Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

Influence of the substituents of the thiol ligand on the optical properties of AuCu14.

Detailed photophysical processes of two AuCu14 clusters with different substituents (-F or -C(CH3)3) of the thiol ligand were studied in this work. The electronic effect of the substituents led to structural shrinkage, thus enhancing the luminous intensity. The internal conversion (IC) and intersystem crossing (ISC) rates in the AuCu14-C(CH3)3 crystal were slower compared with the AuCu14-F crystal, which was caused by the steric effect.

Carborane-Cluster-Wrapped Copper Cluster with Cyclodextrin-like Cavities for Chiral Recognition.

Chiral atomically precise metal clusters, known for their remarkable chiroptical properties, hold great potential for applications in chirality recognition. However, advancements in this field have been constrained by the limited exploration of host-guest chemistry, involving metal clusters. This study reports the synthesis of a chiral Cu16(C2B10H10S2)8 (denoted as Cu16@CB8, where C2B10H12S2H2 = 9,12-(HS)2-1,2-closo-carborane) cluster by an achiral carboranylthiolate ligand. The chiral R-/S-Cu16@CB8 cluster features chiral cavities reminiscent of cyclodextrins, which are surrounded by carborane clusters, yet they crystallize in a racemate. These cyclodextrin-like cavities demonstrated the specific recognition of amino acids, as indicated by the responsive output of circular dichroism and circularly polarized luminescence signals of Cu16 moieties of the Cu16@CB8 cluster. Notably, a quantitative chiroptical analysis of amino acids in a short time and a concomitant deracemization of Cu16@CB8 were achieved. Density functional tight-binding molecular dynamics simulation and noncovalent interaction analysis further unraveled the great importance of the cavities and binding sites for chiral recognition. Dipeptide, tripeptide, and polypeptide containing the corresponding amino acids (Cys, Arg, or His residues) display the same chiral recognition, showing the generality of this approach. The functional synergy of dual clusters, comprising carborane and metal clusters, is for the first time demonstrated in the Cu16@CB8 cluster, resulting in the valuable quantification of the enantiomeric excess (ee) value of amino acids. This work opens a new avenue for chirality sensors based on chiral metal clusters with unique chiroptical properties and inspires the development of carborane clusters in host-guest chemistry.

Pulsed Low-Intensity Focused Ultrasound (LIFU) Activation of Ovarian Follicles.

Objective: A biological system's internal morphological structure or function can be changed as a result of the mechanical effect of focused ultrasound. Pulsed low-intensity focused ultrasound (LIFU) has mechanical effects that might induce follicle development with less damage to ovarian tissue. The potential development of LIFU as a non-invasive method for the treatment of female infertility is being considered, and this study sought to explore and confirm that LIFU can activate ovarian follicles. Results: We found a 50% increase in ovarian weight and in the number of mature follicles on the ultrasound-stimulated side with pulsed LIFU and intraperitoneal injection of 10 IU PMSG in 10-day-old rats. After ultrasound stimulation, the PCOS-like rats had a decrease in androgen levels, restoration of regular estrous cycle and increase in the number of mature follicles and corpora lutea, and the ratio of M1 and M2 type macrophages was altered in antral follicles of PCOS-like rats, consequently promoting further development and maturation of antral follicles. Conclusion: LIFU treatment could trigger actin changes in ovarian cells, which might disrupt the Hippo signal pathway to promote follicle formation, and the mechanical impact on the ovaries of PCOS-like rats improved antral follicle development.

Irbesartan ameliorates diabetic kidney injury in db/db mice by restoring circadian rhythm and cell cycle.

Background and Objectives: Irbesartan has been widely used in the clinical treatment of diabetic kidney disease (DKD). However, the molecular mechanism of its delay of DKD disease progression has not been fully elucidated. The aim of the present study was to investigate the mechanism of irbesartan in the treatment of DKD. Materials and Methods: C57BL/KsJ db/db mice were randomly divided into the model group and irbesartan-treated group. After treatment with irbesartan for 12 weeks, the effects on blood glucose, body weight, 24-h urinary albumin, and renal injuries were evaluated. Microarray was used to determine the differentially expressed genes (DEGs) in the renal cortex of mice. |Log FC| <0.5 and false discovery rate (FDR) <0.25 were set as the screening criteria. Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), protein-protein interaction (PPI) network and modules, and microRNA (miRNA)-DEGs network analysis were applied to analyze the DEGs. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of microarray. Results: The present study demonstrated irbesartan could significantly improve the renal function in db/db mice through decreasing 24-h urinary albumin and alleviating the pathological injury of kidney. Irbesartan may affect the expression of numerous kidney genes involved in circadian rhythm, cell cycle, micoRNAs in cancer, and PI3K-AKT signaling pathway. In the miRNA-DEGs network, miR-1970, miR-703, miR-466f, miR-5135, and miR-132-3p were the potential targets for irbesartan treatment. The validation test confirmed that key genes regulating circadian rhythm (Arntl, Per3, and Dbp) and cell cycle (Prc1, Ccna2, and Ccnb2) were restored in db/db mice on treatment with Irbesartan. Conclusion: Generally, irbesartan can effectively treat DKD by regulating the circadian rhythm and cell cycle. The DEGs and pathways identified in the study will provide new insights into the potential mechanisms of irbesartan in the treatment of DKD.

Irbesartan ameliorates diabetic kidney injury in db/db mice by restoring circadian rhythm and cell cycle.

Background and Objectives: Irbesartan has been widely used in the clinical treatment of diabetic kidney disease (DKD). However, the molecular mechanism of its delay of DKD disease progression has not been fully elucidated. The aim of the present study was to investigate the mechanism of irbesartan in the treatment of DKD. Materials and Methods: C57BL/KsJ db/db mice were randomly divided into the model group and irbesartan-treated group. After treatment with irbesartan for 12 weeks, the effects on blood glucose, body weight, 24-h urinary albumin, and renal injuries were evaluated. Microarray was used to determine the differentially expressed genes (DEGs) in the renal cortex of mice. |Log FC| <0.5 and false discovery rate (FDR) <0.25 were set as the screening criteria. Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), protein-protein interaction (PPI) network and modules, and microRNA (miRNA)-DEGs network analysis were applied to analyze the DEGs. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of microarray. Results: The present study demonstrated irbesartan could significantly improve the renal function in db/db mice through decreasing 24-h urinary albumin and alleviating the pathological injury of kidney. Irbesartan may affect the expression of numerous kidney genes involved in circadian rhythm, cell cycle, micoRNAs in cancer, and PI3K-AKT signaling pathway. In the miRNA-DEGs network, miR-1970, miR-703, miR-466f, miR-5135, and miR-132-3p were the potential targets for irbesartan treatment. The validation test confirmed that key genes regulating circadian rhythm (Arntl, Per3, and Dbp) and cell cycle (Prc1, Ccna2, and Ccnb2) were restored in db/db mice on treatment with Irbesartan. Conclusion: Generally, irbesartan can effectively treat DKD by regulating the circadian rhythm and cell cycle. The DEGs and pathways identified in the study will provide new insights into the potential mechanisms of irbesartan in the treatment of DKD.

Electrocatalytic Nitrate Reduction on Metallic CoNi-Terminated Catalyst with Industrial-Level Current Density in Neutral Medium.

Green ammonia synthesis through electrocatalytic nitrate reduction reaction (eNO3RR) can serve as an effective alternative to the traditional energy-intensive Haber-Bosch process. However, achieving high Faradaic efficiency (FE) at industrially relevant current density in neutral medium poses significant challenges in eNO3RR. Herein, with the guidance of theoretical calculation, a metallic CoNi-terminated catalyst is successfully designed and constructed on copper foam, which achieves an ammonia FE of up to 100% under industrial-level current density and very low overpotential (-0.15 V versus reversible hydrogen electrode) in a neutral medium. Multiple characterization results have confirmed that the maintained metal atom-terminated surface through interaction with copper atoms plays a crucial role in reducing overpotential and achieving high current density. By constructing a homemade gas stripping and absorption device, the complete conversion process for high-purity ammonium nitrate products is demonstrated, displaying the potential for practical application. This work suggests a sustainable and promising process toward directly converting nitrate-containing pollutant solutions into practical nitrogen fertilizers.

Chemical Flexibility of Atomically Precise Metal Clusters.

Ligand-protected metal clusters possess hybrid properties that seamlessly combine an inorganic core with an organic ligand shell, imparting them exceptional chemical flexibility and unlocking remarkable application potential in diverse fields. Leveraging chemical flexibility to expand the library of available materials and stimulate the development of new functionalities is becoming an increasingly pressing requirement. This Review focuses on the origin of chemical flexibility from the structural analysis, including intra-cluster bonding, inter-cluster interactions, cluster-environments interactions, metal-to-ligand ratios, and thermodynamic effects. In the introduction, we briefly outline the development of metal clusters and explain the differences and commonalities of M(I)/M(I/0) coinage metal clusters. Additionally, we distinguish the bonding characteristics of metal atoms in the inorganic core, which give rise to their distinct chemical flexibility. Section 2 delves into the structural analysis, bonding categories, and thermodynamic theories related to metal clusters. In the following sections 3 to 7, we primarily elucidate the mechanisms that trigger chemical flexibility, the dynamic processes in transformation, the resultant alterations in structure, and the ensuing modifications in physical-chemical properties. Section 8 presents the notable applications that have emerged from utilizing metal clusters and their assemblies. Finally, in section 9, we discuss future challenges and opportunities within this area.

Vibration-Dependent Dual-Phosphorescent Cu4 Nanocluster with Remarkable Piezochromic Behavior.

The dual emission (DE) characteristics of atomically precise copper nanoclusters (Cu NCs) are of significant theoretical and practical interest. Despite this, the underlying mechanism driving DE in Cu NCs remains elusive, primarily due to the complexities of excited state processes. Herein, a novel [Cu4(PPh3)4(C≡C-p-NH2C6H4)3]PF6 (Cu4) NC, shielded by alkynyl and exhibiting DE, was synthesized. Hydrostatic pressure was applied to Cu4, for the first time, to investigate the mechanism of DE. With increasing pressure, the higher-energy emission peak of Cu4 gradually disappeared, leaving the lower-energy emission peak as the dominant emission. Additionally, the Cu4 crystal exhibited notable piezochromism transitioning from cyan to orange. Angle-dispersive synchrotron X-ray diffraction results revealed that the reduced inter-cluster distances under pressure brought the peripheral ligands closer, leading to the formation of new C-H⋅⋅⋅N and N-H⋅⋅⋅N hydrogen bonds in Cu4. It is proposed that these strengthened hydrogen bond interactions limit the ligands' vibration, resulting in the vanishing of the higher-energy peak. In situ high-pressure Raman and vibrationally resolved emission spectra demonstrated that the benzene ring C=C stretching vibration is the structural source of the DE in Cu4.

Analysis of Potential Risks in Abnormal Physical Development Due to Dietary Habits in Preschool Children.

Background: The prevalence of abnormal physical development in preschool children is often linked to their dietary habits, necessitating a comprehensive investigation. Understanding the intricacies of these habits is crucial for formulating targeted interventions to enhance the overall health and well-being of this vulnerable population. Objective: This study aims to explore the dietary habits of preschool children in Shijiazhuang and evaluate their impact on abnormal physical development. The primary objective is to identify key dietary issues, particularly focusing on picky eating, and assess their association with undernutrition and obesity in this age group. Methods: Utilizing a stratified sampling approach, the study involves preschool children and their caregivers from various kindergartens in Shijiazhuang. On-site medical examinations are conducted to measure height and weight and calculate body mass index (BMI). Additionally, parents were surveyed to gather information on the general aspects and dietary habits of their children. Binary logistic regression analysis was employed to ascertain the correlation between picky eating and the risk of undernutrition and obesity. Results: The findings indicate that approximately 70% of preschool children maintain a normal BMI, while 16.67% experience undernutrition, and 13.33% face issues of being overweight or obese. Picky eating emerges as the predominant dietary habit issue, affecting 51.33% of the participants. Binary logistic regression analysis identifies picky eating as a significant risk factor for undernutrition and obesity among children. Conclusions: Picky eating stands out as the primary dietary habit concern for preschool children, concurrently posing a substantial risk for abnormal physical development. Urgent measures are warranted to rectify children's suboptimal dietary habits, elevate nutritional standards, and foster their overall health and development. These findings underscore the imperative need for interventions targeting dietary improvement in preschoolers, contributing to improving their well-being and long-term health outcomes.

A Noncentrosymmetric Metal-Free Borophosphate: Achieving a Large Birefringence and Excellent Stability by Covalent-Linkage.

Organic-inorganic hybrid linear and nonlinear optical (NLO) materials have received increasingly wide spread attention in recent years. Herein, the first hybrid noncentrosymmetric (NCS) borophosphate, (C5H6N)2B2O(HPO4)2 (4PBP), is rationally designed and synthesized by a covalent-linkage strategy. 4-pyridyl-boronic acid (4 PB) is considered as a bifunctional unit, which may effectively improve the optical properties and stability of the resultant material. On the one hand, 4 PB units are covalently linked with PO3(OH) groups via strong B-O-P connections, which significantly enhances the thermal stability of 4PBP (decomposition at 321, vs lower 200 °C of most of hybrid materials). On the other hand, the planar π-conjugated C5H6N units and their uniform layered arrangements represent large structural anisotropy and hyperpolarizability, achieving the largest birefringence (0.156 @ 546 nm) in the reported borophosphates and a second-harmonic generation response (0.7 × KDP). 4PBP also exhibits a wide transparency range (0.27-1.50 µm). This work not only provides a promising birefringent material, but also offers a practical covalent-attachment strategy for the rational design of new high-performance optical materials.

Construction of novel Ag(0)-containing silver nanoclusters by regulating auxiliary phosphine ligands.

Controlled synthesis of metal clusters through minor changes in surface ligands holds significant interest because the corresponding entities serve as ideal models for investigating the ligand environment's stereochemical and electronic contributions that impact the corresponding structures and properties of metal clusters. In this work, we obtained two Ag(0)-containing nanoclusters (Ag17 and Ag32) with near-infrared emissions by regulating phosphine auxiliary ligands. Ag17 and Ag32 bear similar shells wherein Ag17 features a trigonal bipyramid Ag5 kernel while Ag32 has a bi-icosahedral interpenetrating an Ag20 kernel. Ag17 and Ag32 showed a near-infrared emission (NIR) of around 830 nm. Benefiting from the rigid structure, Ag17 displayed a more intense near-infrared emission than Ag32. This work provides new insight into the construction of novel superatomic silver nanoclusters by regulating phosphine ligands.

Follicular fluid-derived exosomal LncRNA LIPE-AS1 modulates steroid metabolism and survival of granulosa cells leading to oocyte maturation arrest in polycystic ovary syndrome.

OBJECTIVE: Women who are of reproductive age can suffer from polycystic ovary syndrome (PCOS), an endocrine disorder. Anovulatory infertility is mostly caused by aberrant follicular development, which is seen in PCOS patients. Due to the dysfunction of reproductive and endocrine function in PCOS patients, assisted reproduction treatment is one of the main means to obtain clinical pregnancy for PCOS patients. Long non-coding RNA (lncRNA) as a group of functional RNA molecules have been found to participate in the regulation of oocyte function, hormone metabolism, and proliferation and apoptosis of granulosa cells. In this study, we investigated the role of lncRNAs in follicular fluid-derived exosomes and the underlying mechanism of lncRNA LIPE-AS1. METHODS: We used RNA sequencing to analyze the lncRNA profiles of follicular fluid-derived exosomes in PCOS patients and controls. RT-qPCR was performed to detect the expression levels of these lncRNAs in control (n = 30) and PCOS (n = 30) FF exosome samples. Furthermore, we validated the performance of lncRNA LIPE-AS1 in oocyte maturation by in vitro maturation (IVM) experiments in mouse and steroid metabolism in granulosa cells. RESULTS: We found 501 lncRNAs were exclusively expressed in the control group and another 273 lncRNAs were found to be specifically expressed in the PCOS group. LncRNA LIPE-AS1, highly expressed in PCOS exosomes, was related to a poor oocyte maturation and embryo development in PCOS patients. Reduced number of MII oocytes were observed in the LIPE-AS1 group by in vitro maturation (IVM) experiments in mouse. LIPE-AS1 was also shown to modulate steroid metabolism and granulosa cell proliferation and apoptosis by LIPE-AS1/miR-4306/LHCGR axis. CONCLUSION: These findings suggested that the increased expression of LIPE-AS1, facilitated by follicular fluid exosomes, had a significant impact on both oocyte maturation and embryo development. We demonstrated the ceRNA mechanism involving LIPE-AS1, miR-4306, and LHCGR as a regulator of hormone production and metabolism. These findings indicate that LIPE-AS1 is essential in PCOS oocyte maturation and revealed a ceRNA network of LIPE-AS1 and provided new information on abnormal steroid metabolism and oocyte development in PCOS.

Tangshen formula targets the gut microbiota to treat non-alcoholic fatty liver disease in HFD mice: A 16S rRNA and non-targeted metabolomics analyses.

BACKGROUND: Tangshen formula (TSF) has an ameliorative effect on hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD), but the role played by the gut microbiota in this process is unknown. METHOD: We conducted three batches of experiments to explore the role played by the gut microbiota: TSF administration, antibiotic treatment, and fecal microbial transplantation. NAFLD mice were induced with a high-fat diet to investigate the ameliorative effects of TSF on NAFLD features and intestinal barrier function. 16S rRNA sequencing and serum untargeted metabolomics were performed to further investigate the modulatory effects of TSF on the gut microbiota and metabolic dysregulation in the body. RESULTS: TSF ameliorated insulin resistance, hypercholesterolemia, lipid metabolism disorders, inflammation, and impairment of intestinal barrier function. 16S rRNA sequencing analysis revealed that TSF regulated the composition of the gut microbiota and increased the abundance of beneficial bacteria. Antibiotic treatment and fecal microbiota transplantation confirmed the importance of the gut microbiota in the treatment of NAFLD with TSF. Subsequently, untargeted metabolomics identified 172 differential metabolites due to the treatment of TSF. Functional predictions suggest that metabolisms of choline, glycerophospholipid, linoleic acid, alpha-linolenic acid, and arachidonic acid are the key metabolic pathways by which TSF ameliorates NAFLD and this may be influenced by the gut microbiota. CONCLUSION: TSF treats the NAFLD phenotype by remodeling the gut microbiota and improving metabolic profile, suggesting that TSF is a functional gut microbial and metabolic modulator for the treatment of NAFLD.

Introducing Carborane Clusters into Crystalline Frameworks via Thiol-Yne Click Chemistry for Energetic Materials.

Crystalline frameworks represent a cutting-edge frontier in material science, and recently, there has been a surge of interest in energetic crystalline frameworks. However, the well-established porosity often leads to diminished output energy, necessitating a novel approach for performance enhancement. Thiol-yne coupling, a versatile metal-free click reaction, has been underutilized in crystalline frameworks. As a proof of concept, we herein demonstrate the potential of this approach by introducing the energy-rich, size-matched, and reductive 1,2-dicarbadodecaborane-1-thiol (CB-SH) into an acetylene-functionalized framework, Zn(AIm)2, via thiol-yne click reaction. This innovative decoration strategy resulted in a remarkable 46.6 % increase in energy density, a six-fold reduction in ignition delay time (4 ms) with red fuming nitric acid as the oxidizer, and impressive enhancement of stability. Density functional theory calculations were employed to elucidate the mechanism by which CB-SH promotes hypergolic ignition. The thiol-yne click modification strategy presented here permits engineering of crystalline frameworks for the design of advanced energetic materials.

Staggered Assembly of a Dimeric Au13 Cluster: Impacts on Coupling of Geometric Isomerism.

The specific states of aggregation of metal atoms in sub-nanometer-sized gold clusters are related to the different quantum confinement volumes of electrons, leading to novel optical and electronic properties. These volumes can be tuned by changing the relative positions of the gold atoms to generate isomers. Studying the isomeric gold core and the electron coupling between the basic units is fundamentally important for nanoelectronic devices and luminescence; however, appropriate cases are lacking. In this study, the structure of the first staggered di-superatomic Au25 -S was solved using single-crystal X-ray diffraction. The optical properties of Au25 -S were studied by comparing with eclipsed Au25 -E. From Au25 -E to Au25 -S, changes in the electronic structures occurred, resulting in significantly different optical absorptions originating from the coupling between the two Au13 modules. Au25 -S shows a longer electron decay lifetime of 307.7 ps before populating the lowest triplet emissive state, compared to 1.29 ps for Au25 -E. The experimental and theoretical results show that variations in the geometric isomerism lead to distinct photophysical processes owing to isomerism-dependent electronic coupling. This study offers new insights into the connection between the geometric isomerism of nanosized building blocks and the optical properties of their assemblies, opening new possibilities for constructing function-specific nanomaterials.

Genetic and Epigenetic Landscape for Drug Development in Polycystic Ovary Syndrome.

The treatment of polycystic ovary syndrome (PCOS) faces challenges as all known treatments are merely symptomatic. The U.S. Food and Drug Administration (FDA) has not approved any drug specifically for treating PCOS. As the significance of genetics and epigenetics rises in drug development, their pivotal insights have greatly enhanced the efficacy and success of drug target discovery and validation, offering promise for guiding the advancement of PCOS treatments. In this context, we outline the genetic and epigenetic advancement in PCOS, which provide novel insights into the pathogenesis of this complex disease. We also delve into the prospective method for harnessing genetic and epigenetic strategies to identify potential drug targets and ensure target safety. Additionally, we shed light on the preliminary evidence and distinctive challenges associated with gene and epigenetic therapies in the context of PCOS.

X-ray-triggered through-space charge transfer and photochromism in silver nanoclusters.

Materials exhibiting X-ray-induced photochromism have consistently piqued the interest of researchers. Exploring the photochromic properties of such materials is valuable for understanding the structural changes and electron transfer processes that occur under high energy radiation, such as X-ray irradiation. Here, a crystalline silver(I) nanocluster synthesized from tert-butylacetylene silver was found to have the ability to exhibit color and photoluminescence changes upon exposure to X-ray radiation. The responsive behavior was observed across a wide temperature range of 100-300 K, with the ability to respond particularly well to soft X-rays (λ > 1 Å) and exhibit light responsiveness to hard X-rays (λ < 1 Å). By combining experimental findings including X-ray diffraction, X-ray photoelectron spectroscopy, electron spin resonance, etc. with theoretical calculations, we have proposed that X-ray irradiation induces electron transfer from chloride (Cl-) located in the center of the silver(I) nanocluster to the surrounding Ag14 in the skeleton. This represents the first documented example in which electron transfer induced by X-ray excitation has been observed, accompanied by a photochromism process, in silver nanoclusters. This study contributes to our understanding of X-ray-induced photochromism and the electron transfer process in silver cluster compounds. It also provides valuable insights and potential design strategies for applications such as photochromism, photoluminescence color change, and photoenergy conversion.

Metal Clusters Confined in Chiral Zeolitic Imidazolate Framework for Circularly Polarized-Luminescence Inks.

Chiroptical activities arising in nanoclusters (NCs) are emerging as one of the most dynamic areas of modern science. However, devising an overarching strategy that is capable of concurrently enhancing the photoluminescence (PL) and circularly polarized luminescence (CPL) of metal NCs remains a formidable challenge. Herein, gold and silver nanoclusters (AuNCs, AgNCs) are endowed with CPL, for the first time, through a universal host-guest approach─centered around perturbing a chiral microenvironment within chiral hosts, simultaneously enhancing emissions. Remarkably, the photoluminescence quantum yield (PLQY) of AuNCs has undergone an increase of over 200 times upon confinement, escalating from 0.05% to 12%, and demonstrates a CPL response. Moreover, a three-dimensional (3D) model termed "NCs@CMOF" featuring CPL activity is created using metal cluster-based assembly inks through the process of 3D printing. This work introduces a potentially straightforward and versatile approach for achieving both PL enhancement and CPL activities in metal clusters.

Bavachinin protects the liver in NAFLD by promoting regeneration via targeting PCNA.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease all over the world, and no drug is approved for the treatment of NAFLD. Bavachinin (BVC) is proven to possess liver-protecting effect against NAFLD, but its mechanism is still blurry. OBJECTIVES: With the use of Click Chemistry-Activity-Based Protein Profiling (CC-ABPP) technology, this study aims to identify the target of BVC, and investigate the mechanism by which BVC exerts its liver-protecting effect. METHODS: The high fat diet induced hamster NAFLD model is introduced to investigate BVC's lipid-lowering and liver-protecting effects. Then, a small molecular probe ofBVC is designed and synthesized based on theCC-ABPP technology, and BVC's target is fished out. A series of experiments are performed to identify the target, including competitive inhibition assay, surface-plasmon resonance (SPR), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, and co-immunoprecipitation (Co-IP). Afterward, the pro-regeneration effects of BVC are validated in vitro and in vivo through flow cytometry, immunofluorescence, and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULT: In the hamster NAFLD model, BVC shows lipid-lowing effect and improvement on the histology. PCNA is identified as the target of BVC with the method mentioned above, and BVC facilitates the interaction between PCNA and DNA polymerase delta. BVC promotes HepG2 cells proliferation which is inhibited by T2AA, an inhibitor suppresses the interaction between PCNA and DNA polymerase delta. In NAFLD hamsters, BVC enhances PCNA expression and liver regeneration, reduces hepatocyte apoptosis. CONCLUSION: This study suggests that, besides the anti-lipemic effect, BVC binds to the pocket of PCNA facilitating its interaction with DNA polymerase delta and pro-regeneration effect, thereby exerts the protective effect against HFD induced liver injury.