Fluid Molecules Research Articles

An Overview of Human T-Lymphotropic Virus Type 1 Lung Injury.

Previous studies have demonstrated the development of pulmonary impairment in individuals infected with human T-lymphotropic virus type 1 (HTLV-1). Complications, such as alveolitis and bronchiectasis, were found in individuals who developed tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP-HAM) due to chronic inflammation. These patients exhibited increased levels of lymphocytes (CD4+ and CD25+), cytokines (IL-2, IL-12, and IFN-γ), inflammatory chemokines (MIP-1α and IP-10), and cell adhesion molecules (ICAM-1) in the bronchoalveolar lavage fluid, with the result of chronic inflammation and lung injury. The main lesions observed at Chest high-resolution computed tomography were centrilobular nodules, parenchymal bands, lung cysts, bronchiectasis, ground-glass opacity, mosaic attenuation, and pleural thickening. It can lead to progressive changes in pulmonary function with the development of restrictive and obstructive diseases. Recent studies suggest a causal relationship between HTLV-1 and pulmonary diseases, with intensification of lesions and progressive decrease in pulmonary function. This summary updates a previous publication and addresses the general lack of knowledge regarding the relationship between TSP-HAM and pulmonary disease, providing direction for future work and the management of these individuals.

Affinity-based isolation of extracellular vesicles and the effects on downstream molecular analysis.

Extracellular vesicles (EVs) are transport vesicles with diameters ranging from 30 to 1000nm, secreted by cells in both physiological and pathological conditions. By using the EV shuttling system, biomolecular cargo such as proteins and genetic materials travels between cells resulting in intercellular communication and epigenetic regulation. Because the presence of EVs and cargo molecules in body fluids can predict the state of the parental cells, EV isolation techniques from complex biofluids have been developed. Further exploration of EVs through downstream molecular analysis depends heavily on those isolation technologies. Methodologies based either on physical separation or on affinity binding have been used to isolate EVs. Affinity-based methods for EV isolation are known to produce highly specific and efficient isolation results. However, so far, there is a lack of literature summarizing these methods and their effects on downstream EV molecular analysis. In the present work, we reviewed recent efforts on developing affinity-based methods for the isolation of EVs, with an emphasis on comparing their effects on downstream analysis of EV molecular cargo. Antibody-based isolation techniques produce highly pure EVs, but the harsh eluents damage the EV structure, and some antibodies stay bound to the EVs after elution. Aptamer-based methods use relatively mild elution conditions and release EVs in their native form, but their isolation efficiencies need to be improved. The membrane affinity-based method and other affinity-based methods based on the properties of the EV lipid bilayer also isolate intact EVs, but they can also result in contaminants. From the perspective of affinity-based methods, we investigated the influence of the isolation methods of choice on downstream EV molecular analysis.

The Effect of Size and Working Fluid on the Multi-Objective Design of High-Speed Centrifugal Compressors

The impact of size and working fluid on the efficiency, operating range, and axial thrust on bearings is examined for high-speed, oil-free centrifugal compressors. First, the development and validation of a reduced-order model based on scaling principles is documented. Then, the validated compressor model is used to generate design maps for stages operating with arbitrary fluid molecules, and characterized by different size. The results show that compressors operating with fluids made by heavy and complex molecules provide lower efficiency over the entire design space, if compared to their simple-molecule counterparts. However, compressors for complex-molecule fluids require lower rotational speed, and generate lower axial thrust on bearings, thus making them particularly suitable for small-scale applications. Furthermore, a decreasing value of the size parameter has a detrimental effect on the stage efficiency, as a result of manufacturing constraints. The results computed by the compressor model suggest that the efficiency penalty is more sensitive to variations of clearance gap than to surface finishing. Lastly, the reduced-order model has been used to perform a design exercise, i.e., the multi-objective optimization of the first compressor stage of the heat pump test rig being realized at Delft University of Technology. The key characteristics of the optimal compressor design has been compared to those derived from the design maps, to corroborate their validity. The optimal design has been extensively characterized by means of CFD, providing further evidence that efficient mini-compressors operating with organic fluids, and featuring pressure ratios up to five at off-design, are feasible.

Potential risk resulting from the influence of static magnetic field upon living organisms. Numerically-simulated effects of the static magnetic field upon carbohydrates

Background: Recognising effects of static magnetic field (SMF) of varying flux density on flora and fauna is attempted. For this purpose, the influence of SMF upon molecules ofα- andβ-D-glucose,α- andβ-D-galactose,α- andβ-fructopyranoses,α- andβ-fructofuranoses andα- andβ-D-xylofuranoses andαandβ-D-xylopyranoses is studied.Methods: Computations of the effect of static magnetic field (SMF) of 0.0, 0.1, 1, 10 and 100 AFU (1 AFU > 1000 T) flux density were performed in silico for SMF changes distribution of the electron density in these molecules.Hyper-Chem 8.0 software was used together with the AM1 method for optimisation of the conformation of the molecules of monosaccharides under study. Then polarisability, charge distribution, potential and dipole moment for molecules placed in SMF were calculated involving DFT 3-21G method.Results: Application of SMF induced polarisability of electrons, atoms and dipoles, the latter resulting in eventual re-orientation of the molecules along the applied field of the molecules and the electron density redistribution at particular atoms. Increase in the field strength generated mostly irregular changes of the electron densities at particular atoms of the molecules as well as polarisabilities. Energy of these molecules and their dipole moments also varied with the SMF flux density applied.Conclusions: Saccharides present in the living organisms may participate in the response of the living organisms to SMF affecting metabolism of the molecules in the body fluids by fitting molecules to the enzymes. Structural changes of saccharide components of the cell membranes can influence the membrane permeability.

Sensing Soluble Immune Checkpoint Molecules and Disease-Relevant Cytokines in Cancer: A Novel Paradigm in Disease Diagnosis and Monitoring

Conventional detection of cancer involves highly invasive and expensive diagnostic procedures, often leading to non-compliance from patients. Therefore, there is a strong requirement for the development of non-invasive techniques that can facilitate rapid and timely diagnosis of the disease. The tumor-immune interaction often leads to anomalous expression of different soluble immune signaling molecules like cytokines and chemokines, thus making them promising candidates for sensing disease development and progression. Furthermore, differential expression of soluble isoforms of several immune-checkpoint molecules like PD-L1, CTLA-4 etc., has been found to have strong correlation with tissue-specific tumor development, disease progression and in many cases, disease prognosis. Therefore, development of biosensors, to rapidly detect and analyze the levels of these soluble immune molecules in different body fluids, requiring minimal sample volume, has the potential to be a game-changer in the field of cancer diagnosis. In addition, real time monitoring of these soluble immune checkpoint molecules in patient-derived biofluids may serve as decision support tools for patient selection for immunotherapeutic interventions. Majority of the biosensors designed to detect the soluble immune biomarkers, have used a two-antibody based sandwich system to capture the target analyte. However, new technologies using bioreceptors like the aptamers or nano-yeast scFv antibody fragments have made possible multiplexed detection of several analytes simultaneously. The use of gold nanoparticles or carbon nanotubes on the electrode surface serves to increase the sensitivity of detection, due to their high electrical conductivity. Further, fabrication of the biosensors on microfluidic platforms enable the detection of these analytes at ultra-low levels. This review discusses the recent advances made in the development of biosensors for specific and selective detection of these immune-markers that can be successfully translated to the clinics as a new paradigm in disease diagnosis and monitoring.

Extracellular vesicles from follicular fluid may improve the nuclear maturation rate of in vitro matured mare oocytes

The in vitro maturation (IVM) of equine oocytes is still not efficient and does not yield consistent results. The specific requirements of equine oocytes during this process are still largely unknown, which hinders the development of assisted reproductive techniques (ART) in this species. Because the ovarian follicle microenvironment supports oocytes in their acquisition of developmental competence, follicular fluid seems to be a substantial source of bioactive factors that could support the IVM process. Extracellular vesicles (EVs) are cell-secreted molecules in body fluids that are able to deliver molecular signals and transfer genetic information (mRNA, miRNA) between donor and recipient cells. Hence, our hypothesis is that follicular fluid EVs (ffEVs) from small (<20 mm) ovarian follicles can improve the in vitro maturation rate of mare oocytes. To test our hypothesis, equine ovarian follicular fluid was aspirated and ffEVs were isolated by ultracentrifugation, then characterized using nanoparticle tracking analysis and flow cytometry. Additionally, ffEVs were labeled using the ExoGlow-protein EV labeling kit (System Biosciences, Palo Alto, CA). Cumulus-oocyte complexes (COCs) were matured using a one-step method (Method I, continuous culture for 24–38 h) or a two-step method (Method II, initial denudation after 24 h), in the presence (200 μg protein/ml) or absence of ffEVs. The results show the internalization of ffEVs by equine cumulus cells and, for the first time, also by oocytes. The ffEV treatment during two-step culture had a positive effect on the maturation rate of compacted COCs compared to the control group (45.7% and 20.5%, respectively; p < 0.05). No effect of supplementation was observed on the maturation rate during one-step culture. Our results indicate that the supplementation of culture media with EVs isolated from the follicular fluid of small follicles can improve the IVM rate of mare oocytes, suggesting that ffEVs play an important role during this process and may enhance the development of equine ART.

Flow and heat transfer due to partially heated moving lid in a trapezoidal cavity with different constraints at inner circular obstacle

The main emphasis of the current work is to deal with the forced convection of magnetohydrodynamics (MHD) flow and its heat transfer due to force convection generated by a moving lid in a trapezoidal enclosure. Various cases of temperature at the surface of the circular obstacle inside the cavity are determined. The trapezoidal cavity has a moveable and partially heated top lid while the bottom wall is kept at a low temperature. The linearly inclined walls on the left and right sides of the cavity are both adiabatic. The finite element method is applied for computations validated with existing work. Numerical simulations are conducted to analyze this trapezoidal cavity model for various thermal conditions of the inner circular obstacle, various heated lengths (0 ≤ LH ≤ 1), various Reynolds number (100 ≤ Re ≤ 700), Richardson number (0.001 ≤ Ri ≤ 10) and Hartmann number (0 ≤ Ha ≤ 100). The entire analysis describes that high Reynolds numbers improve the thermal performance of liquid. However, moving lid generates fluid molecules specifically directed according to wall movement. The force convection phenomenon becomes more dominant as the Reynolds number and heated length increase. A cold circular obstacle resists the circulation of heat in the cavity whereas the local Nusselt number drops when the simultaneous effects of the moving lid force and heated sources move away from the surface.

Analisis Spektroskopi Ftir Untuk Karakterisasi Kimia Fisik Fluida Mata Air Panas Di Kawasan Wisata Hutan Pinus Tomohon Sulawesi Utara

Geothermal is one of the alternative energy sources that are classified as new and renewable (new and renewable). This is because geothermal energy sources are still relatively new and are said to be renewable because production waste in the form of water is re-injected and produces a recycle process that allows sustainability. The process of exploration, exploitation and production does not produce toxic gas emissions. In terms of prospects, geothermal itself is a promising energy in the future because the source is heat from within the earth that will never run out. One of the areas in North Sulawesi that has the potential for geothermal project development is located in the Tomohon area, North Sulawesi Province. Based on the preliminary survey that has been carried out, at this location found manifestations in the form of hot springs located in the Pine Forest. The purpose of this study was to determine the type of fluid and functional groups of molecules manifesting hot springs in the Tomohon pine forest tourism area. Analysis of the ion content in the fluid using spectrophotometer characterization, and analysis of molecular functional groups using FTIR (Fourier Transform Infra Red) spectroscopy. The results showed that the type of fluid manifestation of the hot springs in the Tomohon Pine Forest Tourism Area has the type of bicarbonate (HCO3). Analysis of functional groups of fluid molecules in the manifestation of hot springs in the Tomohon Pine Forest Tourism Area has functional groups C=O, C≡C and O-H.

A statistical thermodynamics-based equation of state and phase equilibrium calculation for confined hydrocarbons in shale reservoirs

The phase behavior of confined fluid in nanopores of shale reservoirs deviates significantly from that of bulk fluid. Confined fluid refers to fluid whose thermal motion is affected by nanopores, since nanopores have a comparative size to the mean free path of fluid molecules. To describe deviated phase behavior in nanopores, Travalloni et al. proposed PR-C EOS by introducing empirical modifications to the canonical partition function. The modifications consider the two main mechanisms that cause nanopore phase behavior to deviate: the finite volume effect and the fluid-pore wall interaction effect. However, in addition to its weakness on a theoretical basis, PR-C EOS possesses imperfections when applied to predict nanopore phase behaviors. In this work, we propose a new EOS derived from statistical thermodynamics for slit-like nanopores, named PR-X EOS. The PR-X EOS has an extra term to represent the fluid-pore wall interaction effect and a modification to the cubic EOS parameter to represent the finite volume effect. PR-C EOS and PR-X EOS are non-cubic, and each has some new parameters. The new parameters can be determined by fitting adsorption isotherms. When pore size approaches infinity, PR-C EOS and PR-X EOS both degenerate into classic PR EOS. To apply these two non-cubic EOS in reservoir simulators, we improve gas-oil phase equilibrium calculation methods. The improved simulator can model chemical potential equilibrium between the nanopore grid and the bulk grid, with chemical potentials of the two grids calculated using the modified EOS and conventional EOS, respectively, so that bulk grid pressure can be obtained. As a consequence, we can plot the adsorption isotherm or phase diagram under bulk pressure, which is practically measurable pressure. Therefore, we can validate the modified EOS with experimental or molecular simulation data. Validations demonstrate that PR-X EOS can match type I and type IV adsorption isotherms; whereas, PR-C EOS fails to match the type IV adsorption isotherm. Moreover, the phase diagrams calculated using PR-X EOS consistently shrink as pore size decreases, while PR-C EOS cannot guarantee this consistency. These two facts show that PR-X EOS is superior to PR-C EOS in modeling phase behavior of confined hydrocarbons. Furthermore, shale oil reservoir simulation shows that considering the confinement effect would lead to lower GOR.

Thermodynamic modeling for confined fluids in nanopores using an external potential-advanced equation of state

Quantitatively understanding thermodynamic properties of confined fluids in nanoporous media is of great significance to the development of shale gas. Due to the complex intermolecular forces in the nanopore, it is difficult to accurately predict the thermodynamic properties of fluid molecules. Focusing on the fluid-fluid and fluid-wall molecules interactions in shale reservoir system, the thermodynamic model of fluid molecules in pores is constructed, and a modified equation of state is proposed by systematically coupling the original Soave-Redlich-Kwong equation of state with Tjatjopoulos-Feke-Mann potential model in this work. The advanced EoS could facilitate a good prediction on thermodynamic properties of confined fluids without any introduction of new empirical parameters. For verification, fluid density as the important thermodynamic property was targeted and pure methane at a wide pressure range was employed to represent the fluid. The results indicated that the calculated densities accord well with the reported ones in the free gas zone. The deviation of discrete density ranges from 0.239% to 1.7329%. The fluid density distribution in the nanopores is found to be nonuniform, exhibiting a greater value near the wall than that in the pore center, which would be ascribed to the more dominant fluid wall molecule interaction. For example, the local density is 16.90 kg/m3 in the pore center, while it increases to 26.67 kg/m3 in the region which is 0.76 nm to the wall at 350 K, 3 MPa, and 5 nm (radius). Moreover, effects of other critical factors on fluid density distribution were also conducted, and it was indicated that higher pressure, lower temperature, and smaller pore size could be favorable for the occurrence of confined fluid. In general, the novel EoS could provide a quantitative and simple method in predicting the thermodynamic properties of confined fluids relating to applications of shale gas storage and exploitation.

Protein-Induced Fluorescence Enhancement and Quenching in a Homogeneous DNA-Based Assay for Rapid Detection of Small-Molecule Drugs in Human Plasma.

Homogeneous assays for determining the concentration of small molecules in biological fluids are of importance for monitoring blood levels of critical drugs in patients. We have developed a strand displacement competition assay for the drugs dabigatran, methotrexate, and linezolid, which allows detection and determination of the concentration of the drugs in plasma; however, a surprising kinetic behavior of the assay was observed with an initial rapid change in apparent FRET values. We found that protein-induced fluorescent enhancement or quenching (PIFE/Q) caused the initial change in fluorescence within the first minute after addition of protein, which could be exploited to construct assays for concentration determination within minutes in the low nanomolar range in plasma. A kinetic model for the assay was established, and when taking the new finding into account, the in silico simulations were in good agreement with the experimentally observed results. Utilizing these findings, a simpler assay was constructed for detection of dabigatran, which allowed for detection within minutes without any time dependencies.

Study of diffusion coefficients and molecular adsorption laws for the slit-hole coal model under the thermal-gas-liuid coupling effect with hot nitrogen injection

To solve the serious filtering problems of fracturing fluid during active hydraulic fracturing of coalbed methane, which blocks gas migration channels with residual fracturing fluid and results in a rapid decline in coalbed methane production, several preliminary experiment of thermal nitrogen injection was carried out. To explain the process and mechanism of thermal nitrogen injection at the nanoscale, an adsorption and diffusion model was established to study the adsorption and diffusion of methane, water and fracturing fluid during thermal nitrogen injection. The results showed that the self-diffusion coefficient of methane was increased by 23%, 45% and 32%, the self-diffusion coefficient of water molecule was increased by 108%, 185% and 138%, the self-diffusion coefficient of fracturing fluid molecule was increased by 169%, 275% and 181%, and the total number of atoms in the slit hole was decreased by 15%, 25% and 37%, respectively, when hot nitrogen was injected at 2, 4 and 6 Mpa, respectively. This shows that the numbers of methane, water and fracturing fluid molecules in the slit hole were significantly decreased by the thermal and displacement effects of hot nitrogen injection. The self-diffusion coefficient was significantly improved, and the effects of plug removal was remarkable.

An analytical model for evaluating fluid flux across carbon-based membrane

A mass transfer model of fluid across membranes is developed by taking into account the entrance/exit effect and molecular slipping in nanopores. This model, involving the molecular interaction parameters between fluid and nanopore, can accurately predict water fluxes across different practical membranes, and the discrepancy between predictions and reported experimental measurements can be reduced to 2.45%. By analyzing the flux dependence on membrane thickness and pore size, a physical correspondence is unraveled that an optimal flux can be achieved when the pore size of a membrane takes about 5 times the involved fluid molecule diameter (∼1.50 nm for water flux). In addition, an upper bound of the water flux across CNT membranes is identified by regulating the entrance/exit resistance, and we find a thin membrane with neutrally wettable exterior surface (with contact angle θ ≈ 60°) can greatly boost the water flux. This work not only provides a workhorse for predicting fluid flux but also casts insights for designing high-performance membranes. • An analytical and convenient flux model of fluid across membranes is developed. • The predicted fluxes are of the same order of magnitude with the measured ones. • Optimal flux exists when pore diameter is about 5 times the fluid molecule size. • An upper bound of the water flux across CNT membranes is identified.

An Immunoproteomic Survey of the Antibody Landscape: Insights and Opportunities Revealed by Serological Repertoire Profiling.

Immunoproteomics has emerged as a versatile tool for analyzing the antibody repertoire in various disease contexts. Until recently, characterization of antibody molecules in biological fluids was limited to bulk serology, which identifies clinically relevant features of polyclonal antibody responses. The past decade, however, has seen the rise of mass-spectrometry-enabled proteomics methods that have allowed profiling of the antibody response at the molecular level, with the disease-specific serological repertoire elucidated in unprecedented detail. In this review, we present an up-to-date survey of insights into the disease-specific immunological repertoire by examining how quantitative proteomics-based approaches have shed light on the humoral immune response to infection and vaccination in pathogenic illnesses, the molecular basis of autoimmune disease, and the tumor-specific repertoire in cancer. We address limitations of this technology with a focus on emerging potential solutions and discuss the promise of high-resolution immunoproteomics in therapeutic discovery and novel vaccine design.

Engineered three-dimensional Au-Cu bimetallic dendritic nanosensor for ultrasensitive drug detection in urine samples and in vitro human embryonic kidney cells model

Bimetallic dendrites are hierarchical, self-assembled, and multi-branched nanostructures with unique and enhanced properties than their monometallic counterparts. In this direction, a novel gold copper (AuCu) bimetallic dendritic nanostructure has been engineered on the glassy carbon electrode (GCE) by tuning the electrodeposition parameters with enhanced electrocatalytic activity. GCE/AuCuND sensor probe was systematically characterized by various physical and analytical techniques to study its physical and electrochemical properties. Acetaminophen (AP), an important clinical drug which is routinely used to treat pain and fever was tested as a model compound to evaluate the analytical performance of the fabricated sensor. The final sensor probe achieved a low limit of detection of 7.5 (±0.03) nM with a linear dynamic range of 100–1000 nM. The selectivity of the sensor probe was tested towards AP in presence of various co-existing molecules in body fluids, and negligible signals were observed towards such molecules. Human urine samples and in vitro human embryonic kidney cells were used to evaluate the sensor performance, where 89.5 to 96.4% of AP was recovered without any interference, indicating the sensors applicability in clinical settings. The sensor was found to be stable for 12 weeks, and the variation in current responses of probe to probe was found to be negligible. The fabrication and testing of AP using the sensor takes merely 12 min, hence extremely powerful in point-of-care testing in hospitals.

Perspective: Re-defining "Pheromone" in a Mammalian Context to Encompass Seminal Fluid.

The classical view of “pheromone”—an air-borne chemical signal—is challenged by the camelids in which ovulation is triggered by ß-nerve growth factor carried in seminal plasma, effectively extending the pheromone concept to a new medium. We propose further extension of “pheromone” to include a separate class of seminal fluid molecules that acts on the female reproductive tract to enhance the prospect of pregnancy. These molecules include transforming growth factor-ß, 19-OH prostaglandins, various ligands of Toll-like receptor-4 (TLR4), and cyclic ADP ribose hydrolase (CD38). They modulate the immune response to “foreign” male-derived histocompatibility antigens on both sperm and the conceptus, determine pre-implantation embryo development, and then promote implantation by increasing uterine receptivity to the embryo. The relative abundance of these immunological molecules in seminal plasma determines the strength and quality of the immune tolerance that is generated in the female. This phenomenon has profound implications in reproductive biology because it provides a pathway, independent of the fertilizing sperm, by which paternal factors can influence the likelihood of reproductive success, as well as the phenotype and health status of offspring. Moreover, the female actively participates in this exchange—information in seminal fluid is subject to “cryptic female choice,” a process by which females interrogate the reproductive fitness of prospective mates and invest reproductive resources accordingly. These processes participate in driving the evolution of male accessory glands, ensuring optimal female reproductive investment and maximal progeny fitness. An expanded pheromone concept will avoid a constraint in our understanding of mammalian reproductive biology.

Atomistic insight into the lubrication of glycerol aqueous solution: The role of the solid interface‐induced microstructure of fluid molecules

AbstractMolecular dynamics simulations are performed to investigate the solid surface‐induced microstructure and friction coefficient of glycerol aqueous solutions with different water contents confined in graphene and FeO nanoslits. Results show that the friction coefficient of glycerol aqueous solutions confined in both nanoslits presents similar nonlinear variation tendencies with increasing water content, but their lowest value and the corresponding water contents differ. Distinctive microstructures of the near‐surface liquid layer induced by surfaces with different hydrophilicity are responsible for their difference in lubrication. The sliding primarily occurs at the solid–liquid interface for the hydrophobic graphene nanoslit owing to almost the same velocity difference in fluid molecules. By contrast, the sliding mainly occurs at the liquid–liquid interface for the hydrophilic FeO nanoslit because of the large velocity difference in fluid molecules. The weaker the interaction force at the sliding position, the lower the friction coefficient.

Effects of Mating on Gene Expression in Female Insects: Unifying the Field.

Simple SummaryInsects play many important roles including in ecosystems, food production, pathogen transmission, and production of materials. As a result, humans are interested in understanding how to control insect population sizes for control, propagation, or conservation efforts. In many insect species, female reproductive output is promoted by mating and components of the ejaculate. Beyond just the impact of receiving sperm, mating and ejaculate components can result in increased rate of oocyte development, ovulation, and oviposition as well as other changes such as reduced mating receptivity. To understand how mating causes these changes, researchers have investigated changes in female gene expression that occur after mating. In this review, we summarize the current state of knowledge on mating-induced gene expression changes in female insects and the methods used for conducting such studies. We find that genes related to immune response, chemosensation, and metabolism are commonly regulated across species. We suggest future research paths to facilitate the comparison of studies on mating-regulated gene expression across insect species.There is intense interest in controlling insect reproductive output. In many insect species, reproductive output is profoundly influenced by mating, including the receipt of sperm and seminal fluid molecules, through physiological and behavior changes. To understand these changes, many researchers have investigated post-mating gene expression regulation. In this review, we synthesize information from studies both across and within different species about the impact of mating, or components of mating, on female gene expression patterns. We found that genes related to the roles of metabolism, immune-response, and chemosensation are regulated by mating across many different insect species. We highlight the few studies that have taken the important next step of examining the functional consequences of gene expression regulation which is crucial in order to understand the mechanisms underlying the mating-regulated control of female lifespan and reproduction and to make use of such knowledge to propagate or control insect populations. The potential of cross-study comparisons is diminished by different studies using different methods. Thus, we also include a consideration of how future studies could be designed to facilitate cross-study comparisons and a call for collaboration across researchers studying different insect species and different aspects of insect biology.

Experimental characterization and molecular modeling of kerogen in Silurian deep gas shale from southern Sichuan Basin, China

A representative molecular model of kerogen is the prerequisite to the study on molecular interaction of fluid molecules with organic nanopores of shale. The molecular kerogen model in Silurian deep gas shale from southern China remains to be developed. In this work, the chemical structure of the targeted deep shale kerogen is characterized by organic geochemical measurements. The derived structural parameters are utilized to build the molecular structure of the kerogen unit. The kerogen unit shows a good representation of realistic kerogen structure in shale reservoir in terms of carbon skeleton, heteroatomic compositions and groups. The kerogen matrix and a extended kerogen slit model are constructed based on the kerogen unit, which match well with the experimental results in matrix density and kerogen porosity, respectively. The kerogen matrix is overall disordered with gentle stacking of polyaromatic fragments, due to the bendable aliphatic linkages and large-size aromatic units. The kerogen nanopores are not saturated with methane at deep shale reservoir conditions. At high pressure, the absolute adsorption tends to reach a maximum, while the excess adsorption shows a decreasing trend. The effect of pressure on the dissolved gas density is not pronounced. The generated kerogen model can serve as a starting point for further theoretical investigations on fluid storage and transport in organic nanopores of deep shale reservoir at microscopic scale.

Advances in the design of new types of inhaled medicines.

Inhalation of small molecule drugs has proven very efficacious for the treatment of respiratory diseases due to enhanced efficacy and a favourable therapeutic index compared with other dosing routes. It enables targeted delivery to the lung with rapid onset of therapeutic action, low systemic drug exposure, and thereby reduced systemic side effects. An increasing number of pharmaceutical companies and biotechs are investing in new modalities-for this review defined as therapeutic molecules with a molecular weight >800Da and therefore beyond usual inhaled small molecule drug-like space. However, our experience with inhaled administration of PROTACs, peptides, oligonucleotides (antisense oligonucleotides, siRNAs, miRs and antagomirs), diverse protein scaffolds, antibodies and antibody fragments is still limited. Investigating the retention and metabolism of these types of molecules in lung tissue and fluid will contribute to understanding which are best suited for inhalation. Nonetheless, the first such therapeutic molecules have already reached the clinic. This review will provide information on the physiology of healthy and diseased lungs and their capacity for drug metabolism. It will outline the stability, aggregation and immunogenicity aspects of new modalities, as well as recap on formulation and delivery aspects. It concludes by summarising clinical trial outcomes with inhaled new modalities based on information available at the end of 2021.