Iron supplementation and iron accumulation promote adipocyte thermogenesis through PGC1α-ATGL-mediated lipolysis.

Iron homeostasis is essential for maintaining metabolic health and iron disorder has been linked to chronic metabolic diseases. Increasing thermogenic capacity in adipose tissue has been considered as a potential approach to regulate energy homeostasis. Both mitochondrial biogenesis and mitochondrial function are iron-dependent and essential for adipocyte thermogenic capacity, but the underlying relationships between iron accumulation and adipose thermogenesis is unclear. Firstly, we confirmed that iron homeostasis and the iron regulatory markers (e.g., Tfr1 and Hfe) are involved in cold-induced thermogenesis in subcutaneous adipose tissues using RNA-seq and bioinformatic analysis. Secondly, an Hfe (Hfe-/-)-deficient mouse model, in which tissues become overloaded with iron, was employed. We found iron accumulation caused by Hfe deficiency enhanced mitochondrial respiratory chain expression in subcutaneous white adipose in vivo and resulted in enhanced tissue thermogenesis with upregulation of PGC-1α and adipose triglyceride lipase, mitochondrial biogenesis and lipolysis. To investigate the thermogenic capacity in vitro, stromal vascular fraction from adipose tissues was isolated, followed with adipogenic differentiation. Primary adipocyte from Hfe-/- mice exhibited higher cellular oxygen consumption, associated with enhanced expression of mitochondrial oxidative respiratory chain protein, while primary adipocytes or stromal vascular fractions from WT mice supplemented with iron citrate) exhibited similar effect in thermogenic capacity. Taken together, these findings indicate iron supplementation and iron accumulation (Hfe deficiency) can regulate adipocyte thermogenic capacity, suggesting a potential role for iron homeostasis in adipose tissues.

Effects of the photovoltaic fishery culture model on muscle nutritional quality and volatile flavor compounds of Litopenaeus vannamei.

This study used Litopenaeus vannamei to compare the muscle nutritional quality and volatile flavor compounds of animals raised in the photovoltaic fishery culture model (PM) and the common pond breeding model (CM). Amino acids, fatty acids, and volatile flavor substances were identified and analyzed using an automatic amino acid analyzer and headspace solid phase microextraction(HS-SPME) combined with GC/MS. There were no significant differences between the two culture models in terms of general nutrients, mineral contents, and amino acid compositions in the muscles of L. vannamei. In the PM group, the proportion of flavor amino acids in total amino acids was higher. Based on the amino acid score (AAS) and chemical score (CS), it was found that methionine and cystine were the first limiting amino acids in the muscle samples. The essential amino acid index (EAAI) value was approximately 77 for both models, indicating high-quality proteins. The muscles contained nine types of fatty acids, with the PM group showing significantly higher levels of both monounsaturated and total fatty acids. A total of 23 volatile flavor compounds were identified in both models. The contents of 1-nonanal, n-tridecane, and alpha-terpineol were higher when cultured in the PM. Conversely, the contents of hexanal, 2-ethylhexanol, and dipentene were lower in the PM group. The photovoltaic fishery culture model has the potential to enhance income through photovoltaic power generation. In addition, this study found that the fatty acid composition of L. vannamei was improved in the PM, without compromising muscle composition or flavor. These results provide a theoretical basis for evaluating the meat quality of L. vannamei under different culture models and offer data to support and guide the promotion of the PM.

Enhanced fluorescence properties of polyfluorene-based polymer dots through an ascorbic acid-photoaging treatment for living cell imaging.

The polymer dots (Pdots) prepared by the conjugated polymer (PFO, poly (9,9-dihexylfluorene-2,7-diyl)) have high fluorescence intensity and are often used in biological fluorescence imaging. However, due to the chain defects, the PFO Pdots suffer from stability issues such as photoinactivation and photobleaching. To solve this problem, we drew inspiration from the preparation process of organic planar light-emitting devices and added an optimization processing after Pdots was prepared. We used illumination as the driving force to activate defects on its chain, and ascorbic acid as a reducing substance to restore the chain defects of the polymer to a more stable state. Through this method, we increased the fluorescence intensity by nearly 1.9 times, and significantly improving their long and short-term stability. In addition, it ensures other properties remain unchanged. This optimization scheme is also fully compatible with the entire biological imaging process, ensuring that other important properties such as cytotoxicity do not undergo unnecessary changes. Furthermore, we conducted material characterization and theoretical simulation, revealing that the optimization scheme mainly serves to repair C-9 alkyl defects on the polyfluorene unit. This study has improved and enhanced the fluorescence performance of PFO Pdots, and also provides a way to optimize the treatment of other similar conjugated polymer material systems.

Enhancing Oxygen Evolution Reaction Performance of Metal-Organic Frameworks through Cathode Activation.

Due to their abundant active sites and porous structures, metal-organic frameworks (MOFs) have garnered significant interest as oxygen evolution reaction (OER) electrocatalysts. Nevertheless, the development of MOF s-based electrocatalysts with efficient OER activity and excellent stability simultaneously still face challenges. Herein, a cathodic activation strategy was used to enhance the OER electrocatalytic performance of M-HHTP for the first time, where M refers to Ni, Cu, Co, Fe, while HHTP denotes 2, 3, 6, 7, 10, 11-hexahydroxytriphenylene. As a prototype, the activated Ni-HHTP (HA-Ni-HHTP) demonstrates outstanding OER performance, with an overpotential as low as 140 mV at 20 mA cm-2 and a small Tafel slope of 78.7 mV-1, surpassing commercial RuO2 and rivaling state-of-the-art MOFs-based electrocatalysts. Characterizations and density functional theory calculations reveal that the superior performance of HA-Ni-HHTP is primarily ascribed to changes in semiconductor type, contact angle, and oxygen vacancy content induced by cathodic activation. Electrochemical impedance spectroscopy analysis using the transmission line model confirms that cathodic activation accelerates charge transport, enhancing the OER process. Furthermore, the cathodic activation strategy holds promise for improving the water oxidation performance of other MOFs such as Fe-HHTP, Co-HHTP, and Cu-HHTP.

Integration of conventional surface science techniques with surface-sensitive azimuthal and polarization dependent femtosecond-resolved sum frequency generation spectroscopy.

Experimental insight into the elementary processes underlying charge transfer across interfaces has blossomed with the wide-spread availability of ultra-high vacuum (UHV) setups that allow the preparation and characterization of solid surfaces with well-defined molecular adsorbates over a wide range of temperatures. Within the last 15 years, such insights have extended to charge transfer heterostructures containing solids overlain by one or more atomically thin two dimensional materials. Such systems are of wide potential interest both because they appear to offer a path to separate surface reactivity from bulk chemical properties and because some offer completely novel physics, unrealizable in bulk three dimensional solids. Thick layers of molecular adsorbates or heterostructures of 2D materials generally preclude the use of electrons or atoms as probes. However, with linear photon-in/photon-out techniques, it is often challenging to assign the observed optical response to a particular portion of the interface. We and prior workers have demonstrated that by full characterization of the symmetry of the second order nonlinear optical susceptibility, i.e., the χ(2), in sum frequency generation (SFG) spectroscopy, this problem can be overcome. Here, we describe an UHV system built to allow conventional UHV sample preparation and characterization, femtosecond and polarization resolved SFG spectroscopy, the azimuthal sample rotation necessary to fully describe χ(2) symmetry, and sufficient stability to allow scanning SFG microscopy. We demonstrate these capabilities in proof-of-principle measurements on CO adsorbed on Pt(111) and on the clean Ag(111) surface. Because this setup allows both full characterization of the nonlinear susceptibility and the temperature control and sample preparation/characterization of conventional UHV setups, we expect it to be of great utility in the investigation of both the basic physics and applications of solid, 2D material heterostructures.

The Effects of Aging on Microstructures and Rheological Properties of Modified Asphalt with GO/SBS Composite.

This work aimed to investigate the effects of aging on the microstructures and rheological properties of modified asphalt with a GO/SBS composite, since the styrene-butadiene-styrene block copolymer is potentially compatible with graphene oxide (GO). The GO/SBS composites, which were used as a kind of modifier, were prepared via the solution-blending method. GO/SBS composites with varying GO contents were employed to prepare the GO/SBS-compound-modified asphalt (GO/SBS-MA). Then, the GO/SBS-MA underwent PAV (pressure aging vessel) or UV (ultraviolet) aging tests to simulate different aging circumstances. The microstructures of the asphalt binders were studied using FTIR (Fourier-transform infrared spectroscopy) and AFM (atomic force microscope) tests. Moreover, DSR (dynamic shear rheometer) and BBR (bending beam rheometer) experiments were carried out to investigate the rheological properties of the GO/SBS-MA. The results showed that the addition of GO improved the high-temperature stability of the asphalt binder while slightly impairing its performance at low temperatures. GO restrained the formation of carbonyl and sulfoxide groups as well as the breakdown of C=C bonds in the polybutadiene (PB) segment, promoting the anti-aging performance of GO/SBS-MA. Furthermore, the interactions between the GO/SBS and the asphalt binder resulted in the formation of needle-like aggregates, enhancing the stability of the asphalt binder. The asphalt binders with a higher content of graphene oxide (GO) exhibited not only a better high-temperature performance, but also a better aging resistance. It was concluded that the macroscopic properties and microstructures were significantly affected by GO, and a moderate increase in the amount of GO could contribute to a better aging resistance for GO/SBS-MA.

Simultaneously Selective Separation of Zearalenone and Four Aflatoxins From Rice Samples Using Co-Pseudo-Template Imprinted Polymers With MIL-101(Cr)-NH2 as Core.

A novel approach for the simultaneous separation of zearalenone (ZEN) and four types of aflatoxins (AFB1, AFB2, AFG1 and AFG2) from rice samples was presented. This approach utilized modified MIL-101(Cr)-NH2 as core, with molecularly imprinted polymers (MIPs) serving as the shell. The MIL-101(Cr)-NH2 was prepared via ring-opening reaction, while the imprinted polymers were synthesized using warfarin and 4-methylumbelliferyl acetate as co-pseudo template, ethylene glycol dimethacrylate as the cross-linker and azobisisobutyronitrile as initiator. The resulting co-pseudo-template-MIPs (CPT-MIPs) were thoroughly characterized and evaluated. Adsorption studies demonstrate that the adsorption process of CPT-MIPs follows a chemical monolayer adsorption mechanism, with imprinted factors ranging from 1.24 to 1.52 and selective factors ranging from 1.29 to 1.52. Self-made columns were prepared, and the method for separation was developed and validated. The limit of detections ranged from 0.12 to 2.09 µg/kg, and the limit of qualifications ranged from 1.2 to 6.25 µg/kg. To assess the reliability of the method, ZEN and AFs were spiked at three different levels, and the recoveries ranged from 79.53 to 94.58%, with relative standard deviations of 2.90-5.78%.

Unlocking Giant Third-Order Optical Nonlinearity in (MA)2CuX4 through Introducing Jahn-Teller Distortion.

Nonlinear absorption coefficient and modulation depth stand as pivotal properties of nonlinear optical (NLO) materials, while the existing NLO materials exhibit limitations such as low nonlinear absorption coefficients and/or small modulation depths, thereby severely impeding their practical application. Here we unveil that introducing Jahn-Teller distortion in a Mott-Hubbard system, (MA)2CuX4 (MA=methylammonium; X=Cl, Br) affords the simultaneous attainment of a giant nonlinear absorption coefficient and substantial modulation depth. The optimized compound, (MA)2CuCl4, demonstrates a nonlinear absorption coefficient of (1.5±0.08)×105 cm GW-1, a modulation depth of 60 %, and a relatively low optical limiting threshold of 1.22×10-5 J cm-2. These outstanding attributes surpass those of most reported NLO materials. Our investigation reveals that a more pronounced distortion of the [CuX6]4- octahedron emerges as a crucial factor in augmenting optical nonlinearity. Mechanism study involving structural and spectral characterization along with theoretical calculations indicates a correlation between the compelling performance and the Mott-Hubbard band structure of the materials, coupled with the Jahn-Teller distortion-induced d-d transition. This study not only introduces a promising category of high-performance NLO materials but also provides novel insights into enhancing the performance of such materials.

A method to enhance drivers' hazard perception at night based on "knowledge-attitude-practice" theory.

During nighttime driving, the inherent challenges of low-illuminance conditions often lead to an increased crash rate and higher fatalities by impairing drivers' ability to recognize imminent hazards. While the severity of this issue is widely recognized, a significant research void exists with regard to strategies to enhance hazard perception under such circumstances. To address this lacuna, our study examined the potential of an intervention grounded in the knowledge-attitude-practice (KAP) framework to bolster nighttime hazard detection among drivers. We engaged a cohort of sixty drivers split randomly into an intervention group (undergoing specialized training) and a control group and employed a holistic assessment that combined eye movement analytics, physiological response monitoring, and driving performance evaluations during simulated scenarios pre- and post-intervention. The data showed that the KAP-centric intervention honed drivers' visual search techniques during nighttime driving, allowing them to confront potential threats with reduced physiological tension and ensuring more adept vehicle handling. These compelling findings support the integration of this methodology in driver training curricula and present an innovative strategy to enhance road safety during nighttime journeys.

An Unprecedented [BO2]-Based Deep-Ultraviolet Transparent Nonlinear Optical Crystal by Superhalogen Substitution.

Solid-state structures with the superhalogen [BO2]- have thus far only been observed with a few compounds whose syntheses require high reaction temperatures and complicated procedures, while their optical properties remain almost completely unexplored. Herein, we report a facile, energy-efficient synthesis of the first [BO2]-based deep-ultraviolet (deep-UV) transparent oxide K9[B4O5(OH)4]3(CO3)(BO2) ⋅ 7H2O (KBCOB). Detailed structural characterization and analysis confirm that KBCOB possesses a rare four-in-one three-dimensional quasi-honeycomb framework, with three π-conjugated anions ([BO2]-, [BO3]3-, and [CO3]2-) and one non-π-conjugated anion ([BO4]5-) in the one crystal. The evolution from the traditional halogenated nonlinear optical (NLO) analogues to KBCOB by superhalogen [BO2]- substitution confers deep-UV transparency (<190 nm), a large second-harmonic generation response (1.0×KH2PO4 @ 1064 nm), and a 15-fold increase in birefringence. This study affords a new route to the facile synthesis of functional [BO2]-based oxides, paving the way for the development of next-generation high-performing deep-UV NLO materials.

Record Second-Harmonic Generation and Birefringence in an Ultraviolet Antimonate by Bond Engineering.

Oxides have attracted considerable attention owing to their potential for nonlinear optical (NLO) applications. Although significant progress has been achieved in optimizing the structural characteristics of primitives (corresponding to the simplest constituent groups, namely, cations/anions/neutral molecules) comprising the crystalline oxides, the role of the primitives' interaction in determining the resultant functional structure and optical properties has long been underappreciated and remains unclear. In this study, we employ a π-conjugated organic primitive confinement strategy to manipulate the interactions between primitives in antimonates and thereby significantly enhance the optical nonlinearity. Chemical bonds and relatively weak H-bonding interactions promote the formation of cis- and trans-Sb(III)-based dimer configurations in (C5H5NO)(Sb2OF4) (4-HPYSOF) and (C5H7N2)(Sb2F7) (4-APSF), respectively, resulting in very different second-harmonic generation (SHG) efficiencies and birefringences. In particular, 4-HPYSOF displays an exceptionally strong SHG response (12 × KH2PO4 at 1064 nm) and a large birefringence (0.513 at 546 nm) for a Sb(III)-based NLO oxide as well as a UV cutoff edge. Structural analyses and theoretical studies indicate that polarized ionic bond interactions facilitate the favorable arrangement of both the inorganic and organic primitives, thereby significantly enhancing the optical nonlinearity in 4-HPYSOF. Our findings shed new light on the intricate correlations between the interactions of primitives, inorganic primitive configuration, and SHG properties, and, more broadly, our approach provides a new perspective in the development of advanced NLO materials through the interatomic bond engineering of oxides.

Effects of different temperatures on Leiocassis longirostris gill structure and intestinal microbial composition.

Fish are poikilothermic vertebrates and their physiological activities are affected by water temperature. In recent years, extreme weather has occurred frequently, and temperature changes have adversely affected the growth of farmed fish. To explore the changes in gill tissue structure caused by changing the water temperature and the relationship between the intestinal microbiota and the Leiocassis longirostris host adaptation mechanism, gill tissue sections and intestinal microbial 16S rRNA amplicon sequencing were conducted under different temperature stress (low temperature 4 °C, normal temperature 26 °C and high temperature 32 °C). The results showed that heat stress and cold stress caused injury and swelling, terminal congestion, cell vacuolation, and necrosis of the gill tissue of L. longirostris. For intestinal microbiota, the abundances of Pseudomonadota and Bacillota increased at the cold stress, while the abundances of Fusobacteriota and Bacteroidota increased at the heat stress. The number of opportunistic bacteria, mainly Aeromonas and Acinetobacter, was the highest under cold stress. In addition, the richness of the intestinal microbiota decreased significantly at heat and cold stresses, while evenness increased. Prediction of intestinal microbiota function showed that most common functions, such as metabolism of cofactors and vitamins, energy metabolism and replication and repair, were decreased significantly at heat stress and cold stress, and phylogenetic relationship analysis revealed significant differences among the groups. In conclusion, the change of temperature altered the gill tissue structure, and affected the structure and homeostasis of the intestinal microbiota, thus affecting the survival time of L. longirostris, and cold stress had a greater effect than heat stress.

Association of lipoprotein lipase (LPL) gene variants with hyperlipidemic acute pancreatitis in southeastern Chinese population.

Objective: The study aims to explore the relationship between lipoprotein lipase (LPL) variants and hyperlipidemic acute pancreatitis (HLAP) in the southeastern Chinese population. Subjects and methods: In total, 80 participants were involved in this study (54 patients with HLAP and 26 controls). All coding regions and intron-exon boundaries of the LPL gene were sequenced. The correlations between variants and phenotypes were also analysed. Results: The rate of rare LPL variants in the HLAP group is 14.81% (8 of 54), higher than in controls. Among the detected four variants (rs3735959, rs371282890, rs761886494 and rs761265900), the most common variant was rs371282890. Further analysis demonstrated that subjects with rs371282890 "GC" genotype had a 2.843-fold higher risk for HLAP (odds ratio [OR]: 2.843, 95% confidence interval [CI]: 1.119-7.225, p = 0.028) than subjects with the "CC" genotype. After adjusting for sex, the association remained significant (adjusted OR: 3.083, 95% CI: 1.208-7.869, p = 0.018). Subjects with rs371282890 "GC" genotype also exhibited significantly elevated total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels in all the participants and the HLAP group (p < 0.05). Conclusion: Detecting rare variants in LPL might be valuable for identifying higher-risk patients with HLAP and guiding future individualised therapeutic strategies.

Peroxiredoxin 3 has a crucial role in the macrophage polarization by regulating mitochondrial homeostasis.

Acute lung injury (ALI) is one of the life-threatening complications of sepsis, and macrophage polarization plays a crucial role in the sepsis-associated ALI. However, the regulatory mechanisms of macrophage polarization in ALI and in the development of inflammation are largely unknown. In this study, we demonstrated that macrophage polarization occurs in sepsis-associated ALI and is accompanied by mitochondrial dysfunction and inflammation, and a decrease of PRDX3 promotes the initiation of macrophage polarization and mitochondrial dysfunction. Mechanistically, PRDX3 overexpression promotes M1 macrophages to differentiate into M2 macrophages, and enhances mitochondrial functional recovery after injury by reducing the level of glycolysis and increasing TCA cycle activity. In conclusion, we identified PRDX3 as a critical hub integrating oxidative stress, inflammation, and metabolic reprogramming in macrophage polarization. The findings illustrate an adaptive mechanism underlying the link between macrophage polarization and sepsis-associated ALI.

circ-Amotl1 in extracellular vesicles derived from ADSCs improves wound healing by upregulating SPARC translation.

Aim: This study aims to explore the mechanism of circ- AMOT-like protein 1 (Amotl1) in extracellular vesicles (Evs) derived from adipose-derived stromal cells (ADSCs) regulating SPARC translation in wound healing process. Methods: The morphology, wound healing rate of the wounds and Ki67 positive rate in mouse wound healing models were assessed by H&E staining and immunohistochemistry (IHC). The binding of IGF2BP2 and SPARC was verified by RNA pull-down. Adipose-derived stromal cells (ADSCs) were isolated and verified. The Evs from ADSCs (ADSC-Evs) were analyzed. Results: Overexpression of SPARC can promote the wound healing process in mouse models. IGF2BP2 can elevate SPARC expression to promote the proliferation and migration of HSFs. circ-Amotl1 in ADSC-Evs can increase SPARC expression by binding IGF2BP2 to promote the proliferation and migration of HSFs. Conclusion: ADSC-Evs derived circ-Amotl1 can bind IGF2BP2 to increase SPARC expression and further promote wound healing process.

Giant Optical Anisotropy in a Covalent Molybdenum Tellurite via Oxyanion Polymerization.

Large birefringence is a crucial but hard-to-achieve optical parameter that is a necessity for birefringent crystals in practical applications involving modulation of the polarization of light in modern opto-electronic areas. Herein, an oxyanion polymerization strategy that involves the combination of two different types of second-order Jahn-Teller distorted units is employed to realize giant anisotropy in a covalent molybdenum tellurite. Mo(H2O)Te2O7 (MTO) exhibits a record birefringence value for an inorganic UV-transparent oxide crystalline material of 0.528 @ 546 nm, which is also significantly larger than those of all commercial birefringent crystals. MTO has a UV absorption edge of 366 nm and displays a strong powder second-harmonic generation response of 5.4 times that of KH2PO4. The dominant roles of the condensed polytellurite oxyanions [Te8O20]8- in combination with the [MoO6]6- polyhedra in achieving the giant birefringence in MTO are clarified by structural analysis and first-principles calculations. The results suggest that polymerization of polarizability-anisotropic oxyanions may unlock the promise of birefringent crystals with exceptional birefringence.

Evaluation of the impact of repeated intravenous phage doses on mammalian host-phage interactions.

Phage therapy has shown great promise for the treatment of multidrug-resistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. Here, we administered different purified phages (Salmonella phage SE_SZW1, Acinetobacter phage AB_SZ6, and Pseudomonas phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses resulted in a 2-3 Log10 decline of the plasma phage titer at 5 min compared to the first dose, regardless of the type of phage administered in rats. Host innate immune responses were activated including splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. In conclusion, the mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy.IMPORTANCEPhage therapy has demonstrated potential in addressing multidrug-resistant bacterial infections. However, an insufficient understanding of phage-host interactions has impeded its broader clinical application. In our study, specific phages were administered intravenously (IV) to both rats and monkeys to elucidate phage-host interactions and evaluate phage pharmacokinetics (PK). Results revealed that with successive IV administrations, there was a decrease in plasma phage concentrations. Concurrently, these administrations elicited both innate and adaptive immune responses in the subjects. Notably, the observed immune responses and PK profiles exhibited variation contingent upon the phage type and the mammalian host. Despite these variations, the tested mammals exhibited a favorable tolerance to the IV-administered phages. This underscores the significance of comprehending these interactions for the optimization of phage therapy outcomes.

Akkermansia muciniphila might improve anti-PD-1 therapy against HCC by changing host bile acid metabolism.

PD-1 monoclonal antibodies (mAb) have demonstrated remarkable efficacy in a variety of cancers, including Hepatocellular carcinoma (HCC). However, the patient response rates remain suboptimal, and a significant proportion of initial responders may develop resistance to this therapeutic approach. Akkermansia muciniphila (AKK), a microorganism implicated in multiple human diseases, has been reported to be more abundant in patients who exhibit favorable responses to PD-1mAb. However, the underlying mechanism has yet to be elucidated. In our study, we found that AKK could enhance the efficacy of PD-1mAb against HCC in a tumor-bearing mouse model. It promotes HCC tumor cells apoptosis and raise the CD8+ T proportion in the tumor microenvironment. Additionally, AKK downregulates PD-L1 expression in tumor cells. Furthermore, the analysis of metabonomics demonstrates that AKK induces alterations in the host's bile acid metabolism, leading to a significant increase in serum TUDCA levels. Considering the immunosuppresive roles of TUDCA in HCC development, it is plausible to speculate that AKK may reinforce the immunotherapy of PD-1mAb against HCC through its impact on bile acid metabolism.

The mechanism of Semen Persicae-Flos Carthami in treating hypertrophic scar: A study based on network pharmacological analysis and in vitro experiments.

Traditional medicine believes that hypertrophic scar (HS) falls into the category of "blood stasis". Chinese herbs for promoting blood circulation and removing blood stasis, activating meridians, and relieving pain are usually selected to treat HS by traditional Chinese medicine (TCM). Both Semen Persicae (SP) and Flos Carthami (FC) are confirmed to be effective for HS. Clinically, SP and FC are often used in combination with each other. However, the pharmacodynamic mechanism and molecular target of SP-FC in the treatment of HS are still unclear. Therefore, this study is intended to explore the mechanism and target of SP-FC in the treatment of HS through network pharmacology combined with in vitro cell and molecular biology experiments. Target genes of SP-FC were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and targets of HS-related diseases were searched from databases such as Disgenet and GeneCards. Based on the targets searched and obtained, a Venn diagram was plotted to acquire common targets of SP-FC-HS. Next, STRING 11.0 was employed for protein-protein interaction (PPI) network analysis of common targets; and cytoscape 3.9.0 for connection relationship analysis of PPI and plotting of a "drug-component-target" network diagram. Besides, a modified explant culture method was applied to separate primary hypertrophic scar fibroblasts (HSFs); MTT assay to detect cell viability of HSFs after treatment by SP-FC for 24 h; Annexin V-FITC/PI double staining combined with flow cytometry to test apoptosis; western blot to check the protein expression level of p53; and real-time fluorescence quantitative PCR to determine mRNA level of p53. In the analysis of network pharmacology, 269 pharmacological targets of SP, 449 pharmacological targets of FC, and 2569 targets of HS-related diseases were screened from the databases. After plotting the Venn diagram, 116 common targets of SP-FC-HS were acquired. In vitro experiments showed that the expression of p53 in HSFs was decreased. SP-FC significantly reduces the viability of HSFs, increases p53 levels in HSFs, and promotes apoptosis. SP-FC can reduce scar formation by promoting p53 expression.

Secondary-Bond-Driven Construction of a Polar Material Exhibiting Strong Broad-Spectrum Second-Harmonic Generation and Large Birefringence.

Considerable effort has been invested in the development of non-centrosymmetric (NCS) inorganic solids for ferroelectricity-, piezoelectricity- and, particularly, optical nonlinearity-related applications. While great progress has been made, a persistent problem is the difficulty in constructing NCS materials, which probably stems from non-directionality and unsaturation of the ionic bonds between metal counter-cations and covalent anionic modules. We report herein a secondary-bond-driven approach that circumvents the cancellation of dipole moments between adjacent anionic modules that has plagued second-harmonic generation (SHG) material design, and which thereby affords a polar structure with strong SHG properties. The resultant first NCS counter-cation-free iodate, VO2 (H2 O)(IO3 ) (VIO), a new class of iodate, crystallizes in a polar lattice with ∞ 1 [ ${{}_{{\rm { \infty }}}{}^{{\rm { 1}}}{\rm { [}}}$ VO2 (H2 O)(IO3 )] zigzag chains connected by weak hydrogen bonds and intermolecular forces. VIO exhibits very large SHG responses (18 × KH2 PO4 @ 1200 nm, 1.5 × KTiOPO4 @ 2100 nm) and sufficient birefringence (0.184 @ 546 nm). Calculations and crystal structure analysis attribute the large SHG responses to consistent polarization orientations of the ∞ 1 [ ${{}_{{\rm { \infty }}}{}^{{\rm { 1}}}{\rm { [}}}$ VO2 (H2 O)(IO3 )] chains controlled by secondary bonds. This study highlights the advantages of manipulating the secondary bonds in inorganic solids to control NCS structure and optical nonlinearity, affording a new perspective in the development of high-performance NLO materials.