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Iron plays an essential role in various physiological processes. A disruption in iron homeostasis can lead to severe consequences, including impaired neurodevelopment, neurodegenerative disorders, stroke, and cancer. Interestingly, the link between mental health disorders and iron homeostasis has not received significant attention. Therefore, our understanding of iron metabolism in the context of psychological diseases is incomplete. In this review, we aim to discuss the pathologies and potential mechanisms that relate to iron homeostasis in associated mental disorders. We propose the hypothesis that maintaining brain iron homeostasis can support neuronal physiological functions by impacting key enzymatic activities during neurotransmission, redox balance, and myelination. In conclusion, our review highlights the importance of investigating the relationship between trace element nutrition and the pathological process of mental disorders, focusing on iron. This nutritional perspective can offer valuable insights for the clinical treatment of mental disorders.

Abstract Background Few studies have investigated the differences in clinical features of patients with mastitis following Corynebacterium kroppenstedtii infection, and most focused on the bacterial antimicrobial susceptibility, detection methods and therapy. Methodology There were 133 patients with mastitis infected by C. kroppenstedtii between August 2016 and September 2019. C. kroppenstedtii was identified using mass spectrometry. The demographics, clinical diagnosis, laboratory test results of different types of mastitis combined with bacillus infection, and the effects of different treatments in reducing recurrence were compared. Results The incidence of pus following C. kroppenstedtii infection was higher in patients with non-granulomatous lobular mastitis (NGLM; 56.6%) than in those with granulomatous lobular mastitis (GLM; 33.3%; χ2 = 7.072, p = 0.008). While C-reactive protein (CRP) was higher in the GLM group (12.50 mg/L) than in the NGLM group (6.05 mg/L; Z = − 2.187, p = 0.029). Treatment with local lavage (triamcinolone acetonide) and antibiotics (cefuroxime) showed a recurrent rate of 25.9% in C. kroppenstedtii infection. Conclusion Increased pus, large masses, and an elevated CRP level may occur in patients with mastitis infected by C.kroppenstedtii. These clinical features may guide the determination of the bacterial infection in patients with mastitis. Combining an antibiotic with a triamcinolone acetonide lavage, preferably cefuroxime, may reduce the recurrence.

Tumor-associated macrophages (TAMs) are closely related to tumorigenesis and metastasis of multiple cancer types. The infiltration of TAMs is used for predicting the prognosis of cancers, including colorectal cancer (CRC). However, the density and prognostic significance of M1 and M2 TAM phenotypes in the intratumor versus the invasive front (IF) are largely unknown in CRC. In this study, CD68 was selected as a general marker of TAMs, CD11c, NOS2 and CXCL10 as markers for M1 phenotype and CD163, CD206, CD115 as markers for M2 phenotype. Firstly, immunohistochemistry staining and double-labeling immunofluorescence staining showed that M1 molecular markers (NOS2, CXCL10, CD11c) were lowly expressed at both IF and intratumor, while M2 molecular markers (CD163, CD206, CD115) were highly expressed mainly at IF. Moreover, we also demonstrated that three M1 molecular markers including NOS2, CXCL10 and CD11c were correlated to each other. Meanwhile, three M2 molecular markers including CD163, CD206, and CD115 were also correlated to each other. Patients with low expression of three M1 molecular markers (NOS2/CXCL10/CD11c) exhibited low overall survival (OS) rate, whereas patients with high expression of three M2 molecular markers (CD163/CD206/CD115) exhibited low OS rate. We also observed that the prognostic value of treble markers combination (NOS2/CXCL10/CD11c or CD163/CD206/CD115) was superior to that of single marker. Together, our results reveal the combination of treble TAMs markers (NOS2/CXCL10/CD11c or CD163/CD206/CD115) could better evaluate the prognosis of CRC patients, which might be used as a more comprehensive method for predicting the prognosis of CRC patients.

Abstract Background Tumor budding is included in the routine diagnosis of colorectal cancer (CRC) and is considered a tumor prognostic factor independent of TNM staging. This study aimed to identify the fibroblast-mediated effect of tumor bud-derived C–C chemokine ligand 5 (CCL5) on the tumor microenvironment (TME). Methods Recruitment assays and a human cytokine array were used to detect the main cytokines that CRC tumor buds secrete to recruit fibroblasts. siRNA transfection and inhibitor treatment were used to investigate the role of fibroblast CCL5 receptors in fibroblast recruitment. Subsequently, transcriptome sequencing was performed to explore the molecular changes occurring in fibroblasts upon stimulation with CCL5. Finally, clinical specimens and orthotopic xenograft mouse models were studied to explore the contribution of CCL5 to angiogenesis and collagen synthesis. Results Hematoxylin–eosin staining and immunochemistry revealed a higher number of fibroblasts at the invasive front of CRC tissue showing tumor budding than at sites without tumor budding. In vitro experiments demonstrated that CCL5 derived from tumor buds could recruit fibroblasts by acting on the CCR5 receptors on fibroblasts. Tumor bud-derived CCL5 could also positively regulate solute carrier family 25 member 24 (SLC25A24) expression in fibroblasts, potentially activating pAkt-pmTOR signaling. Moreover, CCL5 could increase the number of α-SMAhigh CD90high FAPlow fibroblasts and thus promote tumor angiogenesis by enhancing VEGFA expression and making fibroblasts transdifferentiate into vascular endothelial cells. Finally, the results also showed that CCL5 could promote collagen synthesis through fibroblasts, thus contributing to tumor progression. Conclusions At the invasive front of CRC, tumor bud-derived CCL5 can recruit fibroblasts via CCR5-SLC25A24 signaling, further promoting angiogenesis and collagen synthesis via recruited fibroblasts, and eventually create a tumor-promoting microenvironment. Therefore, CCL5 may serve as a potential diagnostic marker and therapeutic target for tumor budding in CRC.

Cdc42-interacting protein 4 (CIP4), a member of the F-BAR family, which plays an important role in regulating cell membrane and actin, has been reported to interact with Cdc42 and be closely associated with tumor invadopodia formation. In this study, we found that CIP4 expression was significantly higher in human CRC tissues and correlated with the CRC infiltrating depth and metastasis, as well as the lower survival rate in patients. In cultured CRC cells, knockdown of CIP4 inhibited cell migration and invasion ability in vitro and tumor metastasis in vivo, while the overexpression of CIP4 promoted invadopodia formation and matrix degradation ability. We then identified GTP-Cdc42 as a directly interactive protein of CIP4, which was upregulated and recruited by CIP4. Furthermore, activated NF-κB signaling pathway was found in CIP4 overexpression of CRC cells contributing to invadopodia formation, while the inhibition of either CIP4 or Cdc42 led to the suppression of the NF-κB pathway and resulted in a decreased quantity of invadopodia. Our findings suggested that CIP4 targets to recruit GTP-Cdc42 and directly combines with it to accelerate invadopodia formation and function by activating NF-κB signaling pathway, thus promoting CRC infiltration and metastasis.

Abstract Background Basic life support and advanced life support are essential emergency management skills for medical workers, and pediatricians' first aid skills can be improved through emergency knowledge training. Methods A controlled pre–post-intervention quasi-experimental study design was used. The study setting was a tertiary children's hospital in China. In November 2019, a KSS model of emergency knowledge learning was developed and tested, and pediatric medical workers (N = 1448) were trained with it. The outcome measures were based on an emergency knowledge questionnaire devised by the authors that measured the effectiveness of training by comparing the pre-and post-training scores of the particpants. Results Pediatric medical workers scored significantly higher in total emergency knowledge after the training course than before [75.00 (62.50, 85.00) versus 100.00 (95.00, 100.00); P = 0.00]. Basic life support and advanced life support knowledge score significantly improved after training. Teamwork scores were significantly higher after the training than before [5.00 (5.00, 10.00) versus 10.00 (10.00, 10.00); P = 0.00]. Scores were significantly higher after the training (P

Leaf epidermal characteristics are important for phylogenetic and taxonomic studies of many plants, but there is currently insufficient such data for this application in Zingiber species. Therefore, the leaf epidermal micromorphology of 22 species in three sections of Zingiber was investigated by light microscopy and scanning electron microscopy. Differences between various taxonomic groups of Zingiberaceae were also compared to assess their phylogenetic and taxonomic significance. As in other genera of Zingiberaceae, the epidermal cells in both the adaxial and abaxial epidermis of Zingiber species were found to be hexagonal or polygonal, with non-sinuous anticlinal walls that are arranged parallel to leaf veins. Tetracytic stomata are mostly randomly distributed in the intercostal regions of both surfaces and are more common on the abaxial surface. The stomatal density of the species in sect. Pleuranthesis is significantly lower than that in sects. Zingiber and Cryptanthium. There are two types of trichome in Zingiber: so-called “delicate” trichomes are present in most species, while “stout” trichomes with a swollen base are only found in Z. corallinum and Z. montanum. Oil cells occur in both epidermal layers of some species in sects. Zingiber and Cryptanthium, but only in the abaxial epidermis of Z. ellipticum in sect. Pleuranthesis. Crystals are found in the abaxial epidermis only in all species, but are present in both epidermal layers of Z. corallinum and Z. montanum. Although the epidermal morphology is similar in most Zingiber species, stomatal density, type of trichome and distribution of oil cells and crystals offer valuable information for the systematic and taxonomic studies in this genus.

To clarify the strengthening mechanisms of medium‐chromium stainless steels (SSs) with carbides, ferrite, and martensite, 17%Cr SSs with varying martensite contents have been prepared, and the influence of martensite on microstructure, mechanical properties, and fracture has been investigated. According to THERMOCALC calculations, 17%Cr SS undergo a reversible phase transition between austenite and ferrite + M23C6 through the diffusion of carbon in austenite and M23C6 in the temperature range of 850–1220 °C. As the martensite content increases, M23C6 decreases, the martensite grain size increases, and the ferrite grain size initially increases and then decreases. Meanwhile, the yield strength and ultimate tensile strength increase, while both the uniform and post‐uniform elongation decrease. It is also found a decrease in work‐hardening index and an increase in work‐hardening rate with increasing martensite content. Under tensile loading, three types of voids are present in 17%Cr SS: type A only in the grain boundary (GB) area with M23C6 in martensite‐free material and type B and C in ferrite grains close to martensite grains and at ferrite/martensite GBs, respectively. An increase in martensite content leads to more voids, indicating a reduction in material plasticity caused by martensite. [ABSTRACT FROM AUTHOR]

Background: In December 2023, our hospital confirmed a case of finger infection with Mycobacterium marinum. The patient sought medical attention at our hospital due to a hard scratch on her left middle finger, which was red, swollen, and ulcerated for one month. Physical examination: A lesion of approximately 1.5 cm x 2 cm in the patient's left middle finger, surrounded by redness and swelling, unclear boundaries, surface rupture, partial scabbing, and no tenderness during compression. She was treated at the previous clinic, common infectious diseases were considered, and was given intravenous infusion treatment: cefotaxime and clarithromycin, and erythromycin ointment was applied externally. She came to our hospital after poor treatment results. The patient has had hypertension for 3 years, no other systemic diseases, no similar medical history among family members, no history of drug or food allergies. Methods: Clean the wound and remove the scab from the affected area, and use a surgical blade to scrape off necrotic tissue. Send the scraped tissue for pathogen testing: tissue bacterial culture+identification (matrix assisted laser desorption/ionization time-of-flight mass spectrometry, MALDI-TOF), tissue acid fast staining, and tissue metagenomic next-generation sequencing (mNGS). Other auxiliary examinations: blood routine, urine routine, blood fat, liver function, and kidney function. Results: Tissue bacterial culture+identification: growth of Mycobacterium marinum; Acid fast staining of tissue: positive; Tissue mNGS: Mycobacterium marinum. Clinical treatment plan: clarithromycin 0.5 g bid po+rifampicin 0.45 g qd po+5-aminolevulinic acid photodynamic therapy (ALA-PDT) qw+boric acid wash wet compress tid. After 14 days of treatment, the area of redness and swelling significantly decreased, and the degree of redness and swelling was significantly reduced compared to admission. The degree of ulcer edge protrusion was also reduced compared to admission. There was a small amount of exudation from the wound, and no necrotic tissue was observed. The patient improved and was discharged. Conclusions: This article reports a case of finger infection with Mycobacterium marinum. Mycobacterium marinum was quickly and accurately identified by mNGS, and reasonable treatment measures were adopted clinically. The patient improved and was discharged. This study has important reference significance for the clinical diagnosis and treatment of Mycobacterium infection. In addition, mNGS as a novel detection method has considerable prospects for rapid diagnosis of pathogens. [ABSTRACT FROM AUTHOR]

Iron is essential for life, and the dysregulation of iron homeostasis can lead to severe pathological changes in the neurological system [...]

The walnut (Juglans regia L.) is an important economic tree worldwide, often cultivated in arid and semiarid regions. Improving the drought tolerance is of significance for walnut growth, production, and economic effectiveness. 5-Aminolevulinic acid (ALA) is a novel plant growth regulator which raises plant tolerance to various stressful conditions. Here, foliage application of ALA was carried out to uncover its effect on walnuts under polyethylene glycol (PEG) 6000-stimulated osmotic stress. Our results displayed that exogenous ALA greatly promoted the chlorophyll content, photochemical activities, and gas exchange in walnuts under osmotic stress. ALA led to a considerable accumulation of compatible osmotic solutes, enabling walnuts to maintain osmotic equilibrium against drought stress. Furthermore, ALA alleviated the reactive oxygen species (ROS) damages on osmotically stressed walnuts through enhancing the antioxidant enzyme activities, as well as decreasing the ROS and malondialdehyde (MDA) content. The relative water content (RWC) in the ALA-treated leaves was higher than that of PEG-stressed, while the RWC in the substrate of ALA treatment was significantly lower than that of the PEG-stressed, further suggesting that ALA promotes plant water uptake from the substrate under osmotic stress. These demonstrate that ALA improves the photosynthesis, osmotic adjustment, antioxidant systems and, consequently, the walnuts’ drought tolerance.

The review briefly introduces the natural occurrence, physicochemical properties, and biosynthesis of 5-aminolevuinic acid (ALA) and highlights a variety of applications in the planting industry and its possible mechanisms. It has been known that ALA can be used as biological pesticides, fungicides, and herbicides when the concentrations are higher than 838 mg L−1 (about 5 mmol L−1). When ALA concentrations are 100–300 mg L−1, it can be used to thin surplus flowers in the spring of orchards and promote fruit coloration before maturation. When the concentrations are lower than 100 mg L−1, especially not higher than 10 mg L−1, ALA can be used as a new plant growth regulator to promote seed germination, plant (including root and shoot) growth, enhance stress tolerance, increase crop yield, and improve product quality. In photosynthesis, ALA is involved in the regulation of the whole process. In stress tolerance, ALA induces plant preventive and protective systems through the NO/H2O2 signaling network. In secondary metabolism, ALA regulates many gene expressions encoding transcription factors or function proteins to promote anthocyanin and flavonol biosynthesis and accumulation. In general, ALA promotes plant health and robustness, reduces the use of chemical fertilizers and pesticides—which is conducive to improving the ecological environment, human production, and living conditions—and has a broad application prospect in agroforestry production. As a new plant growth regulator with multiple and powerful functions, the underlying regulatory mechanisms need more study.

Sugars and organic acids significantly impact fruit sensory quality, but their accumulation patterns and regulatory mechanisms during the development of Rosa roxburghii fruit are still unclear. We utilized transcriptomics and metabolomics to investigate genes related to sugar and organic acid metabolism in Rosa roxburghii. Metabolomics data revealed that sucrose, glucose and fructose were the primary sugars, whereas citric acid and malic acid were the primary organic acids in Rosa roxburghii fruit. We constructed the metabolic pathways of major sugars and organic acids in Rosa roxburghii and identified five key genes involved in sugar and organic acid synthesis. In addition, we identified a module containing 132 transcription factors that was significantly associated with sucrose, citric acid and malic acid. Based on quantitative polymerase chain reaction (qPCR), we identified 13 transcription factors involved in sugar and organic acid metabolism, including the transcription factor RrANL2 and the sucrose synthase gene RrSUS3. Further yeast one-hybrid and dual luciferase assays showed that RrANL2 could bind to the promoter of RrSUS3 to increase its expression. These results provide new insights into the metabolism of sugars and organic acids in Rosa roxburghii fruit.

To observe the effect of magnesium ion on vascular function in rats after long-term exhaustive exercise. Forty male SD rats were divided into two groups, the control group (CON group, n = 20) and the exhaustive exercise group (EEE group, n = 20). Exhausted rats performed 1W adaptive swimming exercise (6 times/W, 15min/time), and then followed by 3W formal exhaustive exercise intervention. Hematoxylin and eosin (HE) staining was used to detect the morphological changes of rat thoracic aorta. The contents of interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum of rats were determined by enzyme-linked immunosorbent assay (ELISA), and the contents of malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO) and endothelin 1 (ET-1) in serum of rats were determined by biochemical kit. Vascular ring test detects vascular function. Compared with the CON group, the smooth muscle layer of the EEE group became thicker, the cell arrangement was disordered, and the integrity of endothelial cells was destroyed; the serum Mg2+ in EEE group was decreased; the serum levels of IL-1β, TNF-α, MDA and ROS in EEE group were significantly higher than those in the CON group (P are all less than 0.05); the serum NO content in EEE group was significantly decreased, and the ratio of NO/ET-1 was significantly decreased. In the exhaustion group, the vasoconstriction response to KCl was increased, and the relaxation response to Ach was weakened, while 4.8mM Mg2+ could significantly improve this phenomenon (P are all less than 0.01). The damage of vascular morphology and function in rats after exhaustion exercise may be related to the significant increase of serum IL-1β, TNF-α, ROS, MDA and ET-1/NO ratio in rats after exhaustion exercise, while Mg2+ can significantly improve the vasomotor function of rats after exhaustion exercise.

Melastoma, consisting of ~100 species diversified in tropical Asia and Oceania in the past 1-2 million years, represents an excellent example of rapid speciation in flowering plants. Trichomes on hypanthia, twigs and leaves vary markedly among species of this genus and are the most important diagnostic traits for species identification. These traits also play critical roles in contributing to differential adaptation of these species to their own habitats. Here we sequenced the genome of M. candidum, a common, erect-growing species from southern China, with the aim to provide genomic insights into trichome evolution in this genus. We generated a high-quality, chromosome-level genome assembly of M. candidum, with the genome size of 256.2 Mb and protein-coding gene number of 40,938. The gene families specific to, and significantly expanded in Melastoma are enriched for GO terms related to trichome initiation and differentiation. We provide evidence that Melastoma and its sister genus Osbeckia have undergone two whole genome duplications (WGDs) after the triplication event (γ) shared by all core eudicots. Preferential retention of trichome development-related transcription factor genes such as C2H2, bHLH, HD-ZIP, WRKY, and MYB after both WGDs might provide raw materials for trichome evolution and thus contribute to rapid species diversification in Melastoma. Our study provides candidate transcription factor genes related to trichome evolution in Melastoma, which can be used to evolutionary and functional studies of trichome diversification among species of this genus.

Abstract Met tyrosine kinase, a receptor for a hepatocyte growth factor (HGF), plays a critical role in tumor growth, metastasis, and drug resistance. Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network. Dysregulated mitochondrial dynamics are responsible for the progression and metastasis of many cancers. Here, using structured illumination microscopy (SIM) and high spatial and temporal resolution live cell imaging, we identified mitochondrial trafficking of receptor tyrosine kinase Met. The contacts between activated Met kinase and mitochondria formed dramatically, and an intact HGF/Met axis was necessary for dysregulated mitochondrial fission and cancer cell movements. Mechanically, we found that Met directly phosphorylated outer mitochondrial membrane protein Fis1 at Tyr38 (Fis1 pY38). Fis1 pY38 promoted mitochondrial fission by recruiting the mitochondrial fission GTPase dynamin-related protein-1 (Drp1) to mitochondria. Fragmented mitochondria fueled actin filament remodeling and lamellipodia or invadopodia formation to facilitate cell metastasis in hepatocellular carcinoma (HCC) cells both in vitro and in vivo. These findings reveal a novel and noncanonical pathway of Met receptor tyrosine kinase in the regulation of mitochondrial activities, which may provide a therapeutic target for metastatic HCC.

Hepatocellular carcinoma (HCC) is one of the most common and deadly malignancies worldwide. Approximately, 80% of patients are initially diagnosed at intermediate or advanced stages, which means that curative therapies are unable to be performed. In most cases, systemic treatment is ineffective, especially when conventional cytotoxic agents are used. Sorafenib has been the only systemic agent proven to be effective in treating advanced HCC for over a decade. The rapid development of immunotherapy has remarkably revolutionized the management of advanced HCC. Besides, the combination of immunotherapy with molecular targeted agents or locoregional treatments is emerging as an effective tool for enhancing immunity. In the review, an overview of immunotherapy and its combination therapies for HCC is presented.

Oxidative stress and deficient bioenergetics are key players in the pathological process of cerebral ischemia reperfusion injury (I/R). As a mitochondrial iron storage protein, mitochondrial ferritin (FtMt) plays a pivotal role in protecting neuronal cells from oxidative damage under stress conditions. However, the effects of FtMt in mitochondrial function and activation of apoptosis under cerebral I/R are barely understood. In the present study, we found that FtMt deficiency exacerbates neuronal apoptosis via classical mitochondria-depedent pathway and the endoplasmic reticulum (ER) stress pathway in brains exposed to I/R. Conversely, FtMt overexpression significantly inhibited oxygen and glucose deprivation and reperfusion (OGD/R)-induced apoptosis and the activation of ER stress response. Meanwhile, FtMt overexpression rescued OGD/R-induced mitochondrial iron overload, mitochondrial dysfunction, the generation of reactive oxygen species (ROS) and increased neuronal GSH content. Using the Seahorse and O2K cellular respiration analyser, we demonstrated that FtMt remarkably improved the ATP content and the spare respiratory capacity under I/R conditions. Importantly, we found that glucose consumption was augmented in FtMt overexpressing cells after OGD/R insult; overexpression of FtMt facilitated the activation of glucose 6-phosphate dehydrogenase and the production of NADPH in cells after OGD/R, indicating that the pentose-phosphate pathway is enhanced in FtMt overexpressing cells, thus strengthening the antioxidant capacity of neuronal cells. In summary, our results reveal that FtMt protects against I/R-induced apoptosis through enhancing mitochondrial bioenergetics and regulating glucose metabolism via the pentose-phosphate pathway, thus preventing ROS overproduction, and preserving energy metabolism.