The human gut microbiota is a functioning endocrine organ and stands at the intersection between dietary components and health or disease. There are very many microbial metabolites with numerous ...structures and functions arising from the gut microbial fermentation of foods and become signals for biological communication in the human body. These small molecules can be absorbed and delivered to distant organs through the circulatory system to build the gut–systemic axis. The gut microbial metabolomes are thus believed to play important roles in regulating cardiometabolic health and provide opportunities in mechanistic research and new drug discovery. Measurement of these novel microbial metabolites in clinical samples may serve as a tool for investigating disease biomarkers. In the past decade, the development of untargeted and targeted metabolomics approaches using NMR, LC/MS, and GC/MS has contributed to the exploration of gut microbial metabolomes in cardiometabolic health and disease. Some important targets are currently being translated into clinical applications. In this review article, we introduce an oral carnitine challenge test developed as an example to demonstrate the potential applications in personalized nutrition based on the function of gut microbiota. It is a method taking the gut microbiota as a bioreactor and provides fermentable materials as inputs and measures the outputs of targeted microbial byproducts in the blood or urine. This challenge test may be extended to measure metabolites from microbial fermentation related to other endocrinological or inflammatory diseases. We review current gut metabolome research approaches and propose a gut microbial functional measurement using a challenge test. We suggest that the maturation in measuring gut microbial metabolites may provide an important piece to complete the puzzle of precision medicine.
Spontaneous intracranial hypotension (SIH) typically presents as an acute orthostatic headache during an upright position, secondary to spinal cerebrospinal fluid leaks. New evidence indicates that a ...lumbar puncture may not be essential for diagnosing every patient with SIH. Spinal neuroimaging protocols used for diagnosing and localizing spinal cerebrospinal fluid leaks include brain/spinal MRI, computed tomography myelography, digital subtraction myelography, and radionuclide cisternography. Complications of SIH include subdural hematoma, cerebral venous thrombosis, and superficial siderosis. Treatment options encompass conservative management, epidural blood patches, and surgical interventions. The early application of epidural blood patches in all patients with SIH is suggested.
Pharmaceutical crystallization has an impact on the properties of active pharmaceutical ingredients as it determines the purity, crystal size distribution and polymorphs, among other attributes. ...Focused beam reflectance measurement (FBRM) is a common process analytical technology (PAT) tool used for monitoring, predicting, and control of crystal size and size distribution (CSD) characteristics during crystallization processes. Models for the prediction of crystal size distribution from FBRM statistics (
i.e.
chord length distribution, CLD) have been widely developed in academia and pharmaceutical industries but limited work has been done on the verification and validation of CLD to CSD models. This work demonstrates the development and validation of two CLD-CSD models, theoretical and empirical, for a model compound. The experiments were based on the cooling crystallization of carbamazepine (CBZ). Also, the precision and robustness of the FBRM statistics, square weighted mean chord length (SWMCL) and total counts, were evaluated. Agitation speed and solid concentration had an impact on the FBRM statistics. The theoretical geometric model evaluated in this study showed high error for the prediction of the CSD and it is not going to be implemented in on-going research efforts in continuous crystallization of CBZ. The data driven model can be implemented as a qualitative monitoring tool in continuous operation. The accuracy and robustness of the data driven model proposed need to be improved to be considered for quantitative monitoring of the CSD.
Pharmaceutical crystallization affects the properties of APIs as it determines the purity and crystal size distribution, among other attributes. This work presents two CLD-CSD models, theoretical and empirical, for a model compound.
The molybdenum‐catalyzed asymmetric ring‐closing metathesis of the various Cs‐symmetric (π‐arene)chromium substrates provides the corresponding bridged planar‐chiral (π‐arene)chromium complexes in ...excellent yields with up to >99 % ee. With a bulky and unsymmetrical substituent, such as N‐indolyl or 1‐naphthyl, at the 2‐positions of the η6‐1,3‐diisopropenylbenzene ligands, both biaryl‐based axial chirality and π‐arene‐based planar chirality are simultaneously induced in the products. The axial chirality is retained even after the removal of the dicarbonylchromium fragment, and the chiral biaryl/heterobiaryl compounds are obtained with complete retention of the enantiopurity.
Enantiomerically enriched planar‐chiral (π‐arene)chromium complexes were prepared by Mo‐catalyzed asymmetric ring‐closing metathesis (RCM) desymmetrization of Cs‐symmetric substrates. The axial chirality of indolyl‐ or naphthyl‐containing substrates was retained after removal of the Cr(CO)2 fragment, and biaryl/heterobiaryl compounds were obtained in high enantiopurity.
Dendrobium officinale Kimura et Migo (D. officinale) is used as herbal medicine and new food resource in China, which is nontoxic and harmless, and can be used as common food. Polysaccharide as one ...of the main bioactive components in D. officinale, mainly composed of glucose and mannose (Manp: Glcp = 2.01:1.00-8.82:1.00), along with galactose, xylose, arabinose, and rhamnose in different molar ratios and types of glycosidic bonds. Polysaccharides of D. officinale exhibit a variety of biological effects, including immunomodulatory, anti-tumor, gastro-protective, hypoglycemic, anti-inflammatory, hepatoprotective, and vasodilating effects. This paper presents the extraction, purification, structural characteristics, bioactivities, structure-activity relationships and analyzes gaps in the current research on D. officinale polysaccharides. In addition, based on in vitro and in vivo experiments, the possible mechanisms of bioactivities of D. officinale polysaccharides were summarized. We hope that this work may provide helpful references and promising directions for further study and development of D. officinale polysaccharides.
•D. officinale polysaccharides are purified by anion exchange and gel permeation chromatography.•D. officinale polysaccharides possess diverse structures and configurations.•D. officinale polysaccharides exhibit diverse biological activities.•Structure-activity relationship of D. officinale polysaccharides should be addressed in future studies.
Fine calculation of bridge temperature fields is significant for accurately evaluating thermal actions in bridge structures. Determining thermal loads on bridge surfaces caused by solar radiation is ...the most challenging part of the numerical thermal analysis because the sunlit and shaded areas on bridge surfaces change continuously with the sun’s rotation. Existing methods have low accuracy in determining thermal loads and cannot be applied to complex bridges. This study presents a new method for calculating temperature fields based on the advantages of building information modeling (BIM) technology in solar radiation analysis (SRA) and information sharing. This method starts with obtaining an accurate hourly insolation distribution on bridge surfaces through SRA implemented in a BIM system. Then, a Python script seamlessly maps the insolation information to finite element surfaces as thermal loads. This paper details the new method’s implementation steps and technical details, and a practical application on a concrete box girder demonstrates its applicability and effectiveness. Compared with previous methods, the proposed method has significant advantages, such as a more accurate calculation for solar radiation, a lower technical threshold, a higher degree of automation, less computational time, and easier finite element modeling.
Two kinds of hybrid two-step multi-soil-layering (MSL) systems loaded with different filter medias (zeolite-ceramsite MSL-1 and ceramsite-red clay MSL-2) were set-up for the low-(C/N)-ratio polluted ...river water treatment. A long-term pollutant removal performance of these two kinds of MSL systems was evaluated for 214 days. By-pass was employed in MSL systems to evaluate its effect on nitrogen removal enhancement. Zeolite-ceramsite single-pass MSL-1 system owns outstanding ammonia removal capability (24 g NH4+-Nm−2d−1), 3 times higher than MSL-2 without zeolite under low aeration rate condition (0.8 × 104 L m−2.h−1). Aeration rate up to 1.6 × 104 L m−2.h−1 well satisfied the requirement of complete nitrification in first unit of both two MSLs. However, weak denitrification in second unit was commonly observed. By-pass of 50% influent into second unit can improve about 20% TN removal rate for both MSL-1 and MSL-2. Complete nitrification and denitrification was achieved in by-pass MSL systems after addition of carbon source with the resulting C/N ratio up to 2.5. The characters of biofilms distributed in different sections inside MSL-1 system well illustrated the nitrogen removal mechanism inside MSL systems. Two kinds of MSLs are both promising as an appealing nitrifying biofilm reactor. Recirculation can be considered further for by-pass MSL-2 system to ensure a complete ammonia removal.
•Zeolite loaded MSL system owns outstanding nitrogen removal capability.•By-pass is a promising approach to improve the TN removal efficiency of MSL systems.•Complete nitrification and denitrification was observed in by-pass MSL systems with the influent C/N ratio at 2.5.
T-cells are crucial in maintanence of intestinal homeostasis, however, it is still unclear how microbiota metabolites regulate T-effector cells. Here we show gut microbiota-derived short-chain fatty ...acids (SCFAs) promote microbiota antigen-specific Th1 cell IL-10 production, mediated by G-protein coupled receptors 43 (GPR43). Microbiota antigen-specific Gpr43
CBir1 transgenic (Tg) Th1 cells, specific for microbiota antigen CBir1 flagellin, induce more severe colitis compared with wide type (WT) CBir1 Tg Th1 cells in Rag
recipient mice. Treatment with SCFAs limits colitis induction by promoting IL-10 production, and administration of anti-IL-10R antibody promotes colitis development. Mechanistically, SCFAs activate Th1 cell STAT3 and mTOR, and consequently upregulate transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1), which mediates SCFA-induction of IL-10. SCFA-treated Blimp1
Th1 cells produce less IL-10 and induce more severe colitis compared to SCFA-treated WT Th1 cells. Our studies, thus, provide insight into how microbiota metabolites regulate Th1 cell functions to maintain intestinal homeostasis.
The WRKY transcription factor family has more than 70 members in the Arabidopsis (Arabidopsis thaliana) genome, and some of them are involved in plant responses to biotic and abiotic stresses. This ...study evaluated the role of WRKY45 in regulating phosphate (Pi) uptake in Arabidopsis. WRKY45 was localized in the nucleus and mainly expressed in roots. During Pi starvation, WRKY45 expression was markedly induced, typically in roots. WRKY45 overexpression in Arabidopsis increased Pi content and uptake, while RNA interference suppression of WRKY45 decreased Pi content and uptake. Furthermore, the WRKY45-overexpressing lines were more sensitive to arsenate, the analog of Pi, compared with wild-type seedlings. These results indicate that WRKY45 positively regulates Arabidopsis Pi uptake. Quantitative real-time polymerase chain reaction and β-glucuronidase staining assays showed that PHOSPHATE TRANSPORTER1;1 (PHT1;1) expression was enhanced in the WRKY45-overexpressing lines and slightly repressed in the WRKY45 RNA interference line. Chromatin immunoprecipitation and electrophoretic mobility shift assay results indicated that WRKY45 can bind to two W-boxes within the PHT1;1 promoter, confirming the role of WRKY45 in directly up-regulating PHT1;1 expression. The pht1;1 mutant showed decreased Pi content and uptake, and overexpression of PHT1;1 resulted in enhanced Pi content and uptake. Furthermore, the PHT1;1-overexpressing line was much more sensitive to arsenate than WRKY45-overexpressing and wild-type seedlings, indicating that PHT1;1 overexpression can enhance Arabidopsis Pi uptake. Moreover, the enhanced Pi uptake and the increased arsenate sensitivity of the WRKY45-overexpressing line was impaired by pht1;1 (35S:WRKY45-18::pht1;1), demonstrating an epistatic genetic regulation between WRKY45 and PHT1;1. Together, our results demonstrate that WRKY45 is involved in Arabidopsis response to Pi starvation by direct up-regulation of PHT1;1 expression.
•Longmaxi shale gas has highest content (95.5–99.6%) and δ13C of CH4 in the world.•The Longmaxi shale gas is characterized by δ13C1>δ13C2>δ13C3 and δ2H1<δ2H2.•The R/Ra values range from 0.01–0.03, ...indicating a crustal origin.•CO2 was from the high temperature decomposition of carbonate sediments.
The marine shale of the Silurian Longmaxi Formation in southern Sichuan Basin, China is characterized by its huge thickness (100–600m), high TOC values (0.35–18.4%), favorable types of organic matter (I and II1), high Ro values (1.8–4.2%), abundant brittle minerals (average 56.3%) and strong gas generation intensity. Particularly, its bottom section, which has TOC>2% and thickness of 20–70m, has recently been a main target for shale gas exploration and development. Geochemical parameters of 13 gas samples from Longmaxi shale from 10 wells were analyzed in this study. Wetness of the gas (molar fraction of ethane through pentanes in total gaseous hydrocarbon) is only 0.24–0.70%, making the Longmaxi shale gas among the driest in the world. Carbon isotopic compositions of the alkane gases from Longmaxi shale are characterized by δ13C1>δ13C2>δ13C3, with the most positive δ13C1 values in the world; a positive relationship was observed between its δ13C1 and δ13C2 values reflecting the extremely high thermal maturity of the source rock. δ2HCH4 values range from −140‰ to −151‰ and the δ2HC2H6 values range from −130‰ to −173‰; the hydrogen isotopic compositions were mainly characterized by δ2HCH4<δ2HC2H6. The helium isotopic composition shows R/Ra values range from 0.01–0.03, indicating a crustal origin from uranium and thorium in the source rock. CO2 was most likely derived from the high temperature decomposition of carbonate sediments, but with some organic contribution, since its δ13C values were mainly 5.4‰ to −2.2‰.
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