TAF1 is needed for the proliferation and maturation of thyroid follicle cells via Notch signaling.

Thyroid dysgenesis (TD) is the common pathogenic mechanism of congenital hypothyroidism (CH). In addition, known pathogenic genes are limited to those that are directly involved in thyroid development. To identify additional candidate pathogenetic genes, we performed forward genetic screening for TD in zebrafish, followed by positional cloning. The candidate gene was confirmed in vitro using the Nthy-ori 3.1 cell line and in vivo using a zebrafish model organism. We obtained a novel zebrafish line with thyroid dysgenesis and identified the candidate pathogenetic mutation TATA-box binding protein associated Factor 1 (taf1) by positional cloning. Further molecular studies revealed that taf1 was needed for the proliferation of thyroid follicular cells by binding to the NOTCH1 promoter region. Knockdown of TAF1 impaired the proliferation and maturation of thyroid cells, thereby leading to thyroid dysplasia. This study showed that TAF1 promoted Notch signaling and that this association played a pivotal role in thyroid development.NEW & NOTEWORTHY In our study, we obtained a novel zebrafish line with thyroid dysgenesis (TD) and identified the candidate pathogenetic mutation TATA-box binding protein associated Factor 1 (taf1). Further researches revealed that taf1 was required for thyroid follicular cells by binding to the NOTCH1 promoter region. Our findings revealed a novel role of TAF1 in thyroid morphogenesis.

Radix Tetrastigma Hemsleyani Flavone represses cutaneous squamous cell carcinoma via Janus kinase/signal transducer and activator of transcription 3 pathway inactivation.

Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant skin tumor and significantly affects patients' quality of life and health. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway activation is involved in CSCC development. Radix Tetrastigma hemsleyani flavone (RTHF) is an active Radix Tetrastigma extract (RTE), which was recently reported to have promising inhibitory effects on CSCC. However, the underlying functional mechanisms of this inhibition remain unknown. In the present study, A431 cells or SCL-1 cells were incubated with 1, 5, and 10 mg/mL RTHF for 48 h, respectively. A significantly increased wound closure rate, decreased number of migrated and invaded cells, decreased colony number, and elevated apoptotic rate were observed after treatment with 1, 5, and 10 mg/mL RTHF. Furthermore, after incubation with RTHF, p-JAK1/JAK1, p-JAK2/JAK2, and p-STAT3/STAT3 levels were drastically reduced. An A431 xenograft model was constructed, followed by oral administration of 15, 30, or 60 mg/kg RTHF for 21 consecutive days. A significantly lower increase in tumor volume and reduced tumor weight were observed in all RTHF-treated groups. In addition, JAK/STAT3 signaling was drastically repressed in tumor tissues. Collectively, RTHF inhibited CSCC progression, which may be associated with JAK/STAT3 pathway inactivation.

Subwavelength Bessel beam arrays with high uniformity based on a metasurface.

Bessel beam arrays are highly attractive due to non-diffraction properties, parallel processing, and large capacity capabilities. However, conventional approaches of generating Bessel beams, such as spatial light modulators, axicons, and diffraction optical elements, suffer from various limitations of system complexity and bulkiness, low uniformity, and limited numerical aperture (NA). The limited NA imposes constraints on achieving minimal full width at half maximum (FWHM) of the Bessel beam, ultimately compromising the resolution of the beam. In this study, we demonstrate a method for generating Bessel beam arrays with regular and random patterns via an ultra-compact metasurface. This approach integrates the phase profile of an optimized beam splitter with a meta-axicon. The Bessel beam arrays exhibit subwavelength dimensions of FWHM (590 nm, ∼0.9λ) and relatively high uniformity of 90% for N A=0.2 and 69% for N A=0.4. Furthermore, the method achieves effective suppression of background noise and zeroth-order intensity compared to methods based on Dammann grating (DG) based metasurfaces. The proposed method highlights potential applications of Bessel beam arrays in various fields, such as laser machining, optical communication, and biomedical imaging.

Heterogenous Slippery Surfaces: Enabling Spontaneous and Rapid Transport of Viscous Liquids with Viscosities Exceeding 10 000 mPa s.

Superhydrophobic and slippery lubricant-infused surfaces have garnered significant attention for their potential to passively transport low-viscosity liquids like water (1 mPa s). Despite exciting progress, these designs have proven ineffective for transporting high-viscosity liquids such as polydimethylsiloxane (5500 mPa s) due to their inherent limitations imposed by the homogenous surface design, resulting in high viscous drags and compromised capillary forces. Here, a heterogenous water-infused divergent surface (WIDS) is proposed that achieves spontaneous, rapid, and long-distance transport of viscous liquids. WIDS reduces viscous drag by spatially isolating the viscous liquids and surface roughness through its heterogenous, slippery topological design, and generates capillary forces through its heterogenous wetting distributions. The essential role of surface heterogeneity in viscous liquid transport is theoretically and experimentally verified. Remarkably, such a heterogenous paradigm enables transporting liquids with viscosities exceeding 12 500 mPa s, which is two orders of magnitude higher than state-of-the-art techniques. Furthermore, this heterogenous design is generic for various viscous liquids and can be made flexible, making it promising for various systems that require viscous liquid management, such as micropatterning.

Self-Adaptive Droplet Bouncing on a Dual Gradient Surface.

Rapid detachment of impacting droplets from underlying substrate is highly preferred for mass, momentum, and energy exchange in many practical applications. Driven by this, the past several years have witnessed a surge in engineering macrotexture to reduce solid-liquid contact time. Despite these advances, these strategies in reducing contact time necessitate the elegant control of either the spatial location for droplet contact or the range of impacting velocity. Here, this work circumvents these limitations by designing a dual gradient surface consisting of a vertical spacing gradient made of tapered pillar arrays and a lateral curvature gradient characterized as macroscopic convex. This design enables the impacting droplets to self-adapt to asymmetric or pancake bouncing mode accordingly, which renders significant contact time reduction (up to ≈70%) for a broad range of impacting velocities (≈0.4-1.4 m s-1 ) irrespective of the spatial impacting location. This new design provides a new insight for designing liquid-repellent surfaces, and offers opportunities for applications including dropwise condensation, energy conversion, and anti-icing.

Novel NQO1 substrates bearing two nitrogen redox centers: Design, synthesis, molecular dynamics simulations, and antitumor evaluation.

By analyzing the crystal structure of NQO1, an additional binding region for the ligand was discovered. In this study, a series of derivatives with a novel skeleton bearing two nitrogen redox centers were designed by introducing amines or hydrazines to fit with the novel binding region of NQO1. Compound 24 with a (4-fluorophenyl)hydrazine substituent was identified as the most efficient substrate for NQO1 with the reduction rate and catalytic efficiency of 1972 ± 82 µmol NADPH/min/µmol NQO1 and 6.4 ± 0.4 × 106 M-1s-1, respectively. Molecular dynamics (MD) simulation revealed that the distances between the nitrogen atom of the redox centers and the key Tyr128 and Tyr126 residues were 3.5 Å (N1-Tyr128) and 3.4 Å (N2-Tyr126), respectively. Compound 24 (IC50/A549 = 0.69 ± 0.09 µM) showed potent antitumor activity against A549 cells both in vitro and in vivo through ROS generation via NQO1-mediated redox cycling, leading to a promising NQO1-targeting antitumor candidate.

The contribution of wetland plant litter to soil carbon pool: Decomposition rates and priming effects.

Plant litter input is an important driver of soil/sediment organic carbon (SOC) turnover. A large number of studies have targeted litter-derived C input tracing at a global level. However, little is known about how litter carbon (C) input via various plant tissues affects SOC accumulation and mineralization. Here, we conducted laboratory incubation to investigate the effects of leaf litter and stem litter input on SOC dynamics using the natural 13C isotope technique. A 122-day laboratory incubation period showed that litter input facilitated SOC accumulation. Leaf and stem litter inputs increased soil total organic carbon content by 37.6% and 15.5%, respectively. Leaf litter input had a higher contribution to SOC accumulation than stem litter input. Throughout the incubation period, the δ13C values of stem litter and leaf litter increased by 1.5‰ and 3.3‰, respectively, while δ13CO2 derived from stem litter and δ13CO2 derived from leaf litter decreased by 4.2‰ and 6.1‰, respectively, suggesting that the magnitude of δ13C in litter and δ13CO2 shifts varied, depending on litter tissues. The cumulative CO2-C emissions of leaf litter input treatments were 27.56%-42.47% higher than those of the stem litter input treatments, and thus leaf litter input promoted SOC mineralization more than stem litter input. Moreover, the proportion of increased CO2-C emissions to cumulative CO2-C emissions (57.18%-92.12%) was greater than the proportion of litter C input to total C (18.7%-36.8%), indicating that litter input could stimulate native SOC mineralization, which offsets litter-derived C in the soil. Overall, litter input caused a net increase in SOC accumulation, but it also accelerated the loss of native SOC. These findings provide a reliable basis for assessing SOC stability and net C sink capacity in wetlands.

Treated wastewater and weak removal mechanisms enhance nitrate pollution in metropolitan rivers.

The focus of urban water environment renovation has shifted to high nitrate (NO3-) load. Nitrate input and nitrogen conversion are responsible for the continuous increase in nitrate levels in urban rivers. This study utilized nitrate stable isotopes (δ15N-NO3- and δ18O-NO3-) to investigate NO3- sources and transformation processes in Suzhou Creek, located in Shanghai. The results demonstrated that NO3- was the most common form of dissolved inorganic nitrogen (DIN), accounting for 66 ± 14% of total DIN with a mean value of 1.86 ± 0.85 mg L-1. The δ15N-NO3- and δ18O-NO3- values ranged from 5.72 to 12.42‰ (mean value: 8.38 ± 1.54‰) and -5.01 to 10.39‰ (mean value: 0.58 ± 1.76‰), respectively. Based on isotopic evidence, the river received a significant amount of nitrate through direct exogenous input and sewage ammonium nitrification, while nitrate removal (denitrification) was insignificant, resulting in nitrate accumulation. Analysis using the MixSIAR model revealed that treated wastewater (68.3 ± 9.7%), soil nitrogen (15.7 ± 4.8%) and nitrogen fertilizer (15.5 ± 4.9%) were the main sources of NO3- in rivers. Despite the fact that Shanghai's urban domestic sewage recovery rate has reached 92%, reducing nitrate concentrations in treated wastewater is crucial for addressing nitrogen pollution in urban rivers. Additional efforts are needed to upgrade urban sewage treatment during low flow periods and/or in the main stream, and to control non-point sources of nitrate, such as soil nitrogen and nitrogen fertilizer, during high flow periods and/or tributaries. This research provides insights into NO3- sources and transformations, and serves as a scientific basis for controlling NO3- in urban rivers.

Emblica officinalis mitigates intestinal toxicity of mice by modulating gut microbiota in lead exposure.

Lead (Pb) contamination has been affecting public health for decades. As a plant-derived medicine, the safety and effectiveness of Emblica officinalis (E. officinalis) fruit extract has been emphasized. The current study focused on mitigating the adverse effects of lead (Pb) exposure in reducing its toxicity worldwide. According to our findings, E. officinalis significantly improved weight loss and colon length shortening (p < 0.05 or p < 0.01). The data of colon histopathology and serum levels of inflammatory cytokines indicated a positive impact to the colonic tissue and inflammatory cell infiltration in a dose-dependent manner. Moreover, we confirmed the expression level improvement of tight junction proteins (TJPs), including ZO-1, Claudin-1, and Occludin. Furthermore, we found that the abundance of some commensal species necessary for maintaining homeostasis and other beneficial function decreased in Pb exposure model, while a remarkable reversion impact was noticed on the intestinal microbiome composition in the treatment group. These findings were consistent with our speculations that E. officinalis could mitigate the adverse effects caused by Pb in alleviating intestinal tissue damage, intestinal barrier disruption, and inflammation. Meanwhile, the variations in gut microbiota might drive the fulfilling current impact. Hence, the present study could provide the theoretical basis for mitigating intestinal toxicity induced by Pb exposure with the help of E. officinalis.

Swertia bimaculata moderated liver damage in mice by regulating intestine microbiota.

Swertia bimaculata (SB) is a medicinal herb in China having an array of therapeutic and biological properties. This study aimed to explore the attenuating effect of SB on carbon tetrachloride (CCl4) induced hepato-toxicity by regulation of gut microbiome in ICR mice. For this purpose, CCl4 was injected intraperitoneally in different mice groups (B, C, D and E) every 4th day for a period of 47 days. Additionally, C, D, and E groups received a daily dose (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) of Ether extract of SB via gavage for the whole study period. The results of serum biochemistry analysis, ELISA, H&E staining, and sequencing of the gut microbiome, indicated that SB significantly alleviates the CCl4-induced liver damage and hepatocyte degeneration. The serum levels of alanine transaminase, aspartate aminotransferase, malondialdehyde, interleukin 1 beta and tumor necrosis factor-alpha were significantly lower in SB treated groups compared to control while levels of glutathione peroxidase were raised. Also, the sequencing data indicate that supplementation with SB could restore the microbiome and its function in CCl4-induced variations in intestinal microbiome of mice by significantly downregulating the abundances of pathogenic intestinal bacteria species including Bacteroides, Enterococcus, Eubacterium, Bifidobacterium while upregulating the levels of beneficial bacteria like Christensenella in the gut. In conclusion, we revealed that SB depicts a beneficial effect against hepatotoxicity induced by CCl4 in mice through the remission of hepatic inflammation and injury, through regulation of oxidative stress, and by restoring gut microbiota dysbiosis.

Plant Polyphenols Attenuate DSS-induced Ulcerative Colitis in Mice via Antioxidation, Anti-inflammation and Microbiota Regulation.

The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately explored. Herein, we studied the antioxidation-structure relationship of several common polyphenols in plants including gallic acid, proanthocyanidin, ellagic acid, and tannic acid. Furthermore, the in vivo effects of the plant polyphenols on C57BL/6 mice with dextran-sulfate-sodium-induced UC were evaluated and the action mechanisms were explored. Moreover, the interplay of several mechanisms was determined. The higher the number of phenolic hydroxyl groups, the stronger the antioxidant activity. All polyphenols markedly ameliorated the symptoms and pathological progression of UC in mice. Furthermore, inflammatory cytokine levels were decreased and the intestinal barrier was repaired. The process was regulated by the antioxidant-signaling pathway of nuclear-erythroid 2-related factor 2. Moreover, the diversity of the intestinal microbiota, Firmicutes-to-Bacteroides ratio, and relative abundance of beneficial bacteria were increased. An interplay was observed between microbiota regulation and oxidative stress, immunity, and inflammatory response. Furthermore, intestinal barrier repair was found to be correlated with inflammatory responses. Our study results can form a basis for comprehensively developing plant-polyphenol-related medicinal products.

Effect and Mechanism of Pharmaceutical Excipients on Berberine to Alleviate Ulcerative Colitis via Regulating Gut Microbiota.

BACKGROUND: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. METHODS: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. RESULTS: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1ß, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. CONCLUSIONS: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs' therapeutic efficiency outcome.

Crystal-Facet Modulated CrOx/γ-Al2O3: Quasi-Liquid Surface Modification by Bonded Polydimethylsiloxane for Catalytic Oxidation of Propene.

The crystal-facet effect of catalytic supports plays a crucial role in tailoring the physicochemical properties of active sites and the surface chemically bonded polymer can also regulate the local environment around active sites for optimizing catalytic performance. Herein, we report the effect of exposed facets of γ-Al2O3 supports and further modification by surface bonded long-chain polydimethylsiloxane (PDMS) on the properties of CrOx/γ-Al2O3 catalysts for selective oxidation of propene. The {111} facets of γ-Al2O3 stabilize "non-redox Cr3+" and promote the overall oxidation rates compared with catalysts on {110} facets of γ-Al2O3. The surface bonded PDMS, with grafting density being about 0.13 chains/nm2, endows a hydrophobic environment to facilitate the enrichment of the hydrophobic substrate and the desorption of hydrophilic products and occupies some acid sites on catalysts to limit acid-catalyzed side reactions. The inherent liquidlike nature of bonded PDMS also forms a setting that can regulate the redox ability of surface Cr species, that lead to modified activation of oxygen toward more surface adsorbed species. As a result, the modified catalysts enhance the whole oxidation process with favorable formation of epoxide product at low reaction temperatures (<225 °C). Our findings highlight the impact of surface chemically bound polydimethylsiloxane (PDMS) upon tailoring the surroundings of the catalyst surface, and that combined with facet-effect of supports can tune the reaction process toward selective ones.

Precise Control Over Kinetics of Molecular Assembly: Production of Particles with Tunable Sizes and Crystalline Forms.

It has been long-pursued but remains a challenge to precisely manipulate the molecular assembly process to obtain desired functional structures. Reported here is the control over the assembly of solute molecules, by a programmed recrystallization of solvent crystal grains, to form micro/nanoparticles with tunable sizes and crystalline forms. A quantitative correlation between the protocol of recrystallization temperature and the assembly kinetics results in precise control over the size of assembled particles, ranging from single-atom catalysts, pure drug nanoparticles, to sub-millimeter organic-semiconductor single crystals. The extensive regulation of the assembly rates leads to the unique and powerful capability of tuning the stacking of molecules, involving the formation of single crystals of notoriously crystallization-resistant molecules and amorphous structures of molecules with a very high propensity to crystallize, which endows it with wide-ranging applications.

Comparison of Raw Data-Based and Complex Image-Based Sparse SAR Imaging Methods.

Sparse signal processing has already been introduced to synthetic aperture radar (SAR), which shows potential in improving imaging performance based on raw data or a complex image. In this paper, the relationship between a raw data-based sparse SAR imaging method (RD-SIM) and a complex image-based sparse SAR imaging method (CI-SIM) is compared and analyzed in detail, which is important to select appropriate algorithms in different cases. It is found that they are equivalent when the raw data is fully sampled. Both of them can effectively suppress noise and sidelobes, and hence improve the image performance compared with a matched filtering (MF) method. In addition, the target-to-background ratio (TBR) or azimuth ambiguity-to-signal ratio (AASR) performance indicators of RD-SIM are superior to those of CI-SIM in down-sampling data-based imaging, nonuniform displace phase center sampling, and sparse SAR imaging model-based azimuth ambiguity suppression.

Unlocking the Potential of Metal-Doping Fe2O3/Rice Husk Ash Catalysts for Low-Temperature CO-SCR Enhancement.

Transition metal oxides are efficient bifunctional catalysts for the selective catalytic reduction (SCR) of nitrogen oxides (NOx) using CO. Nonetheless, their poor activity at lower temperatures constrains broader industrial application. Herein, we propose an optimized Fe2O3-based catalyst through strategic metal doping with Cu, Co, or Ce, which engenders a harmonious balance for the synergistic removal of CO and NOx. Among the developed catalysts, Co-doped Fe2O3, supported by rice husk ash, demonstrates superior low-temperature CO-SCR activity, achieving CO and NOx conversion ratios and N2 selectivity above 98.5% at 100-500 °C. The enhanced catalytic performance is attributed to the catalyst's improved redox properties and acidity, engendered by strong Fe-Ox-Co interactions. Furthermore, the CO-SCR reaction adheres to the Langmuir-Hinshelwood and Eley-Rideal mechanisms. Our findings shed light on the future industrial application of low-temperature CO and NOx near-zero emission technology and provide a strategy for the design of low-cost SCR catalysts.

The structure and function of olfactory receptors.

Olfactory receptors (ORs) form the most important chemosensory receptor family responsible for our sense of smell in the nasal olfactory epithelium. This receptor family belongs to the class A G protein-coupled receptors (GPCRs). Recent research has indicated that ORs are involved in many nonolfactory physiological processes in extranasal tissue, such as the brain, pancreas, and testes, and implies the possible role of their dysregulation in various diseases. The recently released structures of OR51E2 and consensus OR52 have also unveiled the uniqueness of ORs from other class A GPCR members. In this review, we discuss these recent developments and computational modeling efforts toward understanding the structural properties of unresolved ORs, which could guide potential future OR-targeted drug discovery.

Resistance training up-regulates Smyd1 expression and inhibits oxidative stress and endoplasmic reticulum stress in the heart of middle-aged mice.

Persistent oxidative stress and endoplasmic reticulum (ER) stress are the primary mechanisms of age-related cardiovascular diseases. Although exercise training is viewed as an effective anti-aging approach, further exploration is needed to identify the mechanisms and functional targets. In this study, the impact of resistance training (RT) on the expression of Smyd1, the levels of reactive oxygen species (ROS) and the expression of ER stress-related protein in the hearts of mice of different ages were assessed. In addition, the role of Smyd1 in the aging-induced oxidative stress and ER stress were evaluated in d-galactose (D-gal)-treated H9C2 cells. We demonstrated that RT in middle age increased the expression of Smyd1 and restricted heart aging-induced ER stress. Overexpression of Smyd1 restrained oxidative stress and ER stress in D-gal-treated H9C2 cells, while the inhibition of Nrf2 and Smyd1 escalated ER stress. These findings demonstrate that Smyd1 has significant impact in regulating age-related ER stress. RT in middle age can up-regulates Smyd1 expression and inhibits oxidative stress and ER stress in the heart.

The efficient generation of functional human hepatocytes from chemically induced pluripotent stem cells.

Derivation of human hepatocytes from pluripotent stem cells in vitro has important applications including cell therapy and drug discovery. However, the differentiation of pluripotent stem cells into hepatocytes in vitro was not well recapitulated the development of liver. Here, we developed a differentiation protocol by mimicking the two-stage development of hepatoblasts, which permits the efficient generation of hepatic progenitor cells from chemically induced pluripotent stem cells (hCiPSCs). Single-cell RNA sequencing (scRNA-seq) indicates the similarity between hepatoblasts differentiated in vitro and in vivo. Moreover, hCiPSC-derived hepatic progenitor cells can further differentiate into hepatocytes that are similar to primary human hepatocytes with respect to gene expression and key hepatic functions. Our results demonstrate the feasibility of generating hepatic progenitor cells and hepatocytes from hCiPSCs with high efficiency and set the foundation for broad translational applications of hCiPSC-derived hepatocytes.