Targeting AQP9 enhanced the anti-TNF therapy response in Crohn's disease by inhibiting LPA-hippo pathway.

Although anti-TNF antibodies are extensively used to treat Crohn's disease (CD), a significant proportion of patients, up to 40%, exhibit an inadequate response to this therapy. Our objective was to identify potential targets that could improve the effectiveness of anti-TNF therapy in CD. Through the integration and analysis of transcriptomic data from various CD databases, we found that the expression of AQP9 was significantly increased in anti-TNF therapy-resistant specimens. The response to anti-TNF therapy in the CD mouse model was significantly enhanced by specifically inhibiting AQP9. Further experiments found that the blockade of AQP9, which is dominantly expressed in macrophages, decreased inflamed macrophage functions and cytokine expression. Mechanistic studies revealed that AQP9 transported glycerol into macrophages, where it was metabolized to LPA, which was further metabolized to LPA, resulting in the activation of the LPAR2 receptor and downstream hippo pathway, finally promoting the expression of cytokines, especially IL23 and IL1ß⊡ Taken together, the expansion of AQP9+ macrophages is associated with resistance to anti-TNF therapy in Crohn's disease. These findings indicated that AQP9 could be a potential target for enhancing anti-TNF therapy in Crohn's disease.

Workshop environment heterogeneity shaped the microbiome and metabolome profiles during Xiasha round of Jiangxiangxing Baijiu.

Workshop with different fermentation years plays an essential role in the yield and quality of Baijiu. In actual production, the quality of base Baijiu in newly built workshop is inferior to the older one. In this study, the microbiota of workshop environment and fermentation process from two workshops namely N (ferment 2 years) and O (ferment 20 years) and flavor compounds were studied during Xiasha round. Results showed workshop O accumulated more environmental microorganisms and fungi including P. kudriavzevii, Wickerhamomyces anomalus and Saccharomyces sp mainly came from ground. Yeasts including Pichia, Cyberlindnera, Wickerhamomyces and Candida were responsible for flavor substances formation in O while Saccharopolyspora was in N. This study for the first time explored the reasons for the brewing differences among N and O workshop from perspectives of workshop environment, microbial community and flavor substances, providing new ideas for guiding production as well as improvement of Baijiu quality.

Mid-infrared pulsed Er:ZBLAN fiber laser producing mode-switchable cylindrical vector beams.

We demonstrate the generation of both continuous-wave (CW) and Q-switched cylindrical vector beams (CVBs) from a mid-infrared Er3+-doped ZBLAN (Er:ZBLAN) fiber laser at ∼ 2.8 µm. A customized S-waveplate is incorporated as the intracavity mode converter to achieve the mid-infrared CVBs. Switchable modes of CVBs between the radially and azimuthally polarized beam can be realized easily by manipulating the cavity conditions. A maximum output power of ∼250 mW is achieved for the CW CVBs. In the short-pulsed CVBs operation regime, both the active and passive Q-switching modes are realized with a pulse duration of hundreds of nanoseconds. The proposed mid-infrared cylindrical vector lasers can have significant potential for applications in biomedicine, optical trapping, material processing and optical communication.

Origin of p-type conductivity in a WSe2 monolayer.

Transition-metal dichalcogenides have promising potentials for high-performance electronic and optoelectronic applications, which could be deeply influenced by defects, including native defects and dopants. Experiments to date have frequently reported p-type conductivity in the WSe2 monolayer, but the origin remains elusive. Here, using the first-principles calculations, we systematically investigate the point defects in the WSe2 monolayer and show that: (1) no intrinsic point defect is responsible for the p-type doping; (2) hydrogen interstitials (Hi) are possible sources for n-type conductivity; (3) oxygen substitution of Se (OSe) can greatly promote the formation of adjacent W vacancy (VW), and finally make VW relatively shallow acceptors by forming the defect complex nOSe + VW (n = 1 to 6). Our work reveals that nOSe + VW is the origin of the p-type conductivity in the unintentionally doped WSe2 monolayer, given that O is present throughout the synthesis conditions of WSe2.

Tuning magnetocrystalline anisotropy by controlling the orbital electronic configuration of two-dimensional magnetic materials.

A suitable magnetic anisotropy energy (MAE) is a key factor for magnetic materials. However, an effective MAE control method has not yet been achieved. In this study, we propose a novel strategy to manipulate MAE by rearranging the d-orbitals of metal atoms with oxygen functionalized metallophthalocyanine (MPc) by first-principles calculations. By the dual regulation of electric field and atomic adsorption, we have achieved a substantial amplification of the single regulation method. The use of O atoms to modify the metallophthalocyanine (MPc) sheets effectively adjusts the orbital arrangement of the electronic configuration in the d-orbitals of the transition metal near the Fermi level, thereby modulating the MAE of the structure. More importantly, the electric field amplifies the effect of electric-field regulation by adjusting the distance between the O atom and metal atom. Our results demonstrate a new approach to modulating the MAE of two-dimensional magnetic films for practical application in information storage.

Enhancing Hole Density and Suppressing Recombination Centers through Illumination in Kesterite Thin Film Solar Cells.

Enhancing carrier density and increasing carrier lifetime are critical for the good performance of thin film solar cells. We apply illumination during the growth of kesterite Cu2ZnSnS4 (CZTS) to enhance hole density and suppress defects of nonradiative electron-hole recombination centers simultaneously. To examine the effect of the injected carriers generated by illumination, we first extend the scheme of detailed balance equations relating free carriers and defects beyond thermal equilibrium conditions by developing an extended Fermi level (EF') to characterize a homogeneous semiconductor with non-equilibrium carriers. On the basis of this scheme, we find that illumination can promote the formation of carrier-providing defects and suppress the formation of carrier-compensating defects. Then, we demonstrate that applying proper illumination during the growth of CZTS will help achieve a higher hole density and simultaneously suppress the formation of the SnZn antisite significantly, which are beneficial for the performance of CZTS solar cells.

Dimensionality-Inhibited Chemical Doping in Two-Dimensional Semiconductors: The Phosphorene and MoS2 from Charge-Correction Method.

Despite the great appeal of two-dimensional semiconductors for electronics and optoelectronics, to achieve the required charge carrier concentrations by means of chemical doping remains a challenge due to large defect ionization energies (IEs). Here, by decomposing the defect IEs into three parts based on ionization process, we propose a conceptual picture that the large defect IEs are caused by two effects of reduced dimensionality. While the quantum confinement effect makes the neutral single-electron point defect levels deep, the reduced screening effect leads to high energy cost for the electronic relaxation. The first-principles calculations for black phosphorus and MoS2 do demonstrate the general trend. Using BP monolayer either embedded into dielectric continuum or encapsulated between two hBN layers, we demonstrate the feasibility of increasing the screening to reduce the defect IEs. Our analysis is expected to help achieve effective carrier doping and open ways toward more extensive applications of 2D semiconductors.

Prediction of colossal magnetocrystalline anisotropy for transition metal triiodides.

In virtue of first principle calculations based on density functional theory, we have investigated the magnetism of transition metal triiodides XI3 (X = Cr, Mn, Fe, Mo, Tc, Ru, W, Re, Os) monolayers. Our results indicate that CrI3, TcI3, RuI3, ReI3 and OsI3 monolayers are ferromagnetic (FM), while MnI3, FeI3, MoI3 and WI3 monolayers are antiferromagnetic (AFM). Interestingly, TcI3, RuI3, ReI3 and OsI3 monolayers have considerable magnetic anisotropy energy (MAE). Especially, ReI3 monolayer exhibits the largest MAE (-36.22 meV/ReI3) in known two-dimensional (2D) van der Waals (vdW) crystals. We further demonstrate that biaxial strain can greatly change MAEs of ReI3 and OsI3 monolayers. From the electronic structure analysis, the change in MAE is mainly attributed from the charge transfer between the a and e 2 states induced by biaxial strain. In addition, we have also found that a tensile strain can lead to a phase transition of ReI3 from FM to AFM. We predicted that 2D FM XI3 monolayers are promising candidates for the application in tunable magnetic storage technology.

1,25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue.

Leptin is an adipose tissue-derived hormone that plays a critical role in energy homeostasis. Vitamin D has been shown to regulate energy metabolism, but the relationship between vitamin D and leptin is unclear. Leptin expression and secretion was reduced in vitamin D receptor (VDR)-null mice and increased in transgenic (Tg) mice overexpressing the VDR in adipocytes; however, as leptin is mainly determined by fat mass, it is unclear whether the vitamin D hormone directly regulates leptin expression. To address this question, we determined the effect of vitamin D on leptin expression in vivo and ex vivo. One-week treatment of WT mice with the vitamin D analog RO-27-5646 led to a significant increase in adipose leptin mRNA transcript and serum leptin levels. Moreover, in adipose tissue cultures, 1,25-dihydroxyvitamin D markedly stimulated mRNA expression and secretion of leptin, but not resistin, in adipose tissues obtained from WT mice, but not from VDR-null mice, and leptin upregulation induced by 1,25-dihydroxyvitamin D was more robust in adipose tissues obtained from VDR Tg mice compared with WT mice. These data demonstrate that 1,25-dihydroxyvitamin D stimulates adipose leptin production in a VDR-dependent manner, suggesting that vitamin D may affect energy homeostasis through direct regulation of leptin expression.