a mutation angle θω due to the boundary effect.

ß-Asarone improves learning and memory in Aß1-42-induced Alzheimer's disease rats by regulating PINK1-Parkin-mediated mitophagy.

Alzheimer's disease (AD) is a chronic neurodegenerative disease that is characterized by the extracellular accumulation of ß-amyloid (Aß). Many studies have shown a close relationship between autophagy and the formation of Aß. As AD develops and progresses, mitophagy diminishes insoluble Aß, and mitochondrial dysfunction seems to be a determining factor in the pathogenesis of AD. In our previous study, we showed that ß-asarone pharmacological effects in APP/PS1 transgenic mice, reducing Aß expression. However, the specific mechanism of this effect remains unclear. In this study, AD model rats induced by intracerebroventricular injection of Aß1-42 were randomly divided into nine groups, and medical intervention was applied to the animals for 30 days. Subsequently, spatial learning and memory were evaluated by the water maze test. Bcl-2 levels in the hippocampus were determined by western blotting (WB). The protein expression of Aß1-42, Beclin-1, p62, PINK1, and Parkin was assessed by WB and immunohistochemistry (IHC). The data showed that after ß-asarone treatment, the learning and memory of the AD rats were clearly improved compared with those of the model group. Moreover, ß-asarone decreased Aß1-42, Bcl-2, and p62 levels but increased Beclin-1 levels compared with those in the model group. In addition, we treated a group of rats with CsA to inhibit mitophagy. ß-Asarone increased PINK1 and Parkin expression compared with that in the model group. The results showed that ß-asarone can improve the learning and memory of rats with Aß1-42-induced AD by effectively promoting PINK1-Parkin-mediated mitophagy. Taken together, these results suggest that ß-asarone may have the capacity to become a pharmaceutical agent for the treatment of AD in the future.

Fish Gelatin Based Triboelectric Nanogenerator for Harvesting Biomechanical Energy and Self-Powered Sensing of Human Physiological Signals.

Triboelectric nanogenerator (TENG) has been proven effective in converting biomechanical energy into electrical energy, which is expected to be a new energy supply device for wearable electronics and can be utilized as a self-powered sensor. In this work, we have developed a flexible, eco-friendly, and multifunctional fish gelatin based triboelectric nanogenerator (FG-TENG) composed of fish gelatin (FG) film and poly(tetrafluoroethylene)/poly(dimethylsiloxane) (PTFE/PDMS) composite film. The open-circuit voltage (Voc), short-circuit current (Isc), and output power density of this FG-TENG could reach up to 130 V, 0.35 µA, and 45.8 µW cm-2, respectively, which were significantly higher than those of TENGs based on other commonly used positive friction materials such as aluminum foil, poly(ethylene terephthalate) (PET), and print paper. The superior performance of the FG-TENG is attributed to the strong electron-donating ability of the FG during the triboelectric process. The generated electric energy was high enough to light up 50 commercial light-emitting diodes (LEDs) directly. Importantly, owing to the high stability and excellent sensitivity of the FG-TENG, it has been used as a self-powered sensor for real-time monitoring of the human physiological signals such as finger touch, joint movement, and respiration. Furthermore, to expand the usages in real-life applications, a foldable FG-TENG was fabricated by adopting the Miura folding to monitor human movements in real time. This work provides an economical, simple, and environmental-friendly approach to fabricate a biomechanical energy harvester, which has a great potential in powering next-generation wearable electronics and monitoring human physiological signals.

A transparent paper-based platform for multiplexed bioassays by wavelength-dependent absorbance/transmittance.

This communication describes the rational design of a transparent paper-based chemosensing platform for multi-target detection by wavelength-dependent absorbance/transmittance. The platform was successfully applied in the examination of bovine serum albumin (BSA) and cholesterol in serum with a low detection limit of 0.1 µM and 0.1 mM, respectively. With low cost and high sensitivity, the paper-based platform shows great promise for multiplexed bioassays.

Signal-Enhanced Detection of Multiplexed Cardiac Biomarkers by a Paper-Based Fluorogenic Immunodevice Integrated with Zinc Oxide Nanowires.

Using a single test to comprehensively evaluate multiple cardiac biomarkers for early diagnosis and prevention of acute myocardial infarction (AMI) has faced enormous challenges. Here, we have developed paper-based fluorogenic immunodevices for multiplexed detection of three cardiac biomarkers, namely, human heart-type fatty acid binding protein (FABP), cardiac troponin I (cTnI), and myoglobin, simultaneously. The detection is based on a strategy using zinc oxide nanowires (ZnO NWs) to enhance fluorescence signals (∼5-fold compared to that on pure paper). The immunodevices showed high sensitivity and selectivity for FABP, cTnI, and myoglobin with detection limits of 1.36 ng/mL, 1.00 ng/mL, and 2.38 ng/mL, respectively. Additionally, the paper-based immunoassay was rapid (∼5 min to complete the test) and portable (using a homemade chamber with a smartphone and an ultraviolet lamp). The developed devices integrated with ZnO NWs enable quantitative, sensitive, and simultaneous detection of multiple cardiac biomarkers in point-of-care settings, which provides a useful approach for monitoring AMI diseases and may be extended to other medical diagnostics and environmental assessments.

Paper-based fluorescent immunoassay for highly sensitive and selective detection of norfloxacin in milk at picogram level.

Norfloxacin (NOR) in milk may influence mammalian cell replication and bring about a decrease in the efficiency for treating infection in humans. However, current techniques for detecting NOR usually require expensive instruments and trained personnel. In this work, we have developed a low-cost and simple method via paper-based fluorescent immunoassay for highly sensitive and selective detection of NOR in milk at picogram level. The NOR monoclonal antibody labeled with quantum dots is used as a detection probe to recognize the corresponding NOR, which can quantitatively detect NOR on paper-based devices. The detection limits in aqueous solution and milk are 1 pg/mL and 10 pg/mL, respectively. The developed paper-based method provides a cheap, sensitive, eco-friendly, and rapid approach for quantitative detection of trace NOR in milk, which may find wide applications in food safety inspection. Noteworthy, the method is especially suitable for applications at resource-limited and on-site settings.

A comparative study of the five-repetition sit-to-stand test and the 30-second sit-to-stand test to assess exercise tolerance in COPD patients.

Purpose: The sit-to-stand test (STST) has been used to evaluate the exercise tolerance of patients with COPD. However, mutual comparisons to predict poor exercise tolerance have been hindered by the variety of STST modes used in previous studies, which also did not consider patients' subjective perceptions of different STST modes. Our aim was to compare the five-repetition sit-to-stand test (5STS) with the 30-second sit-to-stand test (30STS) for predicting poor performance in the six-minute walking test and to evaluate patients' subjective perceptions to determine the optimal mode for clinical practice. Patients and methods: Patients with stable COPD performed 5STS, 30STS and the 6MWT and then evaluated their feelings about the two STST modes by Borg dyspnea score and a questionnaire. Moreover, we collected data through the pulmonary function test, mMRC dyspnea score, COPD assessment test and quadriceps muscle strength (QMS). A receiver operating characteristic curve analysis of the 5STS and 30STS results was used to predict 6-minute walk distance (6MWD) <350 m. Results: The final analysis included 128 patients. Similar moderate correlations were observed between 6MWT and 5STS (r=-0.508, P<0.001) and between 6MWT and 30STS (r=0.528, P<0.001), and there were similar correlations between QMS and 5STS (r=-0.401, P<0.001) and between QMS and 30STS (r=0.398, P<0.001). The 5STS and 30STS score cutoffs produced sensitivity, specificity and positive and negative predictive values of 76.0%, 62.8%, 56.7% and 80.3% (5STS) and 62.0%, 75.0%, 62.0% and 75.0% (30STS), respectively, for predicting poor 6MWT performance. The 5STS exhibited obvious superiority in terms of the completion rate and the subjective feelings of the participants. Conclusion: As a primary screening test for predicting poor 6MWD, the 5STS is similar to the 30STS in terms of sensitivity and specificity, but the 5STS has a better patient experience.

ß-asarone induces cell apoptosis, inhibits cell proliferation and decreases migration and invasion of glioma cells.

Glioma is the most common primary brain tumor Despite the availability of adjuvant therapies, malignant glioma grows fast and metastasizes via cerebrospinal fluid after tumorectomy or cerebrospinal fluid shunt placement, and the prognosis for patients with glioma remains poor. Our previous study demonstrated that ß-asarone has anti-tumor effects on several kinds of cancer cells, especially for glioma cells. In this study, human glioma U251 cells and rat glioma C6 cells were treated with different concentrations of ß-asarone. Cultured them for 24 h, 48 h, 72 h and evaluated the IC50 with the results of Counting Kit-8 assay. Then, cell apoptosis and cell DNA cycles were evaluated with flow cytometry. Apoptosis related mRNA and protein were analyzed In addition, cell migration and invasion were also detected with wound healing and transwell assays, respectively. What is more, glioma specific proteins: GFAP, NRP-1 and NSE an enzyme-linked immunosorbent assay. The corresponding CCK-8 results showed that ß-asarone altered cell morphology and inhibited cell proliferation. ß-asarone can also induced cell apoptosis, decreased the expression of BCL-2 mRNA and blocked the DNA cycle at the G0/G1 phase for all the two cells. In addition, ß-asarone inhibited cell migration and invasion by reducing the expression of GFAP, NRP-1 and NSE. Co-administration with TMZ showed a more pronounced effect. In summary, ß-asarone induces cell death and inhibits cell migration and invasion in Glioma U251 and C6 cells.

Development of a biomimetic enzyme-linked immunosorbent assay based on molecularly imprinted polymers on paper for the detection of carbaryl.

A biomimetic enzyme-linked immunosorbent assay (BELISA) which was based on molecularly imprinted polymers on paper (MIPs-paper) with specific recognition was developed. As a detector, the surface of paper was modified with γ-MAPS by hydrolytic action and anchored the MIP layer on γ-MAPS modified-paper by copolymerization to construct the artificial antibody Through a series of experimentation and verification, we successful got the MIPs-paper and established BELISA for the detection of carbaryl. The development of MIPs-paper based on BELISA was applied to detect carbaryl in real samples and validated by an enzyme-linked immunosorbent assay (ELISA) based on anti-carbaryl biological antibody. The results of these two methods (BELISA and ELISA) were well correlated (R2=0.944). The established method of MIPs-paper BELISA exhibits the advantages of low cost, higher stability and being re-generable, which can be applied as a convenient tool for the fast and efficient detection of carbaryl.

Development of Quantum Dots-Labeled Antibody Fluorescence Immunoassays for the Detection of Morphine.

Quantum dots (QDs)-labeled antibody fluorescence immunoassays (FLISA) for the detection of morphine were developed. Quantum dots (CdSe/ZnS), which contained carboxyl, were used to label antimorphine antibody by 1-ethyl-3-(3-dimethylaminoprophyl) carbodiimide hydrochloride/N-hydroxysulfosuccinimide, which were used as coupling reagents. The CdSe/ZnS QDs labeled antimorphine antibody (QDs labeled Ab) was characterized by fluorescence spectrum and gel electrophoresis. Plate-based FLISA and nitrocellulose membrane-based flow-through FLISA were developed and applied to quantitative and qualitative detection of morphine. Under the optimal conditions for plate-based FLISA, the linear range spanned from 3.2 × 10-4 to 1 mg/L (R2 = 0.9905), and the detection limit was 2.7 × 10-4 mg/L. The visual detection limit for morphine by membrane-based flow-through FLISA was 0.01 mg/L. These results demonstrated that the developed fluorescence immunoassays could be applied as highly sensitive and convenient tools for rapid detection of morphine, which make it ideally suited for on-site screening of poppy shell added illegally in hot pot soup base.

A microbial fuel cell as power supply for implantable medical devices.

This study seeks a new way to provide lasting and secure power for implantable medical devices (IMDs) using a microbial fuel cell (MFC) which was proposed to be placed in human large intestine and could utilize intestinal contents and microorganisms to generate electricity. Based on the anatomic structure and inner environmental conditions of large intestine, transverse colon was chosen to be the appropriate location for the implantation of MFC. The performance of the MFC which simulated the environmental features of transverse colon by controlling dissolved oxygen (DO) and pH and was inoculated with simulated intestinal fluid (SIF) was investigated. Stable power generation of MFC was obtained after two months operation with open circuit voltage (OCV) of 552.2 mV, maximum power density of 73.3 mW/m(2), and average voltage output of 308 mV (with external resistance of 500 Omega). Moreover, the changes of environmental conditions in the chambers of MFC did not have a significant impact on human body based on the analysis of pH and DO values. Further studies on internal resistance and power density showed that the MFC could generate power of 7-10 mW according to the size of intestinal surface area, which was enough for IMDs. These results suggested that MFCs located in large intestine could be a promising power source for IMDs.