A dedicated hypothalamic oxytocin circuit controls aversive social learning.

To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks1. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvlOXTR cells minimally respond to aggressor cues. During defeat, aVMHvlOXTR cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvlOXTR cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity.

Serum chemokine IL-8 acts as a biomarker for identifying COVID-19-associated persistent severe acute kidney injury.

OBJECTIVES: Persistent severe acute kidney injury (PS-AKI) is associated with poor clinical outcomes. Our study attempted to evaluate the diagnostic value of chemokines for early-stage PS-AKI prediction. METHODS: According to the KDIGO criteria, 115 COVID-19 patients diagnosed with stage 2/3 AKI were recruited from the intensive care unit between December 2022 and February 2023. Primary clinical outcomes included detecting PS-AKI in the first week (≥ KDIGO stage 2 ≥ 72 h). Cytometric Bead Array was used to detect patient plasma levels (interleukin-8 (IL-8), C-C chemokine ligand 5 (CCL5), chemokine (C-X-C Motif) ligand 9 (CXCL9), and interferon-inducible protein 10 (IP-10)) of chemokines within 24 h of enrollment. RESULTS: Of the 115 COVID-19 patients with stage 2/3 AKI, 27 were diagnosed with PS-AKI. Among the four measured chemokines, only the IL-8 level was significantly elevated in the PS-AKI group than in the Non-PS-AKI group. IL-8 was more effective as a biomarker while predicting PS-AKI with an area under the curve of 0.769 (0.675-0.863). This was superior to other biomarkers related to AKI, including serum creatinine. Moreover, plasma IL-8 levels of >32.2 pg/ml on admission could predict PS-AKI risk (sensitivity = 92.6%, specificity = 51.1%). Additionally, the IL-8 level was associated with total protein and IL-6 levels. CONCLUSION: Plasma IL-8 is a promising marker for the early identification of PS-AKI among COVID-19 patients. These findings should be validated in further studies with a larger sample size.

Oxytocin-Modulated Ion Channel Ensemble Controls Depolarization, Integration and Burst Firing in CA2 Pyramidal Neurons.

Oxytocin (OXT) and OXT receptor (OXTR)-mediated signaling control excitability, firing patterns, and plasticity of hippocampal CA2 pyramidal neurons, which are pivotal in generation of brain oscillations and social memory. Nonetheless, the ionic mechanisms underlying OXTR-induced effects in CA2 neurons are not fully understood. Using slice physiology in a reporter mouse line and interleaved current-clamp and voltage-clamp experiments, we systematically identified the ion channels modulated by OXT signaling in CA2 pyramidal cells (PYRs) in mice of both sexes and explored how changes in channel conductance support altered electrical activity. Activation of OXTRs inhibits an outward potassium current mediated by inward rectifier potassium channels (I Kir) and thus favoring membrane depolarization. Concomitantly, OXT signaling also diminishes inward current mediated by hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels (I h), providing a hyperpolarizing drive. The combined reduction in both I Kir and I h synergistically elevate the membrane resistance and favor dendritic integration while the membrane potential is restrained from quickly depolarizing from rest. As a result, the responsiveness of CA2 PYRs to synaptic inputs is highly sharpened during OXTR activation. Unexpectedly, OXTR signaling also strongly enhances a tetrodotoxin-resistant (TTX-R), voltage-gated sodium current that helps drive the membrane potential to spike threshold and thus promote rhythmic firing. This novel array of OXTR-stimulated ionic mechanisms operates in close coordination and underpins OXT-induced burst firing, a key step in CA2 PYRs' contribution to hippocampal information processing and broader influence on brain circuitry. Our study deepens our understanding of underpinnings of OXT-promoted social memory and general neuropeptidergic control of cognitive states.SIGNIFICANCE STATEMENT Oxytocin (OXT) plays key roles in reproduction, parenting and social and emotional behavior, and deficiency in OXT receptor (OXTR) signaling may contribute to neuropsychiatric disorders. We identified a novel array of OXTR-modulated ion channels that operate in close coordination to retune hippocampal CA2 pyramidal neurons, enhancing responsiveness to synaptic inputs and sculpting output. OXTR signaling inhibits both potassium conductance (I Kir) and mixed cation conductance (I h), engaging opposing influences on membrane potential, stabilizing it while synergistically elevating membrane resistance and electrotonic spread. OXT signaling also facilitates a tetrodotoxin-resistant (TTX-R) Na+ current, not previously described in hippocampus (HP), engaged on further depolarization. This TTX-R current lowers the spike threshold and supports rhythmic depolarization and burst firing, a potent driver of downstream circuitry.

On-Off Switching of a Photocatalytic Overall Reaction through Dynamic Spin-State Transition in a Hofmann Clathrate System.

Spin-state transition is a vital factor that dominates catalytic processes, but unveiling its mechanism still faces the great challenge of the lack of catalyst model systems. Herein, we propose that the {Fe-Pt} Hofmann clathrates, whose dynamic spin-state transition of metal centers can be chemically manipulated through iodine treatment, can serve as model systems in the spin-related structural-catalytic relationship study. Taking the photocatalytic synthesis of H2O2 as the basic catalytic reaction, when the spin state of Fe(II) in the clathrate is high spin (HS), sacrificial agents are indispensable to the photosynthesis of H2O2 because only the photocatalytic oxygen reduction reaction (ORR) occurs; when it is low spin (LS), both the ORR and water oxidation reaction (WOR) can take place, enabling a high H2O2 photosynthesis rate of 66 000 µM g-1 h-1 under visible-light irradiation. In situ characterizations combined with density functional theory calculations confirmed that, compared with the HS-state counterpart, the LS state can induce strong charge transfer between the LS Fe(II) and the iodide-coordinating Pt(IV) in the polymer and reduce the energy barriers for both the ORR and WOR processes, dominating the on-off switching upon the photosynthesis of H2O2 in O2-saturated water. What's more, the one-pot tandem reactions were conducted to utilize the synthesized H2O2 for transforming the low-value-added sodium alkenesulfonates into value-added bromohydrin products with decent conversion rates. This work provides a pioneering investigation into on-off switching the photocatalytic overall reaction through manipulating the metallic spin-state transition in spin-crossover systems.

Achieving High-Efficient Photoelectrocatalytic Degradation of 4-Chlorophenol via Functional Reformation of Titanium-Oxo Clusters.

Rational design of crystalline catalysts with superior light absorption and charge transfer for efficient photoelectrocatalytic (PEC) reaction coupled with energy recovery remains a great challenge. In this work, we elaborately construct three stable titanium-oxo clusters (TOCs, Ti10Ac6, Ti10Fc8, and Ti12Fc2Ac4) modified with a monofunctionalized ligand (9-anthracenecarboxylic acid (Ac) or ferrocenecarboxylic acid (Fc)) and bifunctionalized ligands (Ac and Fc). They have tunable light-harvesting and charge transfer capacities and thus can serve as outstanding crystalline catalysts to achieve efficient PEC overall reaction, that is, the integration of anodic organic pollutant 4-chlorophenol (4-CP) degradation and cathodic wastewater-to-H2 conversion. These TOCs can all exhibit very high PEC activity and degradation efficiency of 4-CP. Especially, Ti12Fc2Ac4 decorated with bifunctionalized ligands exhibits better PEC degradation efficiency (over 99%) and H2 generation than Ti10Ac6 and Ti10Fc8 modified with a monofunctionalized ligand. The study of the 4-CP degradation pathway and mechanism revealed that such better PEC performance of Ti12Fc2Ac4 is probably due to its stronger interactions with the 4-CP molecule and better •OH radical production. This work not only presents the effective combination of organic pollutant degradation and simultaneously H2 evolution reaction using crystalline coordination clusters as both anodic and cathodic catalyst but also develops a new PEC application for crystalline coordination compounds.

Shear stress-induced cellular senescence blunts liver regeneration through Notch-sirtuin 1-P21/P16 axis.

BACKGROUND AND AIMS: The mechanisms involved in liver regeneration after partial hepatectomy (pHx) are complicated. Cellular senescence, once linked to aging, plays a pivotal role in wound repair. However, the regulatory effects of cellular senescence on liver regeneration have not been fully elucidated. APPROACH AND RESULTS: Mice subjected to pHx were analyzed 14 days after surgery. The incomplete remodeling of liver sinusoids affected shear stress-induced endothelial nitric oxide synthase (eNOS) signaling on day 14, resulting in the accumulation of senescent LSECs. Removing macrophages to augment LSEC senescence led to a malfunction of the regenerating liver. A dynamic fluctuation in Notch activity accompanied senescent LSEC accumulation during liver regeneration. Endothelial Notch activation by using Cdh5-CreERT NICeCA mice triggered LSEC senescence and senescence-associated secretory phenotype, which disrupted liver regeneration. Blocking the Notch by γ-secretase inhibitor (GSI) diminished senescence and promoted LSEC expansion. Mechanically, Notch-hairy and enhancer of split 1 signaling inhibited sirtuin 1 (Sirt1) transcription by binding to its promoter region. Activation of Sirt1 by SRT1720 neutralized the up-regulation of P53, P21, and P16 caused by Notch activation and eliminated Notch-driven LSEC senescence. Finally, Sirt1 activator promoted liver regeneration by abrogating LSEC senescence and improving sinusoid remodeling. CONCLUSIONS: Shear stress-induced LSEC senescence driven by Notch interferes with liver regeneration after pHx. Sirt1 inhibition accelerates liver regeneration by abrogating Notch-driven senescence, providing a potential opportunity to target senescent cells and facilitate liver repair after injury.

Notch-triggered maladaptation of liver sinusoidal endothelium aggravates nonalcoholic steatohepatitis through endothelial nitric oxide synthase.

BACKGROUND AND AIMS: Although NASH can lead to severe clinical consequences, including cirrhosis and hepatocellular carcinoma, no effective treatment is currently available for this disease. Increasing evidence indicates that LSECs play a critical role in NASH pathogenesis; however, the mechanisms involved in LSEC-mediated NASH remain to be fully elucidated. APPROACH AND RESULTS: In the current study, we found that LSEC homeostasis was disrupted and LSEC-specific gene profiles were altered in methionine-choline-deficient (MCD) diet-induced NASH mouse models. Importantly, Notch signaling was found to be activated in LSECs of NASH mice. To then investigate the role of endothelial Notch in NASH progression, we generated mouse lines with endothelial-specific Notch intracellular domain (NICD) overexpression or RBP-J knockout to respectively activate or inhibit Notch signaling in endothelial cells. Notably, endothelial-specific overexpression of the NICD accelerated LSEC maladaptation and aggravated NASH, whereas endothelial cell-specific inhibition of Notch signaling restored LSEC homeostasis and improved NASH phenotypes. Furthermore, we demonstrated that endothelial-specific Notch activation exacerbated NASH by inhibiting endothelial nitric oxide synthase (eNOS) transcription, whereas administration of the pharmacological eNOS activator YC-1 alleviated hepatic steatosis and lipid accumulation resulting from Notch activation. Finally, to explore the therapeutic potential of using Notch inhibitors in NASH treatment, we applied two gamma-secretase inhibitors-DAPT and LY3039478-in an MCD diet-induced mouse model of NASH, and found that both inhibitors effectively ameliorated hepatic steatosis, inflammation, and liver fibrosis. CONCLUSIONS: Endothelial-specific Notch activation triggered LSEC maladaptation and exacerbated NASH phenotypes in an eNOS-dependent manner. Genetic and pharmacological inhibition of Notch signaling effectively restored LSEC homeostasis and ameliorated NASH progression.

Preoperative Frailty Assessment Predicts Postoperative Mortality, Delirium and Pneumonia in Elderly Lung Cancer Patients: A Retrospective Cohort Study.

BACKGROUND: The purpose of this study was to investigate the predictive value of the 5-factor modified frailty index (mFI-5) for postoperative mortality, delirium and pneumonia in patients over 65 years of age undergoing elective lung cancer surgery. METHODS: Data were collected from a single-center retrospective cohort study conducted in a general tertiary hospital from January 2017 to August 2019. In total, the study included 1372 elderly patients aged over 65 who underwent elective lung cancer surgery. They were divided into frail group (mFI-5, 2-5), prefrail group (mFI-5, 1) and robust group (mFI-5, 0) on the basis of mFI-5 classification. The primary outcome was postoperative 1-year all-cause mortality. Secondary outcomes were postoperative pneumonia and postoperative delirium. RESULTS: Frailty group had the highest incidence of postoperative delirium (frailty 31.2% versus prefrailty 1.6% versus robust 1.5%, p < 0.001), postoperative pneumonia (frailty 23.5% versus prefrailty 7.2% versus robust 7.7%, p < 0.001), and postoperative 1-year mortality (frailty 7.0% versus prefrailty 2.2% versus robust 1.9%. p < 0.001). Frail patients have significantly longer length of hospitalization than those in the robust group and prefrail patients (p < 0.001). Multivariate analysis showed a clear link between frailty and increased risk of postoperative delirium (aOR 2.775, 95% CI 1.776-5.417, p < 0.001), postoperative pneumonia (aOR 3.291, 95% CI 2.169-4.993, p < 0.001) and postoperative 1-year mortality (aOR 3.364, 95% CI, 1.516-7.464, p = 0.003). CONCLUSIONS: mFI-5 has potential clinical utility in predicting postoperative death, delirium and pneumonia incidence in elderly patients undergoing radical lung cancer surgery. Frailty screening of patients (mFI-5) may provide benefits in risk stratification, targeted intervention efforts, and assist physicians in clinical decision-making.

Pentacyclic triterpene-amino acid derivatives induced apoptosis and autophagy in tumor cells, affected the JNK and PI3K/AKT/mTOR pathway.

A series of pentacyclic triterpene-amino acid derivatives were synthesized and tested for anti-proliferative activity. The results showed that most of the target compounds had good anti-proliferative activity. 2c did not contain protecting groups and hydrochloride, had excellent cytotoxicity, so it had been selected for further study in the mechanism of action in T24 cells. The data from transcriptome sequencing indicated that 2c was found to be closely related to apoptosis and autophagy. Observation of fluorescence staining and analysis from flow cytometry demonstrated that 2c induced apoptosis and cause cell cycle arrest in S/G2 phase in T24 cells. Molecular mechanism studies exhibited that 2c induced apoptosis in the intrinsic and extrinsic pathways. 2c also induced cellular autophagy in T24 cells. Results from Western Blotting showed that 2c could activate JNK pathway and inhibit PI3K/AKT/mTOR pathway. In conclusion, 2c was deserved further investigation in the field of anti-tumor.

All-solid-state potentiometric salicylic acid sensor for in-situ measurement of plant.

Using PEDOT as the conductive polymer, an innovative small-scale sensor for directly measuring salicylate ions in plants was developed, which avoided the complicated sample pretreatment of traditional analytical methods and realized the rapid detection of salicylic acid. The results demonstrate that this all-solid-state potentiometric salicylic acid sensor is easy to miniaturize, has a longer lifetime (≥1 month), is more robust, and can be directly used for the detection of salicylate ions in real samples without any additional pretreatment. The developed sensor has a good Nernst slope (63.6 ± 0.7 mV/decade), the linear range is 10-2 ~ 10-6 M, and the detection limit can reach (2.8 × 10-7 M). The selectivity, reproducibility, and stability of the sensor were evaluated. The sensor can perform stable, sensitive, and accurate in situ measurement of salicylic acid in plants, and it is an excellent tool for determining salicylic acid ions in plants in vivo.

Identification of the enantiomeric nature of 2-keto-3-deoxy-galactonate in the catabolic pathway of 3,6-anhydro-L-galactose.

A novel metabolic pathway of 3,6-anhydro-L-galactose (L-AHG), the main sugar component in red macroalgae, was first discovered in the marine bacterium Vibrio sp. EJY3. L-AHG is converted to 2-keto-3-deoxy-galactonate (KDGal) in two metabolic steps. Here, we identified the enantiomeric nature of KDGal in the L-AHG catabolic pathway via stereospecific enzymatic reactions accompanying the biosynthesis of enantiopure L-KDGal and D-KDGal. Enantiopure L-KDGal and D-KDGal were synthesized by enzymatic reactions derived from the fungal galacturonate and bacterial oxidative galactose pathways, respectively. KDGal, which is involved in the L-AHG pathway, was also prepared. The results obtained from the reactions with an L-KDGal aldolase, specifically acting on L-KDGal, showed that KDGal in the L-AHG pathway exists in an L-enantiomeric form. Notably, we demonstrated the utilization of L-KDGal by Escherichia coli for the first time. E. coli cannot utilize L-KDGal as the sole carbon source. However, when a mixture of L-KDGal and D-galacturonate was used, E. coli utilized both. Our study suggests a stereoselective method to determine the absolute configuration of a compound. In addition, our results can be used to explore the novel L-KDGal catabolic pathway in E. coli and to construct an engineered microbial platform that assimilates L-AHG or L-KDGal as substrates. KEY POINTS: • Stereospecific enzyme reactions were used to identify enantiomeric nature of KDGal • KDGal in the L-AHG catabolic pathway exists in an L-enantiomeric form • E. coli can utilize L-KDGal as a carbon source when supplied with D-galacturonate.

Efficacy of Immature Platelet Fraction in Predicting Septic Acute Kidney Injury.

BACKGROUND: Immature platelet fraction (IPF) is a new hematological parameter. Although its value in predicting the severity and mortality of sepsis patients has been shown, no study has assessed whether IPF can predict sepsis-associated acute kidney injury (S-AKI). Thus, this study aimed to analyze the predictive value of IPF in the occurrence and mortality of S-AKI. METHODS: Sepsis patients from the intensive care unit were screened and divided into S-AKI (n = 53) and non-S-AKI (n = 71) groups. IPF values were calculated by using the CDR mode of the BC-6800Plus hematology analyzer (Mindary, Shenzhen, China). Relevant data, such as serum creatinine (Scr) and uric acid (UA) levels, of the patients were obtained through the hospital information-management system. RESULTS: The sepsis patients with S-AKI had lower high-density lipoprotein (HDL) levels, higher IPF values, higher Scr, UA, C-reactive protein (CRP), and procalcitonin (PCT) levels, and higher SOFA and APACHE Ⅱ scores than the non-S-AKI patients (p < 0.05). IPF value was found correlated with Scr, HDL, CRP, and PCT levels and APACHE Ⅱ score but not with age, UA level, urine output in 24 hours, or SOFA score. Multivariate logistic regression analysis suggested that IPF, UA, and HDL are independent risk factors for S-AKI. The area under the curve (AUC) of IPF in the identification of S-AKI incidence was found superior to the AUC of UA and 1/HDL with a cutoff value of 12.15. However, IPF was not found associated with mortality in S-AKI. CONCLUSIONS: IPF can serve as a biomarker to predict S-AKI in sepsis patients.

[Research Progress in the Regulation of Follicle Development by Melatonin].

Melatonin,an endocrine hormone synthesized by the pineal gland,plays an important role in the reproduction.The growth and development of follicles is the basis of female mammalian fertility.Follicles have a high concentration of melatonin.Melatonin receptors exist on ovarian granulosa cells,follicle cells,and oocytes.It regulates the growth and development of these cells and the maturation and atresia of follicles,affecting female fertility.This paper reviews the protective effects and regulatory mechanisms of melatonin on the development of ovarian follicles,granulosa cells,and oocytes and makes an outlook on the therapeutic potential of melatonin for ovarian injury,underpinning the clinical application of melatonin in the future.

Synergistic Metal-Nonmetal Active Sites in a Metal-Organic Cage for Efficient Photocatalytic Synthesis of Hydrogen Peroxide in Pure Water.

Photocatalytic synthesis of hydrogen peroxide (H2 O2 ) is a potential clean method, but the long distance between the oxidation and reduction sites in photocatalysts hinders the rapid transfer of photogenerated charges, limiting the improvement of its performance. Here, a metal-organic cage photocatalyst, Co14 (L-CH3 )24 , is constructed by directly coordinating metal sites (Co sites) used for the O2 reduction reaction (ORR) with non-metallic sites (imidazole sites of ligands) used for the H2 O oxidation reaction (WOR), which shortens the transport path of photogenerated electrons and holes, and improves the transport efficiency of charges and activity of the photocatalyst. Therefore, it can be used as an efficient photocatalyst with a rate of as high as 146.6 µmol g-1 h-1 for H2 O2 production under O2 -saturated pure water without sacrificial agents. Significantly, the combination of photocatalytic experiments and theoretical calculations proves that the functionalized modification of ligands is more conducive to adsorbing key intermediates (*OH for WOR and *HOOH for ORR), resulting in better performance. This work proposed a new catalytic strategy for the first time; i.e., to build a synergistic metal-nonmetal active site in the crystalline catalyst and use the host-guest chemistry inherent in the metal-organic cage (MOC)to increase the contact between the substrate and the catalytically active site, and finally achieve efficient photocatalytic H2 O2 synthesis.

Structural Evolution of Giant Polyoxometalate: From "Keplerate" to "Lantern" Type Mo132 for Improved Oxidation Catalysis.

Structural variants of high-nuclearity clusters are extremely important for their modular assembly study and functional expansion, yet the synthesis of such giant structural variants remains a great challenge. Herein, we prepared a lantern-type giant polymolybdate cluster (L-Mo132 ) containing equal metal nuclearity with the famous Keplerate type Mo132 (K-Mo132 ). The skeleton of L-Mo132 features a rare truncated rhombic triacontrahedron, which is totally different with the truncated icosahedral K-Mo132 . To the best of our knowledge, this is the first time to observe such structural variants in high-nuclearity cluster built up of more than 100 metal atoms. Scanning transmission electron microscopy reveals that L-Mo132 has good stability. More importantly, because the pentagonal [Mo6 O27 ]n- building blocks in L-Mo132 are concave instead of convex in the outer face, it contains multiple terminal coordinated water molecules on its outer surface, which make it expose more active metal sites to display superior phenol oxidation performance, which is more higher than that of K-Mo132 coordinated in M=O bonds on the outer surface.

Keeping Superprotonic Conductivity over a Wide Temperature Region via Sulfate Hopping Sites-Decorated Zirconium-Oxo Clusters.

Metal-oxo clusters have emerged as advanced proton conductors with well-defined and tunable structures. Nevertheless, the exploitation of metal-oxo clusters with high and stable proton conductivity over a relatively wide temperature range still remains a great challenge. Herein, three sulfate groups decorated zirconium-oxo clusters (Zr6 , Zr18 , and Zr70 ) as proton conductors are reported, which exhibit ultrahigh bulk proton conductivities of 1.71 × 10-1 , 2.01 × 10-2 , and 3.73 × 10-2  S cm-1 under 70 °C and 98% relative humidity (RH), respectively. Remarkably, Zr6 and Zr70 with multiple sulfate groups as proton hopping sites show ultralow activation energies of 0.22 and 0.18 eV, respectively, and stable bulk conductivities of >10-2  S cm-1 between 30 and 70 °C at 98% RH. Moreover, a time-dependent proton conductivity test reveals that the best performing Zr6 can maintain high proton conductivity up to 15 h with negligible loss at 70 °C and 98% RH, representing one of the best crystalline cluster-based proton conducting materials.

Experimental Realization of Weyl Exceptional Rings in a Synthetic Three-Dimensional Non-Hermitian Phononic Crystal.

Weyl points-topological monopoles of quantized Berry flux-are predicted to spread to Weyl exceptional rings in the presence of non-Hermiticity. Here, we use a one-dimensional Aubry-Andre-Harper model to construct a Weyl semimetal in a three-dimensional parameter space comprising one reciprocal dimension and two synthetic dimensions. The inclusion of non-Hermiticity in the form of gain and loss produces a synthetic Weyl exceptional ring (SWER). The topology of the SWER is characterized by both its topological charge and non-Hermitian winding numbers. We experimentally observe the SWER and synthetic Fermi arc in a one-dimensional phononic crystal with the non-Hermiticity introduced by active acoustic components. Our findings pave the way for studying the high-dimensional non-Hermitian topological physics in acoustics.

RGD-functionalised melanin nanoparticles for intraoperative photoacoustic imaging-guided breast cancer surgery.

PURPOSE: Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation. METHODS: The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice. RESULTS: The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis. CONCLUSION: These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation.

Genome-wide transcriptional regulation in Saccharomyces cerevisiae in response to carbon dioxide.

Sugar metabolism by Saccharomyces cerevisiae produces ample amounts of CO2 under both aerobic and anaerobic conditions. High solubility of CO2 in fermentation media, contributing to enjoyable sensory properties of sparkling wine and beers by S. cerevisiae, might affect yeast metabolism. To elucidate the overlooked effects of CO2 on yeast metabolism, we examined glucose fermentation by S. cerevisiae under CO2 as compared to N2 and O2 limited conditions. While both CO2 and N2 conditions are considered anaerobic, less glycerol and acetate but more ethanol were produced under CO2 condition. Transcriptomic analysis revealed that significantly decreased mRNA levels of GPP1 coding for glycerol-3-phosphate phosphatase in glycerol synthesis explained the reduced glycerol production under CO2 condition. Besides, transcriptional regulations in signal transduction, carbohydrate synthesis, heme synthesis, membrane and cell wall metabolism, and respiration were detected in response to CO2. Interestingly, signal transduction was uniquely regulated under CO2 condition, where upregulated genes (STE3, MSB2, WSC3, STE12, and TEC1) in the signal sensors and transcriptional factors suggested that MAPK signaling pathway plays a critical role in CO2 sensing and CO2-induced metabolisms in yeast. Our study identifies CO2 as an external stimulus for modulating metabolic activities in yeast and a transcriptional effector for diverse applications.

Ferrocene-Functionalized Crystalline Biomimetic Catalysts for Efficient CO2 Photoreduction.

Photoreducing carbon dioxide (CO2) into highly valued chemicals or energy products has been recognized as one of the most promising proposals to degrade atmospheric CO2 concentration and achieve carbon neutrality. Adenine with a photosensitive amino group and aromatic nitrogen atom can strongly interact with CO2 and has been authenticated for its catalytic activity for the CO2 photoreduction reaction (CO2RR). Herein, two adenine-constructed crystalline biomimetic photocatalysts (Co2-AW and Co2-AF) were designed and synthesized to achieve CO2RR. Between them, Co2-AF displayed higher photocatalytic activity (225.8 µmol g-1 h-1) for CO2-to-HCOOH conversion than that of Co2-AW. It was found that the superior charge transfer capacity of the functional ferrocene group in Co2-AF is the primary reason to facilitate the photocatalytic performance efficiently. Additionally, this work also demonstrated the great potential of the ferrocene group as an electron donor and mediator in improving the photocatalytic activity of crystalline coordination catalysts.