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Twelve liquid crystalline polymer network films were fabricated through photopolymerization of cholesteric liquid-crystalline mixtures containing two aggregation-induced emissive-active luminogens. The films exhibit multicolour and white circularly polarized luminescence with dissymmetry factors up to 0.85 and fluorescence quantum yields up to 90%.

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The gut microbiota is crucial for maintaining the host's intestinal homeostasis and metabolism. This study investigated the effects of fecal microbiota transplantation (FMT) from Ningxiang pigs on the growth performance, fecal microbiota, and serum metabolites of the same-old DLY pigs. The results indicated that the average daily gain of FMT pigs was significantly greater than that of the control (CON) group. Compared to the CON group, the FMT group significantly improved the apparent digestibility of crude fiber, crude ash, gross energy, and calcium of the pigs. The analysis of serum antioxidant status revealed that the activities of total superoxide dismutase and catalase in the serum of pigs in the FMT group were significantly elevated, whereas the level of malondialdehyde was significantly reduced. Furthermore, 16S rRNA sequencing analysis revealed that the Ningxiang pig-derived microbiota altered the fecal microbiota structure and modulated the diversity of the gut microbiota in the DLY pigs. Untargeted LC-MS metabolomics demonstrated that pigs in the FMT group exhibited distinct metabolomic profiles compared to those in the CON group. Significant changes were observed in key metabolites involved in amino acid, lipid, and carbohydrate metabolism. Additionally, a correlation analysis between serum differential metabolites and the gut microbiota revealed that the relative abundance of Lachnospiraceae_NK4A136_group and Corynebacterium was highly correlated with lipid compounds. In conclusion, Ningxiang pig-derived microbiota can alleviate oxidative stress and enhance growth performance in DLY pigs by modulating their gut microbiota and metabolic features.

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Ammonia, with high energy density and easy transportation, holds significant potential to become an integral part of future energy systems. Among tremendous strategies, electrocatalytic ammonia production is no doubt an efficient and eco-friendly method. One particularly intriguing class of electrocatalysts for reducing nitrate to ammonia is transition metal oxides, which have been heavily researched. However, how these catalysts' oxygen vacancy (VO) affects their performance remains elusive. To address this, taking titania (the most important catalyst) as an example, we carried out experimental investigations and simulations. Contrary to the prevailing belief that the concentrated VO would increase the catalytic efficiency of nitrate reduction, it was found that a relatively low level of VO is favorable for maximizing catalytic efficiency. At low cathodic voltages, titania with minimal VO delivered both the highest reduction efficiency and the best selectivity among the different titania samples in this paper. In addition to outlining the merits of lower electron transfer resistance and accelerated reaction dynamics, we also put forth a previously unmentioned factor, the adsorption of hydrogen or the creation of an ordered hydrogen bond network, which put up a hydrogen-rich atmosphere for following nitrate reduction. Further simulation study revealed that within the hydrogen-rich atmosphere isolated VO serves as the ideal active center to enable the lowest energy barriers for the reduction of nitrate into ammonia. These findings offer fresh insights into the working mechanism of oxide-based electrocatalysts for ammonia production.

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In this work, the relationship between electrochemiluminescence (ECL) signal and driving voltage was first studied by self-made reduced and oxidized closed bipolar electrodes (CBPEs). It was found that when the driving voltage was large enough, the maximum ECL signals for the two kinds of CBPEs were the same but their required drive voltages were different. Zinc cobalt nitrogen doped carbon material (ZnCoN-C) had an outstanding electric double layer (EDL) property and conductivity. Therefore, it could significantly reduce the driving voltage of two kinds of CBPE systems, reaching the maximum ECL signal of Ru(bpy)32+. Interestingly, when the ZnCoN-C modified electrode reached the maximum ECL signal, the bare electrode signal was zero. As a proof-of-concept application, a zero-background dual-mode CBPE-ECL biosensor was constructed for the ultrasensitive detection of ochratoxin A (OTA) in beer. Considering that beer samples contained a large number of reducing substances, a reduced CBPE system was selected to build the biosensor. Furthermore, a convenient ECL imaging platform using a smartphone was built for the detection of OTA. This work used a unique EDL material ZnCoN-C to regulate the driving voltage of CBPE for the first time; thus, a novel zero-background ECL sensor was constructed. Further, this work provided a deeper understanding of the CBPE-ECL system and opened a new door for zero-background detection.

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Weaning is a critical stage in the growth and development of piglets, often inducing stress reactions. This study aims to investigate the effects of Parabacteroides distasonis (PBd) derived from Ningxiang pigs on growth performance, intestinal apoptosis, oxidative damage, and inflammation in ETEC-challenged weaned piglets. A total of 22 Duroc × Landrace × Yorkshire (DLY) piglets, 24 days old with similar body weights, were randomly divided into three groups: Control (n = 7), ETEC (n = 7), and PBd + ETEC (n = 8). The results show that, compared to the Control group, ETEC challenge led to decreased growth performance, reduced villus height in the duodenum and jejunum, increased crypt depth in the duodenum, a decreased villus-height-to-crypt-depth ratio, increased expression of apoptosis-related genes (Caspase-8 and Caspase-9), increased expression of oxidative damage-related genes (Nrf2, GSH-PX, mTOR, and Beclin1), increased expression of inflammation-related genes (Myd88, P65, TNF-α, and IL-6), and reduced the contents of SCFAs in the colonic chyme (acetate, propionate, butyrate, valerate, and total SCFAs). Compared to the ETEC group, the PBd + ETEC group alleviated the reduction in growth performance, mitigated intestinal morphological damage, and reduced the expression of the aforementioned apoptosis, oxidative damage, and inflammation-related genes with the increase in SCFAs. In conclusion, PBd derived from Ningxiang pigs effectively reduces ETEC-induced intestinal damage in weaned piglets, improves intestinal health, and increases the content of SCFAs in the colonic chyme, thereby enhancing growth performance.

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In this work, a new photoelectrochemical (PEC) biosensor based on triple quenching effect of nanozyme catalyzed precipitation to PEC signal of MgIn2S4 was constructed for ultrasensitive detection of circulating tumor DNA (ctDNA). Enzyme-free amplification technology was used to convert target ctDNA into a large number of product chains (PC) to improve the detection sensitivity. Co3O4 nanozyme with excellent peroxidase (POD)-like activity was introduced to the surface of MgIn2S4 by PC. Co3O4 could oxidize chromogenic agent 3-Amino-9-ethylcarbazole (AEC) to produce red insoluble precipitation in the presence of H2O2, resulting in the PEC signal "off" of MgIn2S4 to achieve ultrasensitive detection of ctDNA. In particular, Co3O4 nanozyme showed three synergistic quenching effects on PEC signal of MgIn2S4, which contributed greatly to improving the detection sensitivity. Firstly, the light absorption range of Co3O4 could reach 1000 nm, and compete with MgIn2S4 for light absorption. Secondly, the produced red precipitation belonged to the insulating material and had large electrochemical impedance, which hindered the transmission of photogenerated carriers. Thirdly, the precipitation also prevented the electron donor ascorbic acid (AA) from transferring electrons to MgIn2S4. This biosensor provided a promising sensitive PEC detection technology for ctDNA, and further broadened the application of nanozymes in the field of PEC analysis.

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Skin aging is characterized by the disruption of skin homeostasis and impaired skin injury repair. Treatment of aging skin has long been limited by the unclear intervention targets and delivery techniques. Engineering extracellular vesicles (EVs) as an upgraded version of natural EVs holds great potential in regenerative medicine. In this study, we found that the expression of the critical antioxidant and detoxification gene Gstm2 was significantly reduced in aging skin. Thus, we constructed the skin primary fibroblasts-derived EVs encapsulating Gstm2 mRNA (EVsGstm2), and found that EVsGstm2 could significantly improve skin homeostasis and accelerate wound healing in aged mice. Mechanistically, we found that EVsGstm2 alleviated oxidative stress damage of aging dermal fibroblasts by modulating mitochondrial oxidative phosphorylation, and promoted dermal fibroblasts to regulate skin epidermal cell function by paracrine secretion of Nascent Polypeptide-Associated Complex Alpha subunit (NACA). Furthermore, we confirmed that NACA is a novel skin epidermal cell protective molecule that regulates skin epidermal cell turnover through the ROS-ERK-ETS-Cyclin D pathway. Our findings demonstrate the feasibility and efficacy of EVs-mediated delivery of Gstm2 for aged skin treatment and unveil novel roles of GSTM2 and NACA for improving aging skin.

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Bone marrow mesenchymal stem cells (BMMSCs) are a type of stem cell with multi-directional differentiation potential. Compared with BMMSCs derived from appendicular bones, BMMSCs derived from the jaw have greater proliferative and osteogenic differentiation ability, gradually becoming important seed cells for jaw defect repair. However, the mandible has a complex bony structure and less cancellous content than appendicular bones. It is difficult to acquire a large number of high-quality jaw-derived marrow mesenchymal stem cells using traditional methods. This study presents a 'niche-based approach on stemness' for isolating and culturing rat jaw bone marrow mesenchymal stem cells (JBMMSCs). Primary rat JBMMSCs were isolated and cultured using the whole bone marrow adherent method combined with the bone slice digestion method. The isolated cells were identified as JBMMSCs through cell morphology observation, detection of cell surface markers, and multi-directional differentiation induction. The cells extracted by this method exhibit a 'fibroblast-like' spindle shape. The cells are long, spindle-shaped and fibroblast-like. The flow cytometry analysis shows these cells are positive for CD29, CD44, and CD90 but negative for CD11b/c, CD34, and CD45, which is congruent with BMMSCs characteristics. The cells show strong proliferation capacity and can undergo osteogenic, adipogenic, and chondrogenic differentiation. This study provides an effective and stable method for obtaining enough high-quality JBMMSCs with strong differentiation ability in a short time, which could facilitate further studies of the exploration of biological function, regenerative medicine, and related clinical applications.

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The oral delivery of doxorubicin (DOX), an anti-cancer drug, encounters multiple hurdles such as limited gastrointestinal permeability, P-glycoprotein-mediated efflux, brief intestinal residence, and rapid degradation. This study introduced a novel approach utilizing hyaluronic acid (HA)-grafted fatty acid monoglycerides (HGD) to encapsulate DOX, forming HGD-DOX nanoparticles, aimed at enhancing its oral bioavailability. Drug encapsulated by HGD provided several advantages, including extended drug retention in the gastrointestinal tract, controlled release kinetics, and promotion of lymphatic absorption in the intestine. Additionally, HGD-DOX nanoparticles could specifically target CD44 receptors, potentially increasing therapeutic efficacy. The uptake mechanism of HGD-DOX nanoparticles primarily involved clathrin-mediated, caveolin-mediated and macropinocytosis endocytosis. Pharmacokinetic analysis further revealed that HGD significantly prolonged the in vivo residence time of DOX. In vivo imaging and pharmacodynamic studies indicated that HGD possessed tumor-targeting capabilities and exhibited a significant inhibitory effect on tumor growth, while maintaining an acceptable safety profile. Collectively, these findings position HGD-DOX nanoparticles as a promising strategy to boost the oral bioavailability of DOX, offering a potential avenue for improved cancer treatment.

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Breast cancer, the most prevalent malignant tumor among women globally, is significantly influenced by the Wnt/ß-catenin signaling pathway, which plays a crucial role in its initiation and progression. While conventional chemotherapy, the standard clinical treatment, suffers from significant drawbacks like severe side effects, high toxicity, and limited prognostic efficacy, Traditional Chinese Medicine (TCM) provides a promising alternative. TCM employs a multi-targeted therapeutic approach, which results in fewer side effects and offers a high potential for effective treatment. This paper presents a detailed analysis of the therapeutic impacts of TCM on various subtypes of breast cancer, focusing on its interaction with the Wnt/ß-catenin signaling pathway. Additionally, it explores the effectiveness of both monomeric and compound forms of TCM in the management of breast cancer. We also discuss the potential of establishing biomarkers for breast cancer treatment based on key proteins within the Wnt/ß-catenin signaling pathway. Our aim is to offer new insights into the prevention and treatment of breast cancer and to contribute to the standardization of TCM.

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Amorphophallus muelleri is an Araceae plant with perennial tuber, widely used in food, pharmaceutical and chemical industry due to its richness in glucomannan. In April 2022, an outbreak of a target spot on A. muelleri plantlets was observed in a nursery in Ruili, Yunnan, China. The leafstalks of the diseased plantlets in the nursery turned brown and decayed (Fig.1 A-B), then gradually some water-soaked spots on the true leaves developed along the veins (Fig.1 A). Subquencely, the spots on the true leaves turned dark green to white-grayish in the center, which formed light to dark brown concentric rings with a target-like appearance surrounded by a yellow halo (Fig.1 C). When the temperature was 20-34℃ and the relatively humidity was 25-80%, dark-green to black sporodochia with white hypha appeared on the lower and upper leaf surfaces. Finally, 5-8% of the plants surveyed on 800 m2 of one-year-old plantlets in the nursery showed the symptoms and some plants with infected leafstalks would be death. Similar symptoms were also observed on about 10% of the transplanted plants surveyed on 12000 m2 (1.2 ha) of two-year-old plantlets in the field. Five diseased leaves from five distinct plantlets in the nursery were collected for pathogen isolation. Leaf pieces(5 x 5 mm) were cut from the edge of necrotic lesions, and surface-sterilized with 2.5% sodium hypochlorite for 1 min, 75% ethanol for 30 s, then rinsed 5 times by sterilized distilled water, finally put the leaf pieces on sterilized filter paper for 3-5 minutes to dry them and transferred onto potato dextrose agar (PDA) in petri dishes at 25℃ for three days. Five pure cultures identical to colony and conidial characteristics were isolated from five individual plants. The representative pure culture (M1) was grayish-white and circular colonies were 7.50 cm in diamter after 15 days at 25℃, with dark green concentric rings of sporodochia, the dorsal view of the colonies were yellowish. Conidia were aseptate, smooth, cylindrical, 5.00-6.25 (5.71) x 1.25-1.67 (1.63) µm (n = 20) rounded at both ends. A spore suspension (1 x 106 spores/ml) was prepared by harvesting spores from 15-day-old cultures grown in the dark at 25℃, then a thirty-ml of spore suspension was sprayed on the healthy leaves of 10 two-year-old plantlets. Thirty-ml of sterile water was sprayed on the healthy leaves of another 10 seedlings and used as the control. All seedlings were placed in a nursery at 20 to 34℃ and a relative humidity of 25 to 80%. Similar symptoms (Fig.1 D-F) to those observed in the nursery and field developed on all the 10 seedlings inoculated with M1 after two days, but not on the control leaves. The pathogenicity tests were repeated for three times. Fungal cultures reisolated from the infected leaves were identical to the original colonies and conidia, completing Koch's postulates. The internal transcribed spacer (ITS, primers ITS1 and ITS4) region of ribosomal DNA (OQ553785), calmodulin (cmdA, primers CAL-228F and CAL2Rd)(OQ559103), RNA polymerase II second largest subunit (rpb2, primers RPB2-5F2 and RPB2-7cR) (OQ559104) and ß-tubulin (tub2, primers Bt2a and Bt2b) (OQ559105) of M1 had 100%, 98.52%, 98.98% and 98.98% identity with the sequences of Paramyrothecium breviseta CBS544.75 (KU846289 for ITS, KU846262 for cmdA, KU846351 for rpb2, and KU846406 for tub2), respectively. In the phylogenic tree based on ITS, cmdA, rpb2 and tub2 gene sequences, the pure culture M1 clustered with P. breviseta CBS544.75, SDBR-CMU387, DRL4 and DRL3, which has been reported as the pathogen of leaf spot of Coffea arabica in China, C. canephora in China and Thailand (Wu et al. 2021; Withee et al. 2022). Molecular and morphological observations showed the pure culture M1 were P. breviseta (Withee et al. 2022), in addition the disease was named as target spot dueing to the typical target symptom on the leaves. To our knowledge, this is the first report of P. breviseta on A. muelleri from Yunnan, China, as well as worldwide. This disease can caused serious economic losses of A. muelleri dueing to that it can result 5-8% death of the plants in the nursery.

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A spatial-potential-color-resolved bipolar electrode electrochemiluminescence biosensor (BPE-ECL) using a CuMoOx electrocatalyst was constructed for the simultaneous detection and imaging of tetracycline (TET) and lincomycin (LIN). HOF-101 emitted peacock blue light under positive potential scanning, and CdSe quantum dots (QDs) emitted green light under negative potential scanning. CuMoOx could catalyze the electrochemical reduction of H2O2 to greatly increase the Faradic current of BPE and realize the ECL signal amplification. In channel 1, CuMoOx-Aptamer II (TET) probes were introduced into the BPE hole (left groove A) by the dual aptamer sandwich method of TET. During positive potential scanning, the polarity of BPE (left groove A) was negative, resulting in the electrochemical reduction of H2O2 catalyzed by CuMoOx, and the ECL signal of HOF-101 was enhanced for detecting TET. In channel 2, CuMoOx-Aptamer (LIN) probes were adsorbed on the MXene of the driving electrode (DVE) hole (left groove B) by hydrogen-bonding and metal-chelating interactions. LIN bound with its aptamers, causing CuMoOx to fall off. During negative potential scanning, the polarity of DVE (left groove B) was negative and the Faradic current decreased. The ECL signal of CdSe QDs was reduced for detecting LIN. Furthermore, a portable mobile phone imaging platform was built for the colorimetric (CL) detection of TET and LIN. Thus, the multiple mode-resolved detection of TET and LIN could be realized simultaneously with only one potential scan, which greatly improved detection accuracy and efficiency. This study opened a new technology of BPE-ECL sensor application and is expected to shine in microchips and point-of-care testing (POCT).

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Myocardial infarction is one of the leading causes of mortality globally. Currently, the pleiotropic inflammatory cytokine interleukin-6 (IL-6) is considered to be intimately related to the severity of myocardial injury during myocardial infarction. Interventions targeting IL-6 are a promising therapeutic option for myocardial infarction, but the underlying molecular mechanisms are not well understood. Here, we report the novel role of IL-6 in regulating adverse cardiac remodeling mediated by fibroblasts in a mouse model of myocardial infarction. It was found that the elevated expression of IL-6 in myocardium and cardiac fibroblasts was observed after myocardial infarction. Further, fibroblast-specific knockdown of Il6 significantly attenuated cardiac fibrosis and adverse cardiac remodeling and preserved cardiac function induced by myocardial infarction. Mechanistically, the role of Il6 contributing to cardiac fibrosis depends on signal transduction and activation of transcription (STAT)3 signaling activation. Additionally, Stat3 binds to the Il11 promoter region and contributes to the increased expression of Il11, which exacerbates cardiac fibrosis. In conclusion, these results suggest a novel role for IL-6 derived from fibroblasts in mediating Stat3 activation and substantially augmented Il11 expression in promoting cardiac fibrosis, highlighting its potential as a therapeutic target for cardiac fibrosis.

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Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co-expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re-epithelialization and accelerated wound healing in a full-thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.

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A coordination complex, Eu(C12C12dbm)3(phen), with strong emission and a high quantum yield (QY ∼ 51.9%) was synthesized. The EuIII complex, as a fluorescent emitter, was embedded in cholesteric liquid crystal polymer networks (CLCNs). A series of free-standing EuIII-CLCN films were obtained, generating a typical sharp emission band corresponding to the EuIII complex. Tunable handedness of circularly polarized luminescence (CPL) with high |glum| values (up to 0.63) was observed. A series of CPL-active CLCN-coated PET films were also prepared (|glum| values up to 0.63), which can be used for large-area preparations. Moreover, by stacking an emitter-embedded PMMA layer and a CLCN layer, a composite system was built, and a large |glum| value (∼1.42) was achieved. Fluorescence patterns were prepared, and distinct images of CLCN films were recognized under both daylight and UV light. This work not only demonstrated that coordination compounds could be incorporated with CLCN films to prepare CPL-active materials with high |glum| values but also provided a new perspective for emissive CLCN materials used for anticounterfeiting and encryption.

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In this work, a spatial-potential resolved bipolar electrode electrochemiluminescence (BPE-ECL) biosensor based on polarity conversion strategy and CuHCF electrocatalyst was constructed for dual-mode detection of miRNA-122 and carcinoembryonic antigen (CEA). ECL technology was firstly used to systematically study the polarity conversion of BPE. It was found that changing the polarity of the driving voltage would cause the polarity change of BPE, and led to the change of the luminescent position of Ru(bpy)32+. As a "proof-of-concept application", we developed a shielded dual-channel BPE-ECL biosensor for dual-mode detection of miRNA-122 and CEA. In order to further improve the detection sensitivity, a non-precious metal electrocatalyst CuHCF with outstanding electrocatalytic reduction activity of H2O2 was firstly introduced to the BPE-ECL biosensor for signal amplification, which could generate high faradaic current under the excitation of negative potential. Based on the charge neutrality principle of BPE, the enhancement of the faradaic current resulted in the ECL signal amplification of Ru(bpy)32+. The targets in the sensing grooves caused the introduction or fall off of CuHCF, which led to the ECL signal change of Ru(bpy)32+ in the signal grooves, and realized the dual-mode detection of miRNA-122 and CEA. This work provided a deeper understanding of the polarity change of BPE. Furthermore, the introduction of non-precious metal electrocatalyst had broadened the application range of BPE-ECL sensors.

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The twin boundary, a common lattice plane of mirror-symmetric crystals, may have high reactivity due to special atomic coordination. However, twinning platinum and iridium nanocatalysts are grand challenges due to the high stacking fault energies that are nearly 1 order of magnitude larger than those of easy-twinning gold and silver. Here, we demonstrate that Turing structuring, realized by selective etching of superthin metal film, provides 14.3 and 18.9 times increases in twin-boundary densities for platinum and iridium nanonets, comparable to the highly twinned silver nanocatalysts. The Turing configurations with abundant low-coordination atoms contribute to the formation of nanotwins and create a large active surface area. Theoretical calculations reveal that the specific atom arrangement on the twin boundary changes the electronic structure and reduces the energy barrier of water dissociation. The optimal Turing-type platinum nanonets demonstrated excellent hydrogen-evolution-reaction performance with a 25.6 mV overpotential at 10.0 mA·cm-2 and a 14.8-fold increase in mass activity. And the bifunctional Turing iridium catalysts integrated in the water electrolyzer had a mass activity 23.0 times that of commercial iridium catalysts. This work opens a new avenue for nanocrystal twinning as a facile paradigm for designing high-performance nanocatalysts.

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Modern synthetic technology generally invokes high temperatures to control the hydration level of ceramics, but even the state-of-the-art technology can still only control the overall hydration content. Magically, natural organisms can produce bioceramics with tailorable hydration profiles and crystallization traits solely from amorphous precursors under physiological conditions. To mimic the biomineralization tactic, here, we report pressure-controlled hydration and crystallization in fabricated ceramics, solely from the amorphous precursors of purely inorganic gels (PIGs) synthesized from biocompatible aqueous solutions with most common ions in organisms (Ca2+, Mg2+, CO32-, and PO43-). Transparent ceramic tablets are directly produced by compressing the PIGs under mild pressure, while the pressure regulates the hydration characteristics and the subsequent crystallization behaviors of the synthesized ceramics. Among the various hydration species, the moderately bound and ordered water appears to be a key in regulating the crystallization rate. This nature-inspired study offers deeper insights into the magic behind biomineralization.

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KEY MESSAGE: Unreduced megagametophytes via second-division restitution were confirmed through heterozygosity analysis, and four candidate physical centromeres of rubber were located for the first time. The evaluation of maternal heterozygosity restitution (MHR) is vital in identifying the mechanism of 2n gametogenesis and assessing the utilization value of 2n gametes. In this study, three full-sib triploid populations were employed to evaluate the MHR of 2n female gametes of rubber tree clone GT1 and to confirm their genetic derivation. The 2n female gametes of GT1 were derived from second-division restitution (SDR) and transmitted more than half of the parental heterozygosity. In addition, low recombination frequency markers were developed, and four candidate physical centromeres of rubber tree were located for the first time. The confirmation that 2n female gametes of rubber tree clone GT1 are derived from SDR provides insights into the molecular mechanisms of 2n gametogenesis. In addition, the identified centromere location will aid in the development of centromeric markers for the rapid identification of the 2n gametogenesis mechanism.

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BRD4 inhibitors have demonstrated promising potential in cancer therapy. However, their therapeutic efficacy in breast cancer varies depending on the breast cancer subtype, particularly in the treatment of TNBC. In this study, we designed and synthesized 94 derivatives of 4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)phthalazin-1(2H)-one to evaluate their inhibitory activities against BRD4. Notably, compound DDT26 exhibited the most potent inhibitory effect on BRD4, with an IC50 value of 0.237 ± 0.093 µM. DDT26 demonstrated significant anti-proliferative activity against both TNBC cell lines and MCF-7 cells. Intriguingly, the phthalazinone moiety of DDT26 mimicked the PAPR1 substrate, resulting in DDT26 displaying a moderate inhibitory effect on PARP1 with an IC50 value of 4.289 ± 1.807 µM. Further, DDT26 was shown to modulate the expression of c-MYC and γ-H2AX, induce DNA damage, inhibit cell migration and colony formation, and arrest the cell cycle at the G1 phase in MCF-7 cells. Our findings present potential lead compounds for the development of potent anti-breast cancer agents targeting BRD4.