A Combined Measure of the Triglyceride Glucose Index and Trimethylamine N-Oxide in Risk Stratification of ST-Segment Elevation Myocardial Infarction Patients with High-Risk Plaque Features Defined by Optical Coherence Tomography: A Substudy of the OCTAMI Registry Study.

Background and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown. Methods: We studied 274 consecutive aged ≥18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019. Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723-0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p=0.033). A similar tendency was found in the cohort with hyperlipidemia (p=0.016) and diabetes mellitus (p=0.036). Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics. Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.

Intelligence level evaluation and influencing factors analysis of equipment manufacturing industry in the Yangtze River Delta.

The Yangtze River Delta (YRD) bears the vital task of driving the growth of China's equipment manufacturing industry (EMI) intelligence as an advanced region. Fostering the transformation and upgrading of the EMI in the YRD and constructing a modern production mode is vital to developing and reforming China's manufacturing industry. This paper uses industrial robot data to assess the level of intelligence (LoI) in the EMI from 2016 to 2019. The OLS (ordinary least squares) model is used for the measurements, and the MQ (the modified contribution index) is used to estimate the degree of contribution from a host of variables. It is identified that the LoI is on the rise. However, excluding railways, aerospace, shipbuilding, and other transportation equipment manufacturing, the LoI is significantly higher than in other subsectors. It is also identified that technological innovation ability, human capital density, and enterprise cost pressure govern the industry's LoI. Moreover, while there is a difference in the main influencing factors in LoI within different industries, R&D investment, technological innovation ability, and enterprise cost pressure have the most significant impact across most equipment manufacturing sub-industries.

In vitro and in vivo anti-inflammatory properties of an active fucoidan fraction from Sargassum fusiforme and a fraction-based hydrogel.

In a previous study, we separated an active fucoidan (JHCF4) from acid-processed Sargassum fusiforme, then analyzed and confirmed its structure. In the present study, we investigated the potential anti-inflammatory properties of JHCF4 and a JHCF4-based hydrogel in vitro and in vivo. JHCF4 reliably inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages, with an IC50 of 22.35 µg/ml. Furthermore, JHCF4 attenuated the secretion of prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, indicating that JHCF4 regulates inflammatory reactions. In addition, JHCF4 downregulated iNOS and COX-2 and inhibited the activation of the MAPK pathway. According to further in vivo analyses, JHCF4 significantly reduced the generation of reactive oxygen species (ROS), NO production, and cell death in an LPS-induced zebrafish model, suggesting that JHCF4 exhibits anti-inflammatory effects. Additionally, a JHCF4-based hydrogel was developed, and its properties were evaluated. The hydrogel significantly decreased inflammatory and nociceptive responses in carrageenan (carr)-induced mouse paws by reducing the increase in paw thickness and decreasing neutrophil infiltration in the basal and subcutaneous layers of the toe epidermis. These results indicate that JHCF4 exhibits potential anti-inflammatory activity in vitro and in vivo and that JHCF4-based hydrogels have application prospects in the cosmetic and pharmaceutical fields.

Crimean-Congo Hemorrhagic Fever Survivors Elicit Protective Non-Neutralizing Antibodies that Target 11 Overlapping Regions on Viral Glycoprotein GP38.

Crimean-Congo hemorrhagic fever virus can cause lethal disease in humans yet there are no approved medical countermeasures. Viral glycoprotein GP38, unique to Nairoviridae, is a target of protective antibodies, but extensive mapping of the human antibody response to GP38 has not been previously performed. Here, we isolated 188 GP38-specific antibodies from human survivors of infection. Competition experiments showed that these antibodies bind across five distinct antigenic sites, encompassing eleven overlapping regions. Additionally, we reveal structures of GP38 bound with nine of these antibodies targeting different antigenic sites. Although GP38-specific antibodies were non-neutralizing, several antibodies were found to have protection equal to or better than murine antibody 13G8 in two highly stringent rodent models of infection. Together, these data expand our understanding regarding this important viral protein and inform the development of broadly effective CCHFV antibody therapeutics.

Milk fat globule-epidermal growth factor 8 (MFGE8) prevents intestinal fibrosis.

OBJECTIVE: Intestinal fibrosis is considered an inevitable consequence of chronic IBD, leading to stricture formation and need for surgery. During the process of fibrogenesis, extracellular matrix (ECM) components critically regulate the function of mesenchymal cells. We characterised the composition and function of ECM in fibrostenosing Crohn's disease (CD) and control tissues. DESIGN: Decellularised full-thickness intestinal tissue platforms were tested using three different protocols, and ECM composition in different tissue phenotypes was explored by proteomics and validated by quantitative PCR (qPCR) and immunohistochemistry. Primary human intestinal myofibroblasts (HIMFs) treated with milk fat globule-epidermal growth factor 8 (MFGE8) were evaluated regarding the mechanism of their antifibrotic response, and the action of MFGE8 was tested in two experimental intestinal fibrosis models. RESULTS: We established and validated an optimal decellularisation protocol for intestinal IBD tissues. Matrisome analysis revealed elevated MFGE8 expression in CD strictured (CDs) tissue, which was confirmed at the mRNA and protein levels. Treatment with MFGE8 inhibited ECM production in normal control HIMF but not CDs HIMF. Next-generation sequencing uncovered functionally relevant integrin-mediated signalling pathways, and blockade of integrin αvß5 and focal adhesion kinase rendered HIMF non-responsive to MFGE8. MFGE8 prevented and reversed experimental intestinal fibrosis in vitro and in vivo. CONCLUSION: MFGE8 displays antifibrotic effects, and its administration may represent a future approach for prevention of IBD-induced intestinal strictures.

Optimizing Tissue Engineering for Clinical Relevance in Rotator Cuff Repair.

Rotator cuff tear (RCT) is the most common cause of disability in the upper-extremity.1 It results in 4.5 million physician visits in the United States every year and is the most common etiology of shoulder conditions evaluated by orthopedic surgeons.2,3 Over 460,000 RCT repair surgeries are performed in the United States annually.4 Rotator cuff (RC) retear and failure to heal remain significant post-operative complications.5 Literature suggests that the retear rates can range from 29.5% to as high as 94%.6,7 Weakened and irregular enthesis regeneration is a crucial factor in post-surgical failure.8 Although commercially available RC repair grafts have been introduced to augment RC enthesis repair, they have been associated with mixed clinical outcomes.9,10 These grafts lack appropriate biological cues such as stem cells and signaling molecules at the bone-tendon interface. Additionally, they do little to prevent fibrovascular scar tissue formation, which causes the RC to be susceptible to retear. Advances in tissue engineering have demonstrated that mesenchymal stem cells (MSCs) and growth factors (GFs) enhance RC enthesis regeneration in animal models. These models show that delivering MSCs and GFs to the site of RC tear enhances native enthesis repair and leads to greater mechanical strength. Additionally, these models demonstrate that MSCs and GFs may be delivered through a variety of methods including direct injection, saturation of repair materials, and loaded microspheres. Grafts that incorporate MSCs and GFs enhance anti-inflammation, osteogenesis, angiogenesis, and chondrogenesis in the RC repair process. It is crucial that the techniques which have shown success in animal models are incorporated into the clinincal setting. A gap currently exists between the promising biological factors which have been investigated in animal models and the RC repair grafts that can be used in the clinical setting. Future RC repair grafts must allow for stable implantation and fixation, be compatible with current arthroscopic techniques, and have the capability to deliver MSCs and/or GF. References (Full citations include in manuscript) 1.Kovacevic (2020) 2. Moran (2023) 3. Piper (2018) 4. IData (2018) 5. Yamaura (2023) 6. Park (2021) 7. Davey (2023) 8. Smietana (2017) 9. Walton (2007) 10. Soler (2007).

An Expeditious Neutralization Assay for Porcine Reproductive and Respiratory Syndrome Virus Based on a Recombinant Virus Expressing Green Fluorescent Protein.

Due to the extensive genetic and antigenic variation in Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), as well as its rapid mutability and evolution, PRRS prevention and control can be challenging. An expeditious and sensitive neutralization assay for PRRSV is presented to monitor neutralizing antibodies (NAbs) in serum during vaccine research. Here, a PRRSV expressing eGFP was successfully rescued with reverse genetics based on the infectious clone HuN4-F112-eGFP which we constructed. The fluorescent protein expressions of the reporter viruses remained stable for at least five passages. Based on this reporter virus, the neutralization assay can be easily used to evaluate the level of NAbs by counting cells with green fluorescence. Compared with the classical CPE assay, the newly developed assay increases sensitivity by one- to four-fold at the early antibody response stage, thus saving 2 days of assay waiting time. By using this assay to unveil the dynamics of neutralizing antibodies against PRRSV, priming immunity through either a single virulent challenge or only vaccination could produce limited NAbs, but re-infection with PRRSV would induce a faster and stronger NAb response. Overall, the novel HuN4-F112-eGFP-based neutralization assay holds the potential to provide a highly efficient platform for evaluating the next generation of PRRS vaccines.

Policy interplay among social health insurance system, pension system, delayed retirement initiative and implications for the self-rated health status of older workers.

Delayed retirement initiative proposed in China attaches greater importance to the sustainability of pension systems and the labour shortage, but less to the health status of older people. The existing social health insurance and pension system are not well established to match this initiative. This study investigates the policy mix of delayed retirement, employment-based social health insurance, social pension participation for health status of older people. Results of the data from the China Health and Retirement Longitudinal Study (CHARLS-2018) show that late retirement could benefit health status among older adults. Moreover, such effect of late retirement appears more salient for those uninsured by employment-based social health insurance and those still in the pension contribution phase upon reaching the statutory retirement age. Hence, in countries with inadequate health insurance and pension systems, such as China, delayed retirement may serve as an important alternative to social security for the health of older people.

Performance and mechanism of pilot-scale carbon fibers enhanced ecological floating beds for urban tail water treatment in optimized ecological floating beds water surface coverage.

A pilot-scale carbon fibers enhanced ecological floating beds (CF-EFBs) was constructed. Compared to EFBs without carbon fibers enhancement, CF-EFBs have the better removal of total inorganic nitrogen (TIN), total phosphorus (TP), and chemical oxygen demand (COD), the removal efficiencies were 3.19, 3.49, and 2.74 times higher than EFBs. Throughout the pilot test (under three different coverage rates), the concentrations of COD, TIN and TP of effluent were 18.11 ± 4.52 mgL-1, 1.95 ± 0.92 mgL-1 and 0.13 ± 0.08 mgL-1. Meanwhile, the average removal of TIN, TP and COD from tailwater was 0.96 gm-2d-1, 0.07 gm-2d-1 and 2.37 gm-2d-1 respectively. When the coverage was 30 %, the CF-EFBs had better nitrogen removal effectiveness (TIN purification ability of 1.49 gm-2d-1). The enrichment of denitrifying bacteria, such as Aridibacter, Nitrospira, Povalibacter, and Phaeodactylibacter increased denitrification efficiency. These results verified the feasibility of CF-EFBs in tailwater treatment at pilot-scale, which was of great significance for the practical application of CF-EFBs.

Lipid Content Distribution and its Clinical Implication in Patients with Acute Myocardial Infarction-Plaque Erosion: Results from the Prospective OCTAMI Study.

AIMS: Plaque erosion (PE) is one of the main plaque phenotypes of acute coronary syndrome (ACS). However, the underlying plaque component and distribution have not been systematically analysed. This study aims to investigate the distribution of lipid and calcium content in culprit lesions assessed by optical coherence tomography (OCT) in patients with PE and explore its relationship with prognosis in a cohort of ST segment elevation myocardial infarction (STEMI) patients. METHODS: A prospective cohort of 576 patients with STEMI was enrolled in our study. After exclusion, 152 PE patients with clear underlying plaque components were ultimately analysed. The culprit lesion was divided into the border zone, external erosion zone and erosion site in the longitudinal view. Each pullback of the culprit lesions was assessed by 3 independent investigators frame-by-frame, and the quantity and distribution of lipid and calcium components were recorded. RESULTS: Of the 152 PE patients, lipid and calcium contents were more likely to exist in the external erosion zone than in the other regions. In particular, a high level of lipid content proximal to the erosion site was significantly associated with plaque vulnerability and a higher incidence of MACEs. CONCLUSION: This study revealed that high level of lipid content in the proximal external erosion zone was related to high-risk plaque characteristics and poor prognosis, which provided a novel method for risk stratification and precise management in patients with plaque erosion.

Parkin-mediated mitophagy is a potential treatment for oxaliplatin-induced peripheral neuropathy.

Oxaliplatin-induced peripheral nerve pain (OIPNP) is a common chemotherapy-related complication, but the mechanism is complex. Mitochondria are vital for cellular homeostasis and regulating oxidative stress. Parkin-mediated mitophagy is a cellular process that removes damaged mitochondria, exhibiting a protective effect in various diseases; however, its role in OIPNP remains unclear. In this study, we found that Parkin-mediated mitophagy was decreased, and reactive oxygen species (ROS) was upregulated in OIPNP rat dorsal root ganglion (DRG) in vivo and in PC12 cells stimulated with oxaliplatin (OXA) in vitro. Overexpression of Parkin indicated that OXA might cause mitochondrial and cell damage by inhibiting mitophagy. We also showed that salidroside (SAL) upregulated Parkin-mediated mitophagy to eliminate damaged mitochondria and promote PC12 cell survival. Knockdown of Parkin indicated that mitophagy is crucial for apoptosis and mitochondrial homeostasis in PC12 cells. In vivo study also demonstrated that SAL enhances Parkin-mediated mitophagy in the DRG and alleviates peripheral nerve injury and pain. These results suggest that Parkin-mediated mitophagy is involved in the pathogenesis of OIPNP and may be a potential therapeutic target for OIPNP.NEW & NOTEWORTHY This article discusses the effects and mechanisms of Parkin-mediated mitophagy in oxaliplatin-induced peripheral nerve pain (OIPNP) from both in vivo and in vitro. We believe that our study makes a significant contribution to the literature because OIPNP has always been the focus of clinical medicine, and mitochondrial quality regulation mechanisms especially Parkin-mediated mitophagy, have been deeply studied in recent years. We use a variety of molecular biological techniques and animal experiments to support our argument.

Ventral Tegmental Area Glutamatergic Neurons Facilitated Emergence From Isoflurane Anesthesia Involves Excitation of Lateral Septum γ-Aminobutyric Acid-ergic Neurons in Mice.

BACKGROUND: Ventral tegmental area (VTA) glutamatergic neurons promote wakefulness in the sleep-wake cycle; however, their roles and neural circuit mechanisms during isoflurane (ISO) anesthesia remain unclear. METHODS: Fiber photometry and in vivo electrophysiology were used to observe the changes in neuronal or terminal activity during ISO anesthesia and arousal processes. Optogenetic and anesthesia behaviors were used to investigate the effects of VTA glutamatergic neurons and their projections to the lateral septum (LS) during ISO anesthesia and arousal. Anterograde and retrograde tracings were performed to identify the connections between VTA glutamatergic neurons and the LS. RESULTS: Population activity and firing rates of VTA glutamatergic neurons decreased during ISO anesthesia (ISO: 95% confidence interval [CI], 0.83-2.06 Spikes.s-1 vs wake: 95% CI, 3.53-7.83 Spikes.s-1; P =.0001; n = 34 from 4 mice). Optogenetic activation of VTA glutamatergic neurons reduced the burst-suppression ratio in electroencephalography (laser: 95% CI, 13.09%-28.76% vs pre: 95% CI, 52.85%-71.59%; P =.0009; n = 6) and facilitated emergence (ChR2: 95% CI, 343.3-388.0 seconds vs mCherry: 95% CI, 447.6-509.8 seconds; P < .0001; n = 11/12) from ISO anesthesia. VTA glutamatergic neurons monosynaptically innervated LS γ-aminobutyric acid (GABA)-ergic neurons. The activity of VTA glutamatergic terminals in the LS decreased during ISO anesthesia, and optogenetic activation of the VTA glutamatergic terminals in the LS facilitated emergence from ISO anesthesia. Furthermore, optogenetic activation of VTA glutamatergic terminals increased the firing rates of LS γ-aminobutyric acid-ergic (GABAergic) neurons (laser: 95% CI, 0.85-4.03 Spikes.s-1 vs pre: 95% CI, 0.24-0.78 Spikes.s-1; P =.008; n = 23 from 4 mice) during ISO anesthesia. CONCLUSIONS: VTA glutamatergic neurons facilitated emergence from ISO anesthesia involving excitation of LS GABAergic neurons.

Re-evaluating the Contribution of a Fe-Based Current Collector to Bioelectrochemical Methanogenesis: Role and Mechanisms.

The metal-based current collector has been adopted as an essential component of cathodes for electron delivery in microbial electrosynthesis (MES) cells, while the effect of its corrosion on biofilm development and electromethanogenesis activity was overlooked. In this study, the corrosion of the Fe-based current collector was identified to in situ decorate cathode naturally which substantially boosted the performance of CO2 electromethanogenesis in terms of taking over two-thirds less time starting up MES and increasing the CH4 production rate by 3.5 times. Despite the low concentration of Fe (0.13 at%), the electrochemical analysis indicated that it was possible for these Fe deposits to act as electron shuttles and catalysts for H2 production to benefit methanogenesis. The Fe aggregates weakened the dependence of methanogens on electroactive bacteria (EABs) to conduct methanogenesis via interspecies electron transfer as the proportion of EABs on Bio FeCF (with Fe current collector, where CF is carbon felt) was only 25.5% of that on Bio CF (without Fe current collector). On the contrary, the abundance of genes encoding the proteins to uptake extracellular electrons of methanogens on Bio FeCF was 2.3 times higher than that on Bio CF. The enhanced energy transfer maintained high amounts of methanogens and live microorganisms. This study comprehensively explored the multiple roles of Fe-based current collectors in enhancing CO2 electromethanogenesis.

Atherosclerotic Autoantigen ALDH4A1 as a Novel Immunological Indicator for Plaque Erosion in Patients with ST Segment Elevated Myocardial Infarction.

OBJECTIVE: Aldehyde dehydrogenase 4A1 (ALDH4A1) was recently reported to be a novel autoantigen of atherosclerosis. However, its role in different phenotypes of acute coronary syndrome remains unclear. Herein, we planned to explore the circulating and regional expression of ALDH4A1 in patients with plaque rupture (PR) and plaque erosion (PE) determined by optical coherence tomography (OCT). METHODS AND RESULTS: After applying the inclusion and exclusion criteria, a prospective series of 312 patients with ST segment elevated myocardial infarction (STEMI), including 161 patients with PR and 151 patients with PE determined by OCT, were enrolled for plasma ALDH4A1 testing. In addition, ALDH4A1 was quantified using immunofluorescence in aspirated coronary thrombus samples obtained from 31 patients with PR and 25 patients with PE. In addition, we established an atherosclerosis mouse model and analyzed the distribution of ALDH4A1 expression in different mouse organs. Furthermore, we compared the level of ALDH4A1 in the spleen and carotid artery between Apoe-/- and C57 mice. The results showed that the plasma level of ALDH4A1 was significantly higher in STEMI patients with PE than in those with PR (4.6 ng/mL [2.2-8.7] vs. 3.5 ng/mL [1.6-5.6] p = 0.005). The expression of ALDH4A1 in aspirated coronary thrombi was also significantly higher in patients with PE than in those with PR (mean gray value: 32.0 [23.6-40.6] vs. 16.8 [14.0-24.5], p < 0.001). In animal models, the expression of ALDH4A1 is much higher in the spleen than in other organs, and the level of ALDH4A1 is significantly elevated in the spleen and carotid artery of Apoe-/- mice compared with C57 mice. CONCLUSION: The high levels of ALDH4A1 in the plasma and aspirated coronary thrombi independently correlated with PE in patients with STEMI. These results suggested that ALDH4A1 is involved in the mechanism of PE and serves as a promising biomarker and treatment target for patients with PE.

The impacts of economic policy uncertainty on firm cash holding in China.

Cash holding is an important strategic decision of enterprises. As a macro-level factor, economic policy uncertainty causes risks, affecting enterprises' cash holdings. Taking the quarterly financial data of China's A-share non-financial listed firms for 2010-2020 as a sample, this study adopts the OLS and fixed effect models to investigate how corporate cash holdings are affected by economic policy uncertainty. The findings indicate that economic policy uncertainty is directly proportional to the level of cash that listed corporations hold. The higher the uncertainty, the more cash the company holds. Among them, state-owned enterprises and the manufacturing industry are more significantly affected by economic policy uncertainty. Finally, considering the regional marketization level and the differences in financing constraints enterprises face, it is concluded through grouping empirical studies that enterprises located in regions with lower marketization levels are more susceptible to policy uncertainty, while financially constrained enterprises are more susceptible to economic policy uncertainty. The study of economic policy uncertainty is helpful to guide enterprises to realize the importance of coping strategies in advance under the background of intensifying economic policy uncertainty. Therefore, this paper proposes to introduce policies on the premise of fully considering the smoothness of the economy and the differences in the conditions of firms of different natures, as well as some proposals to alleviate financing constraints, reduce the adverse effects of uncertainty on firms, and bolster the marketization process.

Correlation of NPDC1 Expression and Perineural Invasion Status with Clinicopathological Features in Patients with Colon Cancer.

Background: Colon cancer is a prevalent gastrointestinal malignancy that often exhibits distant metastasis, hindering the effectiveness of surgical interventions. In addition to well-known hematogenous and lymphatic metastasis, perineural invasion (PNI) has emerged as a significant mode of distant metastasis in colon tumors. PNI is closely associated with oncologic pain in advanced cancer patients, but the underlying mechanisms and associated biomarkers, which might be the novel therapeutic targets, remain poorly understood. Methods: In this study, we employed large databases and bioinformatics methods to identify genes strongly linked to PNI in colon cancer and investigated their involvement in tumor nerve invasion, progression mechanisms, and chemotherapy resistance. Immunohistochemical techniques were utilized to validate the expression of target genes in 384 colon cancer tissues, and their expression was correlated with clinicopathological characteristics and patient survival data in our hospital. Furthermore, we conducted a comprehensive literature review to explore the potential functions of the target genes and their associated genes. Results: Our screening revealed a significant correlation between neural proliferation differentiation and control-1 (NPDC1) expression and patient prognosis, suggesting a potential association with neural infiltration in colon cancer. Additionally, NPDC1 may promote tumorigenesis, progression, and chemoresistance through various related pathways. Conclusion: Our study provides novel insights into the utility of NPDC1 as a predictive marker for PNI status, disease-free survival, and overall survival in patients with colon cancer, highlighting the prevalence of NPDC1 overexpression in patients with PNI in colon cancer.

The characteristics and medical applications of antler stem cells.

Antlers are the only fully regenerable mammalian appendages whose annual renewal is initiated by antler stem cells (ASCs), defined as a specialized type of mesenchymal stem cells (MSCs) with embryonic stem cell properties. ASCs possess the same biological features as MSCs, including the capacity for self-renewal and multidirectional differentiation, immunomodulatory functions, and the maintenance of stem cell characteristics after multiple passages. Several preclinical studies have shown that ASCs exhibit promising potential in wound healing, bone repair, osteoarthritis, anti-tissue fibrosis, anti-aging, and hair regeneration. Medical applications based on ASCs and ASC-derived molecules provide a new source of stem cells and therapeutic modalities for regenerative medicine. This review begins with a brief description of antler regeneration and the role of ASCs. Then, the properties and advantages of ASCs are described. Finally, medical research advances regarding ASCs are summarized, and the prospects and challenges of ASCs are highlighted.

Evaluating the Combined Effects of Erythromycin and Levofloxacin on the Growth of Navicula sp. and Understanding the Underlying Mechanisms.

Navicula sp., a type of benthic diatom, plays a crucial role in the carbon cycle as a widely distributed algae in water bodies, making it an essential primary producer in the context of global carbon neutrality. However, using erythromycin (ERY) and levofloxacin (LEV) in medicine, livestock, and aquaculture has introduced a new class of pollutants known as antibiotic pollutants, which pose potential threats to human and animal health. This study aimed to investigate the toxic effects of ERY and LEV, individually or in combination, on the growth, antioxidant system, chlorophyll synthesis, and various cell osmotic pressure indexes (such as soluble protein, proline, and betaine) of Navicula sp. The results indicated that ERY (1 mg/L), LEV (320 mg/L), and their combined effects could inhibit the growth of Navicula sp. Interestingly, the combination of these two drugs exhibited a time-dependent effect on the chlorophyll synthesis of Navicula sp., with ERY inhibiting the process while LEV promoted it. Furthermore, after 96 h of exposure to the drugs, the activities of GSH-Px, POD, CAT, and the contents of MDA, proline, and betaine increased. Conversely, the actions of GST and the contents of GSH and soluble protein decreased in the ERY group. In the LEV group, the activities of POD and CAT and the contents of GSH, MDA, proline, and betaine increased, while the contents of soluble protein decreased. Conversely, the mixed group exhibited increased POD activity and contents of GSH, MDA, proline, betaine, and soluble protein. These findings suggest that antibiotics found in pharmaceutical and personal care products (PPCPs) can harm primary marine benthic eukaryotes. The findings from the research on the possible hazards linked to antibiotic medications in aquatic ecosystems offer valuable knowledge for ensuring the safe application of these drugs in environmental contexts.

Stricturing Crohn's Disease Single-Cell RNA Sequencing Reveals Fibroblast Heterogeneity and Intercellular Interactions.

BACKGROUND & AIMS: Fibroblasts play a key role in stricture formation in Crohn's disease (CD) but understanding its pathogenesis requires a systems-level investigation to uncover new treatment targets. We studied full-thickness CD tissues to characterize fibroblast heterogeneity and function by generating the first single-cell RNA sequencing (scRNAseq) atlas of strictured bowel and providing proof of principle for therapeutic target validation. METHODS: We performed scRNAseq of 13 fresh full-thickness CD resections containing noninvolved, inflamed nonstrictured, and strictured segments as well as 7 normal non-CD bowel segments. Each segment was separated into mucosa/submucosa or muscularis propria and analyzed separately for a total of 99 tissue samples and 409,001 cells. We validated cadherin-11 (CDH11) as a potential therapeutic target by using whole tissues, isolated intestinal cells, NanoString nCounter, next-generation sequencing, proteomics, and animal models. RESULTS: Our integrated dataset revealed fibroblast heterogeneity in strictured CD with the majority of stricture-selective changes detected in the mucosa/submucosa, but not the muscle layer. Cell-cell interaction modeling revealed CXCL14+ as well as MMP/WNT5A+ fibroblasts displaying a central signaling role in CD strictures. CDH11, a fibroblast cell-cell adhesion molecule, was broadly expressed and up-regulated, and its profibrotic function was validated using NanoString nCounter, RNA sequencing, tissue target expression, in vitro gain- and loss-of-function experiments, proteomics, and knock-out and antibody-mediated CDH11 blockade in experimental colitis. CONCLUSIONS: A full-thickness bowel scRNAseq atlas revealed previously unrecognized fibroblast heterogeneity and interactions in CD strictures and CDH11 was validated as a potential therapeutic target. These results provide a new resource for a better understanding of CD stricture formation and open potential therapeutic developments. This work has been posted as a preprint on Biorxiv under doi: 10.1101/2023.04.03.534781.