Immune function of a C-type lectin with long tandem repeats and abundant threonine in the ridgetail white prawn Exopalaemon carinicauda.

C-type lectins (CTLs) are an important class of pattern recognition receptors (PRRs) that exhibit structural and functional diversity in invertebrates. Repetitive DNA sequences are ubiquitous in eukaryotic genomes, representing distinct modes of genome evolution and promoting new gene generation. Our study revealed a new CTL that is composed of two long tandem repeats, abundant threonine, and one carbohydrate recognition domain (CRD) in Exopalaemon carinicauda and has been designated EcTR-CTL. The full-length cDNA of EcTR-CTL was 1242 bp long and had an open reading frame (ORF) of 999 bp that encoded a protein of 332 amino acids. The genome structure of EcTR-CTL contains 4 exons and 3 introns. The length of each repeat unit in EcTR-CTL was 198 bp, which is different from the short tandem repeats reported previously in prawns and crayfish. EcTR-CTL was abundantly expressed in the intestine and hemocytes. After Vibrio parahaemolyticus and white spot syndrome virus (WSSV) challenge, the expression level of EcTR-CTL in the intestine was upregulated. Knockdown of EcTR-CTL downregulated the expression of anti-lipopolysaccharide factor, crustin, and lysozyme during Vibrio infection. The recombinant CRD of EcTR-CTL (rCRD) could bind to bacteria, lipopolysaccharides, and peptidoglycans. Additionally, rCRD can directly bind to WSSV. These findings indicate that 1) CTLs with tandem repeats may be ubiquitous in crustaceans, 2) EcTR-CTL may act as a PRR to participate in the innate immune defense against bacteria via nonself-recognition and antimicrobial peptide regulation, and 3) EcTR-CTL may play a positive or negative role in the process of WSSV infection by capturing virions.

Polydopamine-mediated immobilization of BMP-2 onto electrospun nanofibers enhances bone regeneration.

Dealing with bone defects is a significant challenge to global health. Electrospinning in bone tissue engineering has emerged as a solution to this problem. In this study, we designed a PVDF-b-PTFE block copolymer by incorporating TFE, which induced a phase shift in PVDF fromαtoß, thereby enhancing the piezoelectric effect. Utilizing the electrospinning process, we not only converted the material into a film with a significant surface area and high porosity but also intensified the piezoelectric effect. Then we used polydopamine to immobilize BMP-2 onto PVDF-b-PTFE electrospun nanofibrous membranes, achieving a controlled release of BMP-2. The scaffold's characters were examined using SEM and XRD. To assess its osteogenic effectsin vitro, we monitored the proliferation of MC3T3-E1 cells on the fibers, conducted ARS staining, and measured the expression of osteogenic genes.In vivo, bone regeneration effects were analyzed through micro-CT scanning and HE staining. ELISA assays confirmed that the sustained release of BMP-2 can be maintained for at least 28 d. SEM images and CCK-8 results demonstrated enhanced cell viability and improved adhesion in the experimental group. Furthermore, the experimental group exhibited more calcium nodules and higher expression levels of osteogenic genes, including COL-I, OCN, and RUNX2. HE staining and micro-CT scans revealed enhanced bone tissue regeneration in the defective area of the PDB group. Through extensive experimentation, we evaluated the scaffold's effectiveness in augmenting osteoblast proliferation and differentiation. This study emphasized the potential of piezoelectric PVDF-b-PTFE nanofibrous membranes with controlled BMP-2 release as a promising approach for bone tissue engineering, providing a viable solution for addressing bone defects.

Zinc-Carnosine Metallodrug Network as Dual Metabolism Inhibitor Overcoming Metabolic Reprogramming for Efficient Cancer Therapy.

The targeting of tumor metabolism as a novel strategy for cancer therapy has attracted tremendous attention. Herein, we develop a dual metabolism inhibitor, Zn-carnosine metallodrug network nanoparticles (Zn-Car MNs), which exhibits good Cu-depletion and Cu-responsive drug release, causing potent inhibition of both OXPHOS and glycolysis. Notably, Zn-Car MNs can decrease the activity of cytochrome c oxidase and the content of NAD+, so as to reduce ATP production in cancer cells. Thereby, energy deprivation, together with the depolarized mitochondrial membrane potential and increased oxidative stress, results in apoptosis of cancer cells. In result, Zn-Car MNs exerted more efficient metabolism-targeted therapy than the classic copper chelator, tetrathiomolybdate (TM), in both breast cancer (sensitive to copper depletion) and colon cancer (less sensitive to copper depletion) models. The efficacy and therapy of Zn-Car MNs suggest the possibility to overcome the drug resistance caused by metabolic reprogramming in tumors and has potential clinical relevance.

Ultrasmall PtMn nanoparticles as sensitive manganese release modulator for specificity cancer theranostics.

Manganese-based nanomaterials (Mn-nanomaterials) hold immense potential in cancer diagnosis and therapies. However, most Mn-nanomaterials are limited by the low sensitivity and low efficiency toward mild weak acidity (pH 6.4-6.8) of the tumor microenvironment, resulting in unsatisfactory therapeutic effect and poor magnetic resonance imaging (MRI) performance. This study introduces pH-ultrasensitive PtMn nanoparticles as a novel platform for enhanced ferroptosis-based cancer theranostics. The PtMn nanoparticles were synthesized with different diameters from 5.3 to 2.7 nm with size-dominant catalytic activity and magnetic relaxation, and modified with an acidity-responsive polymer to create pH-sensitive agents. Importantly, R-PtMn-1 (3 nm core) presents "turn-on" oxidase-like activity, affording a significant enhancement ratio (pH 6.0/pH 7.4) in catalytic activity (6.7 folds), compared with R-PtMn-2 (4.2 nm core, 3.7 folds) or R-PtMn-3 (5.3 nm core, 2.1 folds), respectively. Moreover, R-PtMn-1 exhibits dual-mode contrast in high-field MRI. R-PtMn-1 possesses a good enhancement ratio (pH 6.4/pH 7.4) that is 3 or 3.2 folds for T1- or T2-MRI, respectively, which is higher than that of R-PtMn-2 (1.4 or 1.5 folds) or R-PtMn-3 (1.1 or 1.2 folds). Moreover, their pH-ultrasensitivity enabled activation specifically within the tumor microenvironment, avoiding off-target toxicity in normal tissues during delivery. In vitro studies demonstrated elevated intracellular reactive oxygen species production, lipid peroxidation, mitochondrial membrane potential changes, malondialdehyde content, and glutathione depletion, leading to enhanced ferroptosis in cancer cells. Meanwhile, normal cells remained unaffected by the nanoparticles. Overall, the pH-ultrasensitive PtMn nanoparticles offer a promising strategy for accurate cancer diagnosis and ferroptosis-based therapy.

Ratiometric Semiconducting Polymer Nanoparticle for Reliable Photoacoustic Imaging of Pneumonia-Induced Vulnerable Atherosclerotic Plaque in Vivo.

Acute pneumonia can greatly increase the vulnerable risk of atherosclerotic plaque and contribute to the mortality of cardiovascular disease. To accurately assess the rupture risk caused by acute pneumonia, we developed a novel kind of ratiometric semiconducting polymer nanoparticle (RSPN) for photoacoustic imaging of vulnerable plaque in apolipoprotein E-deficient mice complicated with pneumonia. Specifically, RSPN can react with O2•- and exhibit the enhanced photoacoustic signals at about 690 nm, while 800 nm is regarded as an internal photoacoustic reference. As a result, RSPN can provide reliable determination of O2•- within aortic atherosclerosis by analyzing the ratios of photoacoustic signals, which can successfully reflect the oxidative stress level in vulnerable plaque. Therefore, RSPN enable to specifically distinguish plaque-bearing mice and plaque-bearing mice complicated with pneumonia from healthy mice, which provides a promising tool to predict the vulnerability of plaque for reducing the mortality of atherosclerotic-induced cardiovascular disease.

Acacetin inhibits RANKL-induced osteoclastogenesis and LPS-induced bone loss by modulating NFATc1 transcription.

Osteolytic disorders are characterized by impaired bone volume and trabecular structure that leads to severe fragility fractures. Studies have shown that excessive osteoclast activity causes impaired bone microstructure, a sign of osteolytic diseases such as osteoporosis. Approaches of inhibiting osteoclastogenesis and bone resorption specifically could prevent osteoporosis and other osteolytic disorders. Acacetin is a potent molecule extracted from plants with anti-cancer and anti-inflammatory bioactivities. Here, we demonstrated, for the first time, that acacetin repressed osteoclastogenesis, formation of F-actin rings, bone resorption activity, and osteoclast-related gene expression in vitro through modulating ERK, P38, and NF-κB signaling pathways and preventing expression of NFATc1. Micro-CT and H & E staining results indicated that acacetin alleviated LPS-induced osteolysis in vivo. Overall, our findings suggested that acacetin could help to prevent osteoporosis and other osteoclast-related osteolytic disorders.

One-Step Synthesis of 4-Octyl Itaconate through the Structure Control of Lipase.

4-Octyl itaconate is a novel antiviral and immunoregulatory small molecule showing great potential in the treatment of various autoimmune diseases and viral infections. It is difficult to selectively esterify the C4 carboxyl group of itaconate acid via one-step direct esterification using chemical catalysts, while the two-step route with itaconic anhydride as an intermediate is environmentally unfriendly and costly. This research investigated the one-step and green synthesis of 4-octyl itaconate through the structure control of lipase, obtaining 4-octyl itaconate with over 98% yield and over 99% selectivity. Multiscale molecular dynamics simulations were applied to investigate the reaction mechanism. The cavity pocket of lipases resulted in a 4-octyl itaconate selectivity by affecting distribution of substrates toward the catalytic site. Toluene could enhance monoesterification in the C4 carboxyl group and contribute to a nearly 100% conversion from itaconate acid into 4-octyl itaconate by adjusting the catalytic microenvironment around the lipase, producing a shrinkage effect on the channel.

The conversion of linoleic acid into hydroxytetrahydrofuran-structured bio-lubricant.

In this work, a new structured linoleic-based hydroxytetrahydrofuran (HTHF) ester lubricant with excellent properties was developed. A synthesis route through regioselective enzymatic hydration was established, combining highly selective epoxidation with an intramolecular epoxide ring-opening reaction. The results proved that the enzymatic-chemical method is an alternative strategy for the conversion of linoleic acid into bio-lubricants. LiBr was revealed as an efficient catalyst (yields of 95.8%, and selectivity of 98.5%, respectively) for the intramolecular epoxide ring-opening reaction. The tribological properties test indicated that the HTHF bio-lubricants exhibited better performance than the commercial mineral oils. Physicochemical investigation further indicated that the product has a good thermal stability, with the Tonset around 300 °C. The kinematic viscosity and viscosity index indicated that the product is suitable to be applied for lubrication. In contrast with previous findings, this HTHF-structured bio-lubricant oil exhibited a superior low pour point (-64 °C) and provided great potential to be utilized in extreme cold working environments.

The highly-stable immobilization of enzymes on a waste mycelium carrier.

Mycelium is an abundant waste from the fermentation industry, and the environmental problems associated with its required disposal seriously limited the development of fermentation industry. In China, millions of tons of various kinds of mycelium residues were produced each year. Research into providing added-value to mycelium, while avoiding its disposal, is hence of paramount importance. Mycelium can be used as carrier for enzymes, while the enzyme immobilization moreover improves their stability and lifetime performance. Carrier recycling, the natural degradation and disposal of artificial polymer carriers are critical issues in immobilization. This research investigated its use to manufacture a highly-stable immobilized enzyme. An acid pretreatment was employed to enhance the adsorption ability of mycelium, and its adsorption ability was compared with other carriers. Under the optimal conditions, a core-shell immobilized enzyme with porous structure was obtained. The stability and the recycle results of the evaluation indicated the excellent performance of the immobilized enzyme. The mycelium recycling was also investigated to verify the practicability. All the results indicated that the use of a mycelium-based carrier was a promising strategy for the reutilization of the fermentation waste, and this technique provides an alternative way to reduce the total amount of the waste mycelium. Meanwhile, the stability and reusability performance of the mycelium-based immobilization could also decrease the influence of the disposal of the solid waste from denatured enzymes to the environment.

Enhanced electrochemiluminescence of gold nanoclusters via silver doping and their application for ultrasensitive detection of dopamine.

Gold nanoclusters (Au NCs) are a type of emerging ECL emitter with molecule-like properties and low toxicity that hold great potential for sensing application. However, the application of Au NCs in ECL sensing is still limited due to their low ECL efficiency. In this work, we provided an effective way to enhance the ECL efficiency of Au NCs. By doping Ag on GSH-protected Au NCs to form bimetallic clusters (GSH-Ag/Au NCs), the ECL efficiency of Au NCs was greatly improved. Based on the enhanced ECL signal of Au NCs, an ultrasensitive ECL sensor was constructed for the detection of dopamine (DA). DA exhibited a prominent ECL quenching effect towards the formed bimetallic GSH-Ag/Au NCs which can be used for DA detection. The proposed ECL sensor exhibited excellent sensitivity, selectivity and stability and had a wide linear range from 10 nM to 1 mM with a low detection limit of 2.3 nM (S/N = 3). More importantly, this work provided a potential method to improve the ECL properties of Au NCs and widen their analytical application.

STAT1 facilitates oestrogen receptor α transcription and stimulates breast cancer cell proliferation.

Oestrogen receptor α (ERα) is overexpressed in two-thirds of all breast cancer cases and is involved in breast cancer development and progression. Although ERα -positive breast cancer can be effectively treated by endocrine therapy, endocrine resistance is an urgent clinical problem. Thus, further understanding of the underlying mechanisms involved in ERα signalling is critical in dealing with endocrine resistance in patients with breast cancer. In the present study, unbiased RNA sequence analysis was conducted between the MCF-7 and MCF-7 tamoxifen-resistant (LCC2) cell lines in order to identify differentially expressed genes. The whole transcriptomic data indicated that the JAK-STAT pathway is markedly up-regulated, particularly the ISGF3 complex. As the critical effectors, STAT1 and IRF9 were up-regulated 5- and 20-fold, respectively, in LCC2 cells. The biological experiments indicated that STAT1 is important for ERα signalling. Depletion of STAT1 or inhibition of STAT1 function significantly decreased levels of ERα protein, ERα -target gene expression and cell proliferation in both the MCF-7 and LCC2 cell lines. Chromatin immunoprecipitation revealed that ERα transcription is associated with STAT1 recruitment to the ERα promoter region, suggesting that transcriptional regulation is one mechanism by which STAT1 regulates ERα mRNA levels and ERα signalling in breast cancer cells. The present study reveals a possible endocrine-resistant mechanism by which STAT1 modulates ERα signalling and confers tamoxifen resistance. Targeting of STAT1 is a potential treatment strategy for endocrine-resistant breast cancers.

RNF168 facilitates oestrogen receptor ɑ transcription and drives breast cancer proliferation.

Oestrogen receptor ɑ (ERɑ) is overexpressed in two-thirds of all breast cancers and involves in development and breast cancer progression. Although ERɑ-positive breast cancer could be effective treated by endocrine therapy, the endocrine resistance is still an urgent clinical problem. Thus, further understanding of the underlying mechanisms ERɑ signalling is critical in dealing with endocrine resistance in breast cancer patients. MCF-7 and T47D breast cancer cell lines are used to carry out the molecular biological experiments. Western blot is used to assess the relative protein level of ERɑ, RNF168 and actin. Real-time PCR is used the measure the relative ERɑ-related gene mRNA level. Luciferase assay is used to measure the relative ERɑ signalling activity. Chromatin immunoprecipitation is used to measure the RNF168 binding affinity to ERɑ promoter regions. WST assay and flow cytometry are used to measure the cell proliferation capacity. We use Student's t test and one-way ANOVA test for statistical data analysis. Here, we report an important role in ERɑ-positive breast cancer cells for RNF168 protein in supporting cell proliferation by driving the transcription of ERɑ. RNF168 is highly expressed in breast cancer samples, compared with normal breast tissue. In patients with breast cancer, RNF168 expression level is correlated with poor endocrine treatment outcome. Depletion of RNF168 causes decreased cell proliferation in MCF-7 and T47D cells. Besides, depletion RNF168 reduced mRNA level of ERɑ and its target genes, such as PS2 and GREB1. Chromatin immunoprecipitation revealed that ERɑ transcription is associated with RNF168 recruitment to ERɑ promoter region, suggesting that transcriptional regulation is one mechanism by which RNF168 regulates ERɑ mRNA level and ERɑ signalling in breast cancer cells. RNF168 is required for ERɑ-positive breast cancer cell proliferation and facilitate ERɑ signalling activity possibly through promoting transcription of ERɑ.

Single Side-Chain-Modulatory of Hemicyanine for Optimized Fluorescence and Photoacoustic Dual-Modality Imaging of H2S In Vivo.

Near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-modality imaging integrated high-sensitivity fluorescence imaging with deep-penetration PA imaging has been recognized as a reliable tool for disease detection and diagnosis. However, it remains an immense challenge for a molecule probe to achieve the optimal NIRF and PA imaging by adjusting the energy allocation between radiative transition and nonradiative transition. Herein, a simple but effective strategy is reported to engineer a NIRF/PA dual-modality probe (Cl-HDN3) based on the near-infrared hemicyanine scaffold to optimize the energy allocation between radiative and nonradiative transition. Upon activation by H2S, the Cl-HDN3 shows a 3.6-fold enhancement in the PA signal and a 4.3-fold enhancement in the fluorescence signal. To achieve the sensitive and selective detection of H2S in vivo, the Cl-HDN3 is encapsulated within an amphiphilic lipid (DSPE-PEG2000) to form the Cl-HDN3-LP, which can successfully map the changes of H2S in a tumor-bearing mouse model with the NIRF/PA dual-modality imaging. This work presents a promising strategy for optimizing fluorescence and PA effects in a molecule probe, which may be extended to the NIRF/PA dual-modality imaging of other disease-relevant biomarkers.

Enhancing lipid peroxidation via radical chain transfer reaction for MRI guided and effective cancer therapy in mice.

Lipid peroxidation (LPO), the process of membrane lipid oxidation, is a potential new form of cell death for cancer treatment. However, the radical chain reaction involved in LPO is comprised of the initiation, propagation (the slowest step), and termination stages, limiting its effectiveness in vivo. To address this limitation, we introduce the radical chain transfer reaction into the LPO process to target the propagation step and overcome the sluggish rate of lipid peroxidation, thereby promoting endogenous lipid peroxidation and enhancing therapeutic outcomes. Firstly, radical chain transfer agent (CTA-1)/Fe nanoparticles (CTA-Fe NPs-1) was synthesized. Notably, CTA-1 convert low activity peroxyl radicals (ROO·) into high activity alkoxyl radicals (RO·), creating the cycle of free radical oxidation and increasing the propagation of lipid peroxidation. Additionally, CTA-1/Fe ions enhance reactive oxygen species (ROS) generation, consume glutathione (GSH), and thereby inactivate GPX-4, promoting the initiation stage and reducing termination of free radical reaction. CTA-Fe NPs-1 induce a higher level of peroxidation of polyunsaturated fatty acids in lipid membranes, leading to highly effective treatment in cancer cells. In addition, CTA-Fe NPs-1 could be enriched in tumors inducing potent tumor inhibition and exhibit activatable T1-MRI contrast of magnetic resonance imaging (MRI). In summary, CTA-Fe NPs-1 can enhance intracellular lipid peroxidation by accelerating initiation, propagation, and inhibiting termination step, promoting the cycle of free radical reaction, resulting in effective anticancer outcomes in tumor-bearing mice.

Age differences in the impact of dietary salt on metabolism, blood pressure and cognitive function in male rats.

The influence of salt consumption on physiological processes, especially blood pressure (BP), metabolism, and cognition, remains a topical concern. While guidelines endorse reduced salt diets, there are gaps in understanding the age-specific implications and challenges in adherence. The present study delved into the differential effects of salt intake on young adult and aged male rats over a 12-week period, using control, low-, and high-salt diets. Key metrics, such as BP, cognition, and general parameters, were monitored. Our findings revealed significant age-dependent effects of salt intake on survival rates, body weight, blood sodium, blood glucose, blood lipids, BP, heart rates, and cognition. Notably, young adult rats did not show significant sodium level changes on a high-salt diet, whereas aged rats experienced increased sodium levels even on a normal salt diet. Blood glucose levels decreased significantly in aged rats on a high-salt diet but remained stable in young adults. Aged rats had the highest survival rates on low-salt diets. Low-salt diets led to reduced BP in both age groups, more significantly in young adults. Young adult rats displayed increased BP variability on both high- and low-salt diets, while a decrease in BP variability was exclusive to aged rats on a low-salt diet. There were significant differences across age groups in short-term memory, but not in long-term memory. The study provides a nuanced understanding of the age-dependent physiological effects of salt intake, suggesting the necessity of age-specific guidelines for public health.

Investigating the synergy of Shikonin and Valproic acid in inducing apoptosis of osteosarcoma cells via ROS-mediated EGR1 expression.

BACKGROUND: Osteosarcoma is the most prevalent malignant bone tumour with a poor prognosis. Shikonin (SHK) is derived from the traditional Chinese medicine Lithospermum that has been extensively studied for its notable anti-tumour effects, including for osteosarcoma. However, its application has certain limitations. Valproic acid (VPA) is a histone deacetylase inhibitor (HDACI) that has recently been employed as an adjunctive therapeutic agent that allows chromatin to assume a more relaxed state, thereby enhancing anti-tumour efficacy. PURPOSE: This study was aimed to investigate the synergistic anti-tumour efficacy of SHK in combination with VPA and elucidate its underlying mechanism. METHODS/STUDY DESIGN: CCK-8 assays were utilized to calculate the combination index. Additional assays, including colony formation, acridine orange/ethidium bromide double fluorescent staining, and flow cytometry, were employed to evaluate the effects on osteosarcoma cells. Wound healing and transwell assays were utilized to assess cell mobility. RNA sequencing, PCR, and Western blot analyses were conducted to uncover the underlying mechanism. Rescue experiments were performed to validate the mechanism of apoptotic induction. The impact of SHK and VPA combination treatment on primary osteosarcoma cells was also assessed. Finally, in vivo experiments were conducted to validate its anti-tumour effects and mechanism. RESULTS: The combination of SHK and VPA synergistically inhibited the proliferation and migration of osteosarcoma cells in vitro and induced apoptosis in these cells. Through a comprehensive analysis involving RNA sequencing, PCR, Western blot, and rescue experiments, we have substantiated our hypothesis that the combination of SHK and VPA induced apoptosis via the ROS-EGR1-Bax axis. Importantly, our in vivo experiments corroborated these findings, demonstrating the potential of the SHK and VPA combination as a promising therapeutic approach for osteosarcoma. CONCLUSION: The combination of SHK and VPA exerted an anti-tumour effect by inducing apoptosis through the ROS-EGR1-Bax pathway. Repurposing the old drug VPA demonstrated its effectiveness as an adjunctive therapeutic agent for SHK, enhancing its anti-tumour efficacy and revealing its potential value. Furthermore, our study expanded the application of natural compounds in the anti-tumour field and overcame some of their limitations through combination therapy. Finally, we enhanced the understanding of the mechanistic pathways linking reactive oxygen species (ROS) accumulation and apoptosis in osteosarcoma cells. Additionally, we elucidated the role of EGR1 in osteosarcoma cells, offering novel strategies and concepts for the treatment of osteosarcoma.

A nomogram for predicting osteoarthritis based on serum biomarkers of bone turnover in middle age: A cross-sectional study of PTH and ß-CTx.

The objective of this study was to investigate the diagnostic model of osteoarthritis by bone turnover markers in Chinese middle-aged subjects. The study was designed as a cross-sectional investigation with 305 participants aged 45 to 64. Radiographs of tibiofemoral knee joints were used for diagnose osteoarthritis. Radiographic grading, evaluated using the Kellgren and Lawrence grading scale (K-L), was scored by 2 experienced observers who were blinded to the source of subjects. An optimal model was developed by logistic regression. And the prognostic performance of the selected model was assessed by the area under the receiver operating characteristic curve. The prevalence of osteoarthritis was 52.29% (n = 137/262) in middle age. ß-CTx levels tended to increase according to the K-L grades, whereas PTH levels significantly decrease. levels of 25(OH)D, ß-CTx, and PTH were each significantly associated with osteoarthritis risk (P < .05). Based on the estimated parameters of the optimal model, a nomogram was constructed for predicting osteoarthritis. These data suggest that the combination of PTH and ß-CTx could significantly improve the prognosis of osteoarthritis in middle age, and that the nomogram can assist primary physicians in the identification of high-risk men.

Knowledge Mapping and Research Hotspots of Generalized Pustular Psoriasis: A Bibliometric Analysis from 2003 to 2023.

Background: Generalised pustular psoriasis (GPP) is a chronic inflammatory skin disease. We aimed to visualize the research hotspots and trends of GPP using bibliometric analysis to enhance our comprehension of the future advancements in both basic science and clinical research. Methods: Relevant publications from July 2003 to July 2023 were obtained from the Web of Science Core Collection on July 12, 2023. The analysis of countries, institutions, authors, references, and keywords associated with this subject was conducted through the utilisation of CiteSpace 6.2.R4, VOSviewer 1.6.18, and Microsoft Excel 2019. Results: A total of 578 papers were analyzed, authored by 2758 researchers from 191 countries/regions and 1868 institutions, published in 174 academic journals. There was an overall upward trajectory in the volume of annual publications, accompanied by a gradual intensification of research interest in GPP. The United States, UDICE-French Research Universities, and Akiyama M of Nagoya University were the most productive and influential country, institution, and author, respectively. The Journal of Dermatology ranked first with the highest publications, and the Journal of the American Academy of Dermatology received the most citations. High-frequency keywords included "generalized pustular psoriasis", "psoriasis, interleukin-36", "plaque psoriasis", "skin-disease", and "antagonist deficiency". Recent research focuses have included "safety", "secukinumab", "spesolimab", "ap1s3 mutations", and "interleukin-36". Burst detection analysis of keywords showed that "moderate", "ixekizumab treatment", "mutations", "efficacy", and "safety" are current research frontiers in this field. Conclusion: This bibliometric analysis delineated the landmark publications in GPP that have defined current research hotspots and development trends, notably the applications, efficacy, and safety of biological agents. Future research endeavors are warranted to explore other biological therapeutic options for both acute GPP and the long-term management of chronic GPP.

Mesenchymal stem cells and macrophages and their interactions in tendon-bone healing.

Tendon-bone insertion injuries (TBI), such as anterior cruciate ligament (ACL) and rotator cuff injuries, are common degenerative or traumatic pathologies with a negative impact on the patient's daily life, and they cause huge economic losses every year. The healing process after an injury is complex and is dependent on the surrounding environment. Macrophages accumulate during the entire process of tendon and bone healing and their phenotypes progressively transform as they regenerate. As the "sensor and switch of the immune system", mesenchymal stem cells (MSCs) respond to the inflammatory environment and exert immunomodulatory effects during the tendon-bone healing process. When exposed to appropriate stimuli, they can differentiate into different tissues, including chondrocytes, osteocytes, and epithelial cells, promoting reconstruction of the complex transitional structure of the enthesis. It is well known that MSCs and macrophages communicate with each other during tissue repair. In this review, we discuss the roles of macrophages and MSCs in TBI injury and healing. Reciprocal interactions between MSCs and macrophages and some biological processes utilizing their mutual relations in tendon-bone healing are also described. Additionally, we discuss the limitations in our understanding of tendon-bone healing and propose feasible ways to exploit MSC-macrophage interplay to develop an effective therapeutic strategy for TBI injuries. The Translational potential of this article: This paper reviewed the important functions of macrophages and mesenchymal stem cells in tendon-bone healing and described the reciprocal interactions between them during the healing process. By managing macrophage phenotypes, mesenchymal stem cells and the interactions between them, some possible novel therapies for tendon-bone injury may be proposed to promote tendon-bone healing after restoration surgery.