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Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We then validated differences in key pathways through functional studies and determined whether these cultures recapitulate known features of the infant intestinal epithelium. RNA-Seq analysis showed significant differences in the transcriptome of infant and adult HIEs, including differences in genes and pathways associated with cell differentiation and proliferation, tissue development, lipid metabolism, innate immunity, and biological adhesion. Validating these results, we observed a higher abundance of cells expressing specific enterocyte, goblet cell, and enteroendocrine cell markers in differentiated infant HIE monolayers, and greater numbers of proliferative cells in undifferentiated 3D cultures. Compared to adult HIEs, infant HIEs portray characteristics of an immature gastrointestinal epithelium including significantly shorter cell height, lower epithelial barrier integrity, and lower innate immune responses to infection with an oral poliovirus vaccine. HIEs established from infant intestinal tissues reflect characteristics of the infant gut and are distinct from adult cultures. Our data support the use of infant HIEs as an ex vivo model to advance studies of infant-specific diseases and drug discovery for this population., Importance: Tissue or biopsy stem cell-derived human intestinal enteroids are increasingly recognized as physiologically relevant models of the human gastrointestinal epithelium. While enteroids from adults and fetal tissues have been extensively used for studying many infectious and non-infectious diseases, there are few reports on enteroids from infants. We show that infant enteroids exhibit both transcriptomic and morphological differences compared to adult cultures. They also differ in functional responses to barrier disruption and innate immune responses to infection, suggesting that infant and adult enteroids are distinct model systems. Considering the dramatic changes in body composition and physiology that begin during infancy, tools that appropriately reflect intestinal development and diseases are critical. Infant enteroids exhibit key features of the infant gastrointestinal epithelium. This study is significant in establishing infant enteroids as age-appropriate models for infant intestinal physiology, infant-specific diseases, and responses to pathogens., Competing Interests: The authors declare no conflict of interest.

Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial β-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The β-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF., Importance: Neuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy., Competing Interests: The authors declare no conflict of interest.

Marine bacteria play important roles in the degradation and cycling of algal polysaccharides. However, the dynamics of epiphytic bacterial communities and their roles in algal polysaccharide degradation during kelp decay are still unclear. Here, we performed metagenomic analyses to investigate the identities and predicted metabolic abilities of epiphytic bacterial communities during the early and late decay stages of the kelp Saccharina japonica . During kelp decay, the dominant epiphytic bacterial communities shifted from Gammaproteobacteria to Verrucomicrobia and Bacteroidetes. In the early decay stage of S. japonica , epiphytic bacteria primarily targeted kelp-derived labile alginate for degradation, among which the gammaproteobacterial Vibrionaceae (particularly Vibrio ) and Psychromonadaceae (particularly Psychromonas ), abundant in alginate lyases belonging to the polysaccharide lyase (PL) families PL6, PL7, and PL17, were key alginate degraders. More complex fucoidan was preferred to be degraded in the late decay stage of S. japonica by epiphytic bacteria, predominantly from Verrucomicrobia (particularly Lentimonas ), Pirellulaceae of Planctomycetes (particularly Rhodopirellula ), Pontiellaceae of Kiritimatiellota, and Flavobacteriaceae of Bacteroidetes, which depended on using glycoside hydrolases (GHs) from the GH29, GH95, and GH141 families and sulfatases from the S1_15, S1_16, S1_17, and S1_25 families to depolymerize fucoidan. The pathways for algal polysaccharide degradation in dominant epiphytic bacterial groups were reconstructed based on analyses of metagenome-assembled genomes. This study sheds light on the roles of different epiphytic bacteria in the degradation of brown algal polysaccharides.IMPORTANCEKelps are important primary producers in coastal marine ecosystems. Polysaccharides, as major components of brown algal biomass, constitute a large fraction of organic carbon in the ocean. However, knowledge of the identities and pathways of epiphytic bacteria involved in the degradation process of brown algal polysaccharides during kelp decay is still elusive. Here, based on metagenomic analyses, the succession of epiphytic bacterial communities and their metabolic potential were investigated during the early and late decay stages of Saccharina japonica . Our study revealed a transition in algal polysaccharide-degrading bacteria during kelp decay, shifting from alginate-degrading Gammaproteobacteria to fucoidan-degrading Verrucomicrobia, Planctomycetes, Kiritimatiellota, and Bacteroidetes. A model for the dynamic degradation of algal cell wall polysaccharides, a complex organic carbon, by epiphytic microbiota during kelp decay was proposed. This study deepens our understanding of the role of epiphytic bacteria in marine algal carbon cycling as well as pathogen control in algal culture., Competing Interests: The authors declare no conflict of interest.

Background: There has been a rapid increase in the number of human adenovirus type 7 (HAdV-7) and invasive pulmonary fungal infections (IPFIs) co-infection., Methods: In this study, we included patients with confirmed HAdV-7 infection during the period from 2018 to 2019 to explore clinical characteristics of severe HAdV-7 pneumonia combined with IPFIs., Results: Among the 143 patients, 35 cases were co-infected with IPFIs. Others were assigned to the control group (n Z 108). Patients wereprone to be complicated with respiratory failure, heart failure and hemophagocytic syndromein IPFIs group. Thirty-one species of fungi were detected in the IPFIs group, among whichAspergillus was the most common species. Compared to control group, patients had lowerlevels of WBC, CD3þ T lymphocyte counts and CD19þ B lymphocyte counts in IPFIs group., Conclusion: Aspergillus is the most common species in IPFIs combined with severe HAdV-7 pneumonia. For children with severe HAdV-7 pneumonia who are younger, have a long course of disease, and have been admitted to the ICU, we should predict the occurrence of IPFIs when there is multi-system dysfunction and the reduction of CD3+ T lymphocyte counts and CD19+ B lymphocyte counts in course of their disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Fully-hydrogenated germanene, named germanane, represents a new nanostructured material for a variety of potential applications, such as electronics and optoelectronics. However, a critical requirement for developing practical and reliable electronic devices based on germanane consists of achieving a flexibly controllable charge carrier and doping level. Different to the conventional doping methods such as ion implantation and diffusion, by first-principles calculations we demonstrate that tetracyanobenzene (TCNB) molecular adsorption could introduce effective p-type doping in germanane due to the combination of germanane with electroactive acceptor molecule TCNB. The corresponding energy difference between the empty band minimum of the dopant and the valence band maximum for electron excitation is 0.173 eV. More importantly, this nondestructive p-type doping could be linearly tuned under an external E-field. Analysis of charge transfer by means of the equivalent capacitor model and the shift of energy levels in the superstructure of germanane/TCNB further reveals that the superposition of the external E-field and molecular adsorption-induced internal E-field plays a key role in the charge transfer between TCNB and germanane, especially in achieving a controllable p-type molecular doping level in germanane. Such convenient and flexible E-field-engineering of p-type molecular doping in germanane would be very helpful for potential applications of germanane-based electronic and optoelectronic devices in the future.

Germanane, fully hydrogenated germanene, has recently attracted great interest, both theoretical and experimental. In this paper we thoroughly study strain-tunable n/p-type doping in germanane by adsorption of tetrathiafulvalene (TTF)/tetracyanoquinodimethane (TCNQ) molecules through first-principles calculations. The results show that both TTF and TCNQ molecules can non-covalently functionalize the electronic properties of germanane. Not surprisingly, TTF molecular adsorption induces n-type doping in germanane because the TTF molecule is a typical electron donor. Moreover, a linearly tunable band gap of germanane and differing n-type doping strengths can be realized by a biaxial strain ranging from -3% to 3%. Analysis indicates that tensile strain would promote the doping effect whereas compressive strain would inhibit it. Comparatively, TCNQ molecular adsorption induces a germanane/TCNQ system which exhibits metallic characteristics. Surprisingly, however, under a tensile strain of 2.5%, a strong p-type doping effect is achieved in germanene/TCNQ. In particular, with increasing tensile strain over the range 2.5%-3%, the strain-tunable p-type doping effect decreases gradually. Such a multiple effect of molecular adsorption and strain on the electronic properties of germanane could be helpful for potential future applications of germanane-based electron devices.

To better understand the molecular mechanisms responsible for light-induced damage in retinal pigmented epithelial (RPE) cells, we developed an automated device to recapitulate intense light exposure. When compared with human fibroblasts, ARPE-19 cells that had been exposed to blue-rich light-emitting diode-light of 10 000 Lux at 37 °C for 9 h displayed dramatic cellular apoptosis. Collectively, gene expression profiling and qPCR demonstrated that growth arrest and DNA damage-45α (GADD45α) expression was markedly upregulated. Transient knockdown of GADD45α partially attenuated light-damage-induced apoptosis in ARPE-19 cells, whereas GADD45α overexpression dramatically increased it. These results demonstrate the critical function of GADD45α in light-induced RPE cellular apoptosis. Quantitative reverse transcription-PCR and western blotting revealed that the upregulation of GADD45α was under direct control of p53. Moreover, treatment with Ly294002, an inhibitor of AKT phosphorylation, further promoted GADD45α gene transcription in both non-light and light-damaged ARPE-19 cells. Treatment also exacerbated RPE cellular apoptosis after light exposure, confirming that inhibition of Akt phosphorylation increases GADD45α expression. Collectively, our findings reveal that light irrigation induces human RPE cellular apoptosis through upregulation of GADD45α expression mediated through both the p53 and phosphatidylinositol 3-kinase-AKT signaling pathways. These results provide new insights into human retinal diseases elicited by light damage and open a new avenue for disease prevention and treatment.

A general theoretical formulation for the effect of a strong on-site Coulomb interaction on the time-dependent electron transport through a quantum dot under the influence of arbitrary time-varying bias voltages and/or external fields is presented, based on slave bosons and the Keldysh nonequilibrium Green's function (GF) techniques. To avoid the difficulties of computing double-time GFs, we generalize the propagation scheme recently developed by Croy and Saalmann to combine the auxiliary-mode expansion with the celebrated Lacroix's decoupling approximation in dealing with the second-order correlated GFs and then establish a closed set of coupled equations of motion, called second-order quantum rate equations (SOQREs), for an exact description of transient dynamics of electron correlated tunneling. We verify that the stationary solution of our SOQREs is able to correctly describe the Kondo effect on a qualitative level. Moreover, a comparison with other methods, such as the second-order von Neumann approach and Hubbard-I approximation, is performed. As illustrations, we investigate the transient current behaviors in response to a step voltage pulse and a harmonic driving voltage, and linear admittance as well, in the cotunneling regime.

The stability of free-standing silicene in oxygen is worthwhile discussing. In this letter, the oxygen adsorption and dissociation on free-standing silicene is studied using first principles. It is found that free-standing silicene is not stable in oxygen because O2 molecules can be easily adsorbed and dissociated into O atoms on a silicene surface without overcoming any energy barrier. Moreover, dissociated oxygen atoms are difficult to migrate on and desorb from silicene surfaces, leading to the formation of Si-O compounds. To enhance the stability of free-standing silicene in oxygen, fully hydrogenated silicene is used as a stabiliser. Interestingly, compared with no energy barrier on pristine silicene, there are two minor energy barriers of O2 molecule adsorption and dissociation on fully hydrogenated silicene, indicating that hydrogenated silicene has higher stability than free-standing silicene in oxygen. However, once the O2 molecule dissociates into two O atoms on hydrogenated silicene, desorption of O atoms will be very difficult due to its high energy barrier. This work will be helpful to understand the detail of O2 molecule dissociation and dissociation-induced O atoms adsorption on free-standing and hydrogenated silicene in oxygen and will be useful to the application of silicene.

We study dc-current effects on the magnetoresistance oscillation in a two-dimensional electron gas with Rashba spin-orbit coupling, using the balance-equation approach to nonlinear magnetotransport. In the weak current limit the magnetoresistance exhibits periodical Shubnikov-de Haas oscillation with changing Rashba coupling strength for a fixed magnetic field. At finite dc bias, the period of the oscillation halves when the interbranch contribution to resistivity dominates. With further increasing current density, the oscillatory resistivity exhibits phase inversion, i.e., magnetoresistivity minima (maxima) invert to maxima (minima) at certain values of the dc bias, which is due to the current-induced magnetoresistance oscillation.

The platinum copper alloy nanocrystals (NCs) have generated much interest because of their wide applications in fuel cells due primarily to their good catalytic performance and to decreasing sensitivity toward CO poisoning. The exact atomic-level morphology of platinum copper alloy NCs is still not clear in the literature, and research to understanding the poisoning mechanism is still insufficient to date. In this article, we report on density functional calculations of small PtnCu clusters and their adsorption of a CO molecule that provide evidence for degrading adsorption of the CO molecule compared to pure platinum clusters. The lowest-energy geometries of PtnCu and PtnCuCO clusters have been identified. The CO molecule prefers to be adsorbed on the nearest platinum atom by the C-end-on mode, forming linear or quasi-linear O-C-Pt structures. The adsorption energies indicate that the introduction of a copper atom decreases the adsorption ability of the CO molecule. The local density of states of the representative clusters is used to characterize the adsorption properties of the CO molecule on the PtnCu clusters. Results from our theoretical calculations can be helpful for understanding the poisoning mechanism of the CO molecule on the platinum copper alloy NCs.

Considering electron-impurity and electron-phonon scattering, we present a balance-equation-based theoretical examination of thermoelectric power (TEP) in a two-dimensional single-layer graphene away from the carrier neutrality point. Both the boundary scattering and phonon-phonon interaction in phonon relaxation processes are taken into account. We find that, at temperatures T > 10 K, the contribution to TEP mainly comes from diffusive processes and the phonon-drag effect can be ignored. However, at T ≤ 10 K, the phonon-phonon interaction leads to a phonon-drag peak in the temperature dependence of TEP. We also compare our results with experiments.

The low-lying candidates of hydrated calcium ion clusters, [Ca(H(2)O)(n)](2+) with n = 1-20 and 27, have been extensively sought by using density functional theory (DFT) at BLYP/6-311+G(d,p) level. The results showed that the first hydration shell around the calcium ion was fully occupied by six water molecules, whereas the second hydration shell might be fully occupied with different numbers of water molecules. This just corresponds to different growth patterns of the hydrated calcium ion clusters. Furthermore, we revealed that the vibration entropy contributed to the free energy of an isomer significantly. As a result, the stability of some low-lying candidates at zero-temperature was not maintained at finite temperatures. Therefore, we suggested that, at finite temperatures, the realistic products of [Ca(H(2)O)(n)](2+) should be a mixture of the best candidate and some of metastable isomers for a given cluster size. For a cluster having second and/or third shell of water molecules, we found structural transitions between a low-lying structure and the lowest-energy structure undergoing much lower energy barriers. In addition, the IR spectra of the best candidates were predicted, in which the evolution of hydrogen-bond configurations with the cluster size was revealed.

Using a nonequilibrium Green function approach, we systematically investigate the current induced spin polarization (CISP) in a two-dimensional heavy-hole system with cubic Rashba spin-orbit coupling, driven by in-plane electric and magnetic fields. We find that when a magnetic field is applied along the direction of electric field, the longitudinal conductivity drops monotonously with an increase of magnetic-field strength or of hole density. The spin polarization along the electric-field direction is just the Pauli paramagnetism and it quadratically increases with an increase of hole density. The nonvanishing out-of-plane component of spin polarization emerges for both short-range and long-range disorders, and it changes sign with the variation of magnetic field, especially for long-range hole-impurity scattering. In the magnetic-field dependences of this out-of-plane CISP and of the in-plane CISP perpendicular to the electric field, there are singular magnetic fields, below or above which the effects of magnetic field are completely different., (© 2010 IOP Publishing Ltd)

Considering electron-impurity, electron-acoustic-phonon and electron-optical-phonon scatterings, the nonlinear steady-state transport properties of graphene are studied theoretically by means of the balance equation approach. We find that the conductivity as a function of electric field strength, E, exhibits strongly nonlinear behavior for E larger than a critical value, E(c)≈0.1 kV cm(-1). With the increase of E from zero, the conductivity first decreases slowly and then it falls rapidly when E>E(c). The dependence of electron temperature on E is also demonstrated.

We exploit the pumped spin-current and current noise spectra under equilibrium conditions in a single quantum dot connected to two normal leads as an electrical scheme for detection of the electron spin resonance (ESR) and decoherence. We propose spin-resolved quantum rate equations with correlation functions in Laplace space for the analytical derivation of the zero-frequency auto- and cross-shot noise spectra of charge and spin current. Our results show that in the strong Coulomb blockade regime, ESR-induced spin flip generates a finite spin current and quantum partition noises in the absence of net charge transport. Moreover, spin shot noise is closely related to the magnetic Rabi frequency and decoherence and would be a sensitive tool to measure them.

Microwave-radiation induced giant magnetoresistance oscillations recently discovered in high-mobility two-dimensional electron systems are analyzed theoretically. Multiphoton-assisted impurity scatterings are shown to be the primary origin of the oscillation. Based on a theory which considers the interaction of electrons with electromagnetic fields and the effect of the cyclotron resonance in Faraday geometry, we are able not only to reproduce the correct period, phase, and the negative resistivity of the main oscillation, but also to predict the secondary peaks and additional maxima and minima observed in the experiments. These peak-valley structures are identified to relate, respectively, to single-, double-, and triple-photon processes.

Tetramethylpyrazine (TMP), the active principle in Ligusticum wallichii, D-timolol, and L-timolol were compared for their effects on retinal and choroidal blood flow (RCBF), blood pressure (BP), and heart rate (HR). TMP (10 mg.kg-1) increased RCBF by 44% and did not affect systemic BP or HR. D-Timolol (4 mg.kg-1 iv) had a tendency to increase RCBF but did not affect systemic BP and HR either. L-Timolol (0.4 mg.kg-1 iv), on the other hand, decreased RCBF by 18% and reduced both systemic BP and HR. In isolated preparations, TMP increased coronary artery blood flow with slight vasodilation, but vasoconstriction in renal, femoral and mesenteric arteries. These results indicate that TMP could be used to prevent or alleviate certain ischemic retinal degenerations without producing significant cardiovascular side effects. The in vitro vasoconstriction actions of TMP (0.2 mg.ml-1) were blocked by propranolol and phenoxybenzamine, indicating that adrenergic mechanism might be involved in TMP action.

The cardiovascular pharmacology of two Chinese herbs, Salvia miltiorrhiza (SM) and Panax notoginseng (Burk) F. H. Chen (PNG) were studied both in vivo and in vitro. Extracts of both herbs suppressed systemic blood pressure in albino rats and rabbits, an effect which was blocked or reversed by atropine, propranolol, and chlorpheniramine plus cimetidine. This reversed hypertension was blocked by phenoxybenzamine. These results indicate that these herbs have multiple effector sites in the cardiovascular system. This could be due to an increased utilization of extracellular calcium ions since the activity of SM on isolated blood vessels of rabbits was enhanced by 2 mM Ca++. The effects of aqueous extract of SM and purified active principles of SM (tanshinones) on rat and rabbit blood vessels in vitro were very similar both qualitatively and quantitatively. Both caused vasodilation of coronary arteries at all concentrations tested but induced vasodilation of renal, mesenteric and femoral arteries only at low concentrations. At higher concentrations, vasoconstriction was induced in these vessels. These results indicate that an economical decoction of SM is as efficacious as the more expensive isolated tanshinones. Both SM and PNG would be useful as antianginal agents since they dilate coronary vessels. Their use in hypertension is questionable since they induce both vasodilation and vasoconstriction depending on dose and target vessel.

Cardiovascular actions of S. miltiorrhiza (SM) were studied on systemic blood pressure in the rat. Langendorff cardiac preparation in the guinea pig, and four types of vasculature in the dog, including coronary, renal, femoral, and mesenteric arteries. SM induced dose-related hypotension without changing heart rate. The hypotension was antagonized by atropine, propranolol, and chlorpheniramine plus cimetidine. In the isolated whole-heart preparation, SM increased coronary blood flow significantly for 15 min and positive inotropic action for 3 min after pulse injection. SM relaxed all arteries at low concentration (3.0 mg/ml) and contracted all but the coronary artery at higher concentration (10.0 mg/ml). The coronary artery relaxed at all doses of SM tested.