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Polycystic ovary syndrome (PCOS) is a major cause of anovulatory sterility in women, and most PCOS patients exhibit hyperandrogenism (HA). Liver kinase b1 (LKB1) is a tumor suppressor that has recently been reported to be involved in PCOS. However, the mechanism by which LKB1 affects HA has not previously been elucidated. We report here that ovarian LKB1 levels are significantly decreased in a female mouse model of HA. Moreover, we report that LKB1 expression is inhibited by elevated androgens via activation of androgen receptors. In addition, LKB1 treatment was observed to suppress androgen synthesis in theca cells and promote estrogen production in granulosa cells by regulating steroidogenic enzyme expression. As expected, LKB1 knockdown inhibited estrogen levels and enhanced androgen levels, and LKB1‐transgenic mice were protected against HA. The effect of LKB1 appears to be mediated via IGF‐1 signaling. In summary, we describe here a key role for LKB1 in controlling sex hormone levels. [ABSTRACT FROM AUTHOR]

Long retention of therapeutic agents in tumors is imperative for improving the therapeutic index. In this work, the GSH responsive porphyrin molecule (TPP 1) was synthesized, which is amphiphilic and linked by a disulfide bond. TPP 1 molecules could self-assemble into nanoparticles (TPP 1 NPs) with a size of about 100 nm in aqueous solution. The TPP 1 NPs exhibited high stability under different conditions and could form into large microparticles in the presence of glutathione (GSH). The TPP 1 NPs could be internalized by cancer cells, and they emitted enhanced red fluorescence compared to that of TPP 2 NPs (non-sensitive NPs) when cells were pretreated with GSH. In addition, in vitro MTT assays showed that TPP 1 NPs were biocompatible and could further be used as photosensitizers in nanoparticle formation. The cellular photodynamic activity of TPP 1 NPs was obviously higher than that of TPP 2 NPs, due to the increasing retention of TPP in cancer cells, which will generate more reactive oxygen species in cancer cells under light irradiation. These results highlight the potential of developing stimulus responsive nanoparticles for enhanced retention and improved therapeutic outcome. [ABSTRACT FROM AUTHOR]

Controllable synthesis of coordination polymer (CP) isomers and revealing their structure-property relationships remain enormous challenges. Three new supramolecular isomers have been synthesized by tuning the poly(ethylene glycol) (PEG) content in the feed. These supramolecular isomers have the same framework formula of [Cu2I2(tppe)] and different architectures from the classical 2D stacking framework to a 3D entangled system with the coexistence of interpenetration and polycatenation, and a 3D topological framework. Interestingly, these CPs could be utilized for capturing iodine molecules. According to multiple complementary experiments and crystallographic analyses, iodine capture is mainly based on halogen-bond interactions in the inorganic {Cu2I2} building blocks of the framework. The present study describes a structure-property relationship in supramolecular isomerism with distinct topological structures. [ABSTRACT FROM AUTHOR]

Polymer-modified metal-organic frameworks combine the advantages of both soft polymers and crystalline metal-organic frameworks (MOFs). It is a big challenge to develop simple methods for surface modification of MOFs. In this work, MOF@microporous organic polymer (MOP) hybrid nanoparticles (UNP) have been synthesized by epitaxial growth of luminescent boron-dipyrromethene (BODIPYs)-imine MOPs on the surface of UiO-MOF seeds, which exhibit low cytotoxicity, smaller size distribution, well-retained pore integrity, and available functional sites. After folic acid grafting, the enhanced intracellular uptake and bioimaging was validated. [ABSTRACT FROM AUTHOR]

Nanomedicines assembled directly from drug molecules possess several advantages, including precise molecular structure and high content of drugs. Herein, porphyrin-paclitaxel conjugates (Py-s-s-PTX) were synthesized by using a disulfide bond as a linker. The Py-s-s-PTX could self-assemble into nanoparticles (Py-s-s-PTX NPs) with a size of about 100 nm via disulfide-induced assembly. Py-s-s-PTX NPs are highly stable under biological conditions and could be destroyed in the presence of reducing agents as revealed by dynamic light scattering. The obtained Py-s-s-PTX NPs could be internalized by cancer cells via endocytosis and disassociated in the reducing cytoplasm, thus releasing PTX in cancer cells. Endosomal escape triggered upon irradiation could enhance the cytotoxicity of paclitaxel, and Py-s-s-PTX NPs possess cytotoxicity comparable to that of free PTX. We believe that this disulfide-assembled nanomedicine represents a new and important development for chemotherapy in cancer therapy. [ABSTRACT FROM AUTHOR]

Plant root development is mediated by the concerted action of the auxin and cytokinin phytohormones, with cytokinin serving as an antagonist of auxin transport. Here, we identify the AUXIN UP-REGULATED F-BOX PROTEIN1 (AUF1) and its potential paralog AUF2 as important positive modifiers of root elongation that tether auxin movements to cytokinin signaling in Arabidopsis (Arabidopsis thaliana). The AUF1 mRNA level in roots is strongly up-regulated by auxin but not by other phytohormones. Whereas the auf1 single and auf1 auf2 double mutant roots grow normally without exogenous auxin and respond similarly to the wild type upon auxin application, their growth is hypersensitive to auxin transport inhibitors, with the mutant roots also having reduced basipetal and acropetal auxin transport. The effects of auf1 on auxin movements may be mediated in part by the misexpression of several PIN-FORMED (PIN) auxin efflux proteins, which for PIN2 reduces its abundance on the plasma membrane of root cells, auf1 roots are also hypersensitive to cytokinin and have increased expression of several components of cytokinin signaling. Kinematic analyses of root growth and localization of the cyclin B mitotic marker showed that AUF1 does not affect root cell division but promotes cytokinin-mediated cell expansion in the elongation/differentiation zone. Epistasis analyses implicate the cytokinin regulator ARR1 or its effector(s) as the target of the SKP1-Cullin1-F Box (SCF) ubiquitin ligases assembled with AUF1/2. Given the wide distribution of AUF1/2-type proteins among AUF1/2 land plants, we propose that SCF provides additional cross talk between auxin and cytokinin, which modifies auxin distribution and ultimately root elongation. [ABSTRACT FROM AUTHOR]

Plant root development is mediated by the concerted action of the auxin and cytokinin phytohormones, with cytokinin serving as an antagonist of auxin transport. Here, we identify the AUXIN UP-REGULATED F-BOX PROTEIN1 (AUF1) and its potential paralog AUF2 as important positive modifiers of root elongation that tether auxin movements to cytokinin signaling in Arabidopsis (Arabidopsis thaliana). The AUF1 mRNA level in roots is strongly up-regulated by auxin but not by other phytohormones. Whereas the auf1 single and auf1 auf2 double mutant roots grow normally without exogenous auxin and respond similarly to the wild type upon auxin application, their growth is hypersensitive to auxin transport inhibitors, with the mutant roots also having reduced basipetal and acropetal auxin transport. The effects of auf1 on auxin movements may be mediated in part by the misexpression of several PIN-FORMED (PIN) auxin efflux proteins, which for PIN2 reduces its abundance on the plasma membrane of root cells, auf1 roots are also hypersensitive to cytokinin and have increased expression of several components of cytokinin signaling. Kinematic analyses of root growth and localization of the cyclin B mitotic marker showed that AUF1 does not affect root cell division but promotes cytokinin-mediated cell expansion in the elongation/differentiation zone. Epistasis analyses implicate the cytokinin regulator ARR1 or its effector(s) as the target of the SKP1-Cullin1-F Box (SCF) ubiquitin ligases assembled with AUF1/2. Given the wide distribution of AUF1/2-type proteins among AUF1/2 land plants, we propose that SCF provides additional cross talk between auxin and cytokinin, which modifies auxin distribution and ultimately root elongation. [ABSTRACT FROM AUTHOR]

Gas chromatography-mass spectrometry with headspace solid-phase microextraction was used for the analysis of the volatile constituents of celery and water dropwort. Solid-phase microextraction was carried out with a 65 μm polydimethylsiloxane-divinylbenzene fiber at 60°C for 45 min. The fiber was desorbed in the GC injection liner at 250°C for 3 min. Thirty-eight compounds in celery and thirty-five compounds in water dropwort were separated and identified. The main compounds found in both celery and water dropwort included cis-3-hexen-1-ol, α-myrcene, limonene, a-pinene, 1,4-cyclohexadiene, 1,5,5-trimethyl-6-methylene-cyclohexene, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, n-hexadecanoic acid and α-caryophyllene. The precision of the method was studied by five replicate analysis of the main valatile compounds in celery and a relative standard deviation value less than 5.0% showed that the method could provide good reproducibility. [ABSTRACT FROM AUTHOR]

Point-of-care ultrasound demonstrates significant potential in biomedical research due to its noninvasive, real-time visualization, cost-effectiveness, and other biological benefits. Ultrasound irradiation can precisely control the mechanical and physicochemical effects on pathogenic lesions, enabling real-time visualization, tunable tissue penetration depth, and therapeutic applications. This review summarizes recent advancements in ultrasound-enabled diagnostics and therapeutics, focusing on mechanochemical effects that can be directly integrated into biomedical applications. Additionally, the structure-functionality relationships of sonotheranostic nanoplatforms are systematically discussed, providing insights into the underlying biological effects. Finally, the limitations of current ultrasonic medicine are discussed, along with potential expansions to facilitate patient-centered translations. This review summarizes the recent progress in the development of ultrasound-derived systems for ultrasonic molecular bioimaging and ultrasound-activatable therapy, with deep insights into the action mechanism, clinical challenges, and corresponding remedies. [Display omitted] [ABSTRACT FROM AUTHOR]

Using the seasonal cross-multiplication trend model, monthly precipitation of eight national basic weather stations of Shaanxi Province from 2005 to 2010 was predicted, and the forecast results were verified using the rainfall scoring rules of China Meteorological Administration. The verification results show that the average score of annual precipitation prediction in recent six years is higher than that made by a professional forecaster, so this model has a good prospect of application. Moreover, the level of making prediction is steady, and it can be widely used in long-term prediction of rainfall. [ABSTRACT FROM AUTHOR]

Porphyrin-based porous organic polymers are highly potential candidates for cancer theranostics. However, un-controllable particle size and unclear photoactive mechanisms have been deemed to be "Achilles' heels" for their biomedical application. Herein, a facile self-template strategy has been applied to integrate two types of porous materials to build the MOF@POP-PEG nanocomposite (named HUC-PEG). As-synthesized HUC-PEG exhibited controllable particle shape and size, good biocompatibility, and better colloidal stability. Importantly, synergy "0 + 1 > 1" interface effects have been demonstrated to simultaneously enhance both the generation of more singlet oxygen (1O 2) for photodynamic therapy (PDT) and local hyperthermia for photothermal therapy (PTT), thus to achieve favorable proliferation inhibition of tumor cell both in vitro and in vivo. Moreover, the strong X-ray attenuating ability of Hf element and excellent photothermal conversion efficacy endow this nanocomposite with computed tomography (CT)/photothermal imaging functions. We believe that our ingenious design may open a new horizon for the preparation of nanoscale POP-based therapeutic agents and also realize a paradigm shift in the understanding of photoactive mechanism in porous materials. [ABSTRACT FROM AUTHOR]

A conjugated polymer, P4TTD-DPP, based on tetra-fused isoindigo-alt-diketopyrrolopyrrole, has been synthesized as a photothermal therapeutic nanotransducer within the near-infrared-II (NIR-II) window. P4TTD-DPP exhibits a notable mass extinction coefficient of 62.8 L g−1 cm−1 at 1064 nm. Additionally, P4TTD-DPP nanoparticles demonstrate remarkable photothermal conversion efficiency of 91.5% at 1064 nm and exhibit excellent anticancer efficacy under photothermal conditions. [ABSTRACT FROM AUTHOR]

One exercise session can increase subsequent insulin-stimulated glucose uptake (ISGU) by healthy skeletal muscle, and recently published research linked this outcome to exercise-induced elevation in γ3-AMPK activity which leads to greater phosphorylation of Akt substrate of 160 kDa (pAS160) on an AMPK-phosphomotif (Ser704), which in turn favors greater insulin-stimulated pAS160 on a key Akt-phosphomotif (Thr642) that regulates ISGU. Studying healthy muscle is important, but a more urgent need is to understand the mechanisms for enhanced ISGU in insulin resistant muscle. Our primary goal was to determine if exercise, which increases ISGU, also increases γ3-AMPK activity and pAS160 on key regulatory sites at 3-hours post-exercise (3hPEX) in insulin resistant muscle. Rats fed a high fat diet (HFD; 2 week) known to cause muscle insulin resistance performed acute swim exercise (2 h) or remained sedentary (SED). Other chow-fed (low fat diet, LFD; 2 week) SED rats served as healthy controls. Isolated epitrochlearis muscles from 3hPEX rats (and SED controls) were used for ISGU, pAS160 and γ1- and γ3-AMPK isoform-specific activity. ISGU was lower in HFD SED muscles compared to LFD SED, but this decrement was eliminated in the HFD 3hPEX group. The γ3-AMPK activity, but not γ1-AMPK activity, was elevated in HFD 3hPEX muscles versus both SED controls. In addition, insulin-stimulated pAS160 on Thr642 and Ser704 in HFD 3hPEX muscles was elevated above HFD SED controls and equal to values in LFD SED muscles. These novel results demonstrated, for the first time in an insulin-resistant model, that the post-exercise increase in ISGU was accompanied by enhanced pAS160Ser704 and γ3-AMPK activation. Our working hypothesis is that these key signaling events are necessary for acute exercise to restore the ISGU of insulin resistant muscles to values equal to normal LFD SED controls. Disclosure: M.W. Pataky: None. E.B. Arias: None. X. Zheng: None. H. Wang: None. G.D. Cartee: None. Funding: National Institute of Diabetes and Digestive and Kidney Diseases [ABSTRACT FROM AUTHOR]

Ferroptosis featured by iron‐dependent lipid peroxidation plays a critical role in tumor regression, offering an alternative therapeutic target for the treatment of aggressive triple‐negative breast cancer. However, the traditional delivery strategy to enrich iron deposition is limited in producing a surplus of lipid oxidation because of the aggressive antioxidant response established in solid tumors. Here, vitamin B2‐ferric chloride nanocomplex self‐assembled through the coordination of ferric iron and hydroxy groups to simultaneously promote iron accumulation and oxidative stress is employed. It is observed that the self‐assembly nanostructures with appropriate size enable effective delivery of the therapeutic agents to the tumor site and cancer cells. More importantly, sonosensitizer vitamin B2 and ferric chloride cooperatively facilitate the production of reactive oxygen species and amplify nanocatalytic therapy. To further disrupt the antioxidant system, metformin with solute carrier family 7 member 11 inhibitory activity is used to synergistically boost ferroptosis of tumor cells. The combinational ferroptosis promoter exhibits augmented nanocatalytic antitumor efficacy in 4T1 tumor‐bearing mice with negligible adverse effects. Taken together, this study may provide a novel paradigm of self‐assembled vitamin B2‐ferric nanocomplex for ferroptosis regulation. [ABSTRACT FROM AUTHOR]

Drug molecules assembling nanomedicines possess several advantages, including precise molecular structure, various combinations of therapeutic agents and high content of drugs. In this work, paclitaxel dimer and two-photo photosensitizer were devised and synthesized, which could coassemble into nanoparticles (Co-NPs) in aqueous medium through nanoprecipitation method. As-synthesized Co-NPs possess the uniform size of about 80 nm and great stability in physiological condition, and could produce the singlet oxygen upon near-infrared light irradiation. The Co-NPs indicate enhanced cellular uptake and endosomal escape upon irradiation, which result in the synergistic enhancement of cytotoxicity towards cancer cells and growth inhibition of human cervical cancer tumors. We believed this combination therapy based on organic nanoparticles represent a new and important development in the cancer therapy. Image 1 • The first study to apply nanoparticles coassembled by paclitaxel dimer and two-photo photosensitizer. • The nanoparticles indicates the enhanced cellular uptake and endosomal escape upon irradiation due to the production of ROS. • The nanoparticles possesses synergistic enhancement of cytotoxicity towards human cervical cancer tumors. [ABSTRACT FROM AUTHOR]

Targeting imaging to the desired site of action can increase the accuracy and effectiveness of diagnostic and treatment. In this work, a series of fluorescent carbon dots (CDs) were prepared by varying molar ratios of d -glucose (Glu) to l -aspartic acid (Asp). Their photophysical properties, morphologies and structures were investigated in detail. More important, the targeting ability was screened by confocal laser scanning microscopy and flow cytometry. The results indicate that CDs prepared from the optimal molar ratio of Glu/Asp (7:3) exhibit the highest targeting ability on C6 glioma cells. This work highlights the interplay of molecular design and corresponding functions, and open new possibility of developing state-of-art nanoparticles for biomedical applications. [ABSTRACT FROM AUTHOR]

• The diversity in methodologies and compositions made polymer MOF hybrids desirable for biomedical treatment. • Hybridization of polymers and MOFs contributed to the elevation of bioavailability and pharmacokinetics. • By disclosure of the underlying mechanism, the optimized collaborative combination may put forward practical applications. • Multidisciplinary fusion may pave the investigation for unprecedented features orientated by the tailored architecture. Metal-organic frameworks (MOFs) exhibited intrinsic porosity and tunable compositions, which were routinely used for biomedical applications as contrast agents or drug delivery. After modification with biocompatible polymers, the rationally designed hybrids with sophisticated nanostructures integrated the merits from both soft polymers and crystalline MOFs, thus exhibiting unprecedented performance compared to individual ingredients. For biological research, the polymer-MOF hybrids have shown their superiority in bioavailability and pharmacokinetics as well as improved colloidal stability. In this review, typical synthetic procedures to obtain the polymer-MOF hybrids have been summarized. Moreover, recent progress of the polymer-MOF hybrid nanomaterials applied in bioimaging and cancer therapy areas was overviewed with an emphasis on their peculiar features. Especially, strategic hybridization of polymers and MOFs and collaborative combination strategies for enhancing therapeutic performances are highlighted. Finally, perspectives on future trends of polymer-MOF hybrid nanomaterials are presented. Detailed perspectives and suggestions are also proposed to broaden the scope of theranostic functionalities, attempting to bring polymer-MOF hybrid nanomaterials closer to clinical applications. [ABSTRACT FROM AUTHOR]

As a typical class of crystalline porous materials, metal–organic framework possesses unique features including versatile functionality, structural and compositional tunability. After being reduced to two-dimension, ultrathin metal-organic framework layers possess more external excellent properties favoring various technological applications. In this review article, the unique structural properties of the ultrathin metal-organic framework nanosheets benefiting from the planar topography were highlighted, involving light transmittance, and electrical conductivity. Moreover, the design strategy and versatile fabrication methodology were summarized covering discussions on their applicability and accessibility, especially for porphyritic metal-organic framework nanosheet. The current achievements in the bioapplications of two-dimensional metal-organic frameworks were presented comprising biocatalysis, biosensor, and theranostic, with an emphasis on reactive oxygen species-based nanomedicine for oncology treatment. Furthermore, current challenges confronting the utilization of two-dimensional metal-organic frameworks and future opportunities in emerging research frontiers were presented. [ABSTRACT FROM AUTHOR]

Porous carbon is considered one of the most promising anode materials for lithium-ion capacitors due to its high ionic and electronic conductivity, high lithium storage capacitance and high chemical stability. However, the green and low-carbon preparation is a great challenge for the current porous carbon, especially for heteroatoms doped porous carbon. Herein, we report a low-carbon and environmentally friendly method to prepare N-doped porous carbon by the novel reaction of greenhouse gas CO 2 with 5LiH-LiNH 2. N-doped porous carbon delivers a reversible lithium storage capacity of 904 mAh g−1 at 0.1 A g−1, When paired with commercial activated carbon, the as-assembled lithium-ion capacitors provide a high energy density of 112 Wh kg−1 at a power density of 198.6 W kg−1 with a capacitance retention of 72% at 1.0 A g−1 after 6000 cycles. This work provides a green and low-carbon strategy for converting greenhouse gas CO 2 into N-doped porous carbon for high-performance lithium-ion capacitors. • N-doped porous carbon was prepared by the new reactions between CO 2 and 5LiH-LiNH 2. • Preparation mechanism of NPC is discussed based on new reactions and gas flowing. • NPC//AC LICs provides a high energy density of 112 Wh kg−1 at 198.6 W kg−1. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a promising alternative to cancer therapy for its non-invasive advantage. The rational design of ideal photosensitizers (PSs) is especially significant in PDT. Herein, we synthesized a diiodo-substituted BODIPY (SNBDP) with near-infrared (NIR) region absorption and fluorescence emission by Knoevenagel condensation reaction. The SNBDP nanoparticles (NPs) were prepared by the nanoprecipitation method wrapped by poloxamer. As-prepared SNBDP NPs exhibited robust water stability and notable photostability. After cellular endocytosis, the NPs could elicit excellent cancer-killing effects with a low half maximal inhibitory concentration (10.55 μM for HeLa and 13.46 μM for A549 cells) due to good singlet oxygen quantum yield (Φ Δ = 40%) of PS derived from the heavy atom effect. Moreover, the favorable cancer cell inhibition efficacy could efficiently reduce the dark toxicity of drug. We believe this ingenious design could provide a reference value for the exploration of optimal PS for PDT. Organic NIR diiodo-substituted BODIPY nanoparticles with favorable water-stability, photostability, biocompatibility, and photocytotoxicity provide a new alternative for photodynamic therapeutic. Image 1 • A diiodo-substituted NIR BODIPY photosensitizer, SNBDP, is synthesized. • Photophysical properties and DFT calculation of SNBDP are investigated. • SNBDP NPs show good 1O 2 quantum yield and favorable stability. • SNBDP NPs exhibit promising in vitro cell imaging ability. • SNBDP NPs can effectively inhibit cancer cells under light irradiation. [ABSTRACT FROM AUTHOR]