Targeted therapy of kidney disease with nanoparticle drug delivery materials.

With the development of nanomedicine, nanomaterials have been widely used, offering specific drug delivery to target sites, minimal side effects, and significant therapeutic effects. The kidneys have filtration and reabsorption functions, with various potential target cell types and a complex structural environment, making the strategies for kidney function protection and recovery after injury complex. This also lays the foundation for the application of nanomedicine in kidney diseases. Currently, evidence in preclinical and clinical settings supports the feasibility of targeted therapy for kidney diseases using drug delivery based on nanomaterials. The prerequisite for nanomedicine in treating kidney diseases is the use of carriers with good biocompatibility, including nanoparticles, hydrogels, liposomes, micelles, dendrimer polymers, adenoviruses, lysozymes, and elastin-like polypeptides. These carriers have precise renal uptake, longer half-life, and targeted organ distribution, protecting and improving the efficacy of the drugs they carry. Additionally, attention should also be paid to the toxicity and solubility of the carriers. While the carriers mentioned above have been used in preclinical studies for targeted therapy of kidney diseases both in vivo and in vitro, extensive clinical trials are still needed to ensure the short-term and long-term effects of nano drugs in the human body. This review will discuss the advantages and limitations of nanoscale drug carrier materials in treating kidney diseases, provide a more comprehensive catalog of nanocarrier materials, and offer prospects for their drug-loading efficacy and clinical applications.

A CRM1-dependent nuclear export signal in Autographa californica multiple nucleopolyhedrovirus Ac93 is important for the formation of intranuclear microvesicles.

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) Ac93 is highly conserved in all sequenced baculovirus genomes, and it plays important roles in both the nuclear egress of nucleocapsids and the formation of intranuclear microvesicles. In this study, we characterized a cellular CRM1-dependent nuclear export signal (NES) of AcMNPV Ac93. Bioinformatic analysis revealed that AcMNPV Ac93 may contain an NES at amino acids 115-125. Green fluorescent protein (GFP) fused to the NES (GFP:NES) of AcMNPV Ac93 is localized to the cytoplasm of transfected cells. Multiple point mutation analysis demonstrated that NES is important for the nuclear export of GFP:NES. Bimolecular fluorescence complementation experiments and co-immunoprecipitation assays confirmed that Ac93 interacts with Spodoptera frugiperda CRM1 (SfCRM1). However, AcMNPV Ac34 inhibits cellular CRM1-dependent nuclear export of GFP:NES. To determine whether the NES in AcMNPV Ac93 is important for the formation of intranuclear microvesicles, an ac93-null AcMNPV bacmid was constructed; the wild-type and NES-mutated Ac93 were reinserted into the ac93-null AcMNPV bacmid. Immunofluorescence analysis showed that Ac93 and SfCRM1 were predominantly colocalized at intranuclear microvesicles in infected cells, while the construct containing point mutations at residues 123 and 125 of Ac93 resulted in a defect in budded virus production and the abolishment of intranuclear microvesicles. Together, these data demonstrate that Ac93 contains a functional NES, which is required for the production of progeny viruses and the formation of intranuclear microvesicles.IMPORTANCEAutographa californica multiple nucleopolyhedrovirus (AcMNPV) Ac93 is important for the formation of intranuclear microvesicles. However, how the baculovirus manipulates Ac93 for the formation of intranuclear microvesicles is unclear. In this study, we identified a nuclear export signal (NES) at amino acids 115-125 of AcMNPV Ac93. Our results showed that the NES is required for the interaction between Ac93 and Spodoptera frugiperda CRM1 (SfCRM1). However, AcMNPV Ac34 inhibits the nuclear export of green fluorescent protein fused to the NES. Our analysis revealed that Ac93 and SfCRM1 were predominantly colocalized at intranuclear microvesicles in AcMNPV-infected cells. Together, our results indicate that Ac93 participates in the formation of intranuclear microvesicles via the Ac93 NES-mediated CRM1 pathway.

White matter biomarker for predicting de novo Parkinson's disease using tract-based spatial statistics: a machine learning-based model.

Background: Parkinson's disease (PD) is an irreversible, chronic degenerative disease of the central nervous system, potentially associated with cerebral white matter (WM) lesions. Investigating the microstructural alterations within the WM in the early stages of PD can help to identify the disease early and enable intervention to reduce the associated serious threats to health. Methods: This study selected 227 cases from the Parkinson's Progression Markers Initiative (PPMI) database, including 152 de novo PD patients and 75 normal controls (NC). Whole-brain voxel analysis of the WM was performed using the tract-based spatial statistics (TBSS) method. The WM regions with statistically significant differences (P<0.05) between the PD and NC groups were identified and used as masks. The mask was applied to each case's fractional anisotropy (FA) image to extract voxel values as feature vectors. Geometric dimensionality reduction was then applied to eliminate redundant values in the feature vectors. Subsequently, the cases were randomly divided into a training group (158 cases, including 103 PD patients and 55 NC) and a test group (69 cases, including 49 PD patients and 20 NC). The least absolute shrinkage and selection operator (LASSO) regression algorithm was employed to extract the minimal set of relevant features, then the random forest (RF) algorithm was utilized for classification using 5-fold cross validation. The resulting model was further integrated with clinical factors to create a comprehensive prediction model. Results: In comparison to the NC group, the FA values in PD patients exhibited a statistically significant decrease (P<0.05), indicating the presence of widespread WM lesions across multiple brain regions. Moreover, the PD prediction model, constructed based on these WM lesion regions, yielded prediction accuracy (ACC) and area under the receiver operating characteristic (ROC) curve (AUC) values of 0.778 and 0.865 in the validation set, and 0.783 and 0.831 in the test set, respectively. Furthermore, the performance of the integrated model showed some improvement, with ACC and AUC values in the test set reaching 0.804 and 0.844, respectively. Conclusions: The quantitative calculation of WM lesion area on FA images using the TBSS method can serve as a neuroimaging biomarker for diagnosing and predicting early PD at the individual level. When integrated with clinical variables, the predictive performance improves.

Association Between rs2278426 Polymorphism of the ANGPTL8 Gene and Polycystic Ovary Syndrome.

Purpose: To study the relationship between the single nucleotide polymorphism (SNP) rs2278426 in the angiopoietin-like protein 8 gene (ANGPTL8) and polycystic ovary syndrome (PCOS). Patients and methods: A total of 122 patients with PCOS and 108 controls were recruited for comparison of glucose, lipid, insulin, sex hormone, and ANGPTL8 levels. Polymerase chain reaction (PCR) and gene sequencing were performed for comparison of the frequency of the CC, CT, and TT rs2278426 genotypes and the rs2278426 allele distributions between the PCOS and control groups and between the obese and non-obese subgroups of the PCOS and control groups. Results: The frequency of the T allele was significantly higher in the PCOS group than that in the controls (P = 0.037). In the dominant genetic model, the proportion of the CT+TT genotype in the PCOS group was significantly higher than that in the controls (P = 0.047). Subgroup analysis demonstrated that the T allele proportion was significantly higher in obese PCOS group than obese control group (P = 0.027). PCOS with the CT+TT genotype had significantly higher body mass index (BMI; P = 0.001), triglyceride (TG; P = 0.005), homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.035), testosterone (P = 0.041), and ANGPTL8 (P = 0.037) levels and significantly lower high-density lipoprotein (HDL) levels (P = 0.025) than PCOS with the CC genotype. Obese PCOS group with the CT+TT genotype had significantly higher TG (P = 0.015), luteinizing hormone (LH; P = 0.030), fasting insulin (FINS; P = 0.039), HOMA-IR (P = 0.018), and ANGPTL8 (P = 0.049) levels than obese PCOS group with the CC genotype. Conclusion: Polymorphisms of rs2278426 may induce glycolipid metabolic disorders by affecting ANGPTL8 levels and functions in Han Chinese females with obesity from the Shandong region, increasing the risk of PCOS in this population.

Genome-Wide Identification and Expression Analysis of the PUB Gene Family in Zoysia japonica under Salt Stress.

The U-box protein family of ubiquitin ligases is important in the biological processes of plant growth, development, and biotic and abiotic stress responses. Plants in the genus Zoysia are recognized as excellent warm-season turfgrass species with drought, wear and salt tolerance. In this study, we conducted the genome-wide identification of plant U-box (PUB) genes in Zoysia japonica based on U-box domain searching. In total, 71 ZjPUB genes were identified, and a protein tree was constructed of AtPUBs, OsPUBs, and ZjPUBs, clustered into five groups. The gene structures, characteristics, cis-elements and protein interaction prediction network were analyzed. There were mainly ABRE, ERE, MYB and MYC cis-elements distributed in the promoter regions of ZjPUBs. ZjPUBs were predicted to interact with PDR1 and EXO70B1, related to the abscisic acid signaling pathway. To better understand the roles of ZjPUBs under salt stress, the expression levels of 18 ZjPUBs under salt stress were detected using transcriptome data and qRT-PCR analysis, revealing that 16 ZjPUBs were upregulated in the roots under salt treatment. This indicates that ZjPUBs might participate in the Z. japonica salt stress response. This research provides insight into the Z. japonica PUB gene family and may support the genetic improvement in the molecular breeding of salt-tolerant zoysiagrass varieties.

Ultralow-loss optical interconnect enabled by topological unidirectional guided resonance.

Grating couplers that interconnect photonic chips to off-chip components are crucial for various optoelectronics applications. Despite numerous efforts in past decades, the existing grating couplers are still far from optimal in energy efficiency and thus hinder photonic integration toward a larger scale. Here, we propose a strategy to achieve ultralow-loss grating couplers by using unidirectional guided resonances (UGRs), suppressing the useless downward radiation with no mirror on the bottom. By engineering the dispersion and apodizing the geometry of grating, we experimentally realize a grating coupler with a record-low loss of -0.34 dB and 1-dB bandwidth exceeding 30 nm at the telecom wavelength of 1550 nm and further demonstrate an optic via with a loss of only -0.94 dB. Given that UGRs ubiquitously exist in a variety of grating geometries, our work sheds light on a systematic method to achieve energy-efficient optical interconnect and paves the way to large-scale photonic integration.

Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization.

Alveolar bone regeneration has been strongly linked to macrophage polarization. M1 macrophages aggravate alveolar bone loss, whereas M2 macrophages reverse this process. Berberine (BBR), a natural alkaloid isolated and refined from Chinese medicinal plants, has shown therapeutic effects in treating metabolic disorders. In this study, we first discovered that culture supernatant (CS) collected from BBR-treated human bone marrow mesenchymal stem cells (HBMSCs) ameliorated periodontal alveolar bone loss. CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro. To clarify the underlying mechanism, the bioactive materials were applied to different animal models. We discovered macrophage colony-stimulating factor (M-CSF), which regulates macrophage polarization and promotes bone formation, a key macromolecule in the CS. Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats. Colony-stimulating factor 1 receptor (CSF1R) inhibitor or anti-human M-CSF (M-CSF neutralizing antibody, Nab) abolished the therapeutic effects of the CS of BBR-treated HBMSCs. Moreover, AKT phosphorylation in macrophages was activated by the CS, and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab. These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis. Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets. Overall, our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

Gut microbiota metagenomics and mediation of phenol degradation in Bactrocera minax (Diptera, Tephritidae).

BACKGROUND: Gut microbiota mediating insect-plant interactions have many manifestations, either by provisioning missing nutrients, or by overcoming plant defensive reactions. However, the mechanism by which gut microbiota empower insects to survive by overcoming a variety of plant secondary metabolites remains largely unknown. Bactrocera minax larvae develop in immature citrus fruits, which present numerous phenolic compounds that challenge the larvae. To explore the role of gut microbes in host use and adaptability, we uncovered the mechanisms of phenol degradation by gut microbes using metagenomic and metatranscriptomic analyses, and verified the degradation ability of isolated and cultured bacteria. Research on this subject can help develop potential strain for the environmental friendly pest management operations. RESULTS: We demonstrated the ability of gut microbes in B. minax larvae to degrade phenols in unripe citrus. After antibiotic treatment, coniferyl alcohol and coumaric aldehyde significantly reduced the survival rate, body length and body weight of the larvae. The metagenomic and metatranscriptomic analyses in B. minax provided evidence for the presence of genes in bacteria and the related pathway involved in phenol degradation. Among them, Enterococcus faecalis and Serratia marcescens, isolated from the gut of B. minax larvae, played critical roles in phenol degradation. Furthermore, supplementation of E. faecalis and S. marcescens in artificial diets containing coniferyl alcohol and coumaric aldehyde increased the survival rate of larvae. CONCLUSION: In summary, our results provided the first comprehensive analysis of gut bacterial communities by high-throughput sequencing and elucidated the role of bacteria in phenol degradation in B. minax, which shed light on the mechanism underlying specialist insect adaption to host secondary metabolites via gut bacteria. © 2024 Society of Chemical Industry.

Turning Non-Emissive Schiff Bases Into Aggregate Emitters.

Schiff bases are a crucial component in various functional materials but often exhibit non-emissive behavior which significantly limits their potential applications as luminescent materials. However, traditional approaches to convert them into aggregate emitters often require intricate molecular design, tedious synthesis, and significant time and resource consumption. Herein, we present a cocrystallization-induced emission strategy that can transform non-emissive (hetero)aryl-substituted Schiff bases into green-yellow to yellow aggregate emitters via even simple grinding of a mixture of Schiff bases and 1,2,4,5-tetracyanobenzene (TCB) mixtures. The combined experimental and theoretical analysis revealed that the cocrystallization inhibits the C=N isomerization and promotes face-to-face π-π interaction, which restricts access to both the dark state and canonical intersection to ultimately induce emission. Furthermore, the induced emission enables the observation of solid-state molecular diffusion through fluorescence signals, advancing white light emission diodes, and notably, solution-processed organic light-emitting diodes based on cocrystal for the first time. This study not only highlights the potential of developing new C=N structural motifs for AIEgens but also could boost advancements in related structure motifs like C=C and N=N.

Can the digitalization level of agriculture improve its ecological efficiency under carbon constraints: Evidence from China.

The interplay between digitalization and economic development constitutes a pivotal global issue, yet empirical research on agricultural ecological efficiency in developing countries remains limited. This study initially establishes a measurement system and a comprehensive index for the level of agricultural digitalization. Subsequently, it delineates the relationship between agricultural digitalization level and agroecological efficiency using the spatial Durbin model, and ultimately explores the enhancing effect of agricultural digitalization level on agroecological efficiency using China as a case study. Research reveals that the agricultural ecological efficiency across the 31 mainland Chinese provinces demonstrates a generally linear upward trajectory, embodying both agglomeration and heterogeneity. The level of agricultural digitization exerts a significant, positive direct impact and facilitates a spatial spillover effect on agricultural ecological efficiency. Other control variables, such as financial support for agriculture and local economic development, impart a positive direct impact on regional agricultural ecological efficiency, while rural household operating income propels a positive spatial spillover effect on adjacent areas. The findings furnish guidance for developing countries to adeptly execute digital rural construction, aiming to enhance agricultural ecological efficiency amidst carbon constraints.

Multi-organ segmentation: a progressive exploration of learning paradigms under scarce annotation.

Precise delineation of multiple organs or abnormal regions in the human body from medical images plays an essential role in computer-aided diagnosis, surgical simulation, image-guided interventions, and especially in radiotherapy treatment planning. Thus, it is of great significance to explore automatic segmentation approaches, among which deep learning-based approaches have evolved rapidly and witnessed remarkable progress in multi-organ segmentation. However, obtaining an appropriately sized and fine-grained annotated dataset of multiple organs is extremely hard and expensive. Such scarce annotation limits the development of high-performance multi-organ segmentation models but promotes many annotation-efficient learning paradigms. Among these, studies on transfer learning leveraging external datasets, semi-supervised learning using unannotated datasets and partially-supervised learning integrating partially-labeled datasets have led the dominant way to break such dilemma in multi-organ segmentation. We first review the traditional fully supervised method, then present a comprehensive and systematic elaboration of the 3 abovementioned learning paradigms in the context of multi-organ segmentation from both technical and methodological perspectives, and finally summarize their challenges and future trends.

MFN2 suppresses the accumulation of lipid droplets and the progression of clear cell renal cell carcinoma.

Dissolving the lipid droplets in tissue section with alcohol during a hematoxylin and eosin (H&E) stain causes the tumor cells to appear like clear soap bubbles under a microscope, which is a key pathological feature of clear cell renal cell carcinoma (ccRCC). Mitochondrial dynamics have been reported to be closely associated with lipid metabolism and tumor development. However, the relationship between mitochondrial dynamics and lipid metabolism reprogramming in ccRCC remains to be further explored. We conducted bioinformatics analysis to identify key genes regulating mitochondrial dynamics differentially expressed between tumor and normal tissues and immunohistochemistry and Western blot to confirm. After the target was identified, we created stable ccRCC cell lines to test the impact of the target gene on mitochondrial morphology, tumorigenesis in culture cells and xenograft models, and profiles of lipid metabolism. It was found that mitofusin 2 (MFN2) was downregulated in ccRCC tissues and associated with poor prognosis in patients with ccRCC. MFN2 suppressed mitochondrial fragmentation, proliferation, migration, and invasion of ccRCC cells and growth of xenograft tumors. Furthermore, MFN2 impacted lipid metabolism and reduced the accumulation of lipid droplets in ccRCC cells. MFN2 suppressed disease progression and improved prognosis for patients with ccRCC possibly by interrupting cellular lipid metabolism and reducing accumulation of lipid droplets.

Schizosthetus Athias-Henriot, 1982 (Mesostigmata: Parasitidae): the description of a new species from China.

A new species, Schizosthetus baixuelii sp. nov., is described based on females from Ningxia Hui Autonomous Region, China. A key to the known species of the genus is presented.

miR-873-5p Suppression Reinvigorates Aging Mesenchymal Stem Cells and Improves Cardiac Repair after Myocardial Infarction.

Aging poses obstacles to the functionality of human mesenchymal stem cells (MSCs), resulting in a notable decline in their valuable contribution to myocardial infarction (MI). MicroRNAs (miRNAs) play a pivotal role in governing MSC aging; nonetheless, the specific mechanisms remain puzzling. This research delved into the value of miR-873-5p in the management of MSC aging and investigated whether the restraint of miR-873-5p could regenerate aged MSCs (AMSCs), thereby enhancing their healing success for MI. In this study, MSCs were isolated from both young donors (referred to as YMSCs) and aged donors (referred to as AMSCs). The senescence status of these MSCs was evaluated through the application of age-related ß-galactosidase (SA-ß-gal) staining. Following this assessment, the MSCs, including those treated with anti-miR-873-5p-AMSCs, were then transplanted into the hearts of Sprague-Dawley rats experiencing acute myocardial infarction. Increasing miR-873-5p levels in YMSCs resulted in elevated cellular aging, whereas reducing miR-873-5p expression decreased aging in AMSCs. Mechanistically, miR-873-5p inhibited autophagy in MSCs through the AMPK signaling pathway, leading to cellular aging by suppressing the Cab39 expression. Partial alleviation of these effects was achieved by the administration of the autophagy inhibitor 3-methyladenine. Grafting of anti-miR-873-5p-AMSCs, by enhancing angiogenesis and bolstering cell survival, led to an improvement in cardiac function in the rat model, unlike the transplantation of AMSCs. miR-873-5p which serves as a pivotal element in mediating MSC aging through its regulation of the Cab39/AMPK signaling pathway. It represents an innovative target for revitalizing AMSCs and enhancing their heart-protective abilities.

[Nutrients and Ecological Stoichiometry Characteristics of Typical Wetland Soils in the Lower Yellow River].

Carbon, nitrogen, phosphorus, and potassium in the soil are the necessary nutrient elements for plant growth, and their contents and ecological stoichiometry can reflect the status of soil quality and nutrient limitation. The Huayuankou Yellow River Floating Bridge Wetland in the lower Yellow River was selected as the research object. The methods of ANOVA, redundancy analysis, and linear regression fitting were used to study the contents of organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkaline nitrogen (AN), available phosphorus (AP), available potassium (AK), and their ecological stoichiometric ratios as well as the limiting elements of soil nutrients, and the key physicochemical properties that affect soil nutrients and their ecological stoichiometry in the wetland were revealed. The results showed that the mean values of ω(SOC), ω(TN), ω(TP), ω(TK), ω(AN), ω(AP), and ω(AK) in wetland soil were 5.46 g·kg-1, 0.60 g·kg-1, 0.28 g·kg-1, 17.06 g·kg-1, 13.75 mg·kg-1, 6.54 mg·kg-1, and 158.56 mg·kg-1, respectively, which showed an increasing trend from the river bank to the shoaly land and were generally higher at the high vegetation coverage areas than at the low vegetation coverage areas. There were significant correlations among SOC, TN, TP, and TK. Soil C/P, C/K, N/P, and N/K showed a consistent trend with soil nutrients, whereas C/N showed the opposite. The coefficients of variation of SOC, TN, AN, N/P, and N/K in the soil exceeded 50.00%, with significant spatial differences. The average value of C/N in wetland soil was 11.882, which was close to the average level of soils in China, whereas the average values of C/P and N/P were 49.119 and 4.516, respectively, both of which were lower than the average level of soils in China, and the N/P of soil was far less than 14, which indicated that N was limited in the soil. The proportion of clay and electrical conductivity combined to explain 61.4% and 43.9% of the variation in the soil nutrients and their ecological stoichiometry, respectively, which were the dominant soil physicochemical properties affecting the soil nutrients and their ecological stoichiometry of Huayuankou Yellow River Floating Bridge Wetland. The research results are helpful to improve our knowledge of nutrients and their influencing factors in the wetland soil of the lower Yellow River and provide an important scientific basis for the ecological restoration and management of the wetland in the lower Yellow River.

In Situ Remodeling of Efferocytosis via Lesion-Localized Microspheres to Reverse Cartilage Senescence.

Efferocytosis, an intrinsic regulatory mechanism to eliminate apoptotic cells, will be suppressed due to the delayed apoptosis process in aging-related diseases, such as osteoarthritis (OA). In this study, cartilage lesion-localized hydrogel microspheres are developed to remodel the in situ efferocytosis to reverse cartilage senescence and recruit endogenous stem cells to accelerate cartilage repair. Specifically, aldehyde- and methacrylic anhydride (MA)-modified hyaluronic acid hydrogel microspheres (AHM), loaded with pro-apoptotic liposomes (liposomes encapsulating ABT263, A-Lipo) and PDGF-BB, namely A-Lipo/PAHM, are prepared by microfluidic and photo-cross-linking techniques. By a degraded porcine cartilage explant OA model, the in situ cartilage lesion location experiment illustrated that aldehyde-functionalized microspheres promote affinity for degraded cartilage. In vitro data showed that A-Lipo induced apoptosis of senescent chondrocytes (Sn-chondrocytes), which can then be phagocytosed by the efferocytosis of macrophages, and remodeling efferocytosis facilitated the protection of normal chondrocytes and maintained the chondrogenic differentiation capacity of MSCs. In vivo experiments confirmed that hydrogel microspheres localized to cartilage lesion reversed cartilage senescence and promoted cartilage repair in OA. It is believed this in situ efferocytosis remodeling strategy can be of great significance for tissue regeneration in aging-related diseases.

Frontostriatal circuit dysfunction leads to cognitive inflexibility in neuroligin-3 R451C knockin mice.

Cognitive and behavioral rigidity are observed in various psychiatric diseases, including in autism spectrum disorder (ASD). However, the underlying mechanism remains to be elucidated. In this study, we found that neuroligin-3 (NL3) R451C knockin mouse model of autism (KI mice) exhibited deficits in behavioral flexibility in choice selection tasks. Single-unit recording of medium spiny neuron (MSN) activity in the nucleus accumbens (NAc) revealed altered encoding of decision-related cue and impaired updating of choice anticipation in KI mice. Additionally, fiber photometry demonstrated significant disruption in dynamic mesolimbic dopamine (DA) signaling for reward prediction errors (RPEs), along with reduced activity in medial prefrontal cortex (mPFC) neurons projecting to the NAc in KI mice. Interestingly, NL3 re-expression in the mPFC, but not in the NAc, rescued the deficit of flexible behaviors and simultaneously restored NAc-MSN encoding, DA dynamics, and mPFC-NAc output in KI mice. Taken together, this study reveals the frontostriatal circuit dysfunction underlying cognitive inflexibility and establishes a critical role of the mPFC NL3 deficiency in this deficit in KI mice. Therefore, these findings provide new insights into the mechanisms of cognitive and behavioral inflexibility and potential intervention strategies.

The Staphylococcus aureus ArlS Kinase Inhibitor Tilmicosin Has Potent Anti-Biofilm Activity in Both Static and Flow Conditions.

Staphylococcus aureus can form biofilms on biotic surfaces or implanted materials, leading to biofilm-associated diseases in humans and animals that are refractory to conventional antibiotic treatment. Recent studies indicate that the unique ArlRS regulatory system in S. aureus is a promising target for screening inhibitors that may eradicate formed biofilms, retard virulence and break antimicrobial resistance. In this study, by screening in the library of FDA-approved drugs, tilmicosin was found to inhibit ArlS histidine kinase activity (IC50 = 1.09 µM). By constructing a promoter-fluorescence reporter system, we found that tilmicosin at a concentration of 0.75 µM or 1.5 µM displayed strong inhibition on the expression of the ArlRS regulon genes spx and mgrA in the S. aureus USA300 strain. Microplate assay and confocal laser scanning microscopy showed that tilmicosin at a sub-minimal inhibitory concentration (MIC) had a potent inhibitory effect on biofilms formed by multiple S. aureus strains and a strong biofilm-forming strain of S. epidermidis. In addition, tilmicosin at three-fold of MIC disrupted USA300 mature biofilms and had a strong bactericidal effect on embedded bacteria. Furthermore, in a BioFlux flow biofilm assay, tilmicosin showed potent anti-biofilm activity and synergized with oxacillin against USA300.

Efficient Ion Percolating Network for High-Performance All-Solid-State Cathodes.

All-solid-state lithium batteries (ASSLBs) face critical challenges of low cathode loading and poor rate performances, which handicaps their energy/power densities. The widely-accepted aim of high ionic conductivity and low interfacial resistance seems insufficient to overcome these challenges. Here, it is revealed that an efficient ion percolating network in the cathode exerts a more critical influence on the electrochemical performance of ASSLBs. By constructing vertical alignment of Li0.35 La0.55 TiO3 nanowires (LLTO NWs) in solid-state cathode through magnetic manipulation, the ionic conductivity of the cathode increases twice compared with the cathode consisted of randomly distributed LLTO NWs. The all-solid-state LiFePO4 /Li cells using poly(ethylene oxide) as the electrolyte is able to deliver high capacities of 151 mAh g-1 (2 C) and 100 mAh g-1 (5 C) at 60 °C, and a room-temperature capacity of 108 mAh g-1 can be achieved at a charging rate of 2 C. Furthermore, the cell can reach a high areal capacity of 3 mAh cm-2 even with a practical LFP loading of 20 mg cm-2 . The universality of this strategy is also presented showing the demonstration in LiNi0.8 Co0.1 Mn0.1 O2 cathodes. This work offers new pathways for designing ASSLBs with improved energy/power densities.

Hierarchical matching and reasoning for multi-query image retrieval.

As a promising field, Multi-Query Image Retrieval (MQIR) aims at searching for the semantically relevant image given multiple region-specific text queries. Existing works mainly focus on a single-level similarity between image regions and text queries, which neglect the hierarchical guidance of multi-level similarities and result in incomplete alignments. Besides, the high-level semantic correlations that intrinsically connect different region-query pairs are rarely considered. To address above limitations, we propose a novel Hierarchical Matching and Reasoning Network (HMRN) for MQIR. It disentangles MQIR into three hierarchical semantic representations, which is responsible to capture fine-grained local details, contextual global scopes, and high-level inherent correlations. HMRN consists of two modules: Scalar-based Matching (SM) module and Vector-based Reasoning (VR) module. Specifically, the SM module characterizes the multi-level alignment similarity, which consists of a fine-grained local-level similarity and a context-aware global-level similarity. Afterwards, the VR module is developed to excavate the potential semantic correlations among multiple region-query pairs, which further explores the high-level reasoning similarity. Finally, these three-level similarities are aggregated into a joint similarity space to form the ultimate similarity. Extensive experiments on the benchmark dataset demonstrate that our HMRN substantially surpasses the current state-of-the-art methods. For instance, compared with the existing best method Drill-down, the metric R@1 in the last round is improved by 23.4%. Our source codes will be released at https://github.com/LZH-053/HMRN.