Invasive assessment of coronary microvascular dysfunction and cardiovascular outcomes across the full spectrum of CHD: a meta-analysis.

INTRODUCTION AND OBJECTIVES: Coronary microvascular dysfunction (CMD) is highly prevalent and is recognized as an important clinical entity in patients with coronary heart disease (CHD). Nevertheless, the association of CMD with adverse cardiovascular events in the spectrum of CHD has not been systemically quantified. METHODS: We searched electronic databases for studies on patients with CHD in whom coronary microvascular function was measured invasively, and clinical events were recorded. The primary endpoint was major adverse cardiac events (MACE), and the secondary endpoint was all-cause death. Estimates of effect were calculated using a random-effects model from published risk ratios. RESULTS: We included 27 studies with 11 404 patients. Patients with CMD assessed by invasive methods had a higher risk of MACE (RR, 2.18; 95%CI, 1.80-2.64; P<.01) and all-cause death (RR, 1.88; 95%CI, 1.55-2.27; P<.01) than those without CMD. There was no significant difference in the impact of CMD on MACE (interaction P value=.95) among different invasive measurement modalities. The magnitude of risk of CMD assessed by invasive measurements for MACE was greater in acute coronary syndrome patients (RR, 2.84, 95%CI, 2.26-3.57; P<.01) than in chronic coronary syndrome patients (RR, 1.77, 95%CI, 1.44-2.18; P<.01) (interaction P value<.01). CONCLUSIONS: CMD based on invasive measurements was associated with a high incidence of MACE and all-cause death in patients with CHD. The magnitude of risk for cardiovascular events in CMD as assessed by invasive measurements was similar among different methods but varied among CHD populations.

Mapping glymphatic solute transportation through the perivascular space of hippocampal arterioles with 14 Tesla MRI.

The perivascular space (PVS) plays a crucial role in facilitating the clearance of waste products and the exchange of cerebrospinal fluid and interstitial fluid in the central nervous system. While optical imaging methods identify the glymphatic transport of fluorescent tracers through PVS of surface-diving arteries, their limited depth penetration impedes the study of glymphatic dynamics in deep brain regions. In this study, we introduced a novel high-resolution dynamic contrast-enhanced MRI mapping approach based on single-vessel multi-gradient-echo methods. This technique allowed the differentiation of penetrating arterioles and venules from adjacent parenchymal tissue voxels and enabled the detection of Gd-enhanced signals coupled to PVS of penetrating arterioles in the deep cortex and hippocampus. By directly infusing Gd into the lateral ventricle, we eliminated delays in cerebrospinal fluid flow and focused on PVS Gd transport through PVS of hippocampal arterioles. The study revealed significant PVS-specific Gd signal enhancements, shedding light on glymphatic function in deep brain regions. These findings advance our understanding of brain-wide glymphatic dynamics and hold potential implications for neurological conditions characterized by impaired waste clearance, warranting further exploration of their clinical relevance and therapeutic applications.

Comparison of Aroma and Taste Profiles of Kiwi Wine Fermented with/without Peel by Combining Intelligent Sensory, Gas Chromatography-Mass Spectrometry, and Proton Nuclear Magnetic Resonance.

Kiwi wine (KW) is tipically made by fermenting juice from peeled kiwifruit, resulting in the disposal of peel and pomace as by-products. However, the peel contains various beneficial compounds, like phenols and flavonoids. Since the peel is edible and rich in these compounds, incorporating it into the fermentation process of KW presents a potential solution to minimize by-product waste. This study compared the aroma and taste profiles of KW from peeled (PKW) and unpeeled (UKW) kiwifruits by combining intelligent sensory technology, GC-MS, and 1H-NMR. Focusing on aroma profiles, 75 volatile organic compounds (VOCs) were identified in KW fermented with peel, and 73 VOCs in KW without peel, with 62 VOCs common to both. Among these compounds, rose oxide, D-citronellol, and bornylene were more abundant in UKW, while hexyl acetate, isoamyl acetate, and 2,4,5-trichlorobenzene were significantly higher in PKW. For taste profiles, E-tongue analysis revealed differences in the taste profiles of KW from the two sources. A total of 74 molecules were characterized using 1H-NMR. UKW exhibited significantly higher levels of tartrate, galactarate, N-acetylserotonin, 4-hydroxy-3-methoxymandelate, fumarate, and N-acetylglycine, along with a significantly lower level of oxypurinol compared to PKW. This study seeks to develop the theoretical understanding of the fermentation of kiwifruit with peel in sight of the utilization of the whole fruit for KW production, to increase the economic value of kiwifruit production.

Recent progress in stimuli-responsive polymeric micelles for targeted delivery of functional nanoparticles.

Stimuli-responsive polymeric micelles have emerged as a revolutionary approach for enhancing the in vivo stability, biocompatibility, and targeted delivery of functional nanoparticles (FNPs) in biomedicine. This article comprehensively reviews the preparation methods of these polymer micelles, detailing the innovative strategies employed to introduce stimulus responsiveness and surface modifications essential for precise targeting. We delve into the breakthroughs in utilizing these micelles to selectively deliver various FNPs including magnetic nanoparticles, upconversion nanoparticles, gold nanoparticles, and quantum dots, highlighting their transformative impact in the biomedical realm. Concluding, we present an insight into the current research landscape, addressing the challenges at hand, and envisioning the future trajectory in this burgeoning domain. Join us as we navigate the exciting confluence of polymer science and nanotechnology in reshaping biomedical solutions.

Regenerated Ni-Doped LiCoO2 from Spent Lithium-Ion Batteries as a Stable Cathode at 4.5 V.

In the context of the increasing number of spent lithium-ion batteries, it is urgent to explore cathode regeneration and upcycling solutions to reduce environmental pollution, promote resource reuse, and meet the demand for high-energy cathode materials. Here, a closed-loop recycling method is introduced, which not only reclaims cobalt and lithium elements from spent lithium-ion batteries but also converts them into high-voltage LiCoO2 (LCO) materials. This approach involved pretreatment, chlorination roasting, water leaching, and ion doping to regenerate nickel-doped LCO (Ni-RLCO) materials. The doping of nickel effectively enhances the electrochemical stability of the LCO cathode at 4.5 V. The Ni-RLCO cathode exhibited a high discharge specific capacity of 185.28 mAh/g at a rate of 0.5 C with a capacity retention of 86.3% after 50 cycles and excellent rate capacity of 156.21 mAh/g at 2 C. This work offers a approach in significance for upcycling spent LCO into high-energy-density batteries with long-term cycling stability under high voltage.

n-Bu4NI/K2S2O8 Mediated Csp2-Csp2 Bond Cleavage - Transformylation from p-Anisaldehyde to Primary Amides.

n-Bu4NI/K2S2O8 mediated transformylation from p-anisaldehyde to primary amides is reported. The mechanistic studies suggest the reaction occurs via a single electron transfer pathway. Based on the DFT electronic structure calculations of various reaction pathways, the most plausible mechanism involves the formation of a phenyl radical cation and an arenium ion as the key intermediates. It represents the first example where p-anisaldehyde is employed as a formyl source via a non-metal mediated Csp2-Csp2 bond cleavage.

Isolation and characterization of feruloylated oligosaccharides from Phyllostachys acuta and in vitro antioxidant activity.

Feruloylated oligosaccharides (FOs) generated by decomposing plant hemicellulose, offer a wide range of potential applications in both the food and biomedical areas. As a graminaceous plant, bamboo is rich in hemicellulose. However, the structural composition and activity studies of FOs from it were rarely reported. In this study, FOs from Phyllostachys acuta (pFOs) obtained by enzymatic hydrolysis were isolated by AmberliteXAD-2 and C18 SPE columns. Then, pFOs were qualitatively and quantitatively analyzed by UPLC-ESI-MS/MS after labeled by 3-Amino-9-ethyl-carbazole (AEC), and the chemical antioxidant activity of pFOs and effects of pFOs on H2O2-induced oxidative damage were investigated. Finally, 14 of pFOs isomers were distinguished and identified, of which 10 did not contain hexoses and 4 did, and the three most abundant pFO structures were 12 (Iso 7, F1A1X2H2-AEC, 29.04 %), 11 (Iso 6, F1A1X1H2-AEC, 17.96 %), and 4 (Iso 3-1, F1A1X3-AEC, 15.57 %). The results of antioxidant studies showed that pFOs possessed certain reducing power, scavenging DPPH radicals, scavenging superoxide anion radicals, and scavenging hydroxyl radicals. Among them, the ability to clear DPPH radicals was particularly significant. pFOs significantly reduced the viability of RAW264.7 cells after H2O2 induction, whereas pFOs had a significant protective effect (p < 0.001). pFOs increased the viability of T-AOC and SOD enzymes in oxidatively damaged cells, as well as had a significant inhibition effect on ROS elevation (p < 0.001). This study lays the foundation for the structural analysis and antioxidant activity evaluation of bamboo-derived feruloyl oligosaccharides for their application in food and pharmaceutical fields.

Increasing Multienzyme Cascade Efficiency and Stability of MOF via Partitioning Immobilization.

Enhancing the stability of multienzyme cascade reactions in metal-organic frameworks (MOFs) is a challenging task in the fields of biotechnology and chemistry. However, addressing this challenge could yield far-reaching benefits across the application range in the biomedical, food, and environmental sectors. In this study, multienzyme partitioning immobilization that sequentially immobilizes cascade enzymes with hierarchical MOFs is proposed to reduce substrate diffusion resistance. Conversion results of ginsenosides indicate that this strategy improves the cascade efficiency up to 1.26 times. The substrate diffusion model is used to investigate the dual-interenzyme mass transfer behavior of substrates in the restricted domain space and evaluate the substrate channeling effect under partitioning immobilization. Molecular docking and kinetic simulations reveal that the MOFs effectively limit the conformational changes of cascade enzymes at high temperatures and in organic solvents while maintaining a large pocket of active centers. This phenomenon increased efficient substrate docking to the enzyme molecules, further optimizing cascade efficiency. The results of the immobilization of GOX and horseradish peroxidase as model enzymes indicate that the partitioned MOF immobilization strategy could be used for universal adaptation of cascade enzymes.

Upadacitinib for axial spondyloarthritis: a meta-analysis of efficacy and safety.

To explore the effectiveness and safety of upadacitinib for managing axial spondyloarthritis. Four databases (PubMed, EMBASE, Cochrane, and Web of Science) were applied to search randomized controlled trials (RCTs) for assessing upadacitinib treatment for axial spondyloarthritis published until January 2024. Five RCTs involving 1,246 participants were included. The upadacitinib group had significantly higher percentages of participants achieving Assessment of spondyloarthritis international society (ASAS) 20, ASAS40, ASAS partial remission, Bath ankylosing spondylitis disease activity index (BASDAI) 50, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity, ASDAS inactive disease, ASDAS clinically important improvement, and ASDAS major improvement, except for Work Productivity and Activity Impairment (WPAI) absenteeism. Obvious improvements were observed in the upadacitinib group for ASDAS (CRP), BASDAI, Modified BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Canadian Spondyloarthritis Research Consortium (SPARCC) MRI spine, SPARCC MRI sacroiliac joint, Ankylosing Spondylitis Quality of Life (ASQoLS), ASAS Health Index, Bath Ankylosing Spondylitis Metrology Index (BASMI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Total Back Pain, Nocturnal Back Pain, WPAI overall work impairment, WPAI presenteeism, and WPAI activity impairment. Adverse events (AEs) and serious adverse events (SAEs) incidence rates showed no significant difference differ between upadacitinib and placebo groups. Subgroup analysis revealed that disease subtype and age did not significantly affect efficacy, and upadacitinib demonstrated comparable efficacy to adalimumab for axial spondyloarthritis. Upadacitinib exhibited satisfactory efficacy in treating axial spondyloarthritis, reducing disease activity and significantly enhancing patients' physical function, emotional well-being, and social engagement. This meta-analysis offers robust evidence supporting upadacitinib as a new treatment for axial spondyloarthritis patients.

Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.

BACKGROUND: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. METHODS: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. RESULTS: OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. CONCLUSIONS: We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.

Bioactive atropisomers: Unraveling design strategies and synthetic routes for drug discovery.

Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field of medicinal chemistry. It has been shown that atropisomers of a wide range of compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal of chirality in atropisomers poses complexity and obstacles in the process of drug discovery and development. Nonetheless, recent progress in understanding atropisomerism and enhanced characterization methods have greatly assisted medicinal chemists in the effective development of atropisomeric drug molecules. This article provides a comprehensive review of their special design thoughts, synthetic routes, and biological activities, serving as a reference for the synthesis and biological evaluation of bioactive atropisomers in the future.

A Highly-Fluorinated Lithium Borate Main Salt Empowering Stable Lithium Metal Batteries.

Traditional lithium salts are difficult to meet practical application demand of lithium metal batteries (LMBs) under high voltages and temperatures. LiPF6, as the most commonly used lithium salt, still suffers from notorious moisture sensitivity and inferior thermal stability under those conditions. Here, we synthesize a lithium salt of lithium perfluoropinacolatoborate (LiFPB) comprising highly-fluorinated and borate functional groups to address the above issues. It is demonstrated that the LiFPB shows superior thermal and electrochemical stability without any HF generation under high temperatures and voltages. In addition, the LiFPB can form a protective outer-organic and inner-inorganic rich cathode electrolyte interphase on LiCoO2 (LCO) surface. Simultaneously, the FPB- anions tend to integrate into lithium ion solvation structure to form a favorable fast-ion conductive LiBxOy based solid electrolyte interphase on lithium (Li) anode. All these fantastic features of LiFPB endow LCO (1.9 mAh cm-2)/Li metal cells excellent cycling under both high voltages and temperatures (e.g., 80 % capacity retention after 260 cycles at 60 °C and 4.45 V), and even at an extremely elevated temperature of 100 °C. This work emphasizes the important role of salt anions in determining the electrochemical performance of LMBs at both high temperature and voltage conditions.

An integrated approach to prioritizing ecological restoration of abandoned mine lands based on cost-benefit analysis.

How to increase the usable land area by adhering to environmentally friendly ecological restoration of mines with limited funds is a challenge that many cities are currently facing. Cost-benefit analysis (CBA) can provide efficient and effective restoration decisions for abandoned mine land (AML) ecological restoration with limited financial resources. Thus, this study proposes an integrated approach for coupling ecological benefits and restoration costs, including hotspots/coldspots analysis based on five ecosystem services (ESs), landscape connectivity analysis based on graph theory model, hidden costs, and project implementation costs to prioritize AML restoration. The study was conducted on 54 abandoned mine lands (AMLs) in Chaoyang city, the ecological security barrier of China's northern sand prevention belt (NSPB). The comprehensive analysis prioritized the restoration of AMLs into four levels, of which 9 mines were in priority I, where restoration was recommended as a priority, and 22 mines were in priority II, where restoration could be carried out within the affordability of funds. In addition, our model indicates areas with high ecological benefits, in which the ecological source area (7423.66 km2) and the ecosystem service hotspots area (2028.44 km2) are mostly distributed in the southwestern part of Chaoyang city, the two mountain ranges of Songling mountain and Nuruerhu mountain. This study provides scientific spatial guidance to ensure that the AMLs realizes effective restoration and management.

Investigation of the peptides with calcium chelating capacity in hydrolysate derived from spent hen meat.

Calcium peptide chelates are developed as efficient supplements for preventing calcium deficiency. Spent hen meat (SHM) contains a high percentage of proteins but is generally wasted due to the disadvantages such as hard texture. We chose the underutilized SHM to produce peptides to bind calcium by proteolysis and aimed to investigate chelation between calcium and peptides in hydrolysate for a sustainable purpose. The optimized proteolysis conditions calculated from the result of response surface methodology for two-step hydrolysis were 0.30% (wenzyme/wmeat) for papain with a hydrolysis time of 3.5 h and 0.18% (wenzyme/wmeat) for flavourzyme with a hydrolysis time of 2.8 h. The enzymatic hydrolysate (EH) showed a binding capacity of 63.8 ± 1.8 mg calcium/g protein. Ethanol separation for EH improved the capacity up to a higher value of 68.6 ± 0.6 mg calcium/g protein with a high association constant of 420 M-1 (25°C) indicating high stability. The separated fraction with a higher amount of Glu, Asp, Lys, and Arg had higher calcium-binding capacity, which was related to the number of ─COOH and ─NH2 groups in peptide side chains according to the result from amino acid analysis and Fourier transform infrared spectroscopy. Two-step enzymatic hydrolysis and ethanol separation were an efficient combination to produce peptide mixtures derived from SHM with high calcium-binding capacity. The high percentage of hydrophilic amino acids in the separated fraction was concluded to increase calcium-binding capacity. This work provides foundations for increasing spent hen utilization and developing calcium peptide chelates based on underutilized meat.

Disruption of gonadotropin hormone biosynthesis by parabens: A potential development and reproduction-associated adverse outcome pathway.

Parabens are widely used as antibacterial preservatives in foods and personal care products. The knowledge about the modes of toxic action of parabens on development and reproduction remain very limited. The present study attempted to establish a development and reproduction-associated adverse outcome pathway (AOP) by evaluating the effects of methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) on the biosynthesis of gonadotropins, which are key hormones for development and reproduction. MP and BP significantly upregulated the mRNA and protein levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in pituitary gonadotropic cells in a concentration-dependent manner. Activation of gonadotropin-releasing hormone receptor (GnRHR) was required for gonadotropin biosynthesis induced by BP, but not MP. Molecular docking data further demonstrated the higher binding efficiency of BP to human GnRHR than that of MP, suggesting GnRHR as a potential molecular initiative event (MIE) for BP-induced gonadotropin production. L-type voltage-gated calcium channels (VGCCs) were found to be another candidate for MIE in gonadotropic cells response to both MP and BP exposure. The calcium-dependent activation of extracellular signal-regulated kinase 1 (ERK1) and ERK2 was subsequently required for MP- and BP-induced activation of GnRHR and L-type VGCCs pathways. In summary, MP and BP promoted gonadotropin biosynthesis through their interactions with cellular macromolecules GnRHR, L-type VGCCs, and subsequent key event ERK1/2. This is the first study to report the direct interference of parabens with gonadotropin biosynthesis and establish a potential AOP based on pathway-specific mechanism, which contributes to the effective screening of environmental chemicals with developmental and reproductive health risks.

One-Step Purification and Immobilization of Glycosyltransferase with Zn-Ni MOF for the Synthesis of Rare Ginsenoside Rh2.

Uridine diphosphate (UDP)-glucosyltransferases (UGTs) have received increasing attention in the field of ginsenoside Rh2 conversion. By harnessing the metal chelation between transition metal ions and imidazole groups present on His-tagged enzymes, a specific immobilization of the enzyme within metal-organic frameworks (MOFs) is achieved. This innovative approach not only enhances the stability and reusability of the enzyme but also enables one-step purification and immobilization. Consequently, the need for purifying crude enzyme solutions is effectively circumvented, resulting in significant cost savings during experimentation. The use of immobilized enzymes in catalytic reactions has shown great potential for achieving higher conversion rates of ginsenoside Rh2. In this study, highly stable mesoporous Zn-Ni MOF materials were synthesized at 150 °C by a solvothermal method. The UGT immobilized on the Zn-Ni MOF (referred to as UGT@Zn-Ni MOF) exhibited superior pH adaptability and thermal stability, retaining approximately 76% of its initial activity even after undergoing 7 cycles. Furthermore, the relative activity of the immobilized enzyme remained at an impressive 80.22% even after 45 days of storage. The strong specific adsorption property of Zn-Ni MOF on His-tagged UGT was confirmed through analysis using polyacrylamide gel electrophoresis. UGT@Zn-Ni MOF was used to catalyze the conversion reaction, and the concentration of rare ginsenoside Rh2 was generated at 3.15 µg/mL. The results showed that Zn-Ni MOF is a material that can efficiently purify and immobilize His-tagged enzyme in one step and has great potential for industrial applications in enzyme purification and ginsenoside synthesis.

Chiral nanomaterials in tissue engineering.

Addressing significant medical challenges arising from tissue damage and organ failure, the field of tissue engineering has evolved to provide revolutionary approaches for regenerating functional tissues and organs. This involves employing various techniques, including the development and application of novel nanomaterials. Among them, chiral nanomaterials comprising non-superimposable nanostructures with their mirror images have recently emerged as innovative biomaterial candidates to guide tissue regeneration due to their unique characteristics. Chiral nanomaterials including chiral fibre supramolecular hydrogels, polymer-based chiral materials, self-assembling peptides, chiral-patterned surfaces, and the recently developed intrinsically chiroptical nanoparticles have demonstrated remarkable ability to regulate biological processes through routes such as enantioselective catalysis and enhanced antibacterial activity. Despite several recent reviews on chiral nanomaterials, limited attention has been given to the specific potential of these materials in facilitating tissue regeneration processes. Thus, this timely review aims to fill this gap by exploring the fundamental characteristics of chiral nanomaterials, including their chiroptical activities and analytical techniques. Also, the recent advancements in incorporating these materials in tissue engineering applications are highlighted. The review concludes by critically discussing the outlook of utilizing chiral nanomaterials in guiding future strategies for tissue engineering design.

Characteristics and fractionations of sediment oxygen demand in a complex tidal river network area.

Tidal river networks are affected by the tide and influenced by complex factors related to sediment oxygen demand (SOD). In this study, we used chemical inhibition to measure the oxygen consumption of different types of SOD to explore the specific oxygen consumption mechanism of sediments. Then, we evaluated the diffusion fluxes of the sediment-water interface and factors affecting SOD using diffusive gradients in thin films. Total SOD in the tidal river network area of the Pearl River basin was ∼0.5928 g/m2/day, which was 8.47% higher than that in the non-tidal river network area but lower than that in black and odorous water reported previously. In the tidal river network area, biological SOD was 15.6% higher in summer than in winter, and the difference in total SOD was greatly influenced by human activity. We observed a significant effect of sediment on SOD in winter, whereas there were no significant correlations between sediment and SOD in summer. Different particle-size distributions lead to different organic matter contents, resulting in different biological SOD ratios between seasons. Our study found that seasonal tidal changes can affect ion exchange at the sediment water interface, leading to changes in SOD.These findings will be of great significance for the study of phenomena associated with low dissolved oxygen in tidal river networks and provide directions for future sediment pollution control.

The Role of Sensory Nerves in Dental Pulp Homeostasis: Histological Changes and Cellular Consequences after Sensory Denervation.

Homeostatic maintenance is essential for pulp function. Disrupting pulp homeostasis may lead to pulp degeneration, such as fibrosis and calcifications. Sensory nerves constitute a crucial component of the dental pulp. However, the precise involvement of sensory nerves in pulp homeostasis remains uncertain. In this study, we observed the short-term and long-term histological changes in the dental pulp after inferior alveolar nerve transection. Additionally, we cultured primary dental pulp cells (DPCs) from the innervated and denervated groups and compared indicators of cellular senescence and cellular function. The results revealed that pulp fibrosis occurred at 2 w after the operation. Furthermore, the pulp area, as well as the height and width of the pulp cavity, showed accelerated reductions after sensory denervation. Notably, the pulp area at 16 w after the operation was comparable to that of 56 w old rats. Sensory denervation induced excessive extracellular matrix (ECM) deposition and increased predisposition to mineralization. Furthermore, sensory denervation promoted the senescence of DPCs. Denervated DPCs exhibited decelerated cell proliferation, arrest in the G2/M phase of the cell cycle, imbalance in the synthesis and degradation of ECM, and enhanced mineralization. These findings indicate that sensory nerves play an essential role in pulp homeostasis maintenance and dental pulp cell fate decisions, which may provide novel insights into the prevention of pulp degeneration.

Single-cell transcriptomics of peripheral blood mononuclear cells indicates impaired immune and inflammatory responses in alcohol-associated hepatitis.

Alcohol-associated hepatitis (AH) is often diagnosed at advanced stages, and severe AH usually carries poor prognosis and high short-term mortality. In addition, it is challenging to understand the molecular mechanisms of immune dysregulation and inflammation in AH due to the cellular complexity and heterogeneity. Using single-cell RNA sequencing, previous studies found that AH causes dysfunctional innate immune response in monocytes, involving activation of pattern recognition receptors (PRRs) and cytokine signaling pathways. To better understand the coordinated systemic immune response in AH patients, we performed combined single-cell transcriptome, cell-surface protein, and lymphocyte antigen receptor analysis of peripheral blood mononuclear cell (PBMC) samples. Our results showed inflammatory cytokines and chemokines were highly expressed in AH, including IL-2, IL-32, CXC3R1 and CXCL16 in monocytes and NK cells, whereas HLA-DR genes were reduced in monocytes. In addition, we also found altered differentiation of T-helper cells (TH1 and TH17), which could further lead to neutrophil recruitment and macrophage activation. Lastly, our results also suggest impaired NK-cell activation and differentiation in AH with reduced gene expression of KLRC2 and increased gene expression of KLRG1. Our findings indicate different mechanisms may be involved in impaired immune and inflammatory responses for the cellular subtypes of the PBMCs in AH.