Pericyte signaling via soluble guanylate cyclase shapes the vascular niche and microenvironment of tumors.

Pericytes and endothelial cells (ECs) constitute the fundamental components of blood vessels. While the role of ECs in tumor angiogenesis and the tumor microenvironment is well appreciated, pericyte function in tumors remains underexplored. In this study, we used pericyte-specific deletion of the nitric oxide (NO) receptor, soluble guanylate cyclase (sGC), to investigate via single-cell RNA sequencing how pericytes influence the vascular niche and the tumor microenvironment. Our findings demonstrate that pericyte sGC deletion disrupts EC-pericyte interactions, impairing Notch-mediated intercellular communication and triggering extensive transcriptomic reprogramming in both pericytes and ECs. These changes further extended their influence to neighboring cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) through paracrine signaling, collectively suppressing tumor growth. Inhibition of pericyte sGC has minimal impact on quiescent vessels but significantly increases the vulnerability of angiogenic tumor vessels to conventional anti-angiogenic therapy. In conclusion, our findings elucidate the role of pericytes in shaping the tumor vascular niche and tumor microenvironment and support pericyte sGC targeting as a promising strategy for improving anti-angiogenic therapy for cancer treatment.

The 14-3-3 protein OsGF14f interacts with OsbZIP23 and enhances its activity to confer osmotic stress tolerance in rice.

Drought, which can induce osmotic stress, is the leading environmental constraint on crop productivity. Plants in both agricultural and natural settings have developed various mechanisms to cope with drought stress. The identification of genes associated with drought stress tolerance and understanding the underlying regulatory mechanisms are prerequisites for developing molecular manipulation strategies to address this issue. Here, we reported that the G-BOX FACTOR 14-3-3f (14-3-3 protein OsGF14f) positively modulates osmotic stress tolerance in rice (Oryza sativa). OsGF14f transgenic lines had no obvious change in crucial agronomic traits including yield and plant height. OsGF14f is transcriptionally induced by PEG treatment, and in rice, overexpression or knockout of this gene leads to enhanced or weakened osmotic stress tolerance, respectively. Furthermore, OsGF14f positively regulates abscisic acid (ABA) responses by interacting with the core ABA-responsive transcription factor BASIC LEUCINE ZIPPER 23 (OsbZIP23) to enhance its transcriptional regulation activity toward downstream target genes. Further genetic analysis showed that OsGF14f is required for the full function of OsbZIP23 in rice osmotic response, and OsGF14f-mediated osmotic stress tolerance partially depends on OsbZIP23. Interestingly, OsGF14f is a direct target gene of OsbZIP23. Taken together, our findings reveal a genetic and molecular framework by which the OsGF14f-OsbZIP23 complex modulates rice osmotic response, providing targets for developing drought-tolerant crops.

OsFLZ2 interacts with OsMADS51 to fine-tune rice flowering time.

Flowering time is an important agronomic trait affecting crop yield. FCS-LIKE ZINC FINGER (FLZ) proteins are plant-specific regulatory proteins that are involved in multiple biological processes. However, their roles in plant flowering time control have not been clarified. Here, we report that OsFLZ2 is a negative regulator of rice flowering time. OsFLZ2 delays flowering by repressing the expression of key floral integrator genes. Biochemical assays showed OsFLZ2 physically interacts with OsMADS51, a flowering activator under short-day (SD) conditions. Both OsFLZ2 and OsMADS51 are highly expressed in rice leaves before floral transition under natural SD conditions, and their proteins are colocalized in the nucleus. Co-expression of OsFLZ2 can destabilize OsMADS51 and weaken its transcriptional activation of the downstream target gene Early heading date 1 (Ehd1). Taken together, these results indicate that OsFLZ2 can interfere with the function of OsMADS51 to fine-tune rice flowering time.

Carbon Fiber Film with Multi-Hollow Channels to Expedite Oxygen Electrocatalytic Reaction Kinetics for Flexible Zn-Air Battery.

The high oxygen electrocatalytic overpotential of flexible cathodes due to sluggish reaction kinetics result in low energy conversion efficiency of wearable zinc-air batteries (ZABs). Herein, lignin, as a 3D flexible carbon-rich macromolecule, is employed for partial replacement of polyacrylonitrile and constructing flexible freestanding air electrodes (FFAEs) with large amount of mesopores and multi-hollow channels via electrospinning combined with annealing strategy. The presence of lignin with disordered structure decreases the graphitization of carbon fibers, increases the structural defects, and optimizes the pore structure, facilitating the enhancement of electron-transfer kinetics. This unique structure effectively improves the accessibility of graphitic-N/pyridinic-N with oxygen reduction reaction (ORR) activity and pyridinic-N with oxygen evolution reaction (OER) activity for FFAEs, accelerating the mass transfer process of oxygen-active species. The resulting N-doped hollow carbon fiber films (NHCFs) exhibit superior bifunctional ORR/OER performance with a low potential difference of only 0.60 V. The rechargeable ZABs with NHCFs as metal-free cathodes possess a long-term cycling stability. Furthermore, the NHCFs can be used as FFAEs for flexible ZABs which have a high specific capacity and good cycling stability under different bending states. This work paves the way to design and produce highly active metal-free bifunctional FFAEs for electrochemical energy devices.

Ionic Hyperbranched Poly(amido-amine)-Incorporated Nanofiltration Membranes for High-Efficiency Dye Desalination.

High-efficiency dye desalination is crucial in the textile industry, considering its importance for human health, safe aquatic ecological systems, and resource recovery. In order to solve the problem of effective separation of univalent salt and ionic dye under the condition of high salt, ionic hyperbranched poly(amido-amine) (HBPs) were synthesized based on a simple and scalable one-step polycondensation method and then incorporated into the polyamide (PA) selective layers to construct charged nanochannels through interfacial polymerization (IP) on the surface of a polyvinyl chloride ultrafiltration (PVC-UF) hollow fiber membrane. Both the internal nanopores of HBPs (internal nanochannels) and the interfacial voids between HBPs and the PA matrix (external nanochannels) can be regarded as a fast water molecule transport pathway, while the terminal ionic groups of ionic HBPs endow the nanochannels with charge characteristics for improving ionic dye/salt selectivities. The permeate fluxes and dye/salt selectivities of HBP-TAC/PIP (57.3 L m-2 h-1 and rhodamine B (RB)/NaCl selectivity of 224.0) and HBP-PS/PIP (63.7 L m-2 h-1 and lemon yellow (LY)/NaCl selectivity of 664.0) membranes under 0.4 MPa operation pressure are much higher than PIP-only and HBP-NH2/PIP membranes. At the same time, this project also studied the membrane desalination process in a simulated high-salinity dye/salt mixture system to provide a theoretical basis and technical support for the actual dye desalination process.

Highly Stretchable, Fast Self-Healing, Self-Adhesive, and Strain-Sensitive Wearable Sensor Based on Ionic Conductive Hydrogels.

Conductive hydrogels integrate the conductive performance and soft nature, which is like that of human skin. Thus, they are more suitable for the preparation of wearable human-motion sensors. Nevertheless, the integration of outstanding multiple functionalities, such as stretchability, toughness, biocompatibility, self-healing, adhesion, strain sensitivity, and durability, by a simple way is still a huge challenge. Herein, we have developed a multifunctional chitosan/oxidized hyaluronic acid/hydroxypropyl methylcellulose/poly(acrylic acid)/tannic acid/Al3+ hydrogel (CS/OHA/HPMC/PAA/TA/Al3+) by using a two-step method with hydroxypropyl methylcellulose (HPMC), acrylic acid (AA), tannic acid (TA), chitosan (CS), oxidized hyaluronic acid (OHA), and aluminum chloride hexahydrate (AlCl3·6H2O). Due to the synergistic effect of dynamic imine bonds between CS and OHA, dynamic metal coordination bonds between Al3+ and -COOH and/or TA as well as reversible hydrogen, the hydrogel showed excellent tensile property (elongation at break of 3168%) and desirable toughness (0.79 MJ/m3). The mechanical self-healing efficiency can reach 95.5% at 30 min, and the conductivity can recover in 5.2 s at room temperature without stimulation. The favorable attribute of high transparency (98.5% transmittance) facilitates the transmission of the optical signal and enables visualization of the sensor. It also shows good adhesiveness to various materials and is easy to peel off without residue. The resistance of the hydrogel-based sensors shows good electrical conductivity (2.33 S m-1), good durability, high sensing sensitivity (GF value of 4.12 under 1600% strain), low detection limit (less than 1%), and short response/recovery time (0.54/0.31 s). It adhered to human skin and monitored human movements such as the bending movements of joints, swallowing, and speaking successfully. Therefore, the obtained multifunctional conductive hydrogel has great potential applications in wearable strain sensors.

Brønsted acid catalyzed [4 + 2] cycloaddition for the synthesis of bisbenzannulated spiroketals with antifungal activities.

The intermolecular [4 + 2] cycloaddition of o-hydroxy benzyl alcohols with isochroman ketals was realized by CF3CO2H catalysis. A broad range of bisbenzannulated [6,6]-spiroketals were formed under the metal-free mild conditions in moderate to excellent yields (45-98%) with mostly excellent diastereoselectivities (up to >20 : 1 dr). Furthermore, the enantioselective version was also preliminarily investigated and the bisbenzannulated [6,6]-spiroketal was obtained with 61% ee in the presence of Sc(OTf)3/Feng's chiral N,N'-dioxide ligand. Some of the bisbenzannulated [6,6]-spiroketal products showed good in vitro antifungal activities against Sclerotinia sclerotiorum and Rhizoctonia solani.

Intrathecal morphine delivery at prepontine cistern to control refractory cancer-related pain: a case report of extensive metastatic and refractory cancer pain.

BACKGROUND: Extensive metastatic and refractory cancer pain is common, and exhibits a dissatisfactory response to the conventional intrathecal infusion of opioid analgesics. CASE PRESENTATION: The present study reports a case of an extensive metastatic esophageal cancer patient with severe intractable pain, who underwent translumbar subarachnoid puncture with intrathecal catheterization to the prepontine cistern. After continuous infusion of low-dose morphine, the pain was well-controlled with a decrease in the numeric rating scale (NRS) of pain score from 9 to 0, and the few adverse reactions to the treatment disappeared at a low dose of morphine. CONCLUSIONS: The patient achieved a good quality of life during the one-month follow-up period.

Covalent post-synthetic modification of MOFs as a fluorescent sensor for the efficient detection of the biomarker of cystinuria.

Cystinuria is a genetic disorder, and in severe cases, it might lead to kidney failure. As an important biomarker for cystinuria, the level of arginine (Arg) in urine is a vital indicator for cystinuria screening. Therefore, it is urgently needed to detect Arg with high selectivity and sensitivity. In this work, a boric acid functionalized Zr-based metal-organic framework UiO-PhbA is prepared by grafting phenylboronic acid on UiO-66-NH2 through a Schiff base reaction using a covalent post-synthesis modification (CPSM) strategy. The prepared UiO-PhbA exhibits a sensitive and specific fluorescence "turn-on" response to Arg and can be exploited to detect Arg in human serum and urine samples with a broad linear range of 0.6-350 µM and low limit of detection (LOD) of 18.45 nM. This study provides a new and reliable rapid screening protocol for sulfite oxidase deficiency-related diseases.

The Safety of Injections in the Infraorbital Region.

BACKGROUND:  Infraorbital filler injection is a commonly used minimally invasive cosmetic procedure on the face, which can cause vascular complications. OBJECTIVE:  In this study, we aimed to explore the anatomical structure of the infraorbital vasculature and to establish an accurate protocol for infraorbital filler injection. METHODS:  The vascular structure of the infraorbital region was evaluated in 84 hemifacial specimens using computed tomography. Four segments (P1-P4) and five sections (C1-C5) were considered. We recorded the number of identified arteries in each slice and at each location and the number of deep arteries. Furthermore, we also measured the infraorbital artery (IOA) distribution. RESULTS:  At P1-P4, the lowest number of arteries was detected in segment P4, with a 317/1727 (18.4%) and 65/338 (2.3%) probability of total and deep arterial identification, respectively. The probabilities of encountering an identified artery at the five designated locations (C1-C5) were 277/1727 (16%), 318/1727 (18.4%), 410/1727 (23.7%), 397/1727 (23%), and 325/1727 (18.8%), respectively. The probability of an IOA being identified at C2 was 68/84 (81%). CONCLUSION:  We described an effective filler injection technique in the infraorbital region to minimize the associated risks. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Genome-wide study of Cerrena unicolor 87613 laccase gene family and their mode prediction in association with substrate oxidation.

BACKGROUND: Laccases are green biocatalysts with wide industrial applications. The study of efficient and specific laccase producers remains a priority. Cerrena species have been shown to be promising basidiomycete candidates for laccase production. Although two sets of Cerrena genome data have been publicly published, no comprehensive bioinformatics study of laccase gene family in C. unicolor has been reported, particularly concerning the analysis of their three-dimensional (3D) structures and molecular docking to substrates, like ABTS and aflatoxin B1 (AFB1). RESULTS: In this study, we conducted a comprehensive genome-wide analysis of laccase gene family in C. unicolor 87613. We identified eighteen laccase genes (CuLacs) and classified them into three clades using phylogenetic analysis. We characterized these laccases, including their location in contig 5,6,9,12,15,19,26,27, gene structures of different exon-intron arrangements, molecular weight ranging from 47.89 to 141.41 kDa, acidic pI value, 5-15 conserved protein motifs, signaling peptide of extracellular secretion (harbored by 13 CuLacs) and others. In addition, the analysis of cis-acting element in laccase promoters indicated that the transcription response of CuLac gene family was regulatable and complex under different environmental cues. Furthermore, analysis of transcription pattern revealed that CuLac8, 12 and CuLac2, 13 were the predominant laccases in response to copper ions or oxidative stress, respectively. Finally, we focused on the 3D structure analysis of CuLac proteins. Seven laccases with extra transmembrane domains or special sequences were particularly interesting. Predicted structures of each CuLac protein with or without these extra sequences showed altered interacting amino acid residues and binding sites, leading to varied affinities to both ABTS and AFB1. As far as we know, it is the first time to discuss the influence of the extra sequence on laccase's affinity to substrates. CONCLUSIONS: Our findings provide robust genetic data for a better understanding of the laccase gene family in C. unicolor 87613, and create a foundation for the molecular redesign of CuLac proteins to enhance their industrial applications.

Cu(I)-Catalyzed Chemo- and Enantioselective Desymmetrizing C-O Bond Coupling of Acyl Radicals.

Transition-metal-catalyzed enantioselective functionalization of acyl radicals has so far not been realized, probably due to their relatively high reactivity, which renders the chemo- and stereocontrol challenging. Herein, we describe Cu(I)-catalyzed enantioselective desymmetrizing C-O bond coupling of acyl radicals. This reaction is compatible with (hetero)aryl and alkyl aldehydes and, more importantly, displays a very broad scope of challenging alcohol substrates, such as 2,2-disubstituted 1,3-diols, 2-substituted-2-chloro-1,3-diols, 2-substituted 1,2,3-triols, 2-substituted serinols, and meso primary 1,4-diols, providing enantioenriched esters characterized by challenging acyclic tetrasubstituted carbon stereocenters. Partnered by one- or two-step follow-up transformations, this reaction provides a convenient and practical strategy for the rapid preparation of chiral C3 building blocks from readily available alcohols, particularly the industrially relevant glycerol. Mechanistic studies supported the proposed C-O bond coupling of acyl radicals.

Tight Binding and Dual Encapsulation Enabled Stable Thick Silicon/Carbon Anode with Ultrahigh Volumetric Capacity for Lithium Storage.

Silicon (Si) is regarded as one of the most promising anode materials for high-performance lithium-ion batteries (LIBs). However, how to mitigate its poor intrinsic conductivity and the lithiation/delithiation-induced large volume change and thus structural degradation of Si electrodes without compromising their energy density is critical for the practical application of Si in LIBs. Herein, an integration strategy is proposed for preparing a compact micron-sized Si@G/CNF@NC composite with a tight binding and dual-encapsulated architecture that can endow it with superior electrical conductivity and deformation resistance, contributing to excellent cycling stability and good rate performance in thick electrode. At an ultrahigh mass loading of 10.8 mg cm-2 , the Si@G/CNF@NC electrode also presents a large initial areal capacity of 16.7 mA h cm-2 (volumetric capacity of 2197.7 mA h cm-3 ). When paired with LiNi0.95 Co0.02 Mn0.03 O2 , the pouch-type full battery displays a highly competitive gravimetric (volumetric) energy density of ≈459.1 Wh kg-1 (≈1235.4 Wh L-1 ).

Biomass-assisted fabrication of rGO-AuNPs as surface-enhanced Raman scattering substrates for in-situ monitoring methylene blue degradation.

Reduced graphene oxide-gold nanoparticles nanocomposites (rGO-AuNPs) with high surface-enhanced Raman scattering (SERS) activity was created by biomass-assisted green synthesis with Lilium casa blanca petals biomass for the first time, and its application for methylene blue (MB) degradation was explored through in-situ monitoring. Lilium casa blanca petals biomass was used as a reducing agent to reduce GO and chloroauric acid successively when carrying out rGO-AuNPs in-situ synthesis while it also acted as a capping agent. The produced rGO had oxygen-containing functional groups which had an outstanding performance in enhancing the SERS effect. Characterization results confirmed that the AuNPs were grafted onto the rGO sheet, and the mechanism study showed that total flavonoids in Lilium casa blanca petals biomass were the main biological compounds involved in the reduction. rGO-AuNPs had a high Raman enhancement factor (EF) which could reach 3.88 × 107. The synthesized nanocomposite also had a good catalytic activity that could be employed as catalyst in MB degradation, and it could complete degradation within 15min. The reaction rate increased linearly with the amount of rGO-AuNPs, and the degradation could be in-situ monitored both by UV and SERS.

Genome-wide association mapping combined with gene-based haplotype analysis identify a novel gene for shoot length in rice (Oryza sativa L.).

KEY MESSAGE: Genome-wide association mapping revealed a novel QTL for shoot length across multiple environments. Its causal gene, LOC_Os01g68500, was identified firstly through gene-based haplotype analysis, gene expression and knockout transgenic verification. Strong seedling vigor is an important breeding target for rice varieties used in direct seeding. Shoot length (SL) is one of the important traits associated with seedling vigor characterized by rapid growth of seedling, which enhance seedling emergence. Therefore, mining genes for SL and conducting molecular breeding help to develop varieties for direct seeding. However, few QTLs for SL have been fine mapped or cloned so far. In this study, a genome-wide association study of SL was performed in a diverse rice collection consisting of 391 accessions in two years, using phenotypes generated by different cultivation methods according to the production practice, and a total of twenty-four QTLs for SL were identified. Among them, the novel QTL qSL-1f on chromosome 1 could be stably detected across all three cultivation methods in the whole population and indica subpopulation. Through gene-based haplotype analysis of the annotated genes within the putative region of qSL-1f, and validated by gene expression and knockout transgenic experiments, LOC_Os01g68500 (i.e., Os01g0913100 in RAP-DB) was identified as the causal gene for SL, which has a single-base variation (C-to-A transversion) in its CDS region, resulting in the significant difference in SL of rice. LOC_Os01g68500 encodes a DUF538 (Domain of unknown function) containing protein, and the function of DUF538 protein gene on rice seedling growth is firstly reported in this study. These results provide a new clue for exploring the molecular mechanism regulating SL, and promising gene source for the molecular breeding in rice.

Fatal multiple organ dysfunction caused by commensal bacteria of urogenital tract infection in adult lung transplant recipients: two case reports.

BACKGROUND: Infection following lung transplantation has been the focus of clinical concerns. The colonization rate of commensal bacteria of the urogenital tract, including Mycoplasma hominis, Ureaplasma urealyticum (UU), and herpes simplex virus type-2 (HSV-2), is high, which may cause secondary infection after transplantation. CASE PRESENTATION: Twenty-three-year-old and 67-year-old women underwent lung transplantation for different causes. Shortly after the operation, they developed perineal skin ulcers, hypoxia, and intractable epilepsy. Subsequent computed tomography (CT) of the chest showed lung consolidation, and cranial CT showed shallowing sulci and gyri. UU and HSV-2 were detected in bronchoalveolar lavage fluid by next-generation sequencing, and HSV-2 was shown in the cerebrospinal fluid of both patients. Despite active treatment, both suffered irreversible brain function damage within 72 h of the seizure. CONCLUSIONS: Clinicians should know that commensal bacteria of urogenital tract infections can lead to fatal multiple organ dysfunction after lung transplantation.

Eucommiae Folium and Active Compounds Protect Against Mitochondrial Dysfunction-Calcium Overload in Epileptic Hippocampal Neurons Through the Hypertrophic Cardiomyopathy Pathway.

Epilepsy is a chronic brain disease and often occurs suddenly for no reason. Eucommiae folium (EF), an edible herb, can be used in the treatment of various kinds of brain diseases in clinic. From the perspective of safety and efficacy, EF is especially suitable for the treatment of chronic brain diseases. With the help of biolabels, this study was aimed to explore the value and feasibility of EF in the treatment of epilepsy. Proteomics and metabolomics were used to explore the biolabels of EF intervention in brain tissues. Bioinformatics was then applied to topologically analyze its neuroprotective effects and mechanisms and material basis based on biolabels, which were validated in an animal model. The biolabel-led research revealed that EF may exert the therapeutic potential to treat brain diseases through the interaction between multiple compounds and multiple targets, among which its therapeutic potential for epilepsy is particularly prominent. In the pentylenetetrazole-induction model, EF and four active compounds (oleamide, catechol, chlorogenic acid, and kaempferol) protected epileptic hippocampal neurons (Nissl and FJB staining) against mitochondrial dysfunction (MYH6, MYL3, and MYBPC3, etc.) and calcium overload (TNNI3, TNNC1, and TNNT2, etc.) through the hypertrophic cardiomyopathy pathway. This study provides new evidence and insights for the neuroprotective effects of EF, in which four active compounds may be potential drug candidates for the treatment of epilepsy.

Self-healing, self-adhesive, stretchable and flexible conductive hydrogels for high-performance strain sensors.

Conductive hydrogels have been widely studied for their potential application as wearable sensors due to their flexibility and biocompatibility. However, the simultaneous incorporation of excellent stretchability, toughness, conductivity, self-healing, and adhesion via a simple method remains a great challenge. Herein, a multifunctional hydrogel with self-adhesion, self-healing, conductivity, and mechanical properties was fabricated by ionic cross-linking of chitosan (CS), the acrylic acid (AA) polymer, and tea polyphenols (TPs) in the presence of graphitized carbon nanotubes (CNTs) in this work. The resultant hydrogel has unique self-healing properties (94.11% for strain self-healing and 90.60% for stress self-healing) and mechanical properties. The fracture stress was 0.075 MPa when the strain was 1184%, and the toughness reached 0.48 MJ m-3. The synergistic effect of free ions and CNTs endows the hydrogel with an excellent electrical conductivity (6.67 S m-1). Moreover, the hydrogel can adhere to various organic and inorganic materials. It exhibits repeatable self-adhesion to human skin and can be peeled off completely without any residual, irritation or allergic reactions. Additionally, the hydrogel also has good strain sensitivity and exhibits stable output signals in motion monitoring of the human body as a biosensor. Therefore, this work provides a new prospect for the design of multifunctional hydrogels for their potential applications in wearable biosensors.

KANK4 Promotes Arteriogenesis by Potentiating VEGFR2 Signaling in a TALIN-1-Dependent Manner.

BACKGROUND: Arteriogenesis plays a critical role in maintaining adequate tissue blood supply and is related to a favorable prognosis in arterial occlusive diseases. Strategies aimed at promoting arteriogenesis have thus far not been successful because the factors involved in arteriogenesis remain incompletely understood. Previous studies suggest that evolutionarily conserved KANK4 (KN motif and ankyrin repeat domain-containing proteins 4) might involve in vertebrate vessel development. However, how the KANK4 regulates vessel function remains unknown. We aim to determine the role of endothelial cell-specifically expressed KANK4 in arteriogenesis. METHODS: The role of KANK4 in regulating arteriogenesis was evaluated using Kank4-/- and KANK4iECOE mice. Molecular mechanisms underlying KANK4-potentiated arteriogenesis were investigated by employing RNA transcriptomic profiling and mass spectrometry analysis. RESULTS: By analyzing Kank4-EGFP reporter mice, we showed that KANK4 was specifically expressed in endothelial cells. In particular, KANK4 displayed a dynamic expression pattern from being ubiquitously expressed in all endothelial cells of the developing vasculature to being explicitly expressed in the endothelial cells of arterioles and arteries in matured vessels. In vitro microfluidic chip-based vascular morphology analysis and in vivo hindlimb ischemia assays using Kank4-/- and KANK4iECOE mice demonstrated that deletion of KANK4 impaired collateral artery growth and the recovery of blood perfusion, whereas KANK4 overexpression leads to increased vessel caliber and blood perfusion. Bulk RNA sequencing and Co-immunoprecipitation/mass spectrometry (Co-IP/MS) analysis identified that KANK4 promoted EC proliferation and collateral artery remodeling through coupling VEGFR2 (vascular endothelial growth factor receptor 2) to TALIN-1, which augmented the activation of the VEGFR2 signaling cascade. CONCLUSIONS: This study reveals a novel role for KANK4 in arteriogenesis in response to ischemia. KANK4 links VEGFR2 to TALIN-1, resulting in enhanced VEGFR2 activation and increased EC proliferation, highlighting that KANK4 is a potential therapeutic target for promoting arteriogenesis for arterial occlusive diseases.

A novel electrochemical sensing platform based on double-active-center polyimide covalent organic frameworks for sensitive analysis of levofloxacin.

The development of a simple and sensitive electrochemical sensing platform for levofloxacin (LVF) analysis is of great significance to human health. In this work, a covalent organic framework (TP-COF) was in situ grown on the surface of Sn-MoC nanospheres with nanoflower-like morphology through a one-pot method to obtain the TP-COF@Sn-MoC composite. The prepared composite was used to modify a glassy carbon electrode (GCE) to realize the sensitive detection of levofloxacin. TP-COF was formed by polycondensation of 2,4,6-tris(4-aminophenyl)-1,3,5-triazine (TAPT) and pyromellitic dianhydride (PMDA), in which C = O and C = N groups served as double active centers for the recognition and electrocatalytic oxidation of the target molecule. Meanwhile, the introduction of Sn-MoC improved the conductivity of the electrode. The TP-COF@Sn-MoC composite produced a strong synergistic effect and showed a high electrocatalytic ability toward levofloxacin oxidation. The linear range of LVF was 0.6-1000 µM and the limit of detection (LOD) was 0.029 µM (S/N = 3). In addition, the sensor has been successfully applied for the analysis of LVF in human urine and blood serum samples with acceptable recovery rates, demonstrating that the sensor was promising in practical applications.