Programmable Singlet Oxygen Battery for Automated Photodynamic Therapy Enabled by Pyridone-Pyridine Tautomer Engineering.

The efficacy of photodynamic therapy is hindered by the hypoxic environment in tumors and limited light penetration depth. The singlet oxygen battery (SOB) has emerged as a promising solution, enabling oxygen- and light-independent 1O2 release. However, conventional SOB systems typically exhibit an "always-ON" 1O2 release, leading to potential 1O2 leakage before and after treatment. This not only compromises therapeutic outcomes but also raises substantial biosafety concerns. In this work, we introduce a programmable singlet oxygen battery, engineered to address all the issues discussed above. The concept is illustrated through the development of a tumor-microenvironment-responsive pyridone-pyridine switch, PyAce, which exists in two tautomeric forms: PyAce-0 (pyridine) and PyAce (pyridone) with different 1O2 storage half-lives. In its native state, PyAce remains in the pyridone form, capable of storing 1O2 (t1/2 = 18.5 h). Upon reaching the tumor microenvironment, PyAce is switched to the pyridine form, facilitating rapid and thorough 1O2 release (t1/2 = 16 min), followed by quenched 1O2 release post-therapy. This mechanism ensures suppressed 1O2 production pre- and post-therapy with selective and rapid 1O2 release at the tumor site, maximizing therapeutic efficacy while minimizing side effects. The achieved "OFF-ON-OFF" 1O2 therapy showed high spatiotemporal selectivity and was independent of the oxygen supply and light illumination.

Disease-modifying potential of diphenyl diselenide in an experimental osteoarthritis model.

Oxidative stress is a key factor in the disruption of cartilage homeostasis during the development of osteoarthritis (OA). Organic selenium (Se)-containing compounds such as diselenides have excellent antioxidant activity and may prevent related diseases. We aimed to examine the benefits of the synthetic small molecule diphenyl diselenide (DPDSe) in OA models in vitro and in vivo. Our findings showed that DPDSe could maintain extracellular matrix (ECM) homeostasis and inhibit reactive oxygen species (ROS) production in IL-1ß-treated chondrocytes. In a destabilization of the medial meniscus (DMM)-induced OA mouse model, intra-articular administration of DPDSe alleviated joint degeneration, as evidenced by a decrease in the OARSI score and the restoration of collagen II (COL2) and MMP-13 expression in cartilage tissues. We confirmed that DDS activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in IL-1ß-treated chondrocytes, and its chondroprotective effects were significantly counteracted when Nrf2 signaling was blocked by the inhibitor ML385 or by siRNA-mediated Nrf2 knockdown. The relatively strong performance of DPDSe makes it an ideal candidate for further trials as a disease-modifying OA drug (DMOAD).

Rational design of a polypropylene composite foam with open-cell structure via graphite conductive network for sound absorption.

An exciting result is reported in this study where a polypropylene (PP) foam with a high open-cell content was achieved by constructing a thermally conductive network for the first time. PP and nano-graphite particles were used as substrate and filler, respectively, to prepare the PP-graphite (PP-G) composite foam by twin-screw blending, hot pressing, and supercritical CO2 foaming. The nano-graphite particles can effectively adjust the microstructure of the PP-G foam and achieve a high porosity. When the amount of nano-graphite is 10.0 wt%, the PP-G foam exhibits optimal sound absorption performance, compression resistance, heat insulation, and hydrophobic properties. In the human-sensitive frequency range of 1000-6000 Hz, the corresponding average SAC is above 0.9, and the internal tortuosity is 5.27. After 50 cycles of compression, the compressive stress is 980 kPa and the SAC loss is only 7.8%. This study also innovatively proposed a new strategy to achieve the simple and rapid preparation of open-cell PP foams by increasing the thermal conductivity of the foaming substrate.

Associations of dietary inflammatory index with low estimated glomerular filtration rate, albuminuria and chronic kidney disease in U.S adults: Results from the NHANES 2011-2018.

BACKGROUND AND AIMS: Chronic Kidney Disease (CKD) is characterized by a high inflammation status with ever-increasing prevalence, and defined as low estimated glomerular filtration rate (eGFR) or albuminuria. Both low eGFR and albuminuria can have independent effects on the body. The dietary inflammatory index (DII) is a validated tool used to assess the inflammatory potential of the diet. We aim to explore not only the association between DII and CKD, but also the associations of DII with low eGFR and albuminuria, respectively. In addition, their associations in different subgroups remain to be explored. METHODS AND RESULTS: 18,070 participants from the 2011-2018 NHANES with complete data of dietary intake and laboratory data were involved in our study. The data of 24-hour dietary recall interview was used to calculate DII, CKD could be reflected by laboratory data of creatinine and albumin. Then weighted multivariate logistic regression models and subgroup analyses were performed. The prevalence of low eGFR, albuminuria and CKD were 6.8%, 9.8% and 14.5%, respectively. A positive association between DII and low eGFR was observed (OR=1.12, 95%CI: 1.05-1.21), Q2, Q3 and Q4 are positively associated with a significant 39%, 65% and 71% increased risk of low eGFR compared with Q1 (P for trend<0.05). DII was also associated with CKD (OR=1.06, 95%CI: 1.01-1.11). CONCLUSION: Significant positive associations of DII with CKD and low eGFR were observed. But we didn't find such association between DII and albuminuria.

Analysis of differentially expressed genes in torn rotator cuff tendon tissues in diabetic patients through RNA-sequencing.

BACKGROUND: Rotator cuff tears (RCT) is a common musculoskeletal disorder in the shoulder which cause pain and functional disability. Diabetes mellitus (DM) is characterized by impaired ability of producing or responding to insulin and has been reported to act as a risk factor of the progression of rotator cuff tendinopathy and tear. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles involved in RCT of diabetic patients. METHODS: RNA-Sequencing (RNA-Seq) was used in this study to profile differentially expressed lncRNAs and mRNAs in RCT samples between 3 diabetic and 3 nondiabetic patients. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to annotate the function of the differentially expressed genes (DEGs). LncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network were constructed to elucidate the potential molecular mechanisms of DM affecting RCT. RESULTS: In total, 505 lncRNAs and 388 mRNAs were detected to be differentially expressed in RCT samples between diabetic and nondiabetic patients. GO functional analysis indicated that related lncRNAs and mRNAs were involved in metabolic process, immune system process and others. KEGG pathway analysis indicated that related mRNAs were involved in ferroptosis, PI3K-Akt signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway and others. LncRNA-mRNA co-expression network was constructed, and ceRNA network showed the interaction of differentially expressed RNAs, comprising 5 lncRNAs, 2 mRNAs, and 142 miRNAs. TF regulation analysis revealed that STAT affected the progression of RCT by regulating the apoptosis pathway in diabetic patients. CONCLUSIONS: We preliminarily dissected the differential expression profile of lncRNAs and mRNAs in torn rotator cuff tendon between diabetic and nondiabetic patients. And the bioinformatic analysis suggested some important RNAs and signaling pathways regarding inflammation and apoptosis were involved in diabetic RCT. Our findings offer a new perspective on the association between DM and progression of RCT.

Supramolecular Genome Editing: Targeted Delivery and Endogenous Activation of CRISPR/Cas9 by Dynamic Host-Guest Recognition.

We synthesize supramolecular poly(disulfide) (CPS) containing covalently attached cucurbit[7]uril (CB[7]), which is exploited not only as a carrier to deliver plasmid DNA encoding destabilized Cas9 (dsCas9), but also as a host to include trimethoprim (TMP) by CB[7] moieties through the supramolecular complexation to form TMP@CPS/dsCas9. Once the plasmid is transfected into tumor cells by CPS, the presence of polyamines can competitively trigger the decomplexation of TMP@CPS, thereby displacing and releasing TMP from CB[7] to stabilize dsCas9 that can target and edit the genomic locus of PLK1 to inhibit the growth of tumor cells. Following the systemic administration of TMP@CPS/dsCas9 decorated with hyaluronic acid (HA), tumor-specific editing of PLK1 is detected due to the elevated polyamines in tumor microenvironment, greatly minimizing off-target editing in healthy tissues and non-targeted organs. As the metabolism of polyamines is dysregulated in a wide range of disorders, this study offers a supramolecular approach to precisely control CRISPR/Cas9 functions under particular pathological contexts.

Off-the-Shelf Prostate Stem Cell Antigen-Directed Chimeric Antigen Receptor Natural Killer Cell Therapy to Treat Pancreatic Cancer.

BACKGROUND & AIMS: Pancreatic cancer (PC) is the third leading cause of cancer-related death with a 5-year survival rate of approximately 10%. It typically presents as a late-stage incurable cancer and chemotherapy provides modest benefit. Here, we demonstrate the feasibility, safety, and potency of a novel human natural killer (NK) cell-based immunotherapy to treat PC. METHODS: The expression of prostate stem cell antigen (PSCA) was evaluated in primary PC at messenger RNA and protein levels. The processes of retroviral transduction, expansion, activation, and cryopreservation of primary human NK cells obtained from umbilical cord blood were optimized, allowing us to develop frozen, off-the-shelf, allogeneic PSCA chimeric antigen receptor (CAR) NK cells. The safety and efficacy of PSCA CAR NK cells also expressing soluble (s) interleukin 15 (PSCA CAR_s15 NK cells) were evaluated in vitro and in vivo. RESULTS: PSCA was elevated in primary human PC compared with the adjacent or other normal tissues. PSCA CAR_s15 NK cells displayed significant tumor-suppressive effects against PSCA(+) PC in vitro before and after 1 cycle of freeze-thaw. The viability of frozen PSCA CAR_s15 NK cells persisted more than 90 days in vivo after their last infusion and significantly prolonged the survival of mice engrafted with human PC. CONCLUSIONS: PSCA CAR_s15 NK cells showed therapeutic efficacy in human metastatic PC models without signs of systematic toxicity, providing a strong rationale to support clinical development.

A Self-Assembly Nano-Prodrug for Combination Therapy in Triple-Negative Breast Cancer Stem Cells.

Triple-negative breast cancer (TNBC) displays a highly aggressive nature that originates from a small subpopulation of TNBC stem cells (TNBCSCs), and these TNBCSCs give rise to chemoresistance, tumor metastasis, and recurrence. Unfortunately, traditional chemotherapy eradicates normal TNBC cells but fails to kill quiescent TNBCSCs. To explore a new strategy for eradicating TNBCSCs, a disulfide-mediated self-assembly nano-prodrug that can achieve the co-delivery of ferroptosis drug, differentiation-inducing agent, and chemotherapeutics for simultaneous TNBCSCs and TNBC treatment, is reported. In this nano-prodrug, the disulfide bond not only induces self-assembly behavior of different small molecular drug but also serves as a glutathione (GSH)-responsive trigger in controlled drug release. More importantly, the differentiation-inducing agent can transform TNBCSCs into normal TNBC cells, and this differentiation with chemotherapeutics provides an effective approach to indirectly eradicate TNBCSCs. In addition, ferroptosis therapy is essentially different from the apoptosis-induced cell death of differentiation or chemotherapeutic, which causes cell death to both TNBCSCs and normal TNBC cells. In different TNBC mouse models, this nano-prodrug significantly improves anti-tumor efficacy and effectively inhibits the tumor metastasis. This all-in-one strategy enables controlled drug release and reduces stemness-related drug resistance, enhancing the chemotherapeutic sensitivity in TNBC treatment.

RNA Hydrolysis at Mineral-Water Interfaces.

As an essential biomolecule for life, RNA is ubiquitous across environmental systems where it plays a central role in biogeochemical processes and emerging technologies. The persistence of RNA in soils and sediments is thought to be limited by enzymatic or microbial degradation, which occurs on timescales that are orders of magnitude faster than known abiotic pathways. Herein, we unveil a previously unreported abiotic pathway by which RNA rapidly hydrolyzes on the timescale of hours upon adsorption to iron (oxyhydr)oxide minerals such as goethite (α-FeOOH). The hydrolysis products were consistent with iron present in the minerals acting as a Lewis acid to accelerate sequence-independent hydrolysis of phosphodiester bonds comprising the RNA backbone. In contrast to acid- or base-catalyzed RNA hydrolysis in solution, mineral-catalyzed hydrolysis was fastest at circumneutral pH, which allowed for both sufficient RNA adsorption and hydroxide concentration. In addition to goethite, we observed that RNA hydrolysis was also catalyzed by hematite (α-Fe2O3) but not by aluminum-containing minerals (e.g., montmorillonite). Given the extensive adsorption of nucleic acids to environmental surfaces, we anticipate previously overlooked mineral-catalyzed hydrolysis of RNA may be prevalent particularly in iron-rich soils and sediments, which must be considered across biogeochemical applications of nucleic acid analysis in environmental systems.

Concurrent chemoradiotherapy versus radiotherapy alone for stage II nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy.

BACKGROUND: Concurrent chemoradiotherapy has long been a standardized therapy for localized advanced nasopharyngeal cancer. It is widely used in clinical applications. In contrast, NCCN guidelines highlight that the efficacy of concurrent chemoradiotherapy for stage II nasopharyngeal cancer in the new era of intensity-modulated radiotherapy has not been defined. Thus, we systematically reviewed the significance of concurrent chemoradiotherapy for stage II nasopharyngeal cancer. METHODS: We searched the relevant literature in PubMed, EMBASE, and Cochrane, extracting relevant data from the searched literature. The main items extracted were hazard ratios (HRs), risk ratios (RRs) and 95% confidence intervals (CIs). When the HR could not be extracted from the literature, we used Engauge Digitizer software for extraction. Data analysis was accomplished using the Review Manager 5.4 tool. RESULTS: Our study included seven articles involving 1633 cases of stage II nasopharyngeal cancer. The survival outcomes were overall survival (OS) (HR = 1.03, 95% CI (0.71-1.49), P = 0.87), progression-free survival (PFS) (HR = 0.91, 95% CI (0.59-1.39), P = 0.66), distant metastasis-free survival (DMFS) (HR = 1.05, 95% CI (0.57-1.93), P = 0.87), local recurrence-free survival (LRFS) (HR = 0.87, 95% CI (0.41-1.84), P = 0.71, P > 0.05), and locoregional failure-free survival (LFFS) (HR = 1.18, 95% CI (0.52-2.70), P = 0.69). CONCLUSIONS: In the era of intensity-modulated radiotherapy, concurrent chemoradiotherapy and radiotherapy alone have the same survival benefits, and concurrent chemoradiotherapy increases acute hematological toxicity. Subgroup analysis showed that for people with N1 nasopharyngeal cancer at risk of distant metastases, concurrent chemoradiotherapy and radiotherapy alone also had equal survival benefits.

Speckle Reduction in Ultrasound Images of the Common Carotid Artery Based on Integer and Fractional-Order Total Variation.

Designing a technique with higher speckle noise suppressing capability, better edge preserving performance, and lower time complexity is a research objective for the common carotid artery (CCA) ultrasound despeckling. Total variation based techniques have been widely used in the image denoising and have good performance in preserving the edges in the images. However, the total variation based filters can produce the staircase artifacts. To address this issue, second-order total variation based techniques have been proposed for the image denoising. However, the previous study has been proved that the fractional differential model has better performance in reducing the speckles in ultrasound despeckling compared with the second-order model. Thus, to improve the performance of ultrasound despeckling and edge preserving, a novel despeckling model based on integer and fractional-order total variation (IFOTV) is proposed for CCA ultrasound images. Moreover, the minimization problems in our despeckling model are solved by the alternating direction method of multiplier (ADMM). In results with synthetic images, the edge preservation index (EPI) values of proposed method are 0.9524, 0.8797, and 0.7351 as well as 0.9137, 0.8253, and 0.6847 under three different levels of noise, which are the highest among four advanced methods. In results with simulated CCA ultrasound images, the speckle suppression and mean preservation indices of proposed method are 0.5596, 0.6571, and 0.8106 under three different levels of noise, which are the best among four advanced methods. In results with clinical images, the average absolute error of intima-media thickness measurements of proposed method is 0.0660 ± 0.0679 (mean ± std in mm), which is the lowest among four advanced methods. In conclusion, the IFOTV method has improved performance in suppressing the speckle noise and preserving the edge, and is thus a potential alternative to the current filters for the CCA ultrasound despeckling.

An Improved Parameter Estimator of the Homodyned K Distribution Based on the Maximum Likelihood Method for Ultrasound Tissue Characterization.

The homodyned K distribution (HK) can generally describe the ultrasound backscatter envelope statistics distribution with parameters that have specific physical meaning. However, creating robust and reliable HK parameter estimates remains a crucial concern. The maximum likelihood estimator (MLE) usually yields a small variance and bias in parameter estimation. Thus, two recent studies have attempted to use MLE for parameter estimation of HK distribution. However, some of the statements in these studies are not fully justified and they may hinder the application of parameter estimation of HK distribution based on MLE. In this study, we propose a new parameter estimator for the HK distribution based on the MLE (i.e., MLE1), which overcomes the disadvantages of conventional MLE of HK distribution. The MLE1 was compared with other estimators, such as XU estimator (an estimation method based on the first moment of the intensity and tow log-moments) and ANN estimator (an estimation method based on artificial neural networks). We showed that the estimations of parameters α and k are the best overall (in terms of the relative bias, normalized standard deviation, and relative root mean squared errors) using the proposed MLE1 compared with the others based on the simulated data when the sample size was N = 1000. Moreover, we assessed the usefulness of the proposed MLE1 when the number of scatterers per resolution cell was high (i.e., α up to 80) and when the sample size was small (i.e., N = 100), and we found a satisfactory result. Tests on simulated ultrasound images based on Field II were performed and the results confirmed that the proposed MLE1 is feasible and reliable for the parameter estimation from the ultrasonic envelope signal. Therefore, the proposed MLE1 can accurately estimate the HK parameters with lower uncertainty, which presents a potential practical value for further ultrasonic applications.

[Design and implementation for portable ultrasound-aided breast cancer screening system].

Early screening is an important means to reduce breast cancer mortality. In order to solve the problem of low breast cancer screening rates caused by limited medical resources in remote and impoverished areas, this paper designs a breast cancer screening system aided with portable ultrasound Clarius. The system automatically segments the tumor area of the B-ultrasound image on the mobile terminal and uses the ultrasound radio frequency data on the cloud server to automatically classify the benign and malignant tumors. Experimental results in this study show that the accuracy of breast tumor segmentation reaches 98%, and the accuracy of benign and malignant classification reaches 82%, and the system is accurate and reliable. The system is easy to set up and operate, which is convenient for patients in remote and poor areas to carry out early breast cancer screening. It is beneficial to objectively diagnose disease, and it is the first time for the domestic breast cancer auxiliary screening system on the mobile terminal.

Copper-Catalyzed Cyclization/Dimerization of Tryptamines with O2/Air as the Sole Oxidant: Direct Access to Complex Bispyrrolidino[2,3-b]indoline.

The first transition metal catalytic one-step synthesis of the 3a, 3a'-bispyrrolidino [2,3-b] indoline scaffold via tandem cyclization/dimerization of tryptamines has been realized with the environmentally friendly O2/air as the sole oxidant. Different from the traditional direct oxidation of indole "N-H" group by excess amount of metal salts, a copper-catalyzed oxidative cyclization reaction is developed for the formation of the radical pyrrolidinoindoline intermediate in the current strategy. The robustness and practicality of this methodology is demonstrated by the step-economic, divergent total synthesis of natural products (±)-folicanthine and meso-folicanthine.

A review of statistical methods for dietary pattern analysis.

BACKGROUND: Dietary pattern analysis is a promising approach to understanding the complex relationship between diet and health. While many statistical methods exist, the literature predominantly focuses on classical methods such as dietary quality scores, principal component analysis, factor analysis, clustering analysis, and reduced rank regression. There are some emerging methods that have rarely or never been reviewed or discussed adequately. METHODS: This paper presents a landscape review of the existing statistical methods used to derive dietary patterns, especially the finite mixture model, treelet transform, data mining, least absolute shrinkage and selection operator and compositional data analysis, in terms of their underlying concepts, advantages and disadvantages, and available software and packages for implementation. RESULTS: While all statistical methods for dietary pattern analysis have unique features and serve distinct purposes, emerging methods warrant more attention. However, future research is needed to evaluate these emerging methods' performance in terms of reproducibility, validity, and ability to predict different outcomes. CONCLUSION: Selection of the most appropriate method mainly depends on the research questions. As an evolving subject, there is always scope for deriving dietary patterns through new analytic methodologies.

Facet Engineered α-MnO2 for Efficient Catalytic Ozonation of Odor CH3SH: Oxygen Vacancy-Induced Active Centers and Catalytic Mechanism.

The oxygen vacancy in MnO2 is normally proved as the reactive site for the catalytic ozonation, and acquiring a highly reactive crystal facet with abundant oxygen vacancy by facet engineering is advisable for boosting the catalytic activity. In this study, three facet-engineered α-MnO2 was prepared and successfully utilized for catalytic ozonation toward an odorous CH3SH. The as-synthesized 310-MnO2 exhibited superior activity in catalytic ozonation of CH3SH than that of 110-MnO2 and 100-MnO2, which could achieve 100% removal efficiency for 70 ppm of CH3SH within 20 min. The results of XPS, Raman, H2-TPR, and DFT calculation all prove that the (310) facets possess a higher surface energy than other facets can feature the construction of oxygen vacancies, thus facilitating the adsorption and activate O3 into intermediate peroxide species (O2-/O22-) and reactive oxygen species (•O2-/1O2) for eliminating adjacent CH3SH. In situ diffuse reflectance infrared Fourier transform spectroscopy (in situ DRIFTS) revealed that the CH3SH molecular was chemisorbed on S atom to form CH3S-, which was further converted into intermediate CH3SO3- and finally oxidized into SO42- and CO32-/CO2 during the process. Attributed to the deep oxidation of CH3SH on 310-MnO2 via efficient cycling of active oxygen vacancies, the lifetime of 310-MnO2 can be extended to 2.5 h with limited loss of activity, while 110-MnO2 and 100-MnO2 were inactivated within 1 h. This study deepens the comprehension of facet-engineering in MnO2 and presents an efficient and portable catalyst to control odorous pollution.

[Detection of carotid intima and media thicknesses based on ultrasound B-mode images clustered with Gaussian mixture model].

In clinic, intima and media thickness are the main indicators for evaluating the development of atherosclerosis. At present, these indicators are measured by professional doctors manually marking the boundaries of the inner and media on B-mode images, which is complicated, time-consuming and affected by many artificial factors. A grayscale threshold method based on Gaussian Mixture Model (GMM) clustering is therefore proposed to detect the intima and media thickness in carotid arteries from B-mode images in this paper. Firstly, the B-mode images are clustered based on the GMM, and the boundary between the intima and media of the vessel wall is then detected by the gray threshold method, and finally the thickness of the two is measured. Compared with the measurement technique using the gray threshold method directly, the clustering of B-mode images of carotid artery solves the problem of gray boundary blurring of inner and middle membrane, thereby improving the stability and detection accuracy of the gray threshold method. In the clinical trials of 120 healthy carotid arteries, means of 4 manual measurements obtained by two experts are used as reference values. Experimental results show that the normalized root mean square errors (NRMSEs) of the estimated intima and media thickness after GMM clustering were 0.104 7 ± 0.076 2 and 0.097 4 ± 0.068 3, respectively. Compared with the results of the direct gray threshold estimation, means of NRMSEs are reduced by 19.6% and 22.4%, respectively, which indicates that the proposed method has higher measurement accuracy. The standard deviations are reduced by 17.0% and 21.7%, respectively, which indicates that the proposed method has better stability. In summary, this method is helpful for early diagnosis and monitoring of vascular diseases, such as atherosclerosis.

Microbiota in the apical root canal system of tooth with apical periodontitis.

BACKGROUND: Apical periodontitis (AP) is essentially an inflammatory disease of microbial etiology primarily caused by infection of the pulp and root canal system. Variation of the bacterial communities caused by AP, as well as their changes responding to dental therapy, are of utmost importance to understand the pathogensis of the apical periodontitis and establishing effective antimicrobial therapeutic strategies. This study aims to uncover the composition and diversity of microbiota associated to the root apex to identify the relevant bacteria highly involved in AP, with the consideration of root apex samples from the infected teeth (with/without root canal treatment), healthy teeth as well as the healthy oral. METHODS: Four groups of specimens are considered, the apical part of root from diseased teeth with and without root canal treatment, and wisdom teeth extracted to avoid being impacted (tooth healthy control), as well as an additional healthy oral control from biofilm of the buccal mucosa. DNA was extracted from these specimens and the microbiome was examined through focusing on the V3-V4 hypervariable region of the 16S rRNA gene using sequencing on Illumina MiSeq platform. Composition and diversity of the bacterial community were tested for individual samples, and between-group comparisons were done through differential analysis to identify the significant changes. RESULTS: We observed reduced community richness and diversity in microbiota samples from diseased teeth compared to healthy controls. Through differential analysis between AP teeth and healthy teeth, we identified 49 OTUs significantly down-regulated as well as 40 up-regulated OTUs for AP. CONCLUSION: This study provides a global view of the microbial community of the AP associated cohorts, and revealed that AP involved not only bacteria accumulated with a high abundance, but also those significantly reduced ones due to microbial infection.

Michael Addition Reaction Catalyzed by Imidazolium Chloride to Protect Amino Groups and Construct Medium Ring Heterocycles.

An effective approach for amino protection and construction of a seven-membered ring has been developed. The method uses imidazolium chloride to carry out the Michael addition reaction at low temperatures and perform amino deprotection or construction of a seven-membered ring at high temperatures.

Halogen-Metal Exchange on Bromoheterocyclics with Substituents Containing an Acidic Proton via Formation of a Magnesium Intermediate.

A selective and practical bromine-metal exchange on bromoheterocyclics bearing substituents with an acidic proton under non-cryogenic conditions was developed by a simple modification of an existing protocol. Our protocol of using a combination of i-PrMgCl and n-BuLi has not only solved the problem of intermolecular quenching that often occurred when using alkyl lithium alone as the reagent for halogen-lithium exchange, but also offered a highly selective method for performing bromo-metal exchange on dibrominated arene compounds through chelation effect.