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Electrocatalytic CO2 reduction reaction (CO2RR) for CH4 production presents a promising strategy to address carbon neutrality, and the incorporation of a second metal has been proven effective in enhancing catalyst performance. Nevertheless, there remains limited comprehension regarding the fundamental factors responsible for the improved performance. Herein, the critical role of Pd in electrocatalytic CO2 reduction to CH4 on Cu-based catalysts has been revealed at a molecular level using in situ surface-enhanced Raman spectroscopy (SERS). A "borrowing" SERS strategy has been developed by depositing Cu–Pd overlayers on plasmonic Au nanoparticles to achieve the in situ monitoring of the dynamic change of the intermediate during CO2RR. Electrochemical tests demonstrate that Pd incorporation significantly enhances selectivity toward CH4 production, and the Faradaic efficiency (FE) of CH4 is more than two times higher than that for the catalysts without Pd. The key intermediates, including *CO2−, *CO, and *OH, have been directly identified under CO2RR conditions, and their evolution with the electrochemical environments has been determined. It is found that Pd incorporation promotes the activation of both CO2 and H2O molecules and accelerates the formation of abundant active *CO and hydrogen species, thus enhancing the CH4 selectivity. This work offers fundamental insights into the understanding of the molecular mechanism of CO2RR and opens up possibilities for designing more efficient electrocatalysts. [ABSTRACT FROM AUTHOR]

Obtaining accurate lattice thermal conductivity data of LiF under extreme conditions not only provides important reference for performance evaluation, prediction, and control of materials, but also helps to alleviate the significant challenges of precise experimental measurements. The high-temperature phonon properties and lattice thermal conductivity (LTC) of solid LiF were calculated by combining on-the-fly machine learning force fields (MLFFs) with the Green–Kubo method. The introduction of MLFF successfully combines the accuracy of ab initio molecular dynamics with the scalability advantage of classical molecular dynamics. At high temperatures, there is a significant enhancement in the vibrational coupling between the acoustic and optical branches of LiF, as well as resonant effects between Li and F atoms, resulting in strong anharmonicity. Additionally, the main peak of the phonon density of states shows a noticeable redshift compared to the harmonic case. The enhanced coupling of TO and TA modes at high temperature leads to a significant increase in phonon scattering rate. By considering higher-order phonon anharmonicity, the predicted LTC is significantly reduced compared to the results obtained from considering only three-phonon interactions. Along the Hugoniot curve up to 100 GPa (2150 K), the predicted LTC agrees well with the experimental values. These findings demonstrate the crucial role of phonon anharmonicity in promoting phonon scattering. [ABSTRACT FROM AUTHOR]

Determining the source and history of hydrothermal fluids are key to better understanding the genesis of lode gold deposits. However, it is difficult to rigorously constrain the fluid history because the fluids typically have a prolonged and complicated history that may obscure the original source signature. We integrate textural characterization, trace element geochemistry, and in situ oxygen isotope analyses of quartz covering three major paragenetic stages of the world-class Dongping lode gold deposit to fingerprint the ore-fluid source and document the deposit's complex hydrothermal history. Six quartz generations were identified from three paragenetic stages. They consistently display small to large ranges in δ18O values from 13.1 to 0.6‰ (VSMOW), which correspond to calculated δ18O values of 7.4 to –6.0‰ for the quartz-forming fluids. These isotope data are intermediate between the δ18O ranges of magmatic fluids and meteoric water and thus are best interpreted in terms of episodic fluxes of magmatically derived fluids and their subsequent mixing with variable proportions of external meteoric water. Our results highlight the important role of magmatic hydrothermal fluids and their mixing with meteoric water to form the giant Dongping gold deposit. Given the high abundance of quartz that typically spans the entire mineralization process of lode gold deposits, we envisage the versatility and reliability of in situ oxygen isotope analysis of well-characterized quartz in deciphering the origin and complex evolution history of gold-forming fluids. [ABSTRACT FROM AUTHOR]

In this study, a series of organic amine-intercalated α-ZrP were prepared. The crystal phase, structures and properties of these intercalated compounds were analyzed and characterized using several analysis methods. The interlayer distance of organic amine-intercalated α-ZrP has increased regularly along with the increase of chain elongation of organic amine. The composites were applied to adsorb phenol from wastewater. The adsorption equilibrium, kinetics, and dynamic adsorption of phenol onto intercalated α-ZrP were studied. Adsorption isotherms of phenol were determined at different temperatures, and they were well fitted to the Freundlich equation (R2 > 0.99), and the corresponding maximum adsorption capacity of phenol was 0.832 mmol/g. Batch kinetic experiments revealed that the adsorption process followed a quasi-second-order kinetic model. The dynamic adsorption revealed that the adsorption capacity for phenol increased with the increase in temperature. The adsorption process was rapid and equilibrium was reached within 30 min. When the adsorption dosage is 0.1 g/15 mL, the adsorption yield for 10 mmol/L phenol solution can reach 61.2%. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Novel cross-linked fluorinated acrylate latex was successfully synthesized via the semi-continuous seeded emulsion polymerization, in which methyl methacrylate (MMA) and butyl acrylate (BA) were used as the main monomers, and dodecafluoroheptyl methacrylate (DFMA) and N–N methylene bisacrylamide (MBA) were used as the fluorine monomer and the cross-linked monomer, respectively. Potassium persulfate (KPS) and mixed surfactants of sodium lauryl sulfate and alkyl alcohol polyether (EFS-470) were used as the initiator and emulsifier, respectively. The structure of resultant latex film was characterized by Fourier transform infrared spectroscopy (FTIR). The latex films were tested by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), contact angle (CA), cross-linked degree and X-ray diffractometer (XRD). The particle size and its distribution of the latex were measured by the nanoparticle size analyzer and transmission electron microscope (TEM). The factors that have an influence on the properties of the latex and the film are investigated in detail. The stability of the resultant latex was good. The average particles of the latex and its distribution were small and uniform, respectively. In comparison with the conventional latex film, the thermal stability and hydrophobicity of the novel latex film were improved obviously. [ABSTRACT FROM AUTHOR]

Aim: This study explores the efficacy of electroacupuncture (EA) in treating cerebral palsy (CP) in Sprague–Dawley (SD) pups, specifically CP animal models, and its molecular mechanisms. Methods: Gait analysis and Y‐maze were used to detect the improvement of motor ability and cognitive function of CP rats after EA treatment. Transcription sequencing was used to determine the key pathway for EA to improve the symptoms of CP. PPAR agonists were used to verify the causal relationship between the pathway and the improvement of CP phenotype. Results: The motor ability and cognitive function of CP pups were improved after EA treatment. The results of transcriptome sequencing suggest that the improvement of CP phenotype may be caused by the activation of PPAR pathway. PPAR pathway is widely activated in the epithelium of CP pups treated with EA, which is verified by qPCR. Rosiglitazone (Ros), a PPAR agonist, can improve CP phenotype while activating PPAR pathway, which proves the causal relationship between PPAR pathway activation and CP phenotype improvement. Conclusion: Our study demonstrated behavioral improvements and enhanced cognitive functions in CP models after EA treatment by activating PPAR pathway, suggesting new perspectives for CP rehabilitation, and providing theoretical support for acupuncture treatment of CP. [ABSTRACT FROM AUTHOR]

Aiming at the high false negative rate and low accuracy in crowded scenes, a pedestrian detection network based on multi-scale features and mutual supervision is proposed. To effectively extract pedestrian feature information in complex scenes, a network combining PANet pyramid network and mixed dilated convolutions is used to extract feature information. Then, a mutual supervision detection network for head-body detection is designed, which utilizes the mutual supervision of head bounding boxes and full-body bounding boxes to obtain more accurate pedestrian detection results. The proposed network achieves 13.5% MR-2 performance on CrowdHuman dataset, with an improvement of 3.6% compared to the YOLOv5 network, and a simultaneous improvement of 3.5% in average precision (AP). On CityPersons dataset, it achieves 48.2% MR-2 performance, with 2.3% improvement compared to the YOLOv5 network, and a simultaneous improvement of 2.8% in AP. The results indicate that the proposed network demonstrates good detection performance in densely crowded scenes. [ABSTRACT FROM AUTHOR]

Background: Pemphigus is a group of potentially life-threatening autoimmune bullous diseases induced by pathogenic autoantibodies binding to the surface of epidermal cells. The role of the gut microbiota (GM) has been described in various autoimmune diseases. However, the impact of the GM on pemphigus is less understood. This study aimed to investigate whether there was alterations in the composition and function of the GM in pemphigus patients compared to healthy controls (HCs). Methods: Fecal samples were collected from 20 patients with active pemphigus (AP), 11 patients with remission pemphigus (PR), and 47 HCs. To sequence the fecal samples, 16S rRNA was applied, and bioinformatic analyses were performed. Results: We found differences in the abundance of certain bacterial taxa among the three groups. At the family level, the abundance of Prevotellaceae and Coriobacteriaceae positively correlated with pathogenic autoantibodies. At the genus level, the abundance of Klebsiella, Akkermansia, Bifidobacterium, Collinsella, Gemmiger, and Prevotella positively correlated with pathogenic autoantibodies. Meanwhile, the abundance of Veillonella and Clostridium_XlVa negatively correlated with pathogenic autoantibodies. A BugBase analysis revealed that the sum of potentially pathogenic bacteria was elevated in the AP group in comparison to the PR group. Additionally, the proportion of Gram-negative bacteria in the PR group was statistically significantly lower in comparison to the HC group. Conclusion: The differences in GM composition among the three groups, and the correlation between certain bacterial taxa and pathogenic autoantibodies of pemphigus, support a linkage between the GM and pemphigus. [ABSTRACT FROM AUTHOR]

The estimation of the seismic vulnerability of regional structures has contributed positively to the development of seismic risk and resilience in large-scale building clusters. However, the empirical structural seismic damage and ground motion data used to validate the risk model are relatively outdated, resulting in insufficient evaluation accuracy of the established risk model and an urgent use for retrofitting. This study analysed the actual failure peculiarities of typical structures during a recent typical destructive earthquake in China (the Luding earthquake in Sichuan Province on September 5, 2022). A total of 300,000 acceleration records from ten actual monitoring seismic stations were processed and analysed. Nonlinear dynamic time history curves, response spectra, and combined seismic acceleration cloud images were generated considering different directions. Moreover, the traditional instrument intensity calculation equation has been updated, and an instrument intensity curve bunch considering 300,000 earthquake acceleration records has been developed. To study the probabilistic seismic risk of large-scale regional buildings, the developed vulnerability database of typical regional structures (Sichuan Province) was supplemented and optimized, and an updated vulnerability database (413 damage probability matrix) was established, considering the failure of five structures in 32 destructive earthquakes. An updated structural seismic vulnerability model based on extended vulnerability grades was proposed, and a mean vulnerability probability matrix based on structural risk datasets was established. A membership index function for estimating the correlation between different vulnerability grades was innovatively proposed, and the rationality of the model was verified using an improved empirical dataset. A multidimensional failure prediction model was developed based on an improved mean seismic damage index. [ABSTRACT FROM AUTHOR]

Using the experimentally known aromatic icosahedral superatoms Ih B12H122− and D5d 1,12-C2B10H12 as building blocks and based on extensive density functional theory calculations, we predict herein a series of core–shell superpolyhedral boranes and carboranes in a bottom-up approach, including the high-symmetry Th B12@B152H722− (2), C2h C2B10@B152H72 (3), D3d B12@B144H66 (4), Ih B12@C24B120H722− (6), and D5d C2B10@C24B120H72 (7). More interestingly, the superatom-assembled linear D2h B36H322− (8), close-packed planar D3dB84H602− (10), and nearly close-packed core–shell D3d B12@B144H66 (4) can be extended periodically to form the one-dimensional (1D) α-rhombohedral borane nanowire B12H10 (Pmmm) (9), two-dimensional (2D) α-rhombohedral monolayer borophane B12H6 (P 3 ¯ m 1 ) (11), and the experimentally known three-dimensional (3D) α-rhombohedral boron (R 3 ¯ m ) (12) which can be viewed as an assembly of the monolayer B12H6 (11) staggered in vertical direction, setting up a bottom-up strategy to form low-dimensional boron-based nanomaterials from their borane "seeds" via partial or complete dehydrogenations. Detailed bonding analyses indicate that the high stability of these nanostructures originates from the spherical aromaticity of their icosahedral B12 or C2B10 structural units which possess the universal skeleton electronic configuration of 1S21P61D101F8 following the Wade's n+1 rule. The infrared (IR) and Raman spectra of the most-concerned neutral B12@B144H66 (4) and C2B10@C24B120H72 (7) are computationally simulated to facilitate their experimental characterizations. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the quality of guidelines on the pancreatic perioperative enhanced recovery after surgery both domestically and internationally, providing reference and reference for clinical practice. Methods: Systemically retrieved in the guideline websites, professional association websites and databases, such as up to date, BMJ Best Practice, PubMed, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang Data, China Science and Technology Journal Database(VIP), China Biology Medicine disc (CBMdisc), Medlive, Guidelines International Network(GIN), National Guideline Clearinghouse(NGC), National Institute for Health and Care Excellence(NICE), Registered Nurses Association of Ontario(RNAO), Scottish Intercollegiate Guidelines Network(SIGN), Joanna Briggs Institute Library(JBI), including guidelines and expert consensus on enhanced postsurgical recovery in pancreatic surgery published as of December 20, 2023. The Appraisal of Guidelines for Research and Evaluation II(AGREE II) tool was applied to evaluate the quality of the guidelines by four assessors. Results: This study included seven guidelines, all of which were rated as Grade B in terms of quality, with ICC coefficients ranging from 0.752 to 0.884, indicating a high level of consistency. Conclusion: When formulating guidelines in the future, it is recommended to use AGREE II as a reference, emphasizing the standardization of the guideline development process and methods, fully considering patients’ values and preferences, focusing on the applicability of the guidelines, and striving to create high-quality evidence-based recommendations. [ABSTRACT FROM AUTHOR]

Anorectal malformation (ARM), a common congenital anomaly of the digestive tract, is a result of insufficient elongation of the urorectal septum. The cytoplasmic protein Receptor of Activated C‐Kinase 1 (Rack1) is involved in embryonic neural development; however, its role in embryonic digestive tract development and ARM formation is unexplored. Our study explored the hindgut development and cell death mechanisms in ARM‐affected rats using spatial transcriptome analysis. We induced ARM in rats by administering ethylenethiourea via gavage on gestational day (GD) 10. On GDs 14–16, embryos from both normal and ARM groups underwent spatial transcriptome sequencing, which identified key genes and signalling pathways. Rack1 exhibited significant interactions among differentially expressed genes on GDs 15 and 16. Reduced Rack1 expression in the ARM‐affected hindgut, verified by Rack1 silencing in intestinal epithelial cells, led to increased P38 phosphorylation and activation of the MAPK signalling pathway. The suppression of this pathway downregulated Nqo1 and Gpx4 expression, resulting in elevated intracellular levels of ferrous ions, reactive oxygen species (ROS) and lipid peroxides. Downregulation of Gpx4 expression in the ARM hindgut, coupled with Rack1 co‐localisation and consistent mitochondrial morphology, indicated ferroptosis. In summary, Rack1, acting as a hub gene, modulates ferrous ions, lipid peroxides, and ROS via the P38‐MAPK/Nqo1/Gpx4 axis. This modulation induces ferroptosis in intestinal epithelial cells, potentially influencing hindgut development during ARM onset. [ABSTRACT FROM AUTHOR]

In the realm of modern information technology, data compression technology occupies a pivotal position. With advancements in quantum information technology, the need to compress large-scale qubits ensembles has become urgent, aiming to reduce the demand on quantum storage resources. However, existing quantum state compression schemes generally face a limitation: the particles before and after compression must reside in the same dimensional space. In specific scenarios, compressing qubits into particles of higher dimensions not only enhances the efficiency of quantum state compression but also further reduces the usage of quantum storage resources. Here we experimentally demonstrated a quantum state compression between particles of different dimensions, successfully compressing two qubits into a single qutrit. The average fidelity of the resulting qutrit with the ideal quantum state is 0.8835. Our study may have potential applications in future quantum information, such as increasing quantum communication bandwidth and reducing storage resource consumption in quantum computing. [ABSTRACT FROM AUTHOR]

Background: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. Methods: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. Results: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. Conclusion: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies. [ABSTRACT FROM AUTHOR]

Kidney stones are a pervasive disease with notoriously high recurrence rates that require more effective treatment strategies. Herein, tartronic acid is introduced as an efficient inhibitor of calcium oxalate monohydrate (COM) crystallization, which is the most prevalent constituent of human kidney stones. A combination of in situ experimental techniques and simulations are employed to compare the inhibitory effects of tartronic acid with those of its molecular analogs. Tartronic acid exhibits an affinity for binding to rapidly growing apical surfaces of COM crystals, thus setting it apart from other inhibitors such as citric acid, the current preventative treatment for kidney stones. Bulk crystallization and in situ atomic force microscopy (AFM) measurements confirm the mechanism by which tartronic acid interacts with COM crystal surfaces and inhibits growth. These findings are consistent with in vivo studies that reveal the efficacy of tartronic acid is similar to that of citric acid in mouse models of hyperoxaluria regarding their inhibitory effect on stone formation and alleviating stone‐related physical harm. In summary, these findings highlight the potential of tartronic acid as a promising alternative to citric acid for the management of calcium oxalate nephropathies, offering a new option for clinical intervention in cases of kidney stones. [ABSTRACT FROM AUTHOR]

Background: This study addresses the predictive modeling of Enlarged Perivascular Spaces (EPVS) in neuroradiology and neurology, focusing on their impact on Cerebral Small Vessel Disease (CSVD) and neurodegenerative disorders. Methods: A retrospective analysis was conducted on 587 neurology inpatients, utilizing LASSO regression for variable selection and logistic regression for model development. The study included comprehensive demographic, medical history, and laboratory data analyses. Results: The model identified key predictors of EPVS, including Age, Hypertension, Stroke, Lipoprotein a, Platelet Large Cell Ratio, Uric Acid, and Albumin to Globulin Ratio. The predictive nomogram demonstrated strong efficacy in EPVS risk assessment, validated through ROC curve analysis, calibration plots, and Decision Curve Analysis. Conclusion: The study presents a novel, robust EPVS predictive model, providing deeper insights into EPVS mechanisms and risk factors. It underscores the potential for early diagnosis and improved management strategies in neuro-radiology and neurology, highlighting the need for future research in diverse populations and longitudinal settings. [ABSTRACT FROM AUTHOR]

Background: The role of novel circular RNAs (circRNAs) in colorectal cancer (CRC) remains to be determined. This study aimed to identify a novel circRNA involved in CRC pathogenesis, assess its diagnostic value, and construct a regulatory network. Methods: Differential expression analysis was conducted using circRNA datasets to screen for differentially expressed circRNAs. The expression of selected circRNAs was validated in external datasets and clinical samples. Diagnostic value of plasma circRNA levels in CRC was assessed. A competing endogenous RNA (ceRNA) network was constructed for the circRNA using TCGA dataset. Results: Analysis of datasets revealed that hsa_circ_101303 was significantly overexpressed in CRC tissues compared to normal tissues. The upregulation of hsa_circ_101303 in CRC tissues was further confirmed through the GSE138589 dataset and clinical samples. High expression of hsa_circ_101303 was associated with advanced N stage, M stage, and tumor stage in CRC. Plasma levels of hsa_circ_101303 were markedly elevated in CRC patients and exhibited moderate diagnostic ability for CRC (AUC = 0.738). The host gene of hsa_circ_101303 was also found to be related to the TNM stage of CRC. Nine miRNAs were identified as target miRNAs for hsa_circ_101303, and 27 genes were identified as targets of these miRNAs. Subsequently, a ceRNA network for hsa_circ_101303 was constructed to illustrate the interactions between the nine miRNAs and 27 genes. Conclusions: The study identifies hsa_circ_101303 as a highly expressed circRNA in CRC, which is associated with the progression of the disease. Plasma levels of hsa_circ_101303 show promising diagnostic potential for CRC. The ceRNA network for hsa_circ_101303 provides valuable insights into the regulatory mechanisms underlying CRC. [ABSTRACT FROM AUTHOR]

Oxaliplatin resistance poses a significant challenge in colorectal cancer (CRC) therapy, necessitating further investigation into the underlying molecular mechanisms. This study aimed to elucidate the regulatory role of SNHG4 in oxaliplatin resistance and ferroptosis in CRC. Our findings revealed that treatment with oxaliplatin led to downregulation of SNHG4 expression in CRC cells, while resistant CRC cells exhibited higher levels of SNHG4 compared to parental cells. Silencing SNHG4 attenuated oxaliplatin resistance and reduced the expression of resistance-related proteins MRD1 and MPR1. Furthermore, induction of ferroptosis effectively diminished oxaliplatin resistance in both parental and resistant CRC cells. Notably, ferroptosis induction resulted in decreased SNHG4 expression, whereas SNHG4 overexpression suppressed ferroptosis. Through FISH, RIP, and RNA pull-down assays, we identified the cytoplasmic localization of both SNHG4 and PTEN, establishing that SNHG4 directly targets PTEN, thereby reducing mRNA stability in CRC cells. Silencing PTEN abrogated the impact of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells. In vivo experiments further validated the influence of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells through PTEN regulation. In conclusion, SNHG4 promotes resistance to oxaliplatin in CRC cells by suppressing ferroptosis through instability of PTEN, thus serves as a target for patients with oxaliplatin-base chemoresistance. [ABSTRACT FROM AUTHOR]

This study investigated the effects of irrigation with a fully inorganic nutrient solution (control; NNNN) and an organic instead of an inorganic nutrient solution (OIINS) at the flowering–fruit setting (ONNN), fruit expanding (NONN), color turning (NNON), and harvest (NNNO) stages of the first spike on the type and content of tomato fruit volatiles to provide a theoretical basis for tomato aroma improvement and high-quality cultivation. Compared with the control (NNNN), the results showed that all OIINS-related treatments decreased the number of fruit volatiles and increased the relative content of common volatile compounds, characteristic effect compounds, aldehydes, and cis-3-hexenal. In particular, the relative order of performance of the OIINS-related treatments was NNNO > NNON > ONNN > NONN in terms of the relative content of characteristic compounds. For all treatments, the relative cis-3-hexenal and trans-2-hexenal percentages were 20.99–51.49% and 20.22–27.81%, respectively. Moreover, hexanal was only detected in tomato fruits under the NNNN and NNNO treatments. The effects of irrigation with OIINS on tomato fruit volatiles were related to the fruit developmental stage. At the mature stage, the organic nutrient solution was conducive to the accumulation of characteristic compounds and improved the fruit aroma quality. [ABSTRACT FROM AUTHOR]

Based on extensive global minimum searches augmented with first-principles theory calculations, we predict herein the first boron-based perfect tetrahedral clusters Td B16P4 (2) and Td B16As4 (3) which, as aromatic non-metal analogs of the experimentally observed Td Au20 (2003, Science299, 864), all contain a truncated Td B16 (1) cage at the center effectively stabilized by four trivalent non-metal atoms (P, As) at the corners. Detailed natural bonding orbital (NBO) and adaptive natural density partitioning (AdNDP) bonding analyses indicate that the valences of all the trivalent component atoms in these tetrahedral clusters are fully satisfied, rendering spherical aromaticity and extra stability to the systems. The IR, Raman, and photoelectron spectra (PES) of the concerned species are theoretically simulated to facilitate their characterizations in future experiments. [ABSTRACT FROM AUTHOR]

Relapsed and refractory (R/R) idiopathic multicentric Castleman disease (iMCD) is a clinical challenge with no standard treatment. In this preliminary clinical trial, we investigated the efficacy and safety profiles of a Bruton tyrosine kinase inhibitor (BTKi), zanubrutinib, in patients with R/R iMCD. The primary endpoint was the overall response rate at Week 12 according to the Castleman Disease Collaborative Network (CDCN) response criteria. The trial was terminated early due to a lack of treatment response in the first enrolled 5 patients. Although 3 patients achieved symptomatic response, none of the 5 patients had an overall response by Week 12. One patient had progressive disease and the other 4 had stable disease. The study drug was well tolerated without grade 2 or higher adverse events. Our findings suggest that BTKi therapy is not effective for iMCD, and further attempts at single-agent therapy with zanubrutinib or other BTKis for iMCD should be considered with caution and probably avoided. This trial was registered at www.clinialtrials.gov as #NCT04743687. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer's disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aβ). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms. [ABSTRACT FROM AUTHOR]

In response to the problem of poor flexibility of common one-dimensional flexible conductors at low temperatures, this paper proposed a one-dimensional flexible conductive composite material with cotton fiber as the substrate and silver-nanowires as the conductive fillers to meet the demands of flexible conductors in low temperature fields such as space exploration, superconductivity, low-temperature biology, etc. Through a creative "bottom-up" fabricating process, by adjusting the amount of filler added and the degree of intertwining between cotton fibers, 1D flexible nanocomposite with good flexibility, conductivity, strength and stability is obtained. After 10,000 times of flexibility tests at liquid nitrogen temperature (77 K), the resistance change of the 1D nanocomposite is less than ± 0.5%, showing excellent flexibility and stability of the material at low temperature environment. A demonstration was then successfully conducted by connecting the 1D nanocomposite to the circuit as the flexible part of the system in simulated working environment (77 K). The system worked well with good stability under repeated bending of the mechanical arm, demonstrating high applying potential of the 1D nanocomposite in the field of low-temperature flexible conductive materials. [ABSTRACT FROM AUTHOR]

We show herein that 1,10‐dicyano substitution restricts the paragon fluxionality of bullvalene to just 14 isomers which isomerize along a single cycle. The restricted fluxionality of 1,10‐dicyanobullvalene (DCB) is investigated by means of: (i) Bonding analyses of the isomer structures using the adaptive natural density partitioning (AdNDP). (ii) Quantum dynamical simulations of the isomerizations along the cyclic intrinsic reaction coordinate of the potential energy surface (PES). The PES possesses 14 equivalent potential wells supporting 14 isomers which are separated by 14 equivalent potential barriers supporting 14 transition states. Accordingly, at low temperatures, DCB appears as a hindered molecular rotor, without any delocalization of the wavefunction in the 14 potential wells, without any nuclear spin isomers, and with completely negligible tunneling. These results are compared and found to differ from those for molecular boron rotors. (iii) Born‐Oppenheimer molecular dynamics (BOMD) simulations of thermally activated isomerizations. (iv) Calculations of the rate constants in the frame of transition state theory (TST) with reasonable agreement achieved with the BOMD results. (v) Simulations of the equilibration dynamics using rate equations for the isomerizations with TST rate coefficients. Accordingly, in the long‐time limit, isomerizations of the 14 isomers, each with Cs symmetry, approach the "14 Cs → C7v" thermally averaged structure. This is a superposition of the 14 equally populated isomer structures with an overall C7v symmetry. By extrapolation, the results for DCB yield working hypotheses for so far un‐explored properties e.g. for the equilibration dynamics of C10H10. [ABSTRACT FROM AUTHOR]

The Keggin‐type P‐Mo‐W polyoxometalate‐based ionic liquids ([VimAm]Br‐POM, POM is PMo6W6O40) were facilely supported on the green fiber (CA) to obtain a kind of bar‐shaped catalyst. The [VimAm]Br‐POM@CA showed an outstanding oxidative desulfurization performance for model oil and real oils with H2O2 as oxidant, mainly due to the dual role of the [VimAm]Br‐POM with the high activity and its excellent dispersion on CA. The dibenzothiophene (DBT) in model oil could be almost completely removed with [VimAm]Br‐POM@CA‐2 in 60 min at 60 °C without adding other extractants, in which [VimAm]Br acts as this role. Meanwhile, the influences of reaction temperature, molar ratio of H2O2/S, catalyst dosage, and different sulfur‐containing compounds were also investigated. Interestingly, the pretty low activation energy (0.1875 kJ/mol) has been achieved, and no significant loss of activity even after being reused for 5 cycles. The combination of IL‐POM and CA is an efficient strategy to obtain a newly kind desulfurization catalyst, with remarkable results on catalytic efficiency and reuse ability at the same time. [ABSTRACT FROM AUTHOR]

Concomitant polymorphs routinely observed in fine chemical industry could impact product purity and consistency; however, both molecular mechanism and process kinetics of concomitant crystallization remain elusive. Herein, we developed a population balance model to understand process kinetics of concomitantly dipolymorphic crystallization using DL‐methionine as a model compound. Kinetic parameters were estimated from induction time measurements and unseeded crystallization experiments. Experimental and simulation results demonstrate that the stable β form has a comparable nucleation rate with α form thanks to their close nucleation barrier leading to the concurrent nucleation. Several solution chemistry techniques were utilized to examine the speciation of solute molecules, together revealing the solutes' self‐association and the formation of micelle‐like aggregates driven by hydrophobic interactions, not hydrogen bonds. These aggregates show dynamic nature against conventional thoughts of classical nucleation kinetics. Finally, the molecular mechanism of concomitant crystallization was uncovered and the implications for polymorph selection and control were discussed. [ABSTRACT FROM AUTHOR]

In this paper, the characteristics of a nanosecond spark discharge with a pin–pin electrode configuration have been systematically studied. Both a streak camera with high temporal resolution and an intensified charge-coupled device (ICCD) camera are employed together to investigate the breakdown and evolution process of the discharge. The formation of initial breakdown and mode transition from streamer to spark in the electrode gap are clearly observed on the time scale of several nanoseconds with a temporal resolution of 100 ps. In addition, the time-resolved spectra technology is also used to analyze the generation and quenching mechanisms of reactive species, the electron density, and the electron temperature. The results show that there is a 1.25 ns initial discharge breakdown and that a bright cathode spot exists before the transformation from streamer to spark channel. After a faster cathode filament and a slower anode filament propagate and merge at the electrode gap, the spark discharge phase begins. The generation processes of different reactive species depend on the discharge phase to a great extent. The N2* is first generated during the streamer phase while the O*, N*, and N+ are mainly generated under the spark phase, in which the electron temperature calculated by Boltzmann plots is 2.74 eV, and the electron density determined from the Stark broadening of O lines is on the order of 1016 cm−3. [ABSTRACT FROM AUTHOR]

Anorectal malformation (ARM) is a prevalent early pregnancy digestive tract anomaly. The intricate anatomy of the embryonic cloaca region makes it challenging for traditional high-throughput sequencing methods to capture location-specific information. Spatial transcriptomics was used to sequence libraries of frozen sections from embryonic rats at gestational days (GD) 14 to 16, covering both normal and ARM cases. Bioinformatics analyses and predictions were performed using methods such as WGCNA, GSEA, and PROGENy. Immunofluorescence staining was used to verify gene expression levels. Gene expression data was obtained with anatomical annotations of clusters, focusing on the cloaca region's location-specific traits. WGCNA revealed gene modules linked to normal and ARM cloacal anatomy development, with cooperation between modules on GD14 and GD15. Differential gene expression profiles and functional enrichment were presented. Notably, protein levels of Pcsk9, Hmgb2, and Sod1 were found to be downregulated in the GD15 ARM hindgut. The PROGENy algorithm predicted the activity and interplay of common signaling pathways in embryonic sections, highlighting their synergistic and complementary effects. A competing endogenous RNA (ceRNA) regulatory network was constructed from whole transcriptome data. Spatial transcriptomics provided location-specific cloaca region gene expression. Diverse bioinformatics analyses deepened our understanding of ARM's molecular interactions, guiding future research and providing insights into gene regulation in ARM development. [ABSTRACT FROM AUTHOR]

Although ultrahigh photoconductive gain is achieved in organic semiconductor‐sensitized graphene phototransistors, the response speed is limited by the photo‐induced carrier injection at the organic/graphene interface. In this work, an insulating hexagonal boron nitride layer is inserted between the organic heterostructure and graphene to block the interfacial carrier transport. Above the h‐BN layer, the organic heterostructure is adopted as the light‐absorbing layer, and the photoresponse of graphene is realized through electrical gating of the atop h‐BN dielectric layer, by the accumulated carriers in the organic heterostructure. Under this "photo‐induced electrical gating" mechanism, the recombination of nonequilibrium carriers takes place only within the organic heterostructure. Furthermore, monolayer perylene‐3,4,9,10‐tetracarboxylic dianhydride (PTCDA) is deposited on graphene before transfer of the h‐BN, by which the interfacial encapsulated bubbles are effectively reduced. As a step further, the trap states are pre‐filled with background light illumination, then the carrier recombination follows the band‐to‐band pathway. Finally, the response time of the organic/h‐BN/graphene phototransistor is reduced to 7.15 ms, and a high photoresponsivity is achieved even though the carrier multiplication is sacrificed, which is reconciled by the improvement of the device quantum efficiency. [ABSTRACT FROM AUTHOR]

Background: The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. Methods: A total of 30 ESCC patients with lymph node positive (IIB‐IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551‐tumor‐targeted DNA sequencing and 289‐immuno‐oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. Results: The primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One‐year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse‐free survival (univariate, HR: 5.39, 95% CI: 1.67–17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79–30.23, p = 0.006). Transcriptomic results showed non‐relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN‐α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF‐α/NF‐κB (p = 0.001) and PI3K/Akt pathway (p = 0.014). Conclusion: The difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes‐positive ESCC. [ABSTRACT FROM AUTHOR]

Rivers are important ecosystems for carbon emissions and play a crucial role in the global carbon cycle. However, CO2 and CH4 emissions from subtropical rivers are substantially under‐represented in global‐scale estimates. Here, we explored the regional patterns of riverine CO2 and CH4 dynamics in the Pearl River basin with a subtropical monsoon climate. We found that its CO2 and diffusive CH4 emissions showed a decreasing trend with increasing stream order. Seasonality in CO2 and diffusive CH4 emissions was primarily driven by variations in partial pressure of CO2 (pCO2) and CH4 (pCH4) and gas transfer velocities, which were strongly regulated by hydrology and climate. We further estimated the basin‐wide CO2 and diffusive CH4 fluxes at 17.8 ± 7.4 Tg C yr−1 and 191.5 ± 139.9 Gg C yr−1, respectively. When normalized to the water surface, the mean diffusive fluxes were 790.1 and 8.5 mmol m−2 d−1 for CO2 and CH4, respectively, which were 1.3 and 2.5 times higher than the global mean riverine CO2 and CH4 fluxes, respectively. This suggests that the global significance of subtropical rivers is probably underestimated because their substantially higher CH4 fluxes are unaccounted for. Furthermore, compared with measured pCO2, the alkalinity‐based pCO2 could introduce significant errors by 20% at ∼30% of the sampling sites, underscoring the necessity of direct measurements to reduce uncertainty. This study provides the first estimate of basin‐wide CO2 and diffusive CH4 emissions in the PRB through direct pCO2 and pCH4 measurements, and highlights the role of hydrologic and climatic factors in governing riverine carbon emissions. Plain Language Summary: River systems are important components of the global carbon cycle, releasing large quantities of carbon dioxide (CO2) and methane (CH4) into the atmosphere. In this study, we investigated the pattern of dissolved CO2 and CH4 concentrations and emissions in the subtropical Pearl River basin in south China. We discovered that the emission rates of both CO2 and CH4 decreased with increasing stream order. Seasonal variations in emissions were primarily driven by dissolved CO2 and CH4 concentrations as well as the gas transfer velocities across the water‐air interface, both of which were strongly regulated by hydrological processes and climatic conditions. We also found that the areal CO2 and CH4 emissions were 1.3 and 2.5 times higher, respectively, than the global average. Our study provides the first direct measurement‐based estimates of CO2 and diffusive CH4 emissions in the Pearl River basin, shedding light on the role of hydrologic and climatic factors in affecting riverine carbon emissions. This research further suggests that the global significance of CH4 emissions from subtropical river networks may have been substantially underestimated. Key Points: Seasonal pCO2 and pCH4 dynamics in the Pearl River basin were regulated by hydrology and climateMean CO2 and CH4 fluxes in the Pearl River basin were 17.8 Tg C yr−1 and 191.5 Gg C yr−1, respectivelyCH4 evasion in the Pearl River basin was 2.5 times higher than the global mean rate [ABSTRACT FROM AUTHOR]

Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria. [ABSTRACT FROM AUTHOR]

Emulsified meat products contain high animal fat content, and excessive intake of animal fat is not good for health, so people are paying more and more attention to reduced-fat meat products. This study investigated the impact of varying proportions of pork back-fat and/or resistant starch on the proximate composition, water and fat retention, texture properties, color, and rheology characteristic of pork batter. The results found that replacing pork back-fat with resistant starch and ice water significantly decreased the total lipid and energy contents of cooked pork batter (p < 0.05) while improving emulsion stability, cooking yield, texture, and rheology properties. Additionally, when the pork back-fat replacement ratio was no more than 50%, there was a significant increase in emulsion stability, cooking yield, hardiness, springiness, cohesiveness, chewiness, and L* and G' values (p < 0.05). Furthermore, resistant starch and ice water enhanced myosin head and tail thermal stability and increased G' value at 80 °C. However, the initial relaxation times significantly decreased (p < 0.05) and the peak ratio of P21 significantly increased from 84.62% to 94.03%, suggesting reduced fluidity of water. In conclusion, it is feasible to use resistant starch and ice water as a substitute for pork back-fat in order to produce reduced-fat pork batter with favorable gel and rheology properties. [ABSTRACT FROM AUTHOR]

Summary: Idiopathic multicentric Castleman disease (iMCD) is subclassified into iMCD‐thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly (TAFRO) and iMCD‐not otherwise specified (NOS) according to the Castleman Disease Collaborative Network (CDCN) consensus criteria. With a deeper understanding of iMCD, a group of patients with iMCD‐NOS characterised by polyclonal hypergammaglobulinaemia, plasmacytic/mixed‐type lymph node histopathology and thrombocytosis has attracted attention. This group of patients has been previously described as having idiopathic plasmacytic lymphadenopathy (IPL). Whether these patients should be excluded from the current classification system lacks sufficient evidence. This retrospective analysis of 228 patients with iMCD‐NOS identified 103 (45.2%) patients with iMCD‐IPL. The clinical features and outcomes of patients with iMCD‐IPL and iMCD‐NOS without IPL were compared. Patients with iMCD‐IPL showed a significantly higher inflammatory state but longer overall survival. No significant difference in overall survival was observed between severe and non‐severe patients in the iMCD‐IPL group according to the CDCN severity classification. Compared with lymphoma‐like treatments, multiple myeloma‐like and IL‐6‐blocking treatment approaches in the iMCD‐IPL group resulted in significantly higher response rates and longer time to the next treatment. These findings highlight the particularities of iMCD‐IPL and suggest that it should be considered a new subtype of iMCD‐NOS. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the mental health of paediatric cochlear implant users and analyse the relationship between six dimensions (movements, cognitive ability, emotion and will, sociality, living habits and language) and hearing and speech rehabilitation. Methods: Eighty-two cochlear implant users were assessed using the Mental Health Survey Questionnaire. Age at implantation, time of implant use and listening modes were investigated. Categories of Auditory Performance and the Speech Intelligibility Rating Scale were used to score hearing and speech abilities. Results: More recipients scored lower in cognitive ability and language. Age at implantation was statistically significant (p < 0.05) for movements, cognitive ability, emotion and will, and language. The time of implant usage and listening mode indicated statistical significance (p < 0.05) in cognitive ability, sociality and language. Conclusion: Timely attention should be paid to the mental health of paediatric cochlear implant users, and corresponding psychological interventions should be implemented to make personalised rehabilitation plans. [ABSTRACT FROM AUTHOR]

Background: Dimethyl fumarate (DMF) is a fumaric acid ester that exhibits immunoregulatory and anti-inflammatory properties. However, the function of DMF in autoimmune uveitis (AU) is incompletely understood, and studies comprehensively exploring the impact of DMF on immune cells are still lacking. Methods: To explore the function of DMF in uveitis and its underlying mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) on the cervical draining lymph node (CDLN) cells of normal, experimental autoimmune uveitis (EAU), and DMF-treated EAU mice. Additionally, we integrated scRNA-seq data of the retina and CDLNs to identify the potential impact of DMF on ocular immune cell infiltration. Flow cytometry was conducted to verify the potential target molecules of DMF. Results: Our study showed that DMF treatment effectively ameliorated EAU symptoms. The proportional and transcriptional alterations in each immune cell type during EAU were reversed by DMF treatment. Bioinformatics analysis in our study indicated that the enhanced expression of Pim1 and Cxcr4 in EAU was reversed by DMF treatment. Further experiments demonstrated that DMF restored the balance between effector T (Teff) /regulatory T (Treg) cells through inhibiting the pathway of PIM1-protein kinase B (AKT)-Forkhead box O1 (FOXO1). By incorporating the scRNA-seq data of the retina from EAU mice into analysis, our study identified that T cells highly expressing Pim1 and Cxcr4 were enriched in the retina. DMF repressed the ocular infiltration of Teff cells, and this effect might depend on its inhibition of PIM1 and CXCR4 expression. Additionally, our study indicated that DMF might reduce the proportion of plasma cells by inhibiting PIM1 expression in B cells. Conclusions: DMF effectively attenuated EAU symptoms. During EAU, DMF reversed the Teff/Treg cell imbalance and suppressed the ocular infiltration of Teff cells by inhibiting PIM1 and CXCR4 expression. Thus, DMF may act as a new drug option for the treatment of AU. [ABSTRACT FROM AUTHOR]

Chiral nanoscale enantiomers exhibit different biological effects in living systems. However, their chirality effect on the detection sensitivity for chiral biological targets still needs to be explored. Here, we discovered that Co2+ can modulate the luminescence performance of L/D‐glutathione (GSH)‐modified copper nanoclusters (L/D−Cu NCs) and induce strong chiroptical activities as the asymmetric factor was enhanced 223‐fold with their distribution regulating from the ultraviolet to visible region. One Co2+ coordinated with two GSH molecules that modified on the surface of Cu NCs in the way of CoN2O2. On this basis, dual‐modal chiral and luminescent signals of Co2+ coordinated L/D−Cu NCs (L/D−Co−Cu NCs) were used to detect the chiral adenosine triphosphate (ATP) based on the competitive interaction between surficial GSH and ATP molecules with Co2+. The limits of detection of ATP obtained with fluorescence and circular dichroism intensity were 9.15 μM and 15.75 nM for L−Co−Cu NCs, and 5.35 μM and 4.69 nM for D−Co−Cu NCs. This demonstrated that selecting suitable chiral configurations of nanoprobes effectively enhances detection sensitivity. This study presents not only a novel method to modulate and enhance the chiroptical activity of nanomaterials but also a unique perspective of chirality effects on the detection performances for bio‐targets. [ABSTRACT FROM AUTHOR]

Chiral nanoscale enantiomers exhibit different biological effects in living systems. However, their chirality effect on the detection sensitivity for chiral biological targets still needs to be explored. Here, we discovered that Co2+ can modulate the luminescence performance of L/D‐glutathione (GSH)‐modified copper nanoclusters (L/D−Cu NCs) and induce strong chiroptical activities as the asymmetric factor was enhanced 223‐fold with their distribution regulating from the ultraviolet to visible region. One Co2+ coordinated with two GSH molecules that modified on the surface of Cu NCs in the way of CoN2O2. On this basis, dual‐modal chiral and luminescent signals of Co2+ coordinated L/D−Cu NCs (L/D−Co−Cu NCs) were used to detect the chiral adenosine triphosphate (ATP) based on the competitive interaction between surficial GSH and ATP molecules with Co2+. The limits of detection of ATP obtained with fluorescence and circular dichroism intensity were 9.15 μM and 15.75 nM for L−Co−Cu NCs, and 5.35 μM and 4.69 nM for D−Co−Cu NCs. This demonstrated that selecting suitable chiral configurations of nanoprobes effectively enhances detection sensitivity. This study presents not only a novel method to modulate and enhance the chiroptical activity of nanomaterials but also a unique perspective of chirality effects on the detection performances for bio‐targets. [ABSTRACT FROM AUTHOR]

Motor neurons are the final common pathway1 through which the brain controls movement of the body, forming the basic elements from which all movement is composed. Yet how a single motor neuron contributes to control during natural movement remains unclear. Here we anatomically and functionally characterize the individual roles of the motor neurons that control head movement in the fly, Drosophila melanogaster. Counterintuitively, we find that activity in a single motor neuron rotates the head in different directions, depending on the starting posture of the head, such that the head converges towards a pose determined by the identity of the stimulated motor neuron. A feedback model predicts that this convergent behaviour results from motor neuron drive interacting with proprioceptive feedback. We identify and genetically2 suppress a single class of proprioceptive neuron3 that changes the motor neuron-induced convergence as predicted by the feedback model. These data suggest a framework for how the brain controls movements: instead of directly generating movement in a given direction by activating a fixed set of motor neurons, the brain controls movements by adding bias to a continuing proprioceptive–motor loop.Single motor neurons in Drosophila are stimulated to show that they direct head movements towards specific postures rather than generating fixed movement vectors, suggesting that the brain controls movements through a continuing proprioceptive–motor loop. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of chaperone-mediated autophagy (CMA) on the damage of mouse microglial BV2 cells induce by unconjugated bilirubin (UCB). Methods The BV2 cell experiments were divided into two parts. (1) For the CMA activation experiment: control group (treated with an equal volume of dimethyl sulfoxide), QX77 group (treated with 20 µmol/L QX77 for 24 hours), UCB group (treated with 40 µmol/L UCB for 24 hours), and UCB+QX77 group (treated with both 20 µmol/L QX77 and 40 µmol/L UCB for 24 hours). (2) For the cell transfection experiment: LAMP2A silencing control group (treated with an equal volume of dimethyl sulfoxide), LAMP2A silencing control+UCB group (treated with 40 µmol/L UCB for 24 hours), LAMP2A silencing group (treated with an equal volume of dimethyl sulfoxide), and LAMP2A silencing+UCB group (treated with 40 µmol/L UCB for 24 hours). The cell viability was assessed using the modified MTT method. The expression levels of p65, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and cysteinyl aspartate specific proteinase-1 (caspase-1) were detected by Western blot. The relative mRNA expression levels of the inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were determined by real-time quantitative polymerase chain reaction. Levels of IL-6 and TNF-α in the cell culture supernatant were measured using ELISA. The co-localization of heat shock cognate protein 70 with p65 and NLRP3 was detected by immunofluorescence. Results Compared to the UCB group, the cell viability in the UCB+QX77 group increased, and the expression levels of inflammation-related proteins p65, NLRP3, and caspase-1, as well as the mRNA relative expression levels of IL-1β, IL-6, and TNF-α and levels of IL-6 and TNF-α decreased (P<0.05). Compared to the control group, there was co-localization of heat shock cognate protein 70 with p65 and NLRP3 in both the UCB and UCB+QX77 groups. After silencing the LAMP2A gene, compared to the LAMP2A silencing control+UCB group, the LAMP2A silencing+UCB group showed increased expression levels of inflammation- related proteins p65, NLRP3, and caspase-1, as well as increased mRNA relative expression levels of IL-1β, IL-6, and TNF-α and levels of IL-6 and TNF-α (P<0.05). Conclusions CMA is inhibited in UCB-induced BV2 cell damage, and activating CMA may reduce p65 and NLRP3 protein levels, suppress inflammatory responses, and counteract bilirubin neurotoxicity. [ABSTRACT FROM AUTHOR]

Vascular cognitive impairment (VCI) is the second leading cause of dementia with limited treatment options, characterised by cerebral hypoperfusion-induced white matter rarefaction (WMR). Subcortical VCI is the most common form of VCI, but the underlying reasons for region susceptibility remain elusive. Recent studies employing the bilateral cortical artery stenosis (BCAS) method demonstrate that various inflammasomes regulate white matter injury and blood-brain barrier dysfunction but whether caspase-1 inhibition will be beneficial remains unclear. To address this, we performed BCAS on C57/BL6 mice to study the effects of Ac-YVAD-cmk, a caspase-1 inhibitor, on the subcortical and cortical regions. Cerebral blood flow (CBF), WMR, neuroinflammation and the expression of tight junction-related proteins associated with blood-brain barrier integrity were assessed 15 days post BCAS. We observed that Ac-YVAD-cmk restored CBF, attenuated BCAS-induced WMR and restored subcortical myelin expression. Within the subcortical region, BCAS activated the NLRP3/caspase-1/interleukin-1beta axis only within the subcortical region, which was attenuated by Ac-YVAD-cmk. Although we observed that BCAS induced significant increases in VCAM-1 expression in both brain regions that were attenuated with Ac-YVAD-cmk, only ZO-1 and occludin were observed to be significantly altered in the subcortical region. Here we show that caspase-1 may contribute to subcortical regional susceptibility in a mouse model of VCI. In addition, our results support further investigations into the potential of Ac-YVAD-cmk as a novel treatment strategy against subcortical VCI and other conditions exhibiting cerebral hypoperfusion-induced WMR. [ABSTRACT FROM AUTHOR]