Single-cell RNA sequencing reveals the MIF/ACKR3 receptor-ligand interaction between neutrophils and nucleus pulposus cells in intervertebral disc degeneration.

OBJECTIVES: To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD). METHODS: Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo. RESULTS: We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF+ ECMO-neutrophil counts and ACKR3+ effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors. CONCLUSIONS: These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies.

RSU-1 regulates the integrity of dense bodies in muscle cells of aging Caenorhabditis elegans.

Muscle contraction is vital for animal survival, and the sarcomere is the fundamental unit for this process. However, the functions of many conserved sarcomere proteins remain unknown, as their mutants do not exhibit obvious defects. To address this, Caenorhabditis elegans was utilized as a model organism to investigate RSU-1 function in the body wall muscle. RSU-1 is found to colocalize with UNC-97 at the dense body and M-line, and it is particularly crucial for regulating locomotion in aging worms, rather than in young worms. This suggests that RSU-1 has a specific function in maintaining muscle function during aging. Furthermore, the interaction between RSU-1 and UNC-97/PINCH is essential for RSU-1 to modulate locomotion, preserve filament structure, and sustain the M-line and dense body throughout aging. Overall, these findings highlight the significant contribution of RSU-1, through its interaction with UNC-97, in maintaining proper muscle cell function in aging worms.

Appraisal of clinical practice guidelines and consensus statements on obstetric anaesthesia: a systematic review using the AGREE II instrument.

OBJECTIVES: Despite the publication of hundreds of trials on obstetric anaesthesia, the management of these conditions remains suboptimal. We aimed to assess the quality and consistency of guidance documents for obstetric anaesthesia. DESIGN: This is a systematic review and quality assessment using the Appraisal of Guidelines for Research and Evaluation (AGREE) II methodology. DATA SOURCES: Data sources include PubMed and Embase (8 June 2023), three Chinese academic databases, six guideline databases (7 June 2023) and Google and Google scholar (1 August 2023). ELIGIBILITY CRITERIA: We included the latest version of international and national/regional clinical practice guidelines and consensus statements for the anaesthetic management of pregnant patients during labour, non-operative delivery, operative delivery and selected aspects of perioperative monitoring, postpartum care and analgesia, published in English or Chinese. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the searched items and extracted data. Four reviewers independently scored documents using AGREE II. Recommendations from all documents were tabulated and visualised in a coloured grid. RESULTS: Twenty-two guidance documents (14 clinical practice guidelines and 8 consensus statements) were included. Included documents performed well in the domains of scope and purpose (median 76.4%, IQR 69.4%-79.2%) and clarity of presentation (median 72.2%, IQR 61.1%-80.6%), but were unsatisfactory in applicability (median 21.9%, IQR 13.5%-27.1%) and editorial independence (median 47.9%, IQR 6.3%-73.2%). The majority of obstetric anaesthesia guidelines or consensus centred on different topics. Less than 30% of them specifically addressed the management of obstetric anaesthesia perioperatively. Recommendations were concordant on the perioperative preparation, and on some indications for the choice of anaesthesia method. Substantially different recommendations were provided for some items, especially for preoperative blood type and screen, and for the types and doses of neuraxial administration. CONCLUSIONS: The methodological quality in guidance documents for obstetric anaesthesia necessitates enhancement. Despite numerous trials in this area, evidence gaps persist for specific clinical queries in this field. One potential approach to mitigate these challenges involves the endorsement of standardised guidance development methods and the synthesis of robust clinical evidence, aimed at diminishing difference in recommendations.

Direct Observation of Covalently Bound Clusters in Resonantly Stabilized Radical Reactions and Implications for Carbonaceous Particle Growth.

Based on quantum mechanically guided experiments that observed elusive intermediates in the domain of inception that lies between large molecules and soot particles, we provide a new mechanism for the formation of carbonaceous particles from gas-phase molecular precursors. We investigated the clustering behavior of resonantly stabilized radicals (RSRs) and their interactions with unsaturated hydrocarbons through a combination of gas-phase reaction experiments and theoretical calculations. Our research directly observed a sequence of covalently bound clusters (CBCs) as key intermediates in the evolution from small RSRs, such as benzyl (C7H7), indenyl (C9H7), 1-methylnaphthyl (1-C11H9), and 2-methylnaphthyl (2-C11H9), to large polycyclic aromatic hydrocarbons (PAHs) consisting of 28 to 55 carbons. We found that hydrogen abstraction and RSR addition drive the formation and growth of CBCs, leading to progressive H-losses, the generation of large PAHs and PAH radicals, and the formation of white smoke (incipient carbonaceous particles). This mechanism of progressive H-losses from CBCs (PHLCBC) elucidates the crucial relationship among RSRs, CBCs, and PAHs, and this study provides an unprecedentedly seamless path of observed assembly from small RSRs to large nanoparticles. Understanding the PHLCBC mechanism over a wide temperature range may enhance the accuracy of multiscale models of soot formation, guide the synthesis of carbonaceous nanomaterials, and deepen our understanding of the origin and evolution of carbon within our galaxy.

Anti-MRSA mechanism of spirostane saponin in Rohdea pachynema F.T.Wang & tang.

ETHNOPHARMACOLOGY RELEVANCE: Rohdea pachynema F.T.Wang & Tang (R. pachynema), is a traditional folk medicine used for the treatment of stomach pain, stomach ulcers, bruises, and skin infections in China. Some of the diseases may relate to microbial infections in traditional applications. However few reports on its antimicrobial properties and bioactive components. AIM OF THE STUDY: To identify its bioactive constituents against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, and its mechanism. MATERIALS AND METHODS: The anti-MRSA ingredient 6α-O-[ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (XQS) was obtained from R. pachynema by phytochemical isolation. Subsequently, XQS underwent screening using the broth microdilution method and growth inhibition curves to assess its antibacterial activity. The mechanism of XQS was evaluated by multigeneration induction, biofilm resistance assay, scanning electron microscopy, transmission electron microscopy, and metabolomics. Additionally, a mouse skin infection model was established in vivo. RESULTS: 26 compounds were identified from the R. pachynema, in which anti-MRSA spirostane saponin (XQS) was reported for the first time with a minimum inhibitory concentration (MIC) of 8 µg/mL. XQS might bind to peptidoglycan (PGN) of the cell wall, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) of the cell membrane, then destroying the cell wall and the cell membrane, resulting in reduced membrane fluidity and membrane depolarization. Furthermore, XQS affected MRSA lipid metabolism, amino acid metabolism, and ABC transporters by metabolomics analysis, which targeted cell walls and membranes causing less susceptibility to drug resistance. Furthermore, XQS (8 mg/kg) recovered skin wounds in mice infected by MRSA effectively, superior to vancomycin (8 mg/kg). CONCLUSIONS: XQS showed anti-MRSA bioactivity in vitro and in vivo, and its mechanism association with cell walls and membranes was reported for the first, which supported the traditional uses of R. pachynema and explained its sensitivity to MRSA.

Development and characterization of a bacterial enzyme cascade reaction system for efficient and stable PET degradation.

The widespread use of polyethylene terephthalate (PET) in various industries has led to a surge in microplastics (MPs) pollution, posing a significant threat to ecosystems and human health. To address this, we have developed a bacterial enzyme cascade reaction system (BECRS) that focuses on the efficient degradation of PET. This system harnesses the Escherichia coli (E. coli) surface to display CsgA protein, which forms curli fibers, along with the carbohydrate-binding module 3 (CBM3) and PETases, to enhance the adsorption and degradation of PET. The study demonstrated that the BECRS achieved a notable PET film degradation rate of 3437 ± 148 µg/(d*cm²), with a degradation efficiency of 21.40% for crystalline PET MPs, and the degradation products were all converted to TPA. The stability of the system was evidenced by retaining over 80% of its original activity after multiple uses and during one month of storage. Molecular dynamics simulations confirmed that the presence of CsgA did not interfere with the enzymatic activity of PETases. This BECRS represents a significant step forward in the biodegradation of PET, particularly microplastics, offering a practical and sustainable solution for environmental pollution control.

Coupling protein scaffold and biosilicification: A sustainable and recyclable approach for d-mannitol production via one-step purification and immobilization of multienzymes.

Enzymatic synthesis of biochemicals in vitro is vital in synthetic biology for its efficiency, minimal by-products, and easy product separation. However, challenges like enzyme preparation, stability, and reusability persist. Here, we introduced a protein scaffold and biosilicification coupled system, providing a singular process for the purification and immobilization of multiple enzymes. Using d-mannitol as a model, we initially constructed a self-assembling EE/KK protein scaffold for the co-immobilization of glucose dehydrogenase and mannitol dehydrogenase. Under an enzyme-to-scaffold ratio of 1:8, a d-mannitol yield of 0.692 mol/mol was achieved within 4 h, 2.16-fold higher than the free enzymes. The immobilized enzymes retained 70.9 % of the initial joint activity while the free ones diminished nearly to inactivity after 8 h. Furthermore, we incorporated the biosilicification peptide CotB into the EE/KK scaffold, inducing silica deposition, which enabled the one-step purification and immobilization process assisted by Spy/Snoop protein-peptide pairs. The coupled system demonstrated a comparable d-mannitol yield to that of EE/KK scaffold and 1.34-fold higher remaining activities after 36 h. Following 6 cycles of reaction, the immobilized system retained the capability to synthesize 56.4 % of the initial d-mannitol titer. The self-assembly co-immobilization platform offers an effective approach for enzymatic synthesis of d-mannitol and other biochemicals.

The RNA binding protein EHD6 recruits the m6A reader YTH07 and sequesters OsCOL4 mRNA into phase-separated ribonucleoprotein condensates to promote rice flowering.

N6-Methyladenosine (m6A) is one of the most abundant modifications of eukaryotic mRNA, but its comprehensive biological functionality remains further exploration. In this study, we identified and characterized a new flowering-promoting gene, EARLY HEADING DATE6 (EHD6), in rice. EHD6 encodes an RNA recognition motif (RRM)-containing RNA binding protein that is localized in the non-membranous cytoplasm ribonucleoprotein (RNP) granules and can bind both m6A-modified RNA and unmodified RNA indiscriminately. We found that EHD6 can physically interact with YTH07, a YTH (YT521-B homology) domain-containing m6A reader. We showed that their interaction enhances the binding of an m6A-modified RNA and triggers relocation of a portion of YTH07 from the cytoplasm into RNP granules through phase-separated condensation. Within these condensates, the mRNA of a rice flowering repressor, CONSTANS-like 4 (OsCOL4), becomes sequestered, leading to a reduction in its protein abundance and thus accelerated flowering through the Early heading date 1 pathway. Taken together, these results not only shed new light on the molecular mechanism of efficient m6A recognition by the collaboration between an RNA binding protein and YTH family m6A reader, but also uncover the potential for m6A-mediated translation regulation through phase-separated ribonucleoprotein condensation in rice.

OsSRF8 interacts with OsINP1 and OsDAF1 to regulate pollen aperture formation in rice.

In higher plants, mature male gametophytes have distinct apertures. After pollination, pollen grains germinate, and a pollen tube grows from the aperture to deliver sperm cells to the embryo sac, completing fertilization. In rice, the pollen aperture has a single-pore structure with a collar-like annulus and a plug-like operculum. A crucial step in aperture development is the formation of aperture plasma membrane protrusion (APMP) at the distal polar region of the microspore during the late tetrad stage. Previous studies identified OsINP1 and OsDAF1 as essential regulators of APMP and pollen aperture formation in rice, but their precise molecular mechanisms remain unclear. We demonstrate that the Poaceae-specific OsSRF8 gene, encoding a STRUBBELIG-receptor family 8 protein, is essential for pollen aperture formation in Oryza sativa. Mutants lacking functional OsSRF8 exhibit defects in APMP and pollen aperture formation, like loss-of-function OsINP1 mutants. OsSRF8 is specifically expressed during early anther development and initially diffusely distributed in the microsporocytes. At the tetrad stage, OsSRF8 is recruited by OsINP1 to the pre-aperture region through direct protein-protein interaction, promoting APMP formation. The OsSRF8-OsINP1 complex then recruits OsDAF1 to the APMP site to co-regulate annulus formation. Our findings provide insights into the mechanisms controlling pollen aperture formation in cereal species.

LncRNA-NEAT1 blocks the Wnt/ß-catenin signaling pathway by targeting miR-217 to inhibit trophoblast cell migration and invasion.

OBJECTIVE: This study aimed to study the correlation between preeclampsia (PE) and lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and to examine the molecular mechanisms behind the development of PE. METHODS: 30 PE and 30 normal pregnant women placental samples were assessed the levels of NEAT1 and miR-217 by quantitative real-time PCR (qRT-PCR). The trophoblast cell line HTR8/SVneo was used for silencing NEAT1 or miR-217 inhibitor in the absence or presence of an inhibitor and H2O2. Cell counting Kit 8 (CCK-8), flow cytometry, and Transwell were used to detect cell proliferation, apoptosis, migration, and invasion. Luciferase reporter gene assay was utilized to verify the binding between miR-217 and Wnt family member 3 (Wnt3), and between the miR-217 and NEAT1. Proteins related to the Wnt/ß-catenin signaling pathway were detected using western blotting. RESULTS: The PE group exhibited a significantly downregulated expression of miR-217 and a significantly upregulated expression of NEAT1. NEAT1 targeted miR-217, and Wnt is a miR-217 target gene. siRNA-NEAT1 inhibited the apoptosis of trophoblast cells, but promoted their invasion, migration, and proliferation. MiR-217 inhibitor could partially reverse the effects of siRNA-NEAT1. The expression of the Wnt/ß-catenin signaling pathway-related proteins, WNT signaling pathway inhibitor 1 (DKK1), cyclin-D1 and ß-catenin, was significantly increased after siRNA-NEAT1. CONCLUSIONS: NEAT1 could reduce trophoblast cell invasion and migration by suppressing miR-217/Wnt signaling pathway, leading to PE.

Olfactory dysfunction and the role of stem cells in the regeneration of olfactory neurons.

The prevalence of COVID-19 has drawn increasing attention to olfactory dysfunction among researchers. Olfactory dysfunction manifests in various clinical types, influenced by numerous pathogenic factors. Despite this diversity, the underlying pathogenesis remains largely elusive, contributing to a lack of standardized treatment approaches. However, the potential regeneration of olfactory neurons within the nasal cavity presents a promising avenue for addressing olfactory dysfunction effectively. Our review aims to delve into the current research landscape and treatment modalities concerning olfactory dysfunction, emphasizing etiology, pathogenesis, clinical interventions, and the role of stem cells in regenerating olfactory nerves. Through this comprehensive examination, we aim to provide valuable insights into understanding the onset, progression, and treatment of olfactory dysfunction diseases.

Age-related trajectories of the development of social cognition.

Age-related trajectories of intrinsic functional connectivity (iFC), which represent the interconnections between discrete regions of the human brain, for processes related to social cognition (SC) provide evidence for social development through neural imaging and can guide clinical interventions when such development is atypical. However, due to the lack of studies investigating brain development over a wide range of ages, the neural mechanisms of SC remain poorly understood, although considerable behavior-related evidence is available. The present study mapped vortex-wise iFC features between SC networks and the entire cerebral cortex by using common functional networks, creating the corresponding age-related trajectories. Three networks [moral cognition, theory of mind (ToM), and empathy] were selected as representative SC networks. The Enhanced Nathan Kline Institute-Rockland Sample (NKI-RS, N = 316, ages 8-83 years old) was employed delineate iFC characteristics and construct trajectories. The results showed that the SC networks display unique and overlapping iFC profiles. The iFC of the empathy network, an age-sensitive network, with dorsal attention network was found to exhibit a linear increasing pattern, that of the ventral attention network was observed to exhibit a linear decreasing pattern, and that of the somatomotor and dorsal attention networks was noted to exhibit a quadric-concave iFC pattern. Additionally, a sex-specific effect was observed for the empathy network as it exhibits linear and quadric sex-based differences in iFC with the frontoparietal and vision networks, respectively. The iFC of the ToM network with the ventral attention network exhibits a pronounced quadric-convex (inverted U-shape) trajectory. No linear or quadratic trajectories were noted in the iFC of the moral cognition network. These findings indicate that SC networks exhibit iFC with both low-level (somatomotor, vision) and high-level (attention and control) networks along specific developmental trajectories. The age-related trajectories determined in this study advance our understanding of the neural mechanisms of SC, providing valuable references for identification and intervention in cases of development of atypical SC.

G6PD maintains the VSMC synthetic phenotype and accelerates vascular neointimal hyperplasia by inhibiting the VDAC1-Bax-mediated mitochondrial apoptosis pathway.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in vascular smooth muscle cell (VSMC) phenotypic switching, which is an early pathogenic event in various vascular remodeling diseases (VRDs). However, the underlying mechanism is not fully understood. METHODS: An IP‒LC‒MS/MS assay was conducted to identify new binding partners of G6PD involved in the regulation of VSMC phenotypic switching under platelet-derived growth factor-BB (PDGF-BB) stimulation. Co-IP, GST pull-down, and immunofluorescence colocalization were employed to clarify the interaction between G6PD and voltage-dependent anion-selective channel protein 1 (VDAC1). The molecular mechanisms involved were elucidated by examining the interaction between VDAC1 and apoptosis-related biomarkers, as well as the oligomerization state of VDAC1. RESULTS: The G6PD level was significantly elevated and positively correlated with the synthetic characteristics of VSMCs induced by PDGF-BB. We identified VDAC1 as a novel G6PD-interacting molecule essential for apoptosis. Specifically, the G6PD-NTD region was found to predominantly contribute to this interaction. G6PD promotes VSMC survival and accelerates vascular neointimal hyperplasia by inhibiting VSMC apoptosis. Mechanistically, G6PD interacts with VDAC1 upon stimulation with PDGF-BB. By competing with Bax for VDAC1 binding, G6PD reduces VDAC1 oligomerization and counteracts VDAC1-Bax-mediated apoptosis, thereby accelerating neointimal hyperplasia. CONCLUSION: Our study showed that the G6PD-VDAC1-Bax axis is a vital switch in VSMC apoptosis and is essential for VSMC phenotypic switching and neointimal hyperplasia, providing mechanistic insight into early VRDs.

Risk factors for nonunion of osteoporotic vertebral compression fracture: a case‒control study.

BACKGROUND: Early assessment of the risk of nonunion in osteoporotic vertebral compression fracture (OVCF) is beneficial to early clinical decision making. However, a comprehensive understanding of the risk factors for OVCF nonunion is lacking. METHODS: We conducted a case-control study to investigate risk factors for OVCF nonunion. Patients who underwent surgery for nonunited OVCFs between January 2011 and December 2021 were eligible for inclusion as cases. Patients with successful OVCF healing confirmed by MRI over the same period were identified as controls. Patient demographics, comorbidities, and fasting blood test data were extracted for analysis. RESULTS: A total of 201 patients with nonunited OVCFs and 1044 controls were included to evaluate the risk factors for nonunited OVCFs. There were statistically significant differences in sex, age, number of patients with hypertension, number of patients on bed rest after OVCF and T-score of BMD between the two groups. Logistic regression showed that female patients had a higher risk of OVCF nonunion than male patients and that smoking, drinking, diabetes, and hypertension were risk factors for nonunion of OVCFs, while bed rest and spinal support were protective factors against nonunion of OVCFs. We also found that age, BMD, FBG, and ß-CTX were positively correlated with nonunited OVCFs, and that HGB and 1,25-(OH)2VitD3 level were negatively correlated with nonunited OVCFs. CONCLUSION: Smoking, drinking, diabetes and hypertension were risk factors for nonunion of OVCFs, while bed rest and spinal support were protective factors against nonunion of OVCFs. Age, BMD, FBG and ß-CTX were positively correlated with nonunited OVCFs, while HGB and 1,25-(OH)2VitD3 level were negatively correlated with nonunited OVCFs. Based on the results of our study, we suggest that bed rest or spinal support for at least 3 consecutive weeks is necessary to reduce the risk of OVCFs nonunion.

Deinococcus wulumuqiensis R12 synthesized silver nanoparticles with peroxidase-like activity for synergistic antibacterial application.

The use of a combination of several antibacterial agents for therapy holds great promise in reducing the dosage and side effects of these agents, improving their efficiency, and inducing potential synergistic therapeutic effects. Herein, this study provides an innovative antibacterial treatment strategy by synergistically combining R12-AgNPs with H2O2 therapy. R12-AgNPs were simply produced with the supernatant of an ionizing radiation-tolerant bacterium Deinococcus wulumuqiensis R12 by one-step under room temperature. In comparison with chemically synthesized AgNPs, the biosynthesized AgNPs presented fascinating antibacterial activity and peroxidase-like properties, which endowed it with the capability to catalyze the decomposition of H2O2 to generate hydroxyl radical. After the combination of R12-AgNPs and H2O2, an excellent synergistic bacteriostatic activity was observed for both Escherichia coli and Staphylococcus aureus, especially at low concentrations. In addition, in vitro cytotoxicity tests showed R12-AgNPs had good biocompatibility. Thus, this work presents a novel antibacterial agent that exhibits favorable synergistic antibacterial activity and low toxicity, without the use of antibiotics or a complicated synthesis process.

Real-time monitoring of abnormal mitochondrial viscosity in glioblastoma with a novel mitochondria-targeting fluorescent probe.

Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.

Spectroscopic Characterization of Highly Excited Neutral Chromium Tricarbonyl.

Spectroscopic characterization of highly excited neutral transition-metal complexes is important for understanding the multifaceted reaction mechanisms between metals and ligands. In this work, the reactions of neutral chromium atoms with carbon monoxide were probed by size-specific infrared spectroscopy. Interestingly, Cr(CO)3 was found to have an unprecedented 7A2″ septet excited state rather than the singlet ground state. A combination of experiment and theory shows that the gas-phase formation of this highly excited Cr(CO)3 is facile both thermodynamically and kinetically. Electronic structure and bonding analyses indicate that the valence electrons of Cr atoms in the septet Cr(CO)3 are in a relatively stable configuration, which facilitate the highly excited structure and the planar geometric shape (D3h symmetry). The observed septet Cr(CO)3 affords a paradigm for exploring the structure, properties, and formation mechanism of a large variety of excited neutral compounds.

Size-Specific Infrared Spectroscopy of Neutral Hydrated Clusters Based on a Vacuum Ultraviolet Free Electron Laser.

Spectroscopic study of neutral hydrated clusters provides microscopic insights into the local structures and dynamics of complex systems but is very challenging because of the difficulty in size discrimination. Recently, we developed infrared (IR) spectroscopy based on threshold ionization using a tunable vacuum ultraviolet free electron laser (VUV-FEL). This experimental method allows for size-specific IR spectroscopic measurement of numerous neutral clusters without confinement, such as messenger tags, ultraviolet chromophores, and host matrix. This Perspective aims to highlight the latest advances in VUV-FEL-based IR spectroscopic studies on the confinement-free neutral amine-water, sulfur dioxide-water, and metal-water clusters. Fruitful collaborations with high-level quantum chemical calculations are reviewed. Future research directions with relevance to the atmosphere, biology, and catalysis are proposed.

Exploring the combined cooling effect of street canyon geometry and the surrounding built environment.

Exploring the impact of complex urban morphology on the urban heat island (UHI) effect is essential for sustainable environmental management and enhancing human well-being. This study explored the combined cooling effect of street canyon geometry and the surrounding built environment using a CatBoost model and the Shapley method. The findings indicated that in streets with low building height and density, a high proportion of sky and vegetation and a flatter skyline are conductive to mitigate UHI effect. In streets with high building height and density, a lower proportion of sky and vegetation, and a well-proportioned skyline, can effectively mitigate UHI effect. Regardless of the building density and height around the street, street trees are the optimal choice for greening construction and improvement of large and medium-sized cities in China, given their high controllability and the current urban stock background. Therefore, reasonable control and allocation of street trees can effectively adjust the street canyon geometry, providing suitable cooling strategies for streets with different surrounding built environments. This study proposed a method to mitigate the UHI effect through street canyon geometry, which can be extended to other high-density urban thermal environment studies and guide policymakers on street construction and urban design.

Epsilon-poly-l-lysine microneedle patch loaded with amorphous doxycycline nanoparticles for synergistic treatment of skin infection.

The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 µg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.